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PMID:24731 | Enhancement by choline of the induction of adrenal tyrosine hydroxylase by phenoxybenzamine, 6-hydroxydopamine, insulin or exposure to cold. | Treatments that increase the release of acetylcholine from the splanchnic nerve have previously been shown to induce the enzyme tyrosine hydroxylase in adrenal chromaffin cells. Such treatments include the systemic administration of the drugs phenoxybenzamine and 6-hydroxydopamine, insulin-induced hypoglycemia, and prolonged exposure to cold. We have reported that the administration of choline also induces the adrenal enzyme and have suggested that the mechanism of this induction involves an increase in the amount of acetylcholine released each time the splanchnic nerve fires. In the present studies, rats received both choline and one of the above treatments. Choline caused an augmentation of the adrenomedullary response to each of the treatments, but it had no apparent effect on a presynaptic enzyme, choline acetyltransferase. These observations strongly support the view that choline availability determines both the amount of acetylcholine present in nerve terminals and the amount liberated when cholinergic neurons fire. | Enhancement by choline of the induction of adrenal tyrosine hydroxylase by phenoxybenzamine, 6-hydroxydopamine, insulin or exposure to cold. Treatments that increase the release of acetylcholine from the splanchnic nerve have previously been shown to induce the enzyme tyrosine hydroxylase in adrenal chromaffin cells. Such treatments include the systemic administration of the drugs phenoxybenzamine and 6-hydroxydopamine, insulin-induced hypoglycemia, and prolonged exposure to cold. We have reported that the administration of choline also induces the adrenal enzyme and have suggested that the mechanism of this induction involves an increase in the amount of acetylcholine released each time the splanchnic nerve fires. In the present studies, rats received both choline and one of the above treatments. Choline caused an augmentation of the adrenomedullary response to each of the treatments, but it had no apparent effect on a presynaptic enzyme, choline acetyltransferase. These observations strongly support the view that choline availability determines both the amount of acetylcholine present in nerve terminals and the amount liberated when cholinergic neurons fire. | [
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PMID:24734 | The increase in spontaneous transmitter release produced by beta-bungarotoxin and its modification by inorganic ions. | The excitatory phase of the biphasic action on transmitter release of the neurotoxin, beta-bungarotoxin (beta-BuTX; 0.5 microgram ml-1), was studied on miniature end-plate potentials (MEPPs) at frog sciatic nerve-sartorius muscle junctions. The most common type of excitatory response was characterized by a continuous increase in MEPP frequency that reached a plateau; a less common form was characterized by irregular episodic bursts of firing. There was a direct relationship between toxin activity and [K+]O (2.5-10.0 mM) with virtually no effect of the toxin at normal [K]O+ at the concentration of toxin used. In the absence of Mg++, there was a paradoxical inverse relationship between toxin activity and [Ca++]O (0.5-4.0 mM) at higher [K+]O. However, in the presence of 1.0 mM Mg++ the increased MEPP frequency produced by beta-BuTX was independent of [Ca++]O. The action of beta-BuTX was very sensitive to blockade by Mg++. Toxin activity was demonstrated in a Sr++-containing, Ca++-free solution, but not in a Mg++-containing, Ca++-free solution. It is probable that beta-BuTX causes a slight depolarization of the nerve terminals by a mechanism not sensitive to blockade by tetrodotoxin and that the ability of beta-BuTX to depolarize the terminals can account for the enhancement of the response by raising [K+]O and the depression of the response by Mg++. Alternatively, beta-BuTX could be producing its effects by some, as yet undefined, direct action on the release process. | The increase in spontaneous transmitter release produced by beta-bungarotoxin and its modification by inorganic ions. The excitatory phase of the biphasic action on transmitter release of the neurotoxin, beta-bungarotoxin (beta-BuTX; 0.5 microgram ml-1), was studied on miniature end-plate potentials (MEPPs) at frog sciatic nerve-sartorius muscle junctions. The most common type of excitatory response was characterized by a continuous increase in MEPP frequency that reached a plateau; a less common form was characterized by irregular episodic bursts of firing. There was a direct relationship between toxin activity and [K+]O (2.5-10.0 mM) with virtually no effect of the toxin at normal [K]O+ at the concentration of toxin used. In the absence of Mg++, there was a paradoxical inverse relationship between toxin activity and [Ca++]O (0.5-4.0 mM) at higher [K+]O. However, in the presence of 1.0 mM Mg++ the increased MEPP frequency produced by beta-BuTX was independent of [Ca++]O. The action of beta-BuTX was very sensitive to blockade by Mg++. Toxin activity was demonstrated in a Sr++-containing, Ca++-free solution, but not in a Mg++-containing, Ca++-free solution. It is probable that beta-BuTX causes a slight depolarization of the nerve terminals by a mechanism not sensitive to blockade by tetrodotoxin and that the ability of beta-BuTX to depolarize the terminals can account for the enhancement of the response by raising [K+]O and the depression of the response by Mg++. Alternatively, beta-BuTX could be producing its effects by some, as yet undefined, direct action on the release process. | [
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PMID:24735 | The generation of nerve impulses in mammalian axons by changing the concentrations of the normal constituents of extracellular fluid. | 1. Experiments have been performed to determine what changes in normal constituents of extracellular fluid are necessary to generate action potentials in mammalian axons. 2. Single and multifibre preparations of rat spinal roots were tested with Krebs solutions in which Na+, K+, Ca2+, Mg2+, pH, PCO2 or osmotic pressure were varied. 3. [Ca2+] below 1.0 mM produced impulses in all preparations. Lowering [Mg2+] did not generate any impulses but did enhance the response to low [Ca2+]. 4. Increasing [Na+] or [K+] caused excitation in some of the multifibres; increased [Na+] evoked 'off' responses in two single fibre preparations. The response to low [Ca2+] was enhanced by increasing [Na+] and depressed by increasing [K+]. 5. Increasing the osmotic pressure (with glucose) did not generate impulses and depressed the response to low [Ca2+]. 6. Changing the pH of Krebs solution did not generate impulses, but modified the response to other stimuli. The response to low [Ca2+] was increased as pH increased from pH 7.4 to 8.2, and decreased with pH in the range pH 7.4--6.2. 7. Altering pCO2 did not have any effect on the responses to low [Ca2+] unless pH also changed. | The generation of nerve impulses in mammalian axons by changing the concentrations of the normal constituents of extracellular fluid. 1. Experiments have been performed to determine what changes in normal constituents of extracellular fluid are necessary to generate action potentials in mammalian axons. 2. Single and multifibre preparations of rat spinal roots were tested with Krebs solutions in which Na+, K+, Ca2+, Mg2+, pH, PCO2 or osmotic pressure were varied. 3. [Ca2+] below 1.0 mM produced impulses in all preparations. Lowering [Mg2+] did not generate any impulses but did enhance the response to low [Ca2+]. 4. Increasing [Na+] or [K+] caused excitation in some of the multifibres; increased [Na+] evoked 'off' responses in two single fibre preparations. The response to low [Ca2+] was enhanced by increasing [Na+] and depressed by increasing [K+]. 5. Increasing the osmotic pressure (with glucose) did not generate impulses and depressed the response to low [Ca2+]. 6. Changing the pH of Krebs solution did not generate impulses, but modified the response to other stimuli. The response to low [Ca2+] was increased as pH increased from pH 7.4 to 8.2, and decreased with pH in the range pH 7.4--6.2. 7. Altering pCO2 did not have any effect on the responses to low [Ca2+] unless pH also changed. | [
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PMID:24736 | Calcium and strontium concentration changes within skinned muscle preparations following a change in the external bathing solution. | 1. A method for producing rapid [Ca2+] and [Sr2+] changes in the frog skinned muscle fibre preparation while maintaining constant all other cationic concentrations (Moisescu, 1976a, b) is described and analysed in detail. 2. Different experiments, some of them involving the Ca2+-sensitive photoprotein aequorin, as well as theoretical considerations, indicate that with this method one can produce a Ca2+ (or Sr2+) concentration change within 0.1--0.15 sec in a whole preparation having a diameter of 50 micrometer. 3. The rate of force development was similar to that observed in vivo. 4. The radial diffusion coefficient of EGTA in relaxed myofibrillar preparations was measured and found to be 4.6 x 10(-6) cm2sec-1 at 20 degrees C. 5. The sarcoplasmic reticulum in myofibrillar bundles was found to be active with respect to both Ca2+ and Sr2+ in the solutions used ([Mg2+] 1 mM; [Na] 30 mM; [K] 140-170 mM; [Cl] less than or equal to 20 mM; pH 7.10). 6. The amount of Ca released by caffeine from internal stores (previously loaded with Ca) can raise the total Ca concentration in the muscle fibre preparation by at least 1.8 mM. 7. The presence of 10 mM-caffeine in all bathing solutions reduced drastically the ability of the sarcoplasmic reticulum to accumulate both Ca and Sr. | Calcium and strontium concentration changes within skinned muscle preparations following a change in the external bathing solution. 1. A method for producing rapid [Ca2+] and [Sr2+] changes in the frog skinned muscle fibre preparation while maintaining constant all other cationic concentrations (Moisescu, 1976a, b) is described and analysed in detail. 2. Different experiments, some of them involving the Ca2+-sensitive photoprotein aequorin, as well as theoretical considerations, indicate that with this method one can produce a Ca2+ (or Sr2+) concentration change within 0.1--0.15 sec in a whole preparation having a diameter of 50 micrometer. 3. The rate of force development was similar to that observed in vivo. 4. The radial diffusion coefficient of EGTA in relaxed myofibrillar preparations was measured and found to be 4.6 x 10(-6) cm2sec-1 at 20 degrees C. 5. The sarcoplasmic reticulum in myofibrillar bundles was found to be active with respect to both Ca2+ and Sr2+ in the solutions used ([Mg2+] 1 mM; [Na] 30 mM; [K] 140-170 mM; [Cl] less than or equal to 20 mM; pH 7.10). 6. The amount of Ca released by caffeine from internal stores (previously loaded with Ca) can raise the total Ca concentration in the muscle fibre preparation by at least 1.8 mM. 7. The presence of 10 mM-caffeine in all bathing solutions reduced drastically the ability of the sarcoplasmic reticulum to accumulate both Ca and Sr. | [
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PMID:24737 | The effect of external pH on osmotic permeability, ion and fluid transport across isolated frog skin. | 1. The rate of volume flow across frog skin induced by an osmotic gradient was measured when normal (7.4) and low pH (2.28) solutions bathed the outside. The osmotic permeabilities (Pos) were 2.4 +/- 0.4 and 4.8 +/- 1.0 micrometer/sec, respectively. The change in Pos induced by low pH was reversible. 2. Volume flow in the absence of an osmotic gradient was measured at normal and low pH. Values were 0.69 +/- 0.13 and 1.1 +/- 0.2 microliter/hr. cm2, respectively; the paired differences were significant (P less than 0.0025). This change in rate was partially reversible upon return to normal pH. 3. The potential difference (V) and short-circuit current (Is) across skins were measured under several conditions and the following equivalent parameters in a simplified electrical model were computed: total resistance (Rt); shunt resistance (Rs); electromotive force of the pump (ENa); and salt transport at open circuit (JNaCl). Representative figures were (a), at pH 7.4: Is = 14 +/- 1.6 microampere/cm2; Rt = 3.3 +/- 0.4 komega.cm2; Rs = 7.2 +/- 1.0 komega.cm2; ENA = 103 +/- 38 mV; JNaCl = 7.2 +/- 1.2 microampere/cm2; (b) at pH 2.28: Is = 8.3 +/- 2.1 microampere/cm2; Rt = 0.46 +/- 0.12 komega. cm2; Rs = 0.65 +/- 0.06 komega.cm2; ENa = 59 +/- 25 mV; JNaCl = 9.4 +/- 3.3 microampere/cm2. 4. From the electrical parameters measured concomitantly with the rate of fluid transport in given experiments, the expected salt concentration of the transported fluid was 0.30 +/- 0.08 and 0.38 +/- 0.08 mole/l. at normal and low pH, respectively, or some 3-4 times hyperosmotic with respect to the medium. 5. Treatment with low pH on the outside has been found to open the intercellular junctions in previous studies. The present results suggest that, if such an effect occurs, it is localized only to a small fraction of the cell perimeter. Making certain assumptions that fraction could be as low as 0.003. 6. Low pH on the outside reversibly changes the electrical parameters of a 'tight' epithelium like the frog skin into values more typical of 'intermediate' epithelia; both the total and shunt resistances decrease to about 0.1 of their normal values. These changes do not apparently affect the osmolarity of the transported fluid. | The effect of external pH on osmotic permeability, ion and fluid transport across isolated frog skin. 1. The rate of volume flow across frog skin induced by an osmotic gradient was measured when normal (7.4) and low pH (2.28) solutions bathed the outside. The osmotic permeabilities (Pos) were 2.4 +/- 0.4 and 4.8 +/- 1.0 micrometer/sec, respectively. The change in Pos induced by low pH was reversible. 2. Volume flow in the absence of an osmotic gradient was measured at normal and low pH. Values were 0.69 +/- 0.13 and 1.1 +/- 0.2 microliter/hr. cm2, respectively; the paired differences were significant (P less than 0.0025). This change in rate was partially reversible upon return to normal pH. 3. The potential difference (V) and short-circuit current (Is) across skins were measured under several conditions and the following equivalent parameters in a simplified electrical model were computed: total resistance (Rt); shunt resistance (Rs); electromotive force of the pump (ENa); and salt transport at open circuit (JNaCl). Representative figures were (a), at pH 7.4: Is = 14 +/- 1.6 microampere/cm2; Rt = 3.3 +/- 0.4 komega.cm2; Rs = 7.2 +/- 1.0 komega.cm2; ENA = 103 +/- 38 mV; JNaCl = 7.2 +/- 1.2 microampere/cm2; (b) at pH 2.28: Is = 8.3 +/- 2.1 microampere/cm2; Rt = 0.46 +/- 0.12 komega. cm2; Rs = 0.65 +/- 0.06 komega.cm2; ENa = 59 +/- 25 mV; JNaCl = 9.4 +/- 3.3 microampere/cm2. 4. From the electrical parameters measured concomitantly with the rate of fluid transport in given experiments, the expected salt concentration of the transported fluid was 0.30 +/- 0.08 and 0.38 +/- 0.08 mole/l. at normal and low pH, respectively, or some 3-4 times hyperosmotic with respect to the medium. 5. Treatment with low pH on the outside has been found to open the intercellular junctions in previous studies. The present results suggest that, if such an effect occurs, it is localized only to a small fraction of the cell perimeter. Making certain assumptions that fraction could be as low as 0.003. 6. Low pH on the outside reversibly changes the electrical parameters of a 'tight' epithelium like the frog skin into values more typical of 'intermediate' epithelia; both the total and shunt resistances decrease to about 0.1 of their normal values. These changes do not apparently affect the osmolarity of the transported fluid. | [
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PMID:24738 | Measurement of pH in the rat epididymis in vivo. | Antimony microelectrodes were used to measure pH in rat seminiferous tubules and epididymides in vivo. Acidification of fluid leaving the testis occurs primarily in the initial segment and to a lesser extent in the intermediate zone. | Measurement of pH in the rat epididymis in vivo. Antimony microelectrodes were used to measure pH in rat seminiferous tubules and epididymides in vivo. Acidification of fluid leaving the testis occurs primarily in the initial segment and to a lesser extent in the intermediate zone. | [
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PMID:24748 | Chloride conductance of the amphiuma red cell membrane. | Like most other red cells, the giant erythrocytes of Amphiuma means possess a system for rapid exchange of chloride across the membrane. Also, there are indications that the net transport of chloride in these cells is slow. The size of Amphiuma erythrocytes allows direct measurements of membrane potential with microelectrodes. The present work exploits the possibility that such measurements can be used to give a quantitative estimate of the chloride conductance (GCl) of the Amphiuma red cell membrane. The membrane potential was measured as a function of extracellular chloride concentration (5-120mM), using an impermeant anion (Para-amino-hippurate) as a substitute. Furthermore, the effect of different pH values (6.0-7.2) was studied. For each extracellular chloride concentration the membrane potential was determined at a pH at which hydroxyl, hydrogen, and bicarbonate ions were in electrochemical equilibrium. From these membrane potentials and the corresponding chloride concentrations in the medium (at constant intracellular ion concentrations), the GCl of the membrane was calculated to be 3.9 x 10-7 omega-1 cm-2. This value is some six orders of magnitude smaller than that calculated from the rate of tracer exchange under equilibrium conditions. The experimental strategy used gives the values for a "partial transference number" which takes into account only ions which are not in electrochemical equilibrium. Whereas this approach gives a value for GCl, it does not permit calculation of the overall membrane conductance. From the calculated value of GCl it is possible to estimate that the maximal value of the combined conductances of hydroxyl (or proton) and bicarbonate ions is 0.6 x 10-7 omega-1 cm-2. The large discrepancy between the rate of exchange of chloride and its conductance is in agreement with measurements on human and sheep red cells employing the ionophore valinomycin to increase the potassium conductance of the membrane. The results in the present study were, however, obtained without valinomycin and an accompaning assumption of a constant field in the membrane. Therefore, the present measurements give independent support to the above mentioned conclusions. | Chloride conductance of the amphiuma red cell membrane. Like most other red cells, the giant erythrocytes of Amphiuma means possess a system for rapid exchange of chloride across the membrane. Also, there are indications that the net transport of chloride in these cells is slow. The size of Amphiuma erythrocytes allows direct measurements of membrane potential with microelectrodes. The present work exploits the possibility that such measurements can be used to give a quantitative estimate of the chloride conductance (GCl) of the Amphiuma red cell membrane. The membrane potential was measured as a function of extracellular chloride concentration (5-120mM), using an impermeant anion (Para-amino-hippurate) as a substitute. Furthermore, the effect of different pH values (6.0-7.2) was studied. For each extracellular chloride concentration the membrane potential was determined at a pH at which hydroxyl, hydrogen, and bicarbonate ions were in electrochemical equilibrium. From these membrane potentials and the corresponding chloride concentrations in the medium (at constant intracellular ion concentrations), the GCl of the membrane was calculated to be 3.9 x 10-7 omega-1 cm-2. This value is some six orders of magnitude smaller than that calculated from the rate of tracer exchange under equilibrium conditions. The experimental strategy used gives the values for a "partial transference number" which takes into account only ions which are not in electrochemical equilibrium. Whereas this approach gives a value for GCl, it does not permit calculation of the overall membrane conductance. From the calculated value of GCl it is possible to estimate that the maximal value of the combined conductances of hydroxyl (or proton) and bicarbonate ions is 0.6 x 10-7 omega-1 cm-2. The large discrepancy between the rate of exchange of chloride and its conductance is in agreement with measurements on human and sheep red cells employing the ionophore valinomycin to increase the potassium conductance of the membrane. The results in the present study were, however, obtained without valinomycin and an accompaning assumption of a constant field in the membrane. Therefore, the present measurements give independent support to the above mentioned conclusions. | [
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PMID:24754 | Resistance to Marek's disease. Effect of Corynebacterium parvum and Marek's tumor cell vaccines on tumorigenesis in chickens. | A study of nonspecific stimulation of the avian immune system with Corynebacterium parvum and specific stimulation with Marek's tumor cell vaccines revealed that nonspecifically stimulated outbred White Leghorn-type cockerels had higher incidences of tumors than did controls. A study of tumor cell cytotoxicity of sera from Marek's disease virus exposed birds indicated that humoral factors may play some role in tumor resistance. | Resistance to Marek's disease. Effect of Corynebacterium parvum and Marek's tumor cell vaccines on tumorigenesis in chickens. A study of nonspecific stimulation of the avian immune system with Corynebacterium parvum and specific stimulation with Marek's tumor cell vaccines revealed that nonspecifically stimulated outbred White Leghorn-type cockerels had higher incidences of tumors than did controls. A study of tumor cell cytotoxicity of sera from Marek's disease virus exposed birds indicated that humoral factors may play some role in tumor resistance. | [
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PMID:24755 | Traumatic pseudoaneurysm of the dorsalis pedis artery in a child. | A basic principle of children's surgery is to plan it to last for 70 years. The successful reconstruction of the dorsalis pedis artery in an 8-year-old after trauma may be of benefit if he develops peripheral vascular disease as an adult. | Traumatic pseudoaneurysm of the dorsalis pedis artery in a child. A basic principle of children's surgery is to plan it to last for 70 years. The successful reconstruction of the dorsalis pedis artery in an 8-year-old after trauma may be of benefit if he develops peripheral vascular disease as an adult. | [
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PMID:24756 | Multiple endocrine adenomatosis: in support of the common origin theories. | Herein we give clinical support to the theory of a common origin of multiple endocrine adenomatosis. Accurate clinical evaluation of a patient suspected to have endocrine neoplasia requires the search for a much wider range of potential endocrine tumors. Such an approach is now made possible by the radioimmunoassay. Chromosome patterns and histocompatibility antigens are reviewed in a family with the disease. | Multiple endocrine adenomatosis: in support of the common origin theories. Herein we give clinical support to the theory of a common origin of multiple endocrine adenomatosis. Accurate clinical evaluation of a patient suspected to have endocrine neoplasia requires the search for a much wider range of potential endocrine tumors. Such an approach is now made possible by the radioimmunoassay. Chromosome patterns and histocompatibility antigens are reviewed in a family with the disease. | [
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PMID:24757 | Anxiety states in general practice. | Anxiety is commonly encountered in patient seen by the general practitioner. Frequently it either stimulates an organic condition involving one or more systems of the body or may aggravate symptoms of already existent organic pathology. Presence of environmental stresses and of personal conflicts in the life history of patient and the absence of physical findings on physical examination should alert the physician of this condition. Pharmacotherapy with minor tranquilizers and reassurance generally produce amelioration of symptoms. | Anxiety states in general practice. Anxiety is commonly encountered in patient seen by the general practitioner. Frequently it either stimulates an organic condition involving one or more systems of the body or may aggravate symptoms of already existent organic pathology. Presence of environmental stresses and of personal conflicts in the life history of patient and the absence of physical findings on physical examination should alert the physician of this condition. Pharmacotherapy with minor tranquilizers and reassurance generally produce amelioration of symptoms. | [
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PMID:24770 | Laboratory and field assessment of the molluscicidal activity of gogo (Entada phaseoloides) against the amphibious snail intermediate host of Schistosoma japonicum. | A molluscicidal fraction occurs naturally in the bark of a vine (gogo in Tagalog), Entada phaseoloides, which grows indigeneously and abundantly in the Philippines. Butanol fraction of the methanol extracts of the bark was most toxic against Oncomelania quadrasi with the LC50 of 3.6-5.8 ppm. Analytical work on the butanol fraction by thin layer chromatography indicated that the active molluscicidal agents contained at least two kinds of saponins. The potency of E. phaseoloides remained rather stable over a wide range of pH values, in the presence of minerals and yeast cells and after ultraviolet irradiation of solutions. Our preliminary field trials, however, showed that doses as higher than 40 g per square meter would be needed to produce a satisfactory molluscicidal effect under field conditions. | Laboratory and field assessment of the molluscicidal activity of gogo (Entada phaseoloides) against the amphibious snail intermediate host of Schistosoma japonicum. A molluscicidal fraction occurs naturally in the bark of a vine (gogo in Tagalog), Entada phaseoloides, which grows indigeneously and abundantly in the Philippines. Butanol fraction of the methanol extracts of the bark was most toxic against Oncomelania quadrasi with the LC50 of 3.6-5.8 ppm. Analytical work on the butanol fraction by thin layer chromatography indicated that the active molluscicidal agents contained at least two kinds of saponins. The potency of E. phaseoloides remained rather stable over a wide range of pH values, in the presence of minerals and yeast cells and after ultraviolet irradiation of solutions. Our preliminary field trials, however, showed that doses as higher than 40 g per square meter would be needed to produce a satisfactory molluscicidal effect under field conditions. | [
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PMID:24776 | Pharmacology of Sch 11973, N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea, a potential new antianginal agent. | Antianginal drugs were evaluated on the basis of their ability to protect against subepicardial electrogram changes induced by local ventricular ischemia in anesthetized dogs. Sch 11973 [N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea], a potential new antianginal agent, was also effective against local ventricular ischemia with its maximum effect appearing at 1mg/kg, i.v. or i.d. and with a duration of at least 2 hours. Nitroglycerin, at a dose of 0.04 mg/kg given bucally, exerted less protection, lasting on the average less than 15 minutes. Protection by propranolol at 1 mg/kg, i.v., was not better than nitroglycerin, but lasted up to one hour, while dipyridamole was ineffective when given in a dose range of 0.1-10 mg/kg, i.v. Sch 11973 differed from standard antianginal agents which may act via beta-adrenergic blocking activity or alteration of cardiac or circulatory dynamics since no acute pharmacological changes were observed after Sch 11973 was administered. | Pharmacology of Sch 11973, N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea, a potential new antianginal agent. Antianginal drugs were evaluated on the basis of their ability to protect against subepicardial electrogram changes induced by local ventricular ischemia in anesthetized dogs. Sch 11973 [N-(2-phenylisopropyl)-N-p-toluene sulfonyl urea], a potential new antianginal agent, was also effective against local ventricular ischemia with its maximum effect appearing at 1mg/kg, i.v. or i.d. and with a duration of at least 2 hours. Nitroglycerin, at a dose of 0.04 mg/kg given bucally, exerted less protection, lasting on the average less than 15 minutes. Protection by propranolol at 1 mg/kg, i.v., was not better than nitroglycerin, but lasted up to one hour, while dipyridamole was ineffective when given in a dose range of 0.1-10 mg/kg, i.v. Sch 11973 differed from standard antianginal agents which may act via beta-adrenergic blocking activity or alteration of cardiac or circulatory dynamics since no acute pharmacological changes were observed after Sch 11973 was administered. | [
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PMID:24777 | Involvement of histamine H1- and H2-receptors in induced asthmas in dogs. | Participation of histamine H1- and H2-receptors in both asthmas, i.e. experimentally induced bronchoconstriction and bronchosecretion, with ascaris suum and histamine in anesthetized dogs was investigated. Dogs given 0.2% histamine solution or ascaris antigen (3 mg protein) by inhalation showed increases in respiratory resistance (Rrs) and respiratory rate to 2.5-5.0 fold. Airway secretion volume was also significantly increased 3-4 fold. The increase in Rrs by histamine inhalation was effectively inhibited or abolished by a histamine H1-receptor antagonist, chlorpheniramine (0.3-1 mg/kg i.v.), but not by a H2-receptor antagonist, cimetidine (1-3 mg/kg i.v.). The increase in Rrs by antigen inhalation was reduced by relatively high doses of chlorpheniramine (1-3 mg/kg i.v.), and not by cimetidine. In contrast, hypersecretion of tracheobronchial fluid in both asthmas was significantly prevented by either chlorpheniramine or cimetidine. Combinations of both antagonists abolished the hypersecretion. Atropine (2 mg/kg i.v.) significantly inhibited the occurrence of responses in both asthmas. The results suggest that histamine is involved in the allergic asthma produced by ascaris suum and that histamine directly evokes airway constriction through H1-receptors and hypersecretion of tracheobronchial fluid through H1- and H2-receptors, and, in part, indirectly activates the cholinergic pathway. | Involvement of histamine H1- and H2-receptors in induced asthmas in dogs. Participation of histamine H1- and H2-receptors in both asthmas, i.e. experimentally induced bronchoconstriction and bronchosecretion, with ascaris suum and histamine in anesthetized dogs was investigated. Dogs given 0.2% histamine solution or ascaris antigen (3 mg protein) by inhalation showed increases in respiratory resistance (Rrs) and respiratory rate to 2.5-5.0 fold. Airway secretion volume was also significantly increased 3-4 fold. The increase in Rrs by histamine inhalation was effectively inhibited or abolished by a histamine H1-receptor antagonist, chlorpheniramine (0.3-1 mg/kg i.v.), but not by a H2-receptor antagonist, cimetidine (1-3 mg/kg i.v.). The increase in Rrs by antigen inhalation was reduced by relatively high doses of chlorpheniramine (1-3 mg/kg i.v.), and not by cimetidine. In contrast, hypersecretion of tracheobronchial fluid in both asthmas was significantly prevented by either chlorpheniramine or cimetidine. Combinations of both antagonists abolished the hypersecretion. Atropine (2 mg/kg i.v.) significantly inhibited the occurrence of responses in both asthmas. The results suggest that histamine is involved in the allergic asthma produced by ascaris suum and that histamine directly evokes airway constriction through H1-receptors and hypersecretion of tracheobronchial fluid through H1- and H2-receptors, and, in part, indirectly activates the cholinergic pathway. | [
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PMID:24778 | The inhibitory effect of papaverine on respiration-dependent contracture of guinea pig taenia coli in high-K medium. I. The relationship between contracture and respiration. | Papaverine (Pap) inhibited a tonic tension development in guinea pig taenia coli induced by an elevation of the potassium concentration of the medium to 40 mM (40-K). The ID50 of Pap was 4.5 x 10(-6) M. Inhibition of the 40-K induced tonic tension by Pap was dependent on the calculated concentration of non-ionized form, but not the ionized form. Inhibition of the tonic tension by Pap and various metabolic inhibitors was not antagonized by raising the Ca++ concentration in the medium. Results obtained from simultaneous measurement of the 40-K induced O2 consumption and tension illustrated that the inhibition of O2 consumption rapidly induced the inhibition of the tension. Furthermore, glucose removal, amytal or Pap resulted in a progressive relationship between the inhibition of O2 consumption and the inhibition of tension. The inhibition of Pap as determined by O2 consumption was not reversed by application of 10(-4) M 2,4-dinitrophenol (DNP). These results plus graphical analysis of the mechanical response suggest that Pap may penetrate the cell membrane and inhibit mitochondrial respiration, thereby inhibiting this very respiration-dependent contracture. | The inhibitory effect of papaverine on respiration-dependent contracture of guinea pig taenia coli in high-K medium. I. The relationship between contracture and respiration. Papaverine (Pap) inhibited a tonic tension development in guinea pig taenia coli induced by an elevation of the potassium concentration of the medium to 40 mM (40-K). The ID50 of Pap was 4.5 x 10(-6) M. Inhibition of the 40-K induced tonic tension by Pap was dependent on the calculated concentration of non-ionized form, but not the ionized form. Inhibition of the tonic tension by Pap and various metabolic inhibitors was not antagonized by raising the Ca++ concentration in the medium. Results obtained from simultaneous measurement of the 40-K induced O2 consumption and tension illustrated that the inhibition of O2 consumption rapidly induced the inhibition of the tension. Furthermore, glucose removal, amytal or Pap resulted in a progressive relationship between the inhibition of O2 consumption and the inhibition of tension. The inhibition of Pap as determined by O2 consumption was not reversed by application of 10(-4) M 2,4-dinitrophenol (DNP). These results plus graphical analysis of the mechanical response suggest that Pap may penetrate the cell membrane and inhibit mitochondrial respiration, thereby inhibiting this very respiration-dependent contracture. | [
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PMID:24782 | Intraoperative measurement of lower esophageal spincter pressure. | The lower esophageal sphincter pressure has been measured intraoperatively in 200 patients with gastroesophageal reflux and in three patients with achalasia. Lower esophageal sphincter pressure is measured before and during repair. Calibrating the cardia during performance of the median arcuate posterior gastropexy allows a sphincter pressure between 50 and 57 mm. Hg to be obtained at operation. The postoperative pressures have ranged between 15 and 25 mm. Hg, or approximately half of the intraoperative pressure. No patient with a spincter pressure of 15 mm. Hg or greater has reflux according to postoperative pH and pressure studies. Correction of reflux correlates well with relief of symptoms. Three patients with achalasia had intraoperative manometrics during myotomy. The lower esophageal sphincter pressure was lowered and the length of the lower esophageal sphincter was shortened. Dysphagia was corrected without producing reflux. This is the first report of measurement of lower esophageal sphincter pressure in anesthetized patients. Intraoperative measurement of sphincter pressure is a safe, simple, and reliable technique which allows the surgeon, for the first time, to determine the status of the lower esophageal sphincter during the operation. This technique should be standard for all operations on the gastroesophageal junction. | Intraoperative measurement of lower esophageal spincter pressure. The lower esophageal sphincter pressure has been measured intraoperatively in 200 patients with gastroesophageal reflux and in three patients with achalasia. Lower esophageal sphincter pressure is measured before and during repair. Calibrating the cardia during performance of the median arcuate posterior gastropexy allows a sphincter pressure between 50 and 57 mm. Hg to be obtained at operation. The postoperative pressures have ranged between 15 and 25 mm. Hg, or approximately half of the intraoperative pressure. No patient with a spincter pressure of 15 mm. Hg or greater has reflux according to postoperative pH and pressure studies. Correction of reflux correlates well with relief of symptoms. Three patients with achalasia had intraoperative manometrics during myotomy. The lower esophageal sphincter pressure was lowered and the length of the lower esophageal sphincter was shortened. Dysphagia was corrected without producing reflux. This is the first report of measurement of lower esophageal sphincter pressure in anesthetized patients. Intraoperative measurement of sphincter pressure is a safe, simple, and reliable technique which allows the surgeon, for the first time, to determine the status of the lower esophageal sphincter during the operation. This technique should be standard for all operations on the gastroesophageal junction. | [
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PMID:24784 | The mechanism and control of human erythrocyte zinc uptake. | The increasing awareness of the importance of the divalent cation zinc in normal and pathologic cell functions has prompted our investigations into the mechanism and control of human erythrocyte zinc uptake. The albumin in blood plasma appears to be the main zinc binding moiety, effectively limiting zinc availability ot the red cell. In non-protein and non-phosphate-containing buffers (i.e., bicarbonate or Tris buffer) red cells sequester more than 90% of the extracellular zinc within 10--15 minutes at a rate more than 250 times faster than zink uptake by cells in plasma. In an albumin-containing media, the influx on red blood cell zinc is lightly temperature sensitive (decreased) between 37 degrees C and 25 degrees C, whereas with cells in bicarbonate buffer alone temperature sensitivity does not begin until below 25 degrees C. Over the physiological range, pH variation has a minimal effect on zinc uptake regardless of the media employed. Finally, once associated with the red cell zinc tends to remain, with a zinc efflux less than 2% of influx. We conclude that human erythrocytes are highly permeable to zinc, with the rate and amount of zinc taken up controlled primarily by the zinc binding characteristics of the media in which the cells are suspended. | The mechanism and control of human erythrocyte zinc uptake. The increasing awareness of the importance of the divalent cation zinc in normal and pathologic cell functions has prompted our investigations into the mechanism and control of human erythrocyte zinc uptake. The albumin in blood plasma appears to be the main zinc binding moiety, effectively limiting zinc availability ot the red cell. In non-protein and non-phosphate-containing buffers (i.e., bicarbonate or Tris buffer) red cells sequester more than 90% of the extracellular zinc within 10--15 minutes at a rate more than 250 times faster than zink uptake by cells in plasma. In an albumin-containing media, the influx on red blood cell zinc is lightly temperature sensitive (decreased) between 37 degrees C and 25 degrees C, whereas with cells in bicarbonate buffer alone temperature sensitivity does not begin until below 25 degrees C. Over the physiological range, pH variation has a minimal effect on zinc uptake regardless of the media employed. Finally, once associated with the red cell zinc tends to remain, with a zinc efflux less than 2% of influx. We conclude that human erythrocytes are highly permeable to zinc, with the rate and amount of zinc taken up controlled primarily by the zinc binding characteristics of the media in which the cells are suspended. | [
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PMID:24785 | Determinants of lengths of outpatient visits in a prepaid group practice setting. | In this paper we have examined the amount of time that physicians (MDs) and physician's assistants (PAs) expended on office visits. The purpose was to determine the extent to which a series of patient-related and system-related characteristics explain variations in that time. Using regression analyses, we found most of the explained variation generally to be due to system-related characteristics. Whether the provider was an MD or PA made little difference in the length of time spent with patients. The principal determinant of provider time for unscheduled and scheduled 15-minute visits was the patient-load (number of patients per minute); for scheduled 30-minute visits, the number of associated morbidities was relatively more important than patient-load. Discriminant analysis was used to identify factors that could distinguish PA visits that require an MD input from those that do not. The data were collected from three months of observation in the department of medicine of a prepaid group practice. | Determinants of lengths of outpatient visits in a prepaid group practice setting. In this paper we have examined the amount of time that physicians (MDs) and physician's assistants (PAs) expended on office visits. The purpose was to determine the extent to which a series of patient-related and system-related characteristics explain variations in that time. Using regression analyses, we found most of the explained variation generally to be due to system-related characteristics. Whether the provider was an MD or PA made little difference in the length of time spent with patients. The principal determinant of provider time for unscheduled and scheduled 15-minute visits was the patient-load (number of patients per minute); for scheduled 30-minute visits, the number of associated morbidities was relatively more important than patient-load. Discriminant analysis was used to identify factors that could distinguish PA visits that require an MD input from those that do not. The data were collected from three months of observation in the department of medicine of a prepaid group practice. | [
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PMID:24797 | Transport of 14C-L-glycine by the haustorial mycoparasite Tieghemiomyces parasiticus in axenic culture. | Transport of L-glycine by the haustorial mycoparasite Tieghemiomyces parasiticus grown in axenic culture was investigated using endogenously metabolizing cells. Transport occurred against a concentration gradient and required the expenditure of energy supplied by metabolic reactions that were inhibited by catalytic amounts of sodium azide and 2,4-dinitrophenol. The process exhibited both pH and temperature dependence with optima at pH 4 and 35 degrees C, respectively. The energy of activation and Q10 for transport were calculated to be 18,227 cal/mole and 2.82 respectively, between 20 and 30 degrees C. The kinetics of the system were consistent with a mechanism of transport that depended upon a finite number of sites on the cell surface and had a Kt of 1.46 x 10(-5) M. The system for L-glycine transport lacked sterospecificity and was most inhibited in the presence of other neutral amino acids while less inhibition was observed in the presence of the acidic and basic amino acids. These results suggest that L-glycine transport in this mycoparasite occurs by an energy dependent, protein-mediated process characteristic of active transport. | Transport of 14C-L-glycine by the haustorial mycoparasite Tieghemiomyces parasiticus in axenic culture. Transport of L-glycine by the haustorial mycoparasite Tieghemiomyces parasiticus grown in axenic culture was investigated using endogenously metabolizing cells. Transport occurred against a concentration gradient and required the expenditure of energy supplied by metabolic reactions that were inhibited by catalytic amounts of sodium azide and 2,4-dinitrophenol. The process exhibited both pH and temperature dependence with optima at pH 4 and 35 degrees C, respectively. The energy of activation and Q10 for transport were calculated to be 18,227 cal/mole and 2.82 respectively, between 20 and 30 degrees C. The kinetics of the system were consistent with a mechanism of transport that depended upon a finite number of sites on the cell surface and had a Kt of 1.46 x 10(-5) M. The system for L-glycine transport lacked sterospecificity and was most inhibited in the presence of other neutral amino acids while less inhibition was observed in the presence of the acidic and basic amino acids. These results suggest that L-glycine transport in this mycoparasite occurs by an energy dependent, protein-mediated process characteristic of active transport. | [
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PMID:24798 | New approaches to the pathogenesis of peptic ulcer based on the protective action of saliva with special reference to roughage, vegetable fibre and fermented milk products. | Epidemiologic studies have shown differences in the prevalence of peptic ulcer disease among various communities to be related to variation in diet and eating patterns. Results of studies of the effect of diet and pattern of eating on saliva, on gastric juice, and on the amount of bile are reviewed. It is suggested that bile, and not hydrochloric acid, plays the causative role in pathogenesis of peptic ulceration. The role of saliva in the prevention of peptic ulcer is emphasized. The salivary mucus swallowed with food is protective because it decreases the flow rate of bile which, when held in the gall bladder longer, loses its alkalinity and therefore its ability to damage the mucous cells. Roughage, cellulose and vegetable fibres and fermented milk products act in a similar manner. When food is well masticated, containing plenty of vegetable fibres and fermented milk products such as ghee and yoghurt, resulting in an increase in the amount of salivary mucus, peptic ulceration may be prevented and cured and relapses may be prevented. This does not require a big change in the pattern of diet but only a change in the manner of eating so that hasty eating is avoided and good is chewed well. The pattern of diet, especially the relative dietary preponderance of short-chain fatty acids, such as those present in milk, yoghurt and other fermented milk products, have a protective action; the short-chain fatty acids retard gall bladder contraction and thus diminish the amount of bile entering the duodenal lumen. | New approaches to the pathogenesis of peptic ulcer based on the protective action of saliva with special reference to roughage, vegetable fibre and fermented milk products. Epidemiologic studies have shown differences in the prevalence of peptic ulcer disease among various communities to be related to variation in diet and eating patterns. Results of studies of the effect of diet and pattern of eating on saliva, on gastric juice, and on the amount of bile are reviewed. It is suggested that bile, and not hydrochloric acid, plays the causative role in pathogenesis of peptic ulceration. The role of saliva in the prevention of peptic ulcer is emphasized. The salivary mucus swallowed with food is protective because it decreases the flow rate of bile which, when held in the gall bladder longer, loses its alkalinity and therefore its ability to damage the mucous cells. Roughage, cellulose and vegetable fibres and fermented milk products act in a similar manner. When food is well masticated, containing plenty of vegetable fibres and fermented milk products such as ghee and yoghurt, resulting in an increase in the amount of salivary mucus, peptic ulceration may be prevented and cured and relapses may be prevented. This does not require a big change in the pattern of diet but only a change in the manner of eating so that hasty eating is avoided and good is chewed well. The pattern of diet, especially the relative dietary preponderance of short-chain fatty acids, such as those present in milk, yoghurt and other fermented milk products, have a protective action; the short-chain fatty acids retard gall bladder contraction and thus diminish the amount of bile entering the duodenal lumen. | [
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PMID:24802 | [Inhibition of electron transport and photophosphorylation in chloroplasts by quercetin]. | The influence of quercetin on electron transport and photophosphorylation of pea isolated chloroplasts with methylviologen and NADP+ has been studied. Quercetin inhibits ATP synthesis and phosphorylating electron transport but does not affect the basal electron transport in the presence of methylviologen. In view of these data and because of the increase of the proton uptake by chloroplasts in the presence of quercetin we consider it as an inhibitor of energy transfer. Under conditions of NADP+ photoreduction quercetin acts also as an inhibitor of electron transfer, interacting with ferredoxin, though a complete inhibition of electron transfer has not been observed. This last phenomenon may be of importance for the understanding of the detailed mechanism of NADP+ reduction by chloroplasts. | [Inhibition of electron transport and photophosphorylation in chloroplasts by quercetin]. The influence of quercetin on electron transport and photophosphorylation of pea isolated chloroplasts with methylviologen and NADP+ has been studied. Quercetin inhibits ATP synthesis and phosphorylating electron transport but does not affect the basal electron transport in the presence of methylviologen. In view of these data and because of the increase of the proton uptake by chloroplasts in the presence of quercetin we consider it as an inhibitor of energy transfer. Under conditions of NADP+ photoreduction quercetin acts also as an inhibitor of electron transfer, interacting with ferredoxin, though a complete inhibition of electron transfer has not been observed. This last phenomenon may be of importance for the understanding of the detailed mechanism of NADP+ reduction by chloroplasts. | [
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PMID:24803 | [Equilibrium dynamics of the 3-dimensional structure of globular proteins]. | According to the data of many physical and physico-chemical methods for conditions near to physiological, there are two types of spontaneous reversible conformational transitions in native proteins namely, local transconformations and overall unfolding of the molecule. Conformational transitions of both types occur with correlation times of less than 10-1--10-3 sec. Some local transconformations, especially those revealed by the hydrogen exchange method, are characterized by weak temperature dependence of the equilibrium constant (local temperature-independent (TI) transconformations). Combining the data obtained by the hydrogen exchange method with recently published results of energy refinement of protein structure leads us to suggest that the probability of local TI-transconformations is independent of hydrophobic forces and possibly related to the "internal" conformational free energy of the native protein, i.e. the sum of (1) the potentional energy of non-bonded intramolecular interactions, (2) the energy of dihedral and bond angle strain as well as (3) the entropy of the folded protein. In the proposed model of dynamic structure the cooperative nature of local TI-transconformations is a result of close interrelation between the optimization of van der Waals side chain interactions in the nonpolar core and variation of dihedral and valence angles. It is shown that the local TI-conformers are closely related to the functionally important transient key states of native proteins. | [Equilibrium dynamics of the 3-dimensional structure of globular proteins]. According to the data of many physical and physico-chemical methods for conditions near to physiological, there are two types of spontaneous reversible conformational transitions in native proteins namely, local transconformations and overall unfolding of the molecule. Conformational transitions of both types occur with correlation times of less than 10-1--10-3 sec. Some local transconformations, especially those revealed by the hydrogen exchange method, are characterized by weak temperature dependence of the equilibrium constant (local temperature-independent (TI) transconformations). Combining the data obtained by the hydrogen exchange method with recently published results of energy refinement of protein structure leads us to suggest that the probability of local TI-transconformations is independent of hydrophobic forces and possibly related to the "internal" conformational free energy of the native protein, i.e. the sum of (1) the potentional energy of non-bonded intramolecular interactions, (2) the energy of dihedral and bond angle strain as well as (3) the entropy of the folded protein. In the proposed model of dynamic structure the cooperative nature of local TI-transconformations is a result of close interrelation between the optimization of van der Waals side chain interactions in the nonpolar core and variation of dihedral and valence angles. It is shown that the local TI-conformers are closely related to the functionally important transient key states of native proteins. | [
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PMID:24804 | [Stationary kinetics of catalysis by the hydrogenase of Thiocapsa roseopersicina]. | Forward and reverse reactions of catalysis by a hydrogenase from T. roseopersicina in steady state have been investigated. The dependance of reaction rate on the concentration of substrates and of hydrogen ions has been studied. Detailed formal-kinetic analysis of possible mechanisms of enzyme action has been carried out and the classification of mechanisms of the reaction has been given. Comparison of experimental data with the equations obtained from formal-kinetic analysis has been undertaken and mechanisms compatible with experimental data were sorted out. Kinetic and molecular mechanism of the catalytic activity of hydrogenase has been proposed and elementary rate constants for the activation of molecular hydrogen have been calculated. | [Stationary kinetics of catalysis by the hydrogenase of Thiocapsa roseopersicina]. Forward and reverse reactions of catalysis by a hydrogenase from T. roseopersicina in steady state have been investigated. The dependance of reaction rate on the concentration of substrates and of hydrogen ions has been studied. Detailed formal-kinetic analysis of possible mechanisms of enzyme action has been carried out and the classification of mechanisms of the reaction has been given. Comparison of experimental data with the equations obtained from formal-kinetic analysis has been undertaken and mechanisms compatible with experimental data were sorted out. Kinetic and molecular mechanism of the catalytic activity of hydrogenase has been proposed and elementary rate constants for the activation of molecular hydrogen have been calculated. | [
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PMID:24808 | Effect of hypnotic and anxiolytic agents on regional concentration of acetylcholine in rat brain. | Pentobarbital (30 and 60 mg/kg) and chloral hydrate (300 and 600 mg/kg) administered in anesthetic/hypnotic doses produced significant increases in acetylcholine concentration in the cerebral cortex, striatum, hippocampus and brainstem. Hypnotic/anxiolytic agents like diazepam, flurazepam (100 mg/kg each) and triazolam (30 mg/kg) significantly increased the acetylcholine concentration only in the cerebral cortex and striatum. Alprazolam and ketazolam had no significant effect on regional distribution of acetylcholine in the brain. The results have been discussed with respect to the role of central cholinergic system in anesthetic and hypnotic actions of these drugs. | Effect of hypnotic and anxiolytic agents on regional concentration of acetylcholine in rat brain. Pentobarbital (30 and 60 mg/kg) and chloral hydrate (300 and 600 mg/kg) administered in anesthetic/hypnotic doses produced significant increases in acetylcholine concentration in the cerebral cortex, striatum, hippocampus and brainstem. Hypnotic/anxiolytic agents like diazepam, flurazepam (100 mg/kg each) and triazolam (30 mg/kg) significantly increased the acetylcholine concentration only in the cerebral cortex and striatum. Alprazolam and ketazolam had no significant effect on regional distribution of acetylcholine in the brain. The results have been discussed with respect to the role of central cholinergic system in anesthetic and hypnotic actions of these drugs. | [
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PMID:24814 | Effect of estrogen and progesterone on the release of MSH in gonadectomized rats. | The concentration of MSH in serum after estrogen or progesterone injection into gonadectomized rats was measured by a biological assay. Undetectable serum MSH values were found in long-term ovariectomized (OVX) rats. After a single injection of 10 microgram estradiol benzoate (EB) serum MSH exhibited a circadiam rhythm with high levels in the afternoon, while values in the morning were negative. This effect occurred for 4 days following the injection. Progesterone injection into spayed rats also resulted in an increase of serum MSH concentration, but in contrast to the changes observed after EB treatment high values were found in the morning for 3 consecutive days. Afternoon MSH levels were low but measurable. The effect of these steroids on the activity of the hypothalamic enzymes which yielded MIF or MRF upon incubation with oxytocin (OXT) was also studied. Enzymatic activity of both systems was undetectable in OVX rats and was evident after EB treatment. Progesterone increased only the activity of the system which yields MRF. In castrated male rats estrogen elevated baseline MSH levels but a circadian rhythm was not observed, whereas progesterone had no effect. These observations demonstrate a sex difference on steroid-induced MSH release. | Effect of estrogen and progesterone on the release of MSH in gonadectomized rats. The concentration of MSH in serum after estrogen or progesterone injection into gonadectomized rats was measured by a biological assay. Undetectable serum MSH values were found in long-term ovariectomized (OVX) rats. After a single injection of 10 microgram estradiol benzoate (EB) serum MSH exhibited a circadiam rhythm with high levels in the afternoon, while values in the morning were negative. This effect occurred for 4 days following the injection. Progesterone injection into spayed rats also resulted in an increase of serum MSH concentration, but in contrast to the changes observed after EB treatment high values were found in the morning for 3 consecutive days. Afternoon MSH levels were low but measurable. The effect of these steroids on the activity of the hypothalamic enzymes which yielded MIF or MRF upon incubation with oxytocin (OXT) was also studied. Enzymatic activity of both systems was undetectable in OVX rats and was evident after EB treatment. Progesterone increased only the activity of the system which yields MRF. In castrated male rats estrogen elevated baseline MSH levels but a circadian rhythm was not observed, whereas progesterone had no effect. These observations demonstrate a sex difference on steroid-induced MSH release. | [
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PMID:24815 | Prolactin inhibiting activity of dopamine-free subcellular fractions from rat mediobasal hypothalamus. | In order to check the hypothesis of an identity of dopamine (DA) and prolactin inhibiting activity (PIF), their subcellular distribution was studied in the mediobasal hypothalamus (MBH) and the striatum, which served as a control structure. PIF was tested both in vivo and on pituitary incubates. Fractions were also assayed after adsorption of their catecholamine content on alumina, as well as in presence of haloperidol or alpha-flupentixol, potent DA receptor inhibitors. In the MBH, PIF was evenly distributed in the 17,000 g supernatant (S2) and in the crude mitochondrial fraction (P2) which contains synaptosomes. PIF activity was completely removed by alumina adsorption of S2, but not of P2 in spite of an over 99.9% elimination of DA. In contrast, striatal PIF activity was detected only in P2, and disappeared completely upon alumina adsorption, thus indicating that, in this structure, it is entirely due to DA. Addition of haloperidol (10--5M) or alpha-flupentixol (10--6M) reduced PIF activity of crude MBH homogenates, but no longer affected it after alumina adsorption. Quantitative studies suggest that only half of the total MBH PIF activity is accounted for by DA. It is concluded that the MBH contains dopamine-free PIF, which, as already shown for several other neurohormones, is exclusively distributed in nerve-endings. | Prolactin inhibiting activity of dopamine-free subcellular fractions from rat mediobasal hypothalamus. In order to check the hypothesis of an identity of dopamine (DA) and prolactin inhibiting activity (PIF), their subcellular distribution was studied in the mediobasal hypothalamus (MBH) and the striatum, which served as a control structure. PIF was tested both in vivo and on pituitary incubates. Fractions were also assayed after adsorption of their catecholamine content on alumina, as well as in presence of haloperidol or alpha-flupentixol, potent DA receptor inhibitors. In the MBH, PIF was evenly distributed in the 17,000 g supernatant (S2) and in the crude mitochondrial fraction (P2) which contains synaptosomes. PIF activity was completely removed by alumina adsorption of S2, but not of P2 in spite of an over 99.9% elimination of DA. In contrast, striatal PIF activity was detected only in P2, and disappeared completely upon alumina adsorption, thus indicating that, in this structure, it is entirely due to DA. Addition of haloperidol (10--5M) or alpha-flupentixol (10--6M) reduced PIF activity of crude MBH homogenates, but no longer affected it after alumina adsorption. Quantitative studies suggest that only half of the total MBH PIF activity is accounted for by DA. It is concluded that the MBH contains dopamine-free PIF, which, as already shown for several other neurohormones, is exclusively distributed in nerve-endings. | [
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PMID:24820 | An atypical form of Sandhoff's disease. Case report and biochemical studies. | A case of Sandhoff's disease (GM2 gangliosidosis type 2) is reported because of an unusual course with later onset of symptoms, more slow progress and longer survival than those previously described. Otherwise the patient presented most of the classical symptoms of the disease with a final state of blindness, deafness and decerebrate rigidity. The residual acidic hexosaminidase isozymes in liver and brain tissue were Hex A and Hex S, while Hex B was barely detectable. The neutral hexosaminidase form called Hex C was also found. Two urinary oligosaccharides containing N-acetylglucosamine and mannose were found to be execreted by the patient. | An atypical form of Sandhoff's disease. Case report and biochemical studies. A case of Sandhoff's disease (GM2 gangliosidosis type 2) is reported because of an unusual course with later onset of symptoms, more slow progress and longer survival than those previously described. Otherwise the patient presented most of the classical symptoms of the disease with a final state of blindness, deafness and decerebrate rigidity. The residual acidic hexosaminidase isozymes in liver and brain tissue were Hex A and Hex S, while Hex B was barely detectable. The neutral hexosaminidase form called Hex C was also found. Two urinary oligosaccharides containing N-acetylglucosamine and mannose were found to be execreted by the patient. | [
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PMID:24822 | Bilateral adrenalectomy: factors affecting hepatic protein synthesis following a single tube-feeding of tryptophan. | Effect of tryptophan force-feeding to well-fed adrenalectomized rats on the ability of liver cell sap and initiation factors to support protein synthesis in vitro was investigated. 5 h after tryptophan force-feeding, the capacity of liver cell sap, pH 5 enzyme and pH 5 supernatant to support protein synthesis was greatly increased. The capacity of cell sap to support charging of tRNA with either (14C)-leucine or (14C)-phenylalanine was increased following a dose of tryptophan. Initiation factors prepared from tryptophan-fed adrenalectomized rats stimulated polyuridylic-acid-directed polyphenylalanine synthesis to a greater extent than those from livers of water-fed adrenalectomized controls. | Bilateral adrenalectomy: factors affecting hepatic protein synthesis following a single tube-feeding of tryptophan. Effect of tryptophan force-feeding to well-fed adrenalectomized rats on the ability of liver cell sap and initiation factors to support protein synthesis in vitro was investigated. 5 h after tryptophan force-feeding, the capacity of liver cell sap, pH 5 enzyme and pH 5 supernatant to support protein synthesis was greatly increased. The capacity of cell sap to support charging of tRNA with either (14C)-leucine or (14C)-phenylalanine was increased following a dose of tryptophan. Initiation factors prepared from tryptophan-fed adrenalectomized rats stimulated polyuridylic-acid-directed polyphenylalanine synthesis to a greater extent than those from livers of water-fed adrenalectomized controls. | [
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PMID:24828 | Sodium and chloride transport in the isolated human cornea. | 22Na and 36Cl fluxes in isolated human cornea preparations were measured under short-circuited conditions. At pH 7.3-PH 7.6 sodium net flux was directed from aqueous humour to tear side, chloride net flux was statistically not different from zero. Alkalinization of the bathing solution to pH 8.6 stimulated unidirectional sodium and chloride fluxes from aqueous humour to tear side resulting in net sodium and chloride fluxes towards the tear side which both were statistically different from zero. Cyclic AMP (10(-3) M) was found to stimulate sodium and chloride unidirectional fluxes from aqueous humour to tear side, thus leading to significant net sodium and chloride fluxes in the same direction. Epinephrine (10(-4) M) increased the unidirectional chloride flux from aqueous humour to tear side more pronounced than in the opposite direction, producing a significant net chloride flux towards the tear side. The results are consistent with the hypothesis that the electrolyte pumps may under certain conditions contribute to the dehydration of the stroma. | Sodium and chloride transport in the isolated human cornea. 22Na and 36Cl fluxes in isolated human cornea preparations were measured under short-circuited conditions. At pH 7.3-PH 7.6 sodium net flux was directed from aqueous humour to tear side, chloride net flux was statistically not different from zero. Alkalinization of the bathing solution to pH 8.6 stimulated unidirectional sodium and chloride fluxes from aqueous humour to tear side resulting in net sodium and chloride fluxes towards the tear side which both were statistically different from zero. Cyclic AMP (10(-3) M) was found to stimulate sodium and chloride unidirectional fluxes from aqueous humour to tear side, thus leading to significant net sodium and chloride fluxes in the same direction. Epinephrine (10(-4) M) increased the unidirectional chloride flux from aqueous humour to tear side more pronounced than in the opposite direction, producing a significant net chloride flux towards the tear side. The results are consistent with the hypothesis that the electrolyte pumps may under certain conditions contribute to the dehydration of the stroma. | [
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PMID:24829 | [Treatment of acute asthma. Comparison of the effectiveness of corticosteroids and of a combination of corticosteroids and an adrenergic beta-stimulant (author's transl)]. | Two comparable groups of patients hospitalised for acute asthma received an intravenous infusion for two hours, containing corticosteroids in the first group and corticosteroids combined with an adrenergic beta-stimulant in the second. Course was assessed by the hourly measurement of forced expiratory volumen in one second (FEV1), heart rate and blood pressure. It was found that corticosteroids alone had a modest action (5,1% improvement in FEV1). By contrast, the combination of corticosteroids with an adrenergic beta-stimulant resulted in a rapid and pronounced improvement in FEV1 (19,9%), without producing any undisrable side-effects. No changes in arterial blood gases were noted under the influence of treatment. Injectable adrenergic beta-stimulants are therefore worthy of use in the treatment of an asthma attack, in the absencd of any contraindication. | [Treatment of acute asthma. Comparison of the effectiveness of corticosteroids and of a combination of corticosteroids and an adrenergic beta-stimulant (author's transl)]. Two comparable groups of patients hospitalised for acute asthma received an intravenous infusion for two hours, containing corticosteroids in the first group and corticosteroids combined with an adrenergic beta-stimulant in the second. Course was assessed by the hourly measurement of forced expiratory volumen in one second (FEV1), heart rate and blood pressure. It was found that corticosteroids alone had a modest action (5,1% improvement in FEV1). By contrast, the combination of corticosteroids with an adrenergic beta-stimulant resulted in a rapid and pronounced improvement in FEV1 (19,9%), without producing any undisrable side-effects. No changes in arterial blood gases were noted under the influence of treatment. Injectable adrenergic beta-stimulants are therefore worthy of use in the treatment of an asthma attack, in the absencd of any contraindication. | [
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PMID:24833 | Overmethylation of DNAs by the EcoRI methylase. | EcoRI methylase is able to catalyze methy incorporation into DNA at sequences other than the canonical EcoRI site. At high enzyme concentrations and over a wide range of pH and ionic strengths, EcoRI methylase modifies polyoma DNA (which contains one EcoRI site) at a number of sites. This modification prevents EcoRI endonuclease activity, and thus is presumably at or near the EcoRI sequences (5') NAATTN. | Overmethylation of DNAs by the EcoRI methylase. EcoRI methylase is able to catalyze methy incorporation into DNA at sequences other than the canonical EcoRI site. At high enzyme concentrations and over a wide range of pH and ionic strengths, EcoRI methylase modifies polyoma DNA (which contains one EcoRI site) at a number of sites. This modification prevents EcoRI endonuclease activity, and thus is presumably at or near the EcoRI sequences (5') NAATTN. | [
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PMID:24834 | Mammalian tRNA sulfurtransferase: properties of the enzyme in rat liver. | Transfer RNA sulfurtransferase activity was detected in 105,000 x g supernatant preparations from rat liver and several other rat tissues. Sulfur is transferred from [35S] cysteine to tRNA in a reaction which also requires ATP, Mg2+, and supernatant protein. While [35S] beta-mercaptopyruvate appeared to be a substrate for this enzyme, the reaction product was sensitive to deacylation and the reaction was inhibited by [32S] cysteine. Of the various nucleic acids tested, only tRNAs were effective sulfur acceptors, with rat liver tRNA being the poorest substrate. The [35S] reaction product was sensitive to ribonuclease, cochromatographed with tRNA on methylated-albumin kieselguhr columns, and was converted to nucleotide material after alkaline hydrolysis. DEAE-cellulose chromatography of the neutralized [35S] nucleotide digest revealed a single thionucleotide peak. These studies demonstrate that tRNA sulfurtransferase is present in various rat tissues, and that the requirements of the liver enzyme are similar to those of bacterial enzymes. | Mammalian tRNA sulfurtransferase: properties of the enzyme in rat liver. Transfer RNA sulfurtransferase activity was detected in 105,000 x g supernatant preparations from rat liver and several other rat tissues. Sulfur is transferred from [35S] cysteine to tRNA in a reaction which also requires ATP, Mg2+, and supernatant protein. While [35S] beta-mercaptopyruvate appeared to be a substrate for this enzyme, the reaction product was sensitive to deacylation and the reaction was inhibited by [32S] cysteine. Of the various nucleic acids tested, only tRNAs were effective sulfur acceptors, with rat liver tRNA being the poorest substrate. The [35S] reaction product was sensitive to ribonuclease, cochromatographed with tRNA on methylated-albumin kieselguhr columns, and was converted to nucleotide material after alkaline hydrolysis. DEAE-cellulose chromatography of the neutralized [35S] nucleotide digest revealed a single thionucleotide peak. These studies demonstrate that tRNA sulfurtransferase is present in various rat tissues, and that the requirements of the liver enzyme are similar to those of bacterial enzymes. | [
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PMID:24835 | Choosing a drug regimen for obstructive pulmonary disease. 1. Agents to achieve bronchodilatation. | Many patients with pulmonary disease may have significant airflow obstruction. Bronchodilatation is an important aspect of treatment and can be achieved with beta-adrenergic agonists, methylxanthine derivatives, and anticholinergic agents. These can be used singly or in combination, depending on the severity of obstruction. | Choosing a drug regimen for obstructive pulmonary disease. 1. Agents to achieve bronchodilatation. Many patients with pulmonary disease may have significant airflow obstruction. Bronchodilatation is an important aspect of treatment and can be achieved with beta-adrenergic agonists, methylxanthine derivatives, and anticholinergic agents. These can be used singly or in combination, depending on the severity of obstruction. | [
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] |
PMID:24836 | Multiple endocrine adenomatosis (Type I) and familial hyperparathyroidism. | Hyperparathyroidism is the commonest presenting feature in multiple endocrine adenomatosis Type I (MEA Type I), the other manifestations may be delayed for many years or appear only in relatives. A family now diagnosed as MEA Type I, who was previously thought, in 1965, to have familial hyperparathyroidism due to chief cell hyperplasia is now described. The importance is stressed of family surveillance and long-term follow-up in all cases of primary hyperparathyroidism. Those tests that are essential in the long-term surveillance of the patients and their first degree relatives are discussed. | Multiple endocrine adenomatosis (Type I) and familial hyperparathyroidism. Hyperparathyroidism is the commonest presenting feature in multiple endocrine adenomatosis Type I (MEA Type I), the other manifestations may be delayed for many years or appear only in relatives. A family now diagnosed as MEA Type I, who was previously thought, in 1965, to have familial hyperparathyroidism due to chief cell hyperplasia is now described. The importance is stressed of family surveillance and long-term follow-up in all cases of primary hyperparathyroidism. Those tests that are essential in the long-term surveillance of the patients and their first degree relatives are discussed. | [
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PMID:24838 | [Papain immobilization on a fibrous polymer of polyvinyl alcohol]. | The paper discusses papain immobilization on modified polyvinyl alcohol fibers by the ion fixation technique. The effect of the chemical structure of polyvinyl alcohol fibers on the basic properties of the bound enzyme has been examined. The level of activity and tolerance to pH changes of the resultant immobilized enzymes have been shown to depend on the papain arrangement in the polymer molecule. | [Papain immobilization on a fibrous polymer of polyvinyl alcohol]. The paper discusses papain immobilization on modified polyvinyl alcohol fibers by the ion fixation technique. The effect of the chemical structure of polyvinyl alcohol fibers on the basic properties of the bound enzyme has been examined. The level of activity and tolerance to pH changes of the resultant immobilized enzymes have been shown to depend on the papain arrangement in the polymer molecule. | [
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PMID:24839 | [Immobilization of alpha-amylase on porous glass and silochrome]. | Immobilized forms of alpha-amylase from Aspergillus oryzae were prepared on the porous glass and silochrome by the glutaraldehyde method. An addition of calcium ions at a concentration of 0.05 M to the reaction mixture during immobilization stabilized the enzyme activity. pH optimum of the insoluble form of alpha-amylase was 5.8 and that of the soluble form was 4.7. Storage of the insoluble enzyme as water suspension in 0.015 M CaCl2 at 4 degrees C for six months and twenty times repeated specific reaction did not affect significantly the activity of insoluble alpha-amylase. | [Immobilization of alpha-amylase on porous glass and silochrome]. Immobilized forms of alpha-amylase from Aspergillus oryzae were prepared on the porous glass and silochrome by the glutaraldehyde method. An addition of calcium ions at a concentration of 0.05 M to the reaction mixture during immobilization stabilized the enzyme activity. pH optimum of the insoluble form of alpha-amylase was 5.8 and that of the soluble form was 4.7. Storage of the insoluble enzyme as water suspension in 0.015 M CaCl2 at 4 degrees C for six months and twenty times repeated specific reaction did not affect significantly the activity of insoluble alpha-amylase. | [
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] |
PMID:24840 | [Glutamine synthetase immobilization]. | Highly purified glutamine synthetase has been isolated from Chlorella and immobilized on BrCN-sepharose. Its residual activity was 25-35%. Immobilized glutamine synthetase showed far greater thermal stability than glutamine synthetase in solution. During immobilization pH optimum of the enzyme was shifted towards the alkaline area, maximum rate of the reaction was reduced and KM remained unaltered. | [Glutamine synthetase immobilization]. Highly purified glutamine synthetase has been isolated from Chlorella and immobilized on BrCN-sepharose. Its residual activity was 25-35%. Immobilized glutamine synthetase showed far greater thermal stability than glutamine synthetase in solution. During immobilization pH optimum of the enzyme was shifted towards the alkaline area, maximum rate of the reaction was reduced and KM remained unaltered. | [
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PMID:24844 | Interaction of human chorionic gonadotropin with membrane components of rat testes. | Previous studies demonstrating that gangliosides interacted with thyrotropin and human chorionic gonadotropin (hCG) suggested that gangliosides participate in the transduction of the hormonal message across the target cell membrane. As a continuation of these investigations, we examined the effects of down-regulation of hCG receptors on the interaction of hCG with rat testis membrane components. Rat testes contained a complex ganglioside pattern that did not appear to change qualitatively or quantitatively after the injection of hCG into the animals, although testis membranes from hCG-treated rats lost their capacity to bind (125)I-labeled hCG ((125)I-hCG). Gangliosides extracted from the testes of control and treated animals were equally effective inhibitors of (125)I-hCG binding to testis membranes. However, inhibition of binding was observed only under conditions (pH 6.0, low ionic strength) such that unlabeled hCG (>2500-fold excess) did not block (125)I-hCG binding, and (125)I-hCG bound similarly to testis membranes from control and treated rats. Under conditions such that hCG binding was specific (blocked by 250-fold excess of unlabeled hCG), testis gangliosides were noninhibitory. Liposomes containing gangliosides from the testes of control or hCG-treated rats bound similar small amounts of (125)I-hCG. These same liposomes bound 50 and 1000 times more thyrotropin and cholera toxin, respectively, than hCG. Oligosaccharides derived from gangliosides did not inhibit (125)I-hCG binding to testis membranes nor did they alter the fluorescence of hCG conjugated with fluorescent probes, whereas the gangliosides themselves were inhibitory and enhanced the fluorescence intensity of the hCG derivatives. Exposure of testis membranes from hCG-treated rats to 4 M MgCl(2), which displaces bound hCG [Chen, Y.-D. I. & Payne, A. H. (1977) Biochem. Biophys. Res. Commun. 74, 1589-1596], did not restore their ability to bind (125)I-hCG. When membranes were solubilized with Triton X-100, a solubilized receptor was detected from testis membranes of control but not hCG-treated rats. These findings and the absence of demonstrable changes in the composition or quantity of rat testis gangliosides when hCG receptors are down-regulated suggest that gangliosides do not represent the primary binding determinants of hCG receptors. | Interaction of human chorionic gonadotropin with membrane components of rat testes. Previous studies demonstrating that gangliosides interacted with thyrotropin and human chorionic gonadotropin (hCG) suggested that gangliosides participate in the transduction of the hormonal message across the target cell membrane. As a continuation of these investigations, we examined the effects of down-regulation of hCG receptors on the interaction of hCG with rat testis membrane components. Rat testes contained a complex ganglioside pattern that did not appear to change qualitatively or quantitatively after the injection of hCG into the animals, although testis membranes from hCG-treated rats lost their capacity to bind (125)I-labeled hCG ((125)I-hCG). Gangliosides extracted from the testes of control and treated animals were equally effective inhibitors of (125)I-hCG binding to testis membranes. However, inhibition of binding was observed only under conditions (pH 6.0, low ionic strength) such that unlabeled hCG (>2500-fold excess) did not block (125)I-hCG binding, and (125)I-hCG bound similarly to testis membranes from control and treated rats. Under conditions such that hCG binding was specific (blocked by 250-fold excess of unlabeled hCG), testis gangliosides were noninhibitory. Liposomes containing gangliosides from the testes of control or hCG-treated rats bound similar small amounts of (125)I-hCG. These same liposomes bound 50 and 1000 times more thyrotropin and cholera toxin, respectively, than hCG. Oligosaccharides derived from gangliosides did not inhibit (125)I-hCG binding to testis membranes nor did they alter the fluorescence of hCG conjugated with fluorescent probes, whereas the gangliosides themselves were inhibitory and enhanced the fluorescence intensity of the hCG derivatives. Exposure of testis membranes from hCG-treated rats to 4 M MgCl(2), which displaces bound hCG [Chen, Y.-D. I. & Payne, A. H. (1977) Biochem. Biophys. Res. Commun. 74, 1589-1596], did not restore their ability to bind (125)I-hCG. When membranes were solubilized with Triton X-100, a solubilized receptor was detected from testis membranes of control but not hCG-treated rats. These findings and the absence of demonstrable changes in the composition or quantity of rat testis gangliosides when hCG receptors are down-regulated suggest that gangliosides do not represent the primary binding determinants of hCG receptors. | [
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PMID:24841 | [Purification and properties of the NADP-specific glutamate dehydrogenase of Candida tropicalis feed yeasts]. | From the cell-free extract of fodder yeast Candida tropicalis NADP-specific glutamate dehydrogenase was isolated and partially purified (75-fold) by means of fractional precipitation by ammonium sulphate and ion-exchange chromatography on DEAE-cellulose. The preparation was investigated with the aid of polyacrylamide gel electrophoresis. Kinetic characteristics of the enzyme in the cell-free extract and partially purified preparation were derived. | [Purification and properties of the NADP-specific glutamate dehydrogenase of Candida tropicalis feed yeasts]. From the cell-free extract of fodder yeast Candida tropicalis NADP-specific glutamate dehydrogenase was isolated and partially purified (75-fold) by means of fractional precipitation by ammonium sulphate and ion-exchange chromatography on DEAE-cellulose. The preparation was investigated with the aid of polyacrylamide gel electrophoresis. Kinetic characteristics of the enzyme in the cell-free extract and partially purified preparation were derived. | [
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PMID:24845 | Role of anions in parathyroid hormone release from dispersed bovine parathyroid cells. | It is known that permeant anions are required for the release of epinephrine from isolated chromaffin granules and of serotonin from intact platelets. We have now investigated the role of anions in the release of a polypeptide hormone, parathyroid hormone, from dispersed bovine parathyroid cells. The release is inhibited 60%-80% by decreasing either [Cl-] or [OH-] and 60%-70% by replacement of NaCl with the impermeant anion isethionate. By contrast, substitution of various monovalent cations in the medium had no effect on the release. Disodium 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and probenecid, which are known to block anion transport in the erythrocyte, also cause a dose-dependent 90%-100% inhibition of release. Moreover, kinetic analysis of inhibition by probenecid suggests that it is competitive with respect to either OH- or Cl-. These results suggest that anions and the anion transport system may play a role in exocytosis of a polypeptide hormone. The proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone was was also found to block hormone release, and the possibility is discussed of a "chemosmotic" mechanism for exocytosis in this system similar to that previously postulated for chromaffin granules and platelets. | Role of anions in parathyroid hormone release from dispersed bovine parathyroid cells. It is known that permeant anions are required for the release of epinephrine from isolated chromaffin granules and of serotonin from intact platelets. We have now investigated the role of anions in the release of a polypeptide hormone, parathyroid hormone, from dispersed bovine parathyroid cells. The release is inhibited 60%-80% by decreasing either [Cl-] or [OH-] and 60%-70% by replacement of NaCl with the impermeant anion isethionate. By contrast, substitution of various monovalent cations in the medium had no effect on the release. Disodium 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and probenecid, which are known to block anion transport in the erythrocyte, also cause a dose-dependent 90%-100% inhibition of release. Moreover, kinetic analysis of inhibition by probenecid suggests that it is competitive with respect to either OH- or Cl-. These results suggest that anions and the anion transport system may play a role in exocytosis of a polypeptide hormone. The proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone was was also found to block hormone release, and the possibility is discussed of a "chemosmotic" mechanism for exocytosis in this system similar to that previously postulated for chromaffin granules and platelets. | [
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PMID:24846 | Phosphate metabolites in lymphoid, Friend erythroleukemia, and HeLa cells observed by high-resolution 31P nuclear magnetic resonance. | High-resolution phosphorus-31 nuclear magnetic resonance spectra were observed for cell lines from mammalian sources: lymphoid cells, Friend erythroleukemia cells, and HeLa cells. Some phosphate metabolites were identified and their concentrations were found to vary among the different cell lines. ATP/ADP ratios could be measured in the living cells. The phospholipid metabolites phosphorylcholine and phosphorylethanolamine and their glyceryl esters were present in relatively high concentrations in the cells, but their ratios varied considerably. Also, a high concentration of an unidentified diphosphodiester compound was observed in the Friend erythroleukemia and HeLa cells. No appreciable pH gradient across the cell membrance was observed in these three mammalian cell lines, in contrast to the large pH gradient detected in microorganisms. | Phosphate metabolites in lymphoid, Friend erythroleukemia, and HeLa cells observed by high-resolution 31P nuclear magnetic resonance. High-resolution phosphorus-31 nuclear magnetic resonance spectra were observed for cell lines from mammalian sources: lymphoid cells, Friend erythroleukemia cells, and HeLa cells. Some phosphate metabolites were identified and their concentrations were found to vary among the different cell lines. ATP/ADP ratios could be measured in the living cells. The phospholipid metabolites phosphorylcholine and phosphorylethanolamine and their glyceryl esters were present in relatively high concentrations in the cells, but their ratios varied considerably. Also, a high concentration of an unidentified diphosphodiester compound was observed in the Friend erythroleukemia and HeLa cells. No appreciable pH gradient across the cell membrance was observed in these three mammalian cell lines, in contrast to the large pH gradient detected in microorganisms. | [
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PMID:24847 | Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata). | We have recently described the presence of a guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] inhibitor (GCI) in an aqueous extract of the balsam pear (Momordica charantia abbreviata). Because the guanylate cyclase-cyclic GMP system is though to be involved in cell growth, DNA and RNA synthesis, and possible malignant transformation, we examined the effect of the aqueous extract containing GCI on an undifferentiated adenocarcinoma of the rat prostate and concanavalin-A-stimulated [3H]thymidine incorporation into cultured splenic lymphocytes, a process thought to be mediated by cyclic GMP. The results demonstrate that the extract of the balsam pear blocks both the growth of the rat prostatic adencarcinoma in vitro and [3H]thymidine incorporation into DNA. DNA histograms from flow cytometry indicated that the extract containing GCI inhibited in the G2 + M phase of the cell cycle, a presumed locus of cyclic GMP effects. In addition, guanylate cyclase activity was significantly greater in the tumor than normal prostate tissue and was decreased by the extract containing GCI. Cyclic GMP levels in the tumor in culture wer also decreased by addition of the extract. It remains to be determined whether or not the anti-tumor agent and GCI are the same substance. | Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata). We have recently described the presence of a guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] inhibitor (GCI) in an aqueous extract of the balsam pear (Momordica charantia abbreviata). Because the guanylate cyclase-cyclic GMP system is though to be involved in cell growth, DNA and RNA synthesis, and possible malignant transformation, we examined the effect of the aqueous extract containing GCI on an undifferentiated adenocarcinoma of the rat prostate and concanavalin-A-stimulated [3H]thymidine incorporation into cultured splenic lymphocytes, a process thought to be mediated by cyclic GMP. The results demonstrate that the extract of the balsam pear blocks both the growth of the rat prostatic adencarcinoma in vitro and [3H]thymidine incorporation into DNA. DNA histograms from flow cytometry indicated that the extract containing GCI inhibited in the G2 + M phase of the cell cycle, a presumed locus of cyclic GMP effects. In addition, guanylate cyclase activity was significantly greater in the tumor than normal prostate tissue and was decreased by the extract containing GCI. Cyclic GMP levels in the tumor in culture wer also decreased by addition of the extract. It remains to be determined whether or not the anti-tumor agent and GCI are the same substance. | [
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PMID:24842 | [Microbiological transformation of carbohydrates. Glucose isomerization into fructose by washed cells of Streptomyces sp. strain 29]. | Glucose-fructose transformation by washed and packed cells of Streptomyces sp. 29 was studied. The cells grown on the nutrient medium containing xylose and Co and Mg salts were capable to perform glucose-fructose isomerization. The cellular activity depended in a great degree on the temperature, pH and initial glucose concentration; to a lesser extent on Co and Mg ions present in the incubation mixture, and did not depend on the age of the culture (within 8-69 hours). The activity reached its maximum at 70-80 degrees C, pH 7.0 and a low concentration of glucose (10(-3) M). Under these conditions the yield of fructose was 50% from the initial glucose concentration (or 100% from the theoretical value). Washed cells of Streptomyces sp. 29 packed into a thermally controlled column continuously transformed glucose to fructose during 24 days with a yield of 30-44%. | [Microbiological transformation of carbohydrates. Glucose isomerization into fructose by washed cells of Streptomyces sp. strain 29]. Glucose-fructose transformation by washed and packed cells of Streptomyces sp. 29 was studied. The cells grown on the nutrient medium containing xylose and Co and Mg salts were capable to perform glucose-fructose isomerization. The cellular activity depended in a great degree on the temperature, pH and initial glucose concentration; to a lesser extent on Co and Mg ions present in the incubation mixture, and did not depend on the age of the culture (within 8-69 hours). The activity reached its maximum at 70-80 degrees C, pH 7.0 and a low concentration of glucose (10(-3) M). Under these conditions the yield of fructose was 50% from the initial glucose concentration (or 100% from the theoretical value). Washed cells of Streptomyces sp. 29 packed into a thermally controlled column continuously transformed glucose to fructose during 24 days with a yield of 30-44%. | [
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PMID:24843 | [Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. | Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide. | [Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide. | [
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PMID:24855 | Fluorimetric determination of the active form of tetracycline, chloretetracycline and oxytetracycline in partially decomposed solutions. | The content of tetracycline (1), chlortetracycline (2) and oxytetracycline (3) has been determined by use of the fluorimetric method in partially decomposed acqueous solutions of different pH values. The procedure consisted in the extraction of fluorescent calcium and 5.5-diethyl-barbituric acid complexes of 1 and 3 (with 2 calcium complex only) into an organic solvent. In the method, only complexes with undecomposed 1--3 show a strong fluorescence. Products of decomposition of the antibiotics did not affect significantly analytical results. Comparative investigations have been carried out with 1--3 using t.l.c. and turbidimetry. | Fluorimetric determination of the active form of tetracycline, chloretetracycline and oxytetracycline in partially decomposed solutions. The content of tetracycline (1), chlortetracycline (2) and oxytetracycline (3) has been determined by use of the fluorimetric method in partially decomposed acqueous solutions of different pH values. The procedure consisted in the extraction of fluorescent calcium and 5.5-diethyl-barbituric acid complexes of 1 and 3 (with 2 calcium complex only) into an organic solvent. In the method, only complexes with undecomposed 1--3 show a strong fluorescence. Products of decomposition of the antibiotics did not affect significantly analytical results. Comparative investigations have been carried out with 1--3 using t.l.c. and turbidimetry. | [
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PMID:24859 | The effect of stress on the activity of hepatic tryptophan pyrrolase, of tyrosine aminotransferase in various organs and on the level of tryptophan in the liver and plasma of rats. | In rats subjected to 400 revolutions in Noble-Collip drums, hepatic tryptophan pyrrolase activity increases and plasma tryptophan level decreases. After bilateral adrenalectomy, the alterations of plasma tryptophan are even more pronounced and liver tryptophan increases in contrast to tryptophan pyrrolase activity which remains unchanged after injury. The possible significance of the posttraumatic increase of tryptophan pyrrolase in intact animals for brain serotonin metabolism and hepatic gluconeogenesis is underlined. The activity of tyrosine aminotransferase in liver, brain, adrenal, kidney and muscle tissue of rats was determined with special reference to the possible effect of the before-mentioned stress procedure. Organ homogenates were centrifuged at 15000 x g and both supernatants and pellets were investigated for enzyme activity with the exception of the liver, where only the supernatant fraction was used. Tyrosine aminotransferase activity in the liver supernatant considerably exceeded the corresponding values in both supernatant and pellet of the remaining organs, in which a prevalence of the mitochondrial enzyme was obvious. In contrast to the clear-cut increase of the hepatic enzyme during stress, essentially no changes were noted in the brain, the adrenals, kidney or muscle under similar conditions... | The effect of stress on the activity of hepatic tryptophan pyrrolase, of tyrosine aminotransferase in various organs and on the level of tryptophan in the liver and plasma of rats. In rats subjected to 400 revolutions in Noble-Collip drums, hepatic tryptophan pyrrolase activity increases and plasma tryptophan level decreases. After bilateral adrenalectomy, the alterations of plasma tryptophan are even more pronounced and liver tryptophan increases in contrast to tryptophan pyrrolase activity which remains unchanged after injury. The possible significance of the posttraumatic increase of tryptophan pyrrolase in intact animals for brain serotonin metabolism and hepatic gluconeogenesis is underlined. The activity of tyrosine aminotransferase in liver, brain, adrenal, kidney and muscle tissue of rats was determined with special reference to the possible effect of the before-mentioned stress procedure. Organ homogenates were centrifuged at 15000 x g and both supernatants and pellets were investigated for enzyme activity with the exception of the liver, where only the supernatant fraction was used. Tyrosine aminotransferase activity in the liver supernatant considerably exceeded the corresponding values in both supernatant and pellet of the remaining organs, in which a prevalence of the mitochondrial enzyme was obvious. In contrast to the clear-cut increase of the hepatic enzyme during stress, essentially no changes were noted in the brain, the adrenals, kidney or muscle under similar conditions... | [
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PMID:24860 | [Behavioral rehabilitation of nonspecific symptoms occuring after craniocerbral trauma (author's transl)]. | The purpose of this study was to develop a behavioral rehabilitation program for patients with long-term nonspecific symptoms following craniocerebral trauma. In 47 patients we analyzed symptoms typical of "illness behavior" (e.g. complaining tendency, depression, irritability, psychosomatic pain, problems in job performance and social interaction) as possible targets for behavior modification. We then developed a behavioral training program to teach the patients various techniques of self-control (relaxation, desensitization, self-image training, analysis and control of illness behavior, assertiveness, performance techniques), our program being based on studies in the U.S.A. using similar approaches. For a preliminary testing two groups of 8 and 6 patients each were treated by different therapists. The patients worked through a section of the program manual prior to each group session. During the sessions proper (a total of 8 weekly two-hour sessions) the different techniques were practiced under the therapist's supervistion. In both groups a significant reduction in illness behavior as indicated on questionnaires and in 3-month follow-up was found. These encouraging results need to be further substantiated by controlled outcome studies. | [Behavioral rehabilitation of nonspecific symptoms occuring after craniocerbral trauma (author's transl)]. The purpose of this study was to develop a behavioral rehabilitation program for patients with long-term nonspecific symptoms following craniocerebral trauma. In 47 patients we analyzed symptoms typical of "illness behavior" (e.g. complaining tendency, depression, irritability, psychosomatic pain, problems in job performance and social interaction) as possible targets for behavior modification. We then developed a behavioral training program to teach the patients various techniques of self-control (relaxation, desensitization, self-image training, analysis and control of illness behavior, assertiveness, performance techniques), our program being based on studies in the U.S.A. using similar approaches. For a preliminary testing two groups of 8 and 6 patients each were treated by different therapists. The patients worked through a section of the program manual prior to each group session. During the sessions proper (a total of 8 weekly two-hour sessions) the different techniques were practiced under the therapist's supervistion. In both groups a significant reduction in illness behavior as indicated on questionnaires and in 3-month follow-up was found. These encouraging results need to be further substantiated by controlled outcome studies. | [
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PMID:24866 | Oxygen affinity and 2,3-diphosphoglycerate in blood of Australian marsupials of differing body size. | Oxygen carriage and 2,3-diphosphoglycerate (2,3-DPG) levels have been measured in the blood of seven species of Australian marsupials ranging in size from 35 to 0.03 kg. They were Red and Grey Kangaroos, Wallaroo, Tammar Wallaby, Brush-tailed possum, Potoroo, and Brown Marsupial Mouse. Oxygen affinity decreased with decrease in adult body size, standard P50 (at 36 C) varying from 24.6 torr in the largest (Red Kangaroo) to 41.9 torr in the smallest (Brown Marsupial Mouse). The relationship between P50 and body size is similar to the relationship which has been described previously for eutherian mammals. The Bohr factor (--deltalog P50/deltapH) and value for Hill n were generally in the range found for other land-dwelling mammals. All species had 2,3-DPG in their erythrocytes acting as a regulator of oxygen affinity. The polymorphism at position beta 2 in hemoglobin of the Grey Kangaroo was shown to affect the respiratory properties of the molecule. When beta 2 = histidine, which has a positively charged side chain, erythrocyte 2,3-DPG was higher, and P50 was higher, than when beta 2 = glutamine which has a neutral side chain. | Oxygen affinity and 2,3-diphosphoglycerate in blood of Australian marsupials of differing body size. Oxygen carriage and 2,3-diphosphoglycerate (2,3-DPG) levels have been measured in the blood of seven species of Australian marsupials ranging in size from 35 to 0.03 kg. They were Red and Grey Kangaroos, Wallaroo, Tammar Wallaby, Brush-tailed possum, Potoroo, and Brown Marsupial Mouse. Oxygen affinity decreased with decrease in adult body size, standard P50 (at 36 C) varying from 24.6 torr in the largest (Red Kangaroo) to 41.9 torr in the smallest (Brown Marsupial Mouse). The relationship between P50 and body size is similar to the relationship which has been described previously for eutherian mammals. The Bohr factor (--deltalog P50/deltapH) and value for Hill n were generally in the range found for other land-dwelling mammals. All species had 2,3-DPG in their erythrocytes acting as a regulator of oxygen affinity. The polymorphism at position beta 2 in hemoglobin of the Grey Kangaroo was shown to affect the respiratory properties of the molecule. When beta 2 = histidine, which has a positively charged side chain, erythrocyte 2,3-DPG was higher, and P50 was higher, than when beta 2 = glutamine which has a neutral side chain. | [
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PMID:24867 | Metabolic, respiratory and haematological adjustments of the little pocket mouse to circadian torpor cycles. | Metabolic, respiratory and haematological parameters were investigated for the Little Pocket mouse during circadian torpor cycles. The rate of O2 consumption decreased from 7.04 to 0.05 ml O2.g-1.hr-1, with a corresponding decrease in respiratory minute volume from 49.4 to 0.9 ml.min-1 during torpor at an ambient temperature of 10 C. No changes in haemoglobin concentration (19.7 g/100 ml), haematocrit (54%), red blood corpuscle count (12.4 10(6)/microliter), mean corpuscular volume (43.6 micrometer3), mean corpuscular haemoglobin content (16.2 pg), mean corpuscular haemoglobin concentration (37.4%) and [2,3-DPG] (9.6 mumol/g Hb) were observed during torpor cycles. The half saturation tension of P. longimembris haemoglobin was 41 mm Hg (37 C, pH = 7.28) and 19.7 mm Hg (10 degrees C, pH = 7.51). The effect of temperature on P50 was deltalog P50/ C = +0.0106 (pH = 7.4). Venous blood parameters were: euthermic mice (37 C); PCO2 = 36.8 mm Hg, PO2 = 49.5 mm Hg, pH = 7.28, [HCO-3] = 17.3 mmol/l; torpid mice (10 C); PCO2 = 14.6, PO2 = 35.7 pH = 7.51, [HCO-3] = 18.8. These data indicate a new, relatively acidotic acid-base status during torpor, characterised by a higher H+/ OH- ratio. The respiratory sensitivity to inspired CO2 of pocket mice was, despite their being semi-fossorial, typical of other mammals. High concentrations of CO2 did not induce, or facilitate, entry into torpor. | Metabolic, respiratory and haematological adjustments of the little pocket mouse to circadian torpor cycles. Metabolic, respiratory and haematological parameters were investigated for the Little Pocket mouse during circadian torpor cycles. The rate of O2 consumption decreased from 7.04 to 0.05 ml O2.g-1.hr-1, with a corresponding decrease in respiratory minute volume from 49.4 to 0.9 ml.min-1 during torpor at an ambient temperature of 10 C. No changes in haemoglobin concentration (19.7 g/100 ml), haematocrit (54%), red blood corpuscle count (12.4 10(6)/microliter), mean corpuscular volume (43.6 micrometer3), mean corpuscular haemoglobin content (16.2 pg), mean corpuscular haemoglobin concentration (37.4%) and [2,3-DPG] (9.6 mumol/g Hb) were observed during torpor cycles. The half saturation tension of P. longimembris haemoglobin was 41 mm Hg (37 C, pH = 7.28) and 19.7 mm Hg (10 degrees C, pH = 7.51). The effect of temperature on P50 was deltalog P50/ C = +0.0106 (pH = 7.4). Venous blood parameters were: euthermic mice (37 C); PCO2 = 36.8 mm Hg, PO2 = 49.5 mm Hg, pH = 7.28, [HCO-3] = 17.3 mmol/l; torpid mice (10 C); PCO2 = 14.6, PO2 = 35.7 pH = 7.51, [HCO-3] = 18.8. These data indicate a new, relatively acidotic acid-base status during torpor, characterised by a higher H+/ OH- ratio. The respiratory sensitivity to inspired CO2 of pocket mice was, despite their being semi-fossorial, typical of other mammals. High concentrations of CO2 did not induce, or facilitate, entry into torpor. | [
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PMID:24868 | A comparative study of the respiratory properties of bird blood. | Oxygen affinity and Bohr effect have been measured in the blood of four bird species (chicken, pigeon, Japanese quail and sparrow). Under physiological conditions (41 C, pH 7.5, PCO2 approximately 35 Torr) the oxygen half saturation pressure P50 are 50 Torr for the chickens, 38 Torr for the pigeon, 43 Torr for the Japanese quail and 44 Torr for the sparrow. Values for the physiological Bohr factors deltalogP50/deltapH are similar to those obtained in mammalian blood ranging from -0.57 in chicken blood to -0.42 for pigeon blood. A direct effect of CO2 on the oxygen affinity of chicken blood could not be observed, in agreement with results in hemoglobin solutions. However, at a constant pHpl of 7.5 the intracellular pH rise from 7.22 at 39 Torr PCO2 to 7.32 at PCO2 less than 1 Torr. This leads to a decrease of P50 at pHpl 7.5 from 52 to 46 Torr. A convincing correlation between body weight and P50 could not be established, even when including data from other authors. It is concluded that aside from metabolic rate, behavioural as well as environmental factors have influenced whole blood oxygen affinity during evolution. | A comparative study of the respiratory properties of bird blood. Oxygen affinity and Bohr effect have been measured in the blood of four bird species (chicken, pigeon, Japanese quail and sparrow). Under physiological conditions (41 C, pH 7.5, PCO2 approximately 35 Torr) the oxygen half saturation pressure P50 are 50 Torr for the chickens, 38 Torr for the pigeon, 43 Torr for the Japanese quail and 44 Torr for the sparrow. Values for the physiological Bohr factors deltalogP50/deltapH are similar to those obtained in mammalian blood ranging from -0.57 in chicken blood to -0.42 for pigeon blood. A direct effect of CO2 on the oxygen affinity of chicken blood could not be observed, in agreement with results in hemoglobin solutions. However, at a constant pHpl of 7.5 the intracellular pH rise from 7.22 at 39 Torr PCO2 to 7.32 at PCO2 less than 1 Torr. This leads to a decrease of P50 at pHpl 7.5 from 52 to 46 Torr. A convincing correlation between body weight and P50 could not be established, even when including data from other authors. It is concluded that aside from metabolic rate, behavioural as well as environmental factors have influenced whole blood oxygen affinity during evolution. | [
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PMID:24869 | Regulation of arterial PCO2 during inhalation of CO2 in chickens. | Since CO2-sensitive intrapulmonary chemoreceptors have been shown to exist in the avian lung, we conducted a series of experiments to determine if birds could regulate PaCO2 when confronted with an inspired CO2 load. Chickens were anesthetized with either pentobarbital (30 mg.kg-1) or phenobarbital (160 mg.kg-1). The PICO2 was either increased or decreased in successive 7 torr steps between 0 and 35 torr. At each level of PICO2, steady-state measurements of PaCO2, PaO2 and [H+]a were made. In three of ten experiments, tidal volume and respiratory frequency were determined and minute ventilation calculated. Our results indicate that as PICO2 is varied between 0 and 21 torr, minute ventilation increases and arterial homeostasis of PCO2 and [H+] is maintained; as the PICO2 is increased above 21 torr, PaCO2 increases. We conclude that the isocapnic hyperpnea associated with inhalation of CO2 in chickens is a CO2-coupled phenomenon and that it is mediated by CO2-sensitive intrapulmonary chemoreceptors. | Regulation of arterial PCO2 during inhalation of CO2 in chickens. Since CO2-sensitive intrapulmonary chemoreceptors have been shown to exist in the avian lung, we conducted a series of experiments to determine if birds could regulate PaCO2 when confronted with an inspired CO2 load. Chickens were anesthetized with either pentobarbital (30 mg.kg-1) or phenobarbital (160 mg.kg-1). The PICO2 was either increased or decreased in successive 7 torr steps between 0 and 35 torr. At each level of PICO2, steady-state measurements of PaCO2, PaO2 and [H+]a were made. In three of ten experiments, tidal volume and respiratory frequency were determined and minute ventilation calculated. Our results indicate that as PICO2 is varied between 0 and 21 torr, minute ventilation increases and arterial homeostasis of PCO2 and [H+] is maintained; as the PICO2 is increased above 21 torr, PaCO2 increases. We conclude that the isocapnic hyperpnea associated with inhalation of CO2 in chickens is a CO2-coupled phenomenon and that it is mediated by CO2-sensitive intrapulmonary chemoreceptors. | [
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PMID:24870 | The transduction properties of tracheal stretch receptors in vitro. | Extrathoracic tracheal stretch receptors and tracheal tension were recorded in vitro when the trachea was stretched. The receptors responded to an increase in tension produced by displacement in the longitudinal or transverse axis of the trachea. They were sensitive to the rate of change of tension as well as the tension level itself, i.e. there was a dynamic component in the response. A fall in temperature decreased discharge frequency but the receptors were not affected by changes in PCO2 and pH of the perfusion fluid. Contraction of tracheal muscle, induced by acetylcholine, increased discharge frequency showing that the receptors studied were effectively in series with the muscle. | The transduction properties of tracheal stretch receptors in vitro. Extrathoracic tracheal stretch receptors and tracheal tension were recorded in vitro when the trachea was stretched. The receptors responded to an increase in tension produced by displacement in the longitudinal or transverse axis of the trachea. They were sensitive to the rate of change of tension as well as the tension level itself, i.e. there was a dynamic component in the response. A fall in temperature decreased discharge frequency but the receptors were not affected by changes in PCO2 and pH of the perfusion fluid. Contraction of tracheal muscle, induced by acetylcholine, increased discharge frequency showing that the receptors studied were effectively in series with the muscle. | [
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PMID:24889 | Calcium-stimulated ATPase activity in homogenates of the secretory enamel organ in the rat. | The activity of calcium-stimulated ATPase (E.C. 3.6.1.3) in homogenates of the secretory enamel organ of rat incisors was studied biochemically. ATP hydrolysis was estimated from the amount of inorganic phosphate liberated. An analysis of the total degradation of ATP was initially performed to ensure that the enzyme assays pertained to the original substrate, ATP, and were not influenced by reaction products formed. Standard incubations were run in tris-maleate buffer, pH 8.2, with 3 mM ATP, 3 mM Ca2+ and 0.5 mM R 8231 at 37 degrees C. The presence of R 8231 was necessary to inhibit nonspecific alkaline phosphatase. The calcium-stimulated ATPase was completely inhibited when heated at 55-60 degrees C for 5 min. The pH optimum was found to be 8.2. The hydrolysis was substantially dependent on Ca2+ and was fastest when the ATP:Ca2+ ratio was 1:1. High substrate concentrations inhibited the hydrolysis. The addition of 1 mM Zn2+ and Ni2+ to the incubation medium markedly inhibited the hydrolysis as did, though less strongly, p-hydroxymercuribenzoate, oligomycin, EDTA and ruthenium red. l-Cysteine, mercaptoethanol, iodoacetic acid and sodium azide were without effect. F- was without effect unless added to a final concentration above 15 mM to media where Ca2+ had first been allowed to react with ATP. | Calcium-stimulated ATPase activity in homogenates of the secretory enamel organ in the rat. The activity of calcium-stimulated ATPase (E.C. 3.6.1.3) in homogenates of the secretory enamel organ of rat incisors was studied biochemically. ATP hydrolysis was estimated from the amount of inorganic phosphate liberated. An analysis of the total degradation of ATP was initially performed to ensure that the enzyme assays pertained to the original substrate, ATP, and were not influenced by reaction products formed. Standard incubations were run in tris-maleate buffer, pH 8.2, with 3 mM ATP, 3 mM Ca2+ and 0.5 mM R 8231 at 37 degrees C. The presence of R 8231 was necessary to inhibit nonspecific alkaline phosphatase. The calcium-stimulated ATPase was completely inhibited when heated at 55-60 degrees C for 5 min. The pH optimum was found to be 8.2. The hydrolysis was substantially dependent on Ca2+ and was fastest when the ATP:Ca2+ ratio was 1:1. High substrate concentrations inhibited the hydrolysis. The addition of 1 mM Zn2+ and Ni2+ to the incubation medium markedly inhibited the hydrolysis as did, though less strongly, p-hydroxymercuribenzoate, oligomycin, EDTA and ruthenium red. l-Cysteine, mercaptoethanol, iodoacetic acid and sodium azide were without effect. F- was without effect unless added to a final concentration above 15 mM to media where Ca2+ had first been allowed to react with ATP. | [
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PMID:24890 | Demonstration of a K+-stimulated and ouabain-sensitive p-nitrophenyl phosphatase activity in enamel-and dentin-forming tissues in the rat. | p-Nitrophenyl phosphate hydrolysis was studied at neutral pH with tissue preparations of the rat secretory and maturation enamel organs and dental pulp. By introduction of inhibitors to nonspecific alkaline phosphatase activity and stimulants to the K+-stimulated and ouabain-sensitive p-nitrophenyl phosphatase activity, the latter enzyme activity could be demonstrated. This enzyme activity is generally held to be representative of the enzyme sodium- and potassium-stimulated adenosine triphosphatase. The K+-stimulated activity was magnesium dependent and highly sensitive to fluoride. It was inhibited completely by 3 mM fluoride in the incubation medium and about 1 mM produced half the maximum inhibition. The K+-independent enzyme activity was inhibited 50-60% by fluoride in concentrations between 3 and 15 mM. The high fluoride sensitivity of the K+-stimulated activity may perhaps help to explain the vulnerability of dental tissues to fluoride. | Demonstration of a K+-stimulated and ouabain-sensitive p-nitrophenyl phosphatase activity in enamel-and dentin-forming tissues in the rat. p-Nitrophenyl phosphate hydrolysis was studied at neutral pH with tissue preparations of the rat secretory and maturation enamel organs and dental pulp. By introduction of inhibitors to nonspecific alkaline phosphatase activity and stimulants to the K+-stimulated and ouabain-sensitive p-nitrophenyl phosphatase activity, the latter enzyme activity could be demonstrated. This enzyme activity is generally held to be representative of the enzyme sodium- and potassium-stimulated adenosine triphosphatase. The K+-stimulated activity was magnesium dependent and highly sensitive to fluoride. It was inhibited completely by 3 mM fluoride in the incubation medium and about 1 mM produced half the maximum inhibition. The K+-independent enzyme activity was inhibited 50-60% by fluoride in concentrations between 3 and 15 mM. The high fluoride sensitivity of the K+-stimulated activity may perhaps help to explain the vulnerability of dental tissues to fluoride. | [
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PMID:24894 | Bicarbonate ion transport: a mechanism for the acidification of urine in the turtle. | The uricotelic turtle Pseudemys scripta acidifies the urine to a pH as low as 4 in the urinary bladder. Data in this report show that the mechanism of acidification in this bladder is the transport of bicarbonate ion from lumen to serosa, and that the temperature to which the turtles are adapted prior to the in vitro experiment largely determines the direction of the transmural carbon dioxide gradient observed. This temperature effect also serves to reconcile apparently disparate data that were previously reported. A new technique for the direct determination of the partial pressure of carbon dioxide was employed. | Bicarbonate ion transport: a mechanism for the acidification of urine in the turtle. The uricotelic turtle Pseudemys scripta acidifies the urine to a pH as low as 4 in the urinary bladder. Data in this report show that the mechanism of acidification in this bladder is the transport of bicarbonate ion from lumen to serosa, and that the temperature to which the turtles are adapted prior to the in vitro experiment largely determines the direction of the transmural carbon dioxide gradient observed. This temperature effect also serves to reconcile apparently disparate data that were previously reported. A new technique for the direct determination of the partial pressure of carbon dioxide was employed. | [
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PMID:24895 | Oral cocaine: plasma concentrations and central effects. | Cocaine (2.0 milligrams per kilogram) given by the oral route is at least as effective as the same dose given intranasally. Cocaine is not detected in the plasma until 30 minutes after oral administration, but peak plasma concentrations are similar after both routes. The subjective "highs" in man are greater after oral than after intranasal administration. | Oral cocaine: plasma concentrations and central effects. Cocaine (2.0 milligrams per kilogram) given by the oral route is at least as effective as the same dose given intranasally. Cocaine is not detected in the plasma until 30 minutes after oral administration, but peak plasma concentrations are similar after both routes. The subjective "highs" in man are greater after oral than after intranasal administration. | [
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PMID:24896 | MEN type IIa syndrome: dilemmas in modern management. | With the use of newer techniques, the multiple endocrine neoplasm II-A syndrome can now be diagnosed early in its evolution. This article discusses the clinical course of the syndrome, the diagnostic modalities employed, and the therapeutic interventions required. An approach to the individual patient with this syndrome is presented. | MEN type IIa syndrome: dilemmas in modern management. With the use of newer techniques, the multiple endocrine neoplasm II-A syndrome can now be diagnosed early in its evolution. This article discusses the clinical course of the syndrome, the diagnostic modalities employed, and the therapeutic interventions required. An approach to the individual patient with this syndrome is presented. | [
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PMID:24898 | Muscle perfusion and the healing of below knee amputations. | Muscle pH has been used to assess the perfusion of the muscles at the site of below knee amputation in 20 patients having ischemia at the periphery. The results show that a muscle pH above 7.0 did not correlate with the outcome of amputation but that, when the pH was below 7.00, healing was never achieved. | Muscle perfusion and the healing of below knee amputations. Muscle pH has been used to assess the perfusion of the muscles at the site of below knee amputation in 20 patients having ischemia at the periphery. The results show that a muscle pH above 7.0 did not correlate with the outcome of amputation but that, when the pH was below 7.00, healing was never achieved. | [
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PMID:24899 | The role of fibrin formation in the pathogenesis of bacteremic shock in the primate. | In this study, an attempt was made to elucidate further the role of intravascular fibrin formation in the pathogenesis of sepsis in the primate. It was found that injected live Escherichia coli caused death in primates within four to 11 hours as a result of microcirculatory failure and acidosis. Pretreatment with Arvin did not prolong the survival rate, probably because of an overloading of the reticuloendothelial system with fibrin degradation products. This study does not support an obligatory role for intravascular coagulation or fibrin formation in primate sepsis and coincides with an earlier report (6) from this laboratory on cats. Vascular damage and malfunction, secondary to mediators released by platelets, leukocytes, red cells or Hageman factor, are not ruled out. | The role of fibrin formation in the pathogenesis of bacteremic shock in the primate. In this study, an attempt was made to elucidate further the role of intravascular fibrin formation in the pathogenesis of sepsis in the primate. It was found that injected live Escherichia coli caused death in primates within four to 11 hours as a result of microcirculatory failure and acidosis. Pretreatment with Arvin did not prolong the survival rate, probably because of an overloading of the reticuloendothelial system with fibrin degradation products. This study does not support an obligatory role for intravascular coagulation or fibrin formation in primate sepsis and coincides with an earlier report (6) from this laboratory on cats. Vascular damage and malfunction, secondary to mediators released by platelets, leukocytes, red cells or Hageman factor, are not ruled out. | [
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PMID:24901 | Training and use of surgeon's assistants. | "Physician extenders" of various types have been produced in the past few years. The University of Alabama in Birmingham has trained surgeon's assistants over the past 9 years, graduating 53 individuals after a 2-year course of didactic, laboratory, and clinical instruction. The graduates have performed satisfactorily, working with surgeons in the community setting and as part of highly specialized teams in large medical centers. One third work in general surgery, one third in cardiovascular thoracic surgery, and one third in other special areas. The authors conclude that these individuals will play an increasing role in allowing surgical therapy to be delivered in an efficient and effective manner. | Training and use of surgeon's assistants. "Physician extenders" of various types have been produced in the past few years. The University of Alabama in Birmingham has trained surgeon's assistants over the past 9 years, graduating 53 individuals after a 2-year course of didactic, laboratory, and clinical instruction. The graduates have performed satisfactorily, working with surgeons in the community setting and as part of highly specialized teams in large medical centers. One third work in general surgery, one third in cardiovascular thoracic surgery, and one third in other special areas. The authors conclude that these individuals will play an increasing role in allowing surgical therapy to be delivered in an efficient and effective manner. | [
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PMID:24902 | Droperidol, its alpha-adrenergic blocking action on the aortic strip and inhibitory action on norepinephrine uptake of the adrenergic terminal of the left atrial strip of rabbit. | In aortic strips, the dose-response curves for phenylephrine were obtained before and after addition of droperidol. Droperidol caused a parallel shift of the curves dose-dependently toward the right side and its grade of the shift was greater than caused by phentolamine at the same concentration. In the left atrial strip, the potentiation of contraction by tyramine was markedly depressed by droperidol. In the reserpinized preparation, the effect of tyramine was depressed markedly and there was no norepinephrine fluorescence. After incubation with norepinephrine they were restored to the same level as in non-reserpinized preparations. However, incubation with droperidol before norepinephrine blocked the restoration. It is postulated that droperidol may have both alpha-adrenergic blocking action and inhibitory action on norepinephrine uptake by adrenergic terminals. | Droperidol, its alpha-adrenergic blocking action on the aortic strip and inhibitory action on norepinephrine uptake of the adrenergic terminal of the left atrial strip of rabbit. In aortic strips, the dose-response curves for phenylephrine were obtained before and after addition of droperidol. Droperidol caused a parallel shift of the curves dose-dependently toward the right side and its grade of the shift was greater than caused by phentolamine at the same concentration. In the left atrial strip, the potentiation of contraction by tyramine was markedly depressed by droperidol. In the reserpinized preparation, the effect of tyramine was depressed markedly and there was no norepinephrine fluorescence. After incubation with norepinephrine they were restored to the same level as in non-reserpinized preparations. However, incubation with droperidol before norepinephrine blocked the restoration. It is postulated that droperidol may have both alpha-adrenergic blocking action and inhibitory action on norepinephrine uptake by adrenergic terminals. | [
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PMID:24911 | The mechanism of urinary continence after prostatectomy. | An anatomical and neuropharmacological study of the urethra was performed in 19 patients after prostatetectomy to investigate the mechanism of continence. Anatomically, the urethral segment responsible for the postprostatectomy continence was located distal to the open prostatic fossa in the external sphincter which is comprised of intrinsic striated muscle and is called arbitrarily rhabdosphincter by the author. This unique striated muscle in the rhabdosphinecter appears to be primarily under the alpha-adrenergic influence in view of the change in the urethral pressure profile observed following alpha-adrenergic drugs. | The mechanism of urinary continence after prostatectomy. An anatomical and neuropharmacological study of the urethra was performed in 19 patients after prostatetectomy to investigate the mechanism of continence. Anatomically, the urethral segment responsible for the postprostatectomy continence was located distal to the open prostatic fossa in the external sphincter which is comprised of intrinsic striated muscle and is called arbitrarily rhabdosphincter by the author. This unique striated muscle in the rhabdosphinecter appears to be primarily under the alpha-adrenergic influence in view of the change in the urethral pressure profile observed following alpha-adrenergic drugs. | [
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PMID:24912 | Pathology of germ cell tumors of the testis. | Testicular germ cell tumors form a complex group of interrelated entities. Problems of nomenclature remain, but there does appear to be a close agreement between the major classifications in use. The identification of clinically useful markers for certain germ cell testicular tumors has provided a major impetus in this field. Information gained from the study of these markers has promoted an understanding of the histogenesis of germ cell tumors, has improved standard nomenclature, and has stimulated progress in patient care. Radioimmunoassay techniques are now frequently used to measure beta-human chorionic gonadotrophin and alpha-fetoprotein levels in evaluating the clinical course of patients with nonseminomatous germ cell tumors of the testis. It is hoped that the use of these markers will permit earlier detection of tumor recurrence, prompt treatment, and an improved survival rate. The knowledge of the production of alpha-fetoprotein by the human yolk sac has further refined tumor classification. It is against this general background that we have outlined the standard pathology of germ cell tumors of the testis. | Pathology of germ cell tumors of the testis. Testicular germ cell tumors form a complex group of interrelated entities. Problems of nomenclature remain, but there does appear to be a close agreement between the major classifications in use. The identification of clinically useful markers for certain germ cell testicular tumors has provided a major impetus in this field. Information gained from the study of these markers has promoted an understanding of the histogenesis of germ cell tumors, has improved standard nomenclature, and has stimulated progress in patient care. Radioimmunoassay techniques are now frequently used to measure beta-human chorionic gonadotrophin and alpha-fetoprotein levels in evaluating the clinical course of patients with nonseminomatous germ cell tumors of the testis. It is hoped that the use of these markers will permit earlier detection of tumor recurrence, prompt treatment, and an improved survival rate. The knowledge of the production of alpha-fetoprotein by the human yolk sac has further refined tumor classification. It is against this general background that we have outlined the standard pathology of germ cell tumors of the testis. | [
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PMID:24915 | Cytogenic studies of cryptorchid testes. | Twenty-nine patients with unilateral or bilateral cryptochism underwent biopsies of the testis at the time of orchiopexy. Karyotype evaluation of fibroblasts obtained from tissue cultures of the biopsy specimen was completed counting a minimum of twenty-five cells. In 1 patient with multiple anomalies a 46,XYDq+ karyotype was identified. All other karyotypes were normal suggesting cryptorchism is not associated with abnormal testicular cytogenetics. | Cytogenic studies of cryptorchid testes. Twenty-nine patients with unilateral or bilateral cryptochism underwent biopsies of the testis at the time of orchiopexy. Karyotype evaluation of fibroblasts obtained from tissue cultures of the biopsy specimen was completed counting a minimum of twenty-five cells. In 1 patient with multiple anomalies a 46,XYDq+ karyotype was identified. All other karyotypes were normal suggesting cryptorchism is not associated with abnormal testicular cytogenetics. | [
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PMID:24916 | [Evaluation of metabolic profile tests using a computer]. | A programme has been developed for the evaluation of metabolism profile tests in dairy cows by means of the TESLA-200 computer in the FORTRAN language. The computer evaluates and plots the metabolism profile from input data punched on tape in the IBM code by the Consul-253 electronic organization automatic device. The metabolism profile is represented as a column graph (histogram), the levels of individual parameters being confronted with the reference levels with a 95% confidence interval and the deviations are expressed in units defined as 1/2 of the confidence interval for each parameter. Calculation by this procedure enables the construction of a profile record in which any step beyond the 95% confidence interval in any parameters is seen very clearly. The computer also produces a table of exactly calculated values of deviations from the reference levels and makes it possible to determine the numbers of abnormalities for individual parameters in the animals tested. | [Evaluation of metabolic profile tests using a computer]. A programme has been developed for the evaluation of metabolism profile tests in dairy cows by means of the TESLA-200 computer in the FORTRAN language. The computer evaluates and plots the metabolism profile from input data punched on tape in the IBM code by the Consul-253 electronic organization automatic device. The metabolism profile is represented as a column graph (histogram), the levels of individual parameters being confronted with the reference levels with a 95% confidence interval and the deviations are expressed in units defined as 1/2 of the confidence interval for each parameter. Calculation by this procedure enables the construction of a profile record in which any step beyond the 95% confidence interval in any parameters is seen very clearly. The computer also produces a table of exactly calculated values of deviations from the reference levels and makes it possible to determine the numbers of abnormalities for individual parameters in the animals tested. | [
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PMID:24917 | [Intensity of acid-base reactions of the blood and cerebrospinal fluid in sheep after intraluminal stress induced by urea and acetic acid]. | Acid-base indices of the blood and cerebro-spinal fluid were studied on Astrup apparatus (BMS 2) in an experiment with twelve, two- to three-year-old Merino sheep, being in the first half of the gravidity period, under clinical conditions after the administration of 0.8 g urea per 1 kg live weight followed by, in half an hour, the administration of acetic acid (8% vinegar, a dose of 2 ml per 1 kg live weight). Heparinized syringes were used to take blood samples anaerobically before the beginning of the experiment, then after 15, 30, 45, 60, 75, 90, 105, 120 minutes and after 4 and 24 hours. The fluid was taken by heparinized capillaries before the beginning of the experiment, then after 30, 60, 90 and 120 minutes and after 4 and 24 hours. The following indices were obtained, and/or calculated from nomographs: actual pH, carbon dioxide pressure--pCO2, base excess--BE, buffer bases--BB, standard and actual bicarbonate--SB, AB, total carbon dioxide--tCO2. After 15 minutes' interval since the administration of urea significant changes in the values of the indices, especially higher pH values and paradoxical pCO2 drop, were recorded. After the administration of acetic acid overcompensated acidosis of the organism occurred (accompanied even by mortality of the experimental sheep). Towards the end of the experiments the results illustrated basemia. A depressing effect of the lower pH on the toxicity of ammonia was also confirmed. The reaction of the fluid to the urea and acetic acid stress opposite to the venous blood was retarded and the values of the indices studied showed some variability. | [Intensity of acid-base reactions of the blood and cerebrospinal fluid in sheep after intraluminal stress induced by urea and acetic acid]. Acid-base indices of the blood and cerebro-spinal fluid were studied on Astrup apparatus (BMS 2) in an experiment with twelve, two- to three-year-old Merino sheep, being in the first half of the gravidity period, under clinical conditions after the administration of 0.8 g urea per 1 kg live weight followed by, in half an hour, the administration of acetic acid (8% vinegar, a dose of 2 ml per 1 kg live weight). Heparinized syringes were used to take blood samples anaerobically before the beginning of the experiment, then after 15, 30, 45, 60, 75, 90, 105, 120 minutes and after 4 and 24 hours. The fluid was taken by heparinized capillaries before the beginning of the experiment, then after 30, 60, 90 and 120 minutes and after 4 and 24 hours. The following indices were obtained, and/or calculated from nomographs: actual pH, carbon dioxide pressure--pCO2, base excess--BE, buffer bases--BB, standard and actual bicarbonate--SB, AB, total carbon dioxide--tCO2. After 15 minutes' interval since the administration of urea significant changes in the values of the indices, especially higher pH values and paradoxical pCO2 drop, were recorded. After the administration of acetic acid overcompensated acidosis of the organism occurred (accompanied even by mortality of the experimental sheep). Towards the end of the experiments the results illustrated basemia. A depressing effect of the lower pH on the toxicity of ammonia was also confirmed. The reaction of the fluid to the urea and acetic acid stress opposite to the venous blood was retarded and the values of the indices studied showed some variability. | [
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PMID:24918 | Polypoid nonchromaffin paraganglioma of the duodenum. | A polypoid tumor was surgically removed from the second part of the duodenum of a 56-year-old male. The main body consisted of large epithelioid cells arranged in an adenoma like pattern of strands and nests. These cells were argyrophil and had marked nonspecific esterase activity. Unmyelinated nerves with proliferated Schwann cells accompanied these epithelioid cells together with scattered gangliocyte like elements. Ultramicroscopically, the epithelioid cells were seen to contain round electron dense granules, 150 nm in diameter on average. The tumor is considered to be a nonchromaffin paraganglioma, as it probable developed from paraganglion cells associated with small arteries or branches of the vagus nerve, or from the undifferentiated pluripotent APUD cells of the duodenum. | Polypoid nonchromaffin paraganglioma of the duodenum. A polypoid tumor was surgically removed from the second part of the duodenum of a 56-year-old male. The main body consisted of large epithelioid cells arranged in an adenoma like pattern of strands and nests. These cells were argyrophil and had marked nonspecific esterase activity. Unmyelinated nerves with proliferated Schwann cells accompanied these epithelioid cells together with scattered gangliocyte like elements. Ultramicroscopically, the epithelioid cells were seen to contain round electron dense granules, 150 nm in diameter on average. The tumor is considered to be a nonchromaffin paraganglioma, as it probable developed from paraganglion cells associated with small arteries or branches of the vagus nerve, or from the undifferentiated pluripotent APUD cells of the duodenum. | [
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PMID:24919 | [Artificial arterial hypotension during surgical treatment of intracranial aneurysms]. | In studying the content of lactic and pyruvic acids in the cerebrospinal fluid of 31 patients during operation for intracranial aneurysms under halothane anesthesia, the authors established that the performance of these operations under protection of deep (40 mm Hg) and prolonged (up to 2 hrs 25 min) artificial arterial hypotension in an uncomplicated course of the surgical intervention was not attended with hypoxic damage of the brain. The danger of hypoxia developing became greater when acute disturbances of blood flow in the cerebral arteries (clipping of a vessel, spasm) occurred in the period of hypotension. | [Artificial arterial hypotension during surgical treatment of intracranial aneurysms]. In studying the content of lactic and pyruvic acids in the cerebrospinal fluid of 31 patients during operation for intracranial aneurysms under halothane anesthesia, the authors established that the performance of these operations under protection of deep (40 mm Hg) and prolonged (up to 2 hrs 25 min) artificial arterial hypotension in an uncomplicated course of the surgical intervention was not attended with hypoxic damage of the brain. The danger of hypoxia developing became greater when acute disturbances of blood flow in the cerebral arteries (clipping of a vessel, spasm) occurred in the period of hypotension. | [
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PMID:24923 | Dehydrogenation of indanol by rabbit liver 3-hydroxyhexobarbital dehydrogenase. | 1. Among the several enzyme activities in rabbit liver cytosol able to dehydrogenate 1-indanol, only the main activity was not separable from 3-hydroxyhexobarbital dehydrogenase during purification including polyacrylamide gel disc electrophoresis. 2. Results of mixed substrate method indicated that the same enzyme catalyses the dehydrogenation of 1-indanol and 3-hydroxyhexobarbital. The ratio between the two dehydrogenation activities was almost constant as the enzyme underwent thermal inactivation. The Ki values of p-chloromercuribenzoate, the Km values for NAD+, and the Km values for NADP+ were very similar for the two dehydrogenations. These results lead to the conclusion that the same enzyme catalyses the dehydrogenation of 3-hydroxyhexobarbital and 1-indanol. 3. 1-Tetralol, 1-acenaphthenol, 9-fluorenol, thiochroman-4-ol and 4-chromanol also served as substrate of the enzyme, but 2-indanol, 2-tetralol, and trans- and cis-indan-1,2-diol were not oxidized. 4. Reversibility of the reaction was also confirmed using 1-indanone as substrate. | Dehydrogenation of indanol by rabbit liver 3-hydroxyhexobarbital dehydrogenase. 1. Among the several enzyme activities in rabbit liver cytosol able to dehydrogenate 1-indanol, only the main activity was not separable from 3-hydroxyhexobarbital dehydrogenase during purification including polyacrylamide gel disc electrophoresis. 2. Results of mixed substrate method indicated that the same enzyme catalyses the dehydrogenation of 1-indanol and 3-hydroxyhexobarbital. The ratio between the two dehydrogenation activities was almost constant as the enzyme underwent thermal inactivation. The Ki values of p-chloromercuribenzoate, the Km values for NAD+, and the Km values for NADP+ were very similar for the two dehydrogenations. These results lead to the conclusion that the same enzyme catalyses the dehydrogenation of 3-hydroxyhexobarbital and 1-indanol. 3. 1-Tetralol, 1-acenaphthenol, 9-fluorenol, thiochroman-4-ol and 4-chromanol also served as substrate of the enzyme, but 2-indanol, 2-tetralol, and trans- and cis-indan-1,2-diol were not oxidized. 4. Reversibility of the reaction was also confirmed using 1-indanone as substrate. | [
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PMID:24924 | [Anabolic and catabolic enzymes of urea metabolism in a carbohydrate-utilizing strain of Candida guilliermondii]. | The yeast "H" of the genus Candida guilliermondii can grow on hydrocarbons as the only source for carbon. Urea can serve as a nitrogen source for this yeast which lacks detectable urease activity. During urea metabolism ammonia has never been accumulated in the culture medium. However, transferring the yeast from complete urea-medium into an urea containing phophate-buffer, the degradation of urea continues and ammonia is accumulated as well as CO2 evolved. In cell-free extracts of the yeast urea amidolyase activity was detected in the presence of ATP, biotin and specific cations. Obviously, the synthesis of urea amidolyase is induced by urea and arginine and repressed by the catabolite ammonia. Similarly the synthesis of arginase is regulated by arginine and ammonia. The analytical data of the arginase action differ significantly in relation to the carbon source of the culture medium. Both the level of arginase and ornithine carbamyl-transferase change in a characteristic way during the batch-culture. From the lower level of arginase in relation to ornithine carbamyltransferase it can be concluded that especially in alkane-metabolizing yeast the arginine catabolism is not very intensive. | [Anabolic and catabolic enzymes of urea metabolism in a carbohydrate-utilizing strain of Candida guilliermondii]. The yeast "H" of the genus Candida guilliermondii can grow on hydrocarbons as the only source for carbon. Urea can serve as a nitrogen source for this yeast which lacks detectable urease activity. During urea metabolism ammonia has never been accumulated in the culture medium. However, transferring the yeast from complete urea-medium into an urea containing phophate-buffer, the degradation of urea continues and ammonia is accumulated as well as CO2 evolved. In cell-free extracts of the yeast urea amidolyase activity was detected in the presence of ATP, biotin and specific cations. Obviously, the synthesis of urea amidolyase is induced by urea and arginine and repressed by the catabolite ammonia. Similarly the synthesis of arginase is regulated by arginine and ammonia. The analytical data of the arginase action differ significantly in relation to the carbon source of the culture medium. Both the level of arginase and ornithine carbamyl-transferase change in a characteristic way during the batch-culture. From the lower level of arginase in relation to ornithine carbamyltransferase it can be concluded that especially in alkane-metabolizing yeast the arginine catabolism is not very intensive. | [
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PMID:24925 | [On molecular biology of aging. 11th communication. Enzyme adaptation, age (author's transl)]. | Age-dependent modifications of enzyme adaptations in response to a variety of environmental alterations are a biochemical expression of biological ageing. In this paper age-dependent changes of the adaptation of a number of enzymes are described. Experiments from our laboratory indicate that pyruvate kinase is more responsive to starvation and refeeding in young animals. The diminished response of pyruvate kinase in old age is caused by a decreased adaptability of the regulatory isoenzyme PK-L. | [On molecular biology of aging. 11th communication. Enzyme adaptation, age (author's transl)]. Age-dependent modifications of enzyme adaptations in response to a variety of environmental alterations are a biochemical expression of biological ageing. In this paper age-dependent changes of the adaptation of a number of enzymes are described. Experiments from our laboratory indicate that pyruvate kinase is more responsive to starvation and refeeding in young animals. The diminished response of pyruvate kinase in old age is caused by a decreased adaptability of the regulatory isoenzyme PK-L. | [
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PMID:24961 | Effect of lime-pelleting on nodulation and yield of soybean grown in acid soil. | An experiment for studying the effect of lime-pelleting of inoculated seed of soybean [Glycine max. (L.) Merr.] on nodulation, growth, and grain yield was undertaken in red sandy loam of Bangalore, having a pH of 4.0. The results indicated that inoculation alone increased significantly nodulation, plant dry weight, and grain yield. But inoculation plus lime-pelleting significantly increased the dry weight of nodules and plants, but not the grain yield. However, lime-pelleting was found to be beneficial though not essential in acid soils. | Effect of lime-pelleting on nodulation and yield of soybean grown in acid soil. An experiment for studying the effect of lime-pelleting of inoculated seed of soybean [Glycine max. (L.) Merr.] on nodulation, growth, and grain yield was undertaken in red sandy loam of Bangalore, having a pH of 4.0. The results indicated that inoculation alone increased significantly nodulation, plant dry weight, and grain yield. But inoculation plus lime-pelleting significantly increased the dry weight of nodules and plants, but not the grain yield. However, lime-pelleting was found to be beneficial though not essential in acid soils. | [
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PMID:24962 | [Application of a TRICIN-buffered modification of the CMRL-1969 medium in cell and virus cultivation (author's transl)]. | CMRL-1969 medium (Healy et al., 1971) was modified by using 0.02 molar N-[Tris-(hydroxymethyl)-methyl]-glycin (= TRICIN) instead of bicarbonate as the buffer substance. Several permanent cell lines and primary cell cultures did not show growth differences in the two medium variants. Like other non volatile buffers TRICIN abolishes the initial increase of the Ph in freshly split or newly fed closed vessel cultures, but in 0.02 M concentration maintains the same buffering capacity of the medium as compared to bicarbonate. Multiplication of Entero-, Adeno-, Herpes-, Influenza-A-, and Vaccinia-viruses was also not altered. The medium allows open vessel methods like microtiter- and plaque-tests to be conducted under normal atmosphere and seems especially useful when initial pH-values are to be set in the rank of 7.5 to 8.6. For microtiter neutralization tests with enteroviruses a medium adjusted to pH 7.6 and a cell density of 10(5) cells/cm2 was found optimal. Plaque formation of Coxsackie-B-viruses reached a maximal plaque-size and -number when the pH of the double concentrated medium was beyond 8.2. | [Application of a TRICIN-buffered modification of the CMRL-1969 medium in cell and virus cultivation (author's transl)]. CMRL-1969 medium (Healy et al., 1971) was modified by using 0.02 molar N-[Tris-(hydroxymethyl)-methyl]-glycin (= TRICIN) instead of bicarbonate as the buffer substance. Several permanent cell lines and primary cell cultures did not show growth differences in the two medium variants. Like other non volatile buffers TRICIN abolishes the initial increase of the Ph in freshly split or newly fed closed vessel cultures, but in 0.02 M concentration maintains the same buffering capacity of the medium as compared to bicarbonate. Multiplication of Entero-, Adeno-, Herpes-, Influenza-A-, and Vaccinia-viruses was also not altered. The medium allows open vessel methods like microtiter- and plaque-tests to be conducted under normal atmosphere and seems especially useful when initial pH-values are to be set in the rank of 7.5 to 8.6. For microtiter neutralization tests with enteroviruses a medium adjusted to pH 7.6 and a cell density of 10(5) cells/cm2 was found optimal. Plaque formation of Coxsackie-B-viruses reached a maximal plaque-size and -number when the pH of the double concentrated medium was beyond 8.2. | [
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PMID:24963 | Clotting and fibrinolytic activities of Bacteroides melaninogenicus. | 106 strains of Bacteroides melaninogenicus ss. asaccharolyticus, intermedius and melaninogenicus were tested for production of extracellular blood clotting and fibrinolytic factors. 78.3% of tested strains caused clotting of rabbit plasma and 79.2% activated human plasminogen. Strains producing the clotting or fibrinolytic factor only were isolated. Both factors were quite active, as positive results for most strains were detected within one hour of incubation in controlled test system. | Clotting and fibrinolytic activities of Bacteroides melaninogenicus. 106 strains of Bacteroides melaninogenicus ss. asaccharolyticus, intermedius and melaninogenicus were tested for production of extracellular blood clotting and fibrinolytic factors. 78.3% of tested strains caused clotting of rabbit plasma and 79.2% activated human plasminogen. Strains producing the clotting or fibrinolytic factor only were isolated. Both factors were quite active, as positive results for most strains were detected within one hour of incubation in controlled test system. | [
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PMID:24964 | Studies on antituberculotic action of some phenothiazine derivatives in vitro. | Five phenothiazine derivatives (chlorpromazine, levomepromazine, diethazine, promethazine and chlorpromazine) sulphoxyde were tested for antimycobacterial activity. The growth of Mycobacterium tuberculosis, M. bovis and M. butyricum was inhibited by chlorpromazine practically at identical concentrations. The minimum inhibitory concentrations for M. tuberculosis were: chlorpromazine and levomepromazine, 10 microgram/ml; diethazine and promethazine 20 microgram/ml, whilst chlorpromazine sulphoxyde was ineffective even at a concentration of 100 microgram/ml. Chlorpromazine and promethazine exerted a measurable bactericidal activity on M. tuberculosis at 50 microgram/ml; total destruction of the organism and loss of acid fastness in part of the cells were shown at 300 microgram/ml. Preliminary studies, in mouse experiments phenothiazine derivatives were ineffective. | Studies on antituberculotic action of some phenothiazine derivatives in vitro. Five phenothiazine derivatives (chlorpromazine, levomepromazine, diethazine, promethazine and chlorpromazine) sulphoxyde were tested for antimycobacterial activity. The growth of Mycobacterium tuberculosis, M. bovis and M. butyricum was inhibited by chlorpromazine practically at identical concentrations. The minimum inhibitory concentrations for M. tuberculosis were: chlorpromazine and levomepromazine, 10 microgram/ml; diethazine and promethazine 20 microgram/ml, whilst chlorpromazine sulphoxyde was ineffective even at a concentration of 100 microgram/ml. Chlorpromazine and promethazine exerted a measurable bactericidal activity on M. tuberculosis at 50 microgram/ml; total destruction of the organism and loss of acid fastness in part of the cells were shown at 300 microgram/ml. Preliminary studies, in mouse experiments phenothiazine derivatives were ineffective. | [
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PMID:24965 | The nature of clotting and fibrinolytic activities of Bacteroids melaninogenicus. | From the supernatant of B. melaninogenicus ss. asaccharolyticus culture, a protein fraction was isolated by ethanol precipitation. The fraction was tested for the presence of clotting and fibrinolytic activities by application of quantitative techniques and specific substrates for measurement of prothrombin and plasminogen activation, and collagenase and elastase activity. It is postulated that ability of Bacteroides melaninogenicus ss. asaccharolyticus extracellular factors to clot fibrinogen and activate plasminogen, are due to a limited proteolysis by the proteolytic enzymes produced by this microorganism and not to the existence of specific B. melaninogenicus coagulase of plasminogen activator. | The nature of clotting and fibrinolytic activities of Bacteroids melaninogenicus. From the supernatant of B. melaninogenicus ss. asaccharolyticus culture, a protein fraction was isolated by ethanol precipitation. The fraction was tested for the presence of clotting and fibrinolytic activities by application of quantitative techniques and specific substrates for measurement of prothrombin and plasminogen activation, and collagenase and elastase activity. It is postulated that ability of Bacteroides melaninogenicus ss. asaccharolyticus extracellular factors to clot fibrinogen and activate plasminogen, are due to a limited proteolysis by the proteolytic enzymes produced by this microorganism and not to the existence of specific B. melaninogenicus coagulase of plasminogen activator. | [
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PMID:24966 | [Microbial growth on an expansion joint of a reservoir for drinkingwater (author's transl)]. | In a clear water reservoir built in ready construction after a working-period of five months quite a lot of slime could be found on the expansion joint filled with tightening compound on the base of Thiokol. The covering slime could be removed easily with a rubber-screen. The microbiological analysis showed an extremely high number of colonies and additional the slime was secondarily settled with Protozoa. An influence on the water in the reservoir could not be found out under working conditions. | [Microbial growth on an expansion joint of a reservoir for drinkingwater (author's transl)]. In a clear water reservoir built in ready construction after a working-period of five months quite a lot of slime could be found on the expansion joint filled with tightening compound on the base of Thiokol. The covering slime could be removed easily with a rubber-screen. The microbiological analysis showed an extremely high number of colonies and additional the slime was secondarily settled with Protozoa. An influence on the water in the reservoir could not be found out under working conditions. | [
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PMID:24967 | [On the determination of chlorine with a polarographic probe. 2nd communication: experimental arrangement and results under application (author's transl)]. | The examination of the physical properties of the instrument showed several possibilities of meter-error mainly due to constructive disadvantages. After having found this a special experimental arrangement was worked out to exclude errors. Then good linear correlations of the meter-reading and the analytical DPD-Method for free Chlorine were found for pH-values ranging from 3.7 to 11. Further the results of a test under practical conditions in a swimming pool are shown and the possibility to discriminate different types of waters by their chlorine demand under constant-titration. | [On the determination of chlorine with a polarographic probe. 2nd communication: experimental arrangement and results under application (author's transl)]. The examination of the physical properties of the instrument showed several possibilities of meter-error mainly due to constructive disadvantages. After having found this a special experimental arrangement was worked out to exclude errors. Then good linear correlations of the meter-reading and the analytical DPD-Method for free Chlorine were found for pH-values ranging from 3.7 to 11. Further the results of a test under practical conditions in a swimming pool are shown and the possibility to discriminate different types of waters by their chlorine demand under constant-titration. | [
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PMID:24968 | [Acid-base equilibrium in patients with tick-borne encephalitis and similar diseases]. | The study is concerned with the acid-base balance in 92 patients with tick-borne encephalitis, tick-borne fever and meningitis of an obscure etiology. In many cases there was a shift in the direction of a metabolic acidosis, which was most vividly expressed in the meningitic form of tick-borne encephalitis. Some of the patients were treated by sodium bicarbonate which exerted a positive effect. The degree of changed indices of the acid-base balance and the time of their appearance helps in the diagnosis of tick-borne encephalitis correct evaluation of the severity of the condition and timely prescription of correction therapy. | [Acid-base equilibrium in patients with tick-borne encephalitis and similar diseases]. The study is concerned with the acid-base balance in 92 patients with tick-borne encephalitis, tick-borne fever and meningitis of an obscure etiology. In many cases there was a shift in the direction of a metabolic acidosis, which was most vividly expressed in the meningitic form of tick-borne encephalitis. Some of the patients were treated by sodium bicarbonate which exerted a positive effect. The degree of changed indices of the acid-base balance and the time of their appearance helps in the diagnosis of tick-borne encephalitis correct evaluation of the severity of the condition and timely prescription of correction therapy. | [
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PMID:24969 | [Use of neuroleptics for the treatment of chronic alcoholism (psychopathology of the attraction to alcohol)]. | A psychopathological analysis of alcoholic drives in patients with alcoholism demonstrates that along with well-known negative symptoms of an alcoholic mental defect there is a productive psychopathological symptom in the clinical picture as well. Having this view, the author in 148 cases of alcoholism applied etoperasine (trilafon), and neuleptil (propericiasin)--neuroleptical drugs, possessing antipsychotic properties and relatively not toxic. As a result there was a distinct and rapid inhibition of pathological drives to alcohol with a good tolerance to the preparations. The use of these drugs activates the role of the patient in the process of treatment, increases the effectiveness of psychotherapy, and is technically simple in use. They may be prescribed for the prevention of relapses, arrest of bouts when other methods are ineffective. | [Use of neuroleptics for the treatment of chronic alcoholism (psychopathology of the attraction to alcohol)]. A psychopathological analysis of alcoholic drives in patients with alcoholism demonstrates that along with well-known negative symptoms of an alcoholic mental defect there is a productive psychopathological symptom in the clinical picture as well. Having this view, the author in 148 cases of alcoholism applied etoperasine (trilafon), and neuleptil (propericiasin)--neuroleptical drugs, possessing antipsychotic properties and relatively not toxic. As a result there was a distinct and rapid inhibition of pathological drives to alcohol with a good tolerance to the preparations. The use of these drugs activates the role of the patient in the process of treatment, increases the effectiveness of psychotherapy, and is technically simple in use. They may be prescribed for the prevention of relapses, arrest of bouts when other methods are ineffective. | [
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PMID:24970 | Effect of extracellular pH and inhibitors on the gluconeogenesis and ammoniagenesis relationship in rat kidney cortex slices. | 1. Gluconeogenesis from glutamine, fumarate, pyruvate, glutamine plus fumarate, and glutamine plus pyruvate, was generally higher at pH 7.1 than at pH 7.4 and 7.7, whereas ammoniagenesis did not depend on the pH of the medium. 2. The intermediates of the Krebs cycle decreased ammonia formation from glutamine, raising at the same time gluconeogenesis. 3. Arsenite, malonate, maleate, hydrazine and 2,4-dinitrophenol inhibited gluconeogenesis, and enhanced simultaneously ammonia formation irrespective of the pH of the medium. | Effect of extracellular pH and inhibitors on the gluconeogenesis and ammoniagenesis relationship in rat kidney cortex slices. 1. Gluconeogenesis from glutamine, fumarate, pyruvate, glutamine plus fumarate, and glutamine plus pyruvate, was generally higher at pH 7.1 than at pH 7.4 and 7.7, whereas ammoniagenesis did not depend on the pH of the medium. 2. The intermediates of the Krebs cycle decreased ammonia formation from glutamine, raising at the same time gluconeogenesis. 3. Arsenite, malonate, maleate, hydrazine and 2,4-dinitrophenol inhibited gluconeogenesis, and enhanced simultaneously ammonia formation irrespective of the pH of the medium. | [
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PMID:24978 | Neuroleptic blockade of the effect of various neurotransmitter substances. | The antagonistic effect of neuroleptics to acetylcholine, histamine, 5-HT, and noradrenaline was examined in various in vivo and in vitro models. Piflutixol, a new potent thioxanthene neuroleptic, markedly antagonizes the effect of dopamine, noradrenaline, 5-HT and to some extent histamine, whereas the affinity for muscarinic receptors was rather weak. Clozapine and chlorprothixene on the other hand, have high affinity for muscarinic receptors and also antagonize the effect of histamine and 5-HT, whereas clozapine was a weak antagonist of noradrenaline and dopamine when compared to the effect of piflutixol. Chlorprothixene, however, also exhibits a rather good antagonism of noradrenaline and dopamine. Haloperidol proved to be weak in all models when compared with the other neuroleptics examined. Flupenthixol specifically antagonizes dopamine and noradrenaline, whereas fluphenazine was a more potent antagonist of dopamine than of the other transmitters. The data show, that neuroleptic compounds possess very different profiles with regard to interaction with various neurotransmitter substances. It is suggested, that the rather potent anti 5-HT and antihistamine effects observed for certain substances may contribute to the central effect of these drugs. | Neuroleptic blockade of the effect of various neurotransmitter substances. The antagonistic effect of neuroleptics to acetylcholine, histamine, 5-HT, and noradrenaline was examined in various in vivo and in vitro models. Piflutixol, a new potent thioxanthene neuroleptic, markedly antagonizes the effect of dopamine, noradrenaline, 5-HT and to some extent histamine, whereas the affinity for muscarinic receptors was rather weak. Clozapine and chlorprothixene on the other hand, have high affinity for muscarinic receptors and also antagonize the effect of histamine and 5-HT, whereas clozapine was a weak antagonist of noradrenaline and dopamine when compared to the effect of piflutixol. Chlorprothixene, however, also exhibits a rather good antagonism of noradrenaline and dopamine. Haloperidol proved to be weak in all models when compared with the other neuroleptics examined. Flupenthixol specifically antagonizes dopamine and noradrenaline, whereas fluphenazine was a more potent antagonist of dopamine than of the other transmitters. The data show, that neuroleptic compounds possess very different profiles with regard to interaction with various neurotransmitter substances. It is suggested, that the rather potent anti 5-HT and antihistamine effects observed for certain substances may contribute to the central effect of these drugs. | [
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PMID:24980 | Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients. | Efficacy and side effects of flurazepam 15 mg, fosazepam 60 mg, and nitrazepam 5 mg were studied in 17 psychogeriatric patients. The drugs were equipotent in maintaining sleep but nitrazepam had more side effects than the other hypnotics, and it induced a rebound insomnia after withdrawal. All hypnotics lost some of their efficacy towards the end of 7 days' administration. Patients with evident cerebrovascular disease were vulnerable to the side effects of the benzodiazepine hypnotics. The side effects did not correlate with the age of a patient. In addition, no correlations were found between the serum levels of fosazepam or its main metabolite and the side effects. | Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients. Efficacy and side effects of flurazepam 15 mg, fosazepam 60 mg, and nitrazepam 5 mg were studied in 17 psychogeriatric patients. The drugs were equipotent in maintaining sleep but nitrazepam had more side effects than the other hypnotics, and it induced a rebound insomnia after withdrawal. All hypnotics lost some of their efficacy towards the end of 7 days' administration. Patients with evident cerebrovascular disease were vulnerable to the side effects of the benzodiazepine hypnotics. The side effects did not correlate with the age of a patient. In addition, no correlations were found between the serum levels of fosazepam or its main metabolite and the side effects. | [
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PMID:24981 | Three years' maintenance neuroleptic treatment in schizophrenia--before and beyond. | A group of patients with schizophrenia, initially 67 patients, was studied over a period of 3 years. After three years 36 out of 67 patients were still on the same depot neuroleptic. The main aim was to describe and compare maintenance neuroleptic therapy using two depot neuroleptics, fluphenazine decanoate and pipotiazine palmitate, given monthly. Before the outpatient care the patients had participated in the department's comprehensive hospital treatment including depot neuroleptic medication. After a 1-year clinical trial with frequent assessments of the patients, significant symptom reductions were found on all rating scales. During the last 2 years of the study only drug therapy was given. Improvement concerning social function in the community and work level as well as the low-rated psychopathology noted at the start of study also persisted at the 3-year follow-up. The side effects were low in frequency and quality. These results show the clinical value of long-term maintenance treatment with depot neuroleptics. The results also confirm that the favourable effects of the hospital treatment demonstrated before the start of the clinical trial could be maintained. The possibilities of further improving aftercare and outpatient treatment beyond medication alone are discussed. | Three years' maintenance neuroleptic treatment in schizophrenia--before and beyond. A group of patients with schizophrenia, initially 67 patients, was studied over a period of 3 years. After three years 36 out of 67 patients were still on the same depot neuroleptic. The main aim was to describe and compare maintenance neuroleptic therapy using two depot neuroleptics, fluphenazine decanoate and pipotiazine palmitate, given monthly. Before the outpatient care the patients had participated in the department's comprehensive hospital treatment including depot neuroleptic medication. After a 1-year clinical trial with frequent assessments of the patients, significant symptom reductions were found on all rating scales. During the last 2 years of the study only drug therapy was given. Improvement concerning social function in the community and work level as well as the low-rated psychopathology noted at the start of study also persisted at the 3-year follow-up. The side effects were low in frequency and quality. These results show the clinical value of long-term maintenance treatment with depot neuroleptics. The results also confirm that the favourable effects of the hospital treatment demonstrated before the start of the clinical trial could be maintained. The possibilities of further improving aftercare and outpatient treatment beyond medication alone are discussed. | [
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PMID:24982 | How schizophrenic patients change during 3 years' treatment with depot neuroleptics. | A group of patients, initially 67 individuals, with chronic schizophrenia were studied on repeated occasions during 1 year and followed up after 3 years. The patients were given depot neuroleptics, either fluphenazine decanoate or pipotiazine palmitate, at intervals of 1 month. The symptom scores from three rating scales were subjected to factor analysis. Four factors were found to explain the variance satisfactorily: one comprising psychopathological symptoms specific for schizophrenia, one relating to contact disturbances, one psychomotor activity and one representing neurotic symptoms. Analysis of these factors revealed certain differences between the treatment groups over time and demonstrated the effect of combination of psychotherapy and neuroleptic drugs in a subgroup of patients. This type of analysis of treatment results might contribute to improving our knowledge of rehabilitation of schizophrenic patients and help us to draw up giudelines for selection of suitable measures. | How schizophrenic patients change during 3 years' treatment with depot neuroleptics. A group of patients, initially 67 individuals, with chronic schizophrenia were studied on repeated occasions during 1 year and followed up after 3 years. The patients were given depot neuroleptics, either fluphenazine decanoate or pipotiazine palmitate, at intervals of 1 month. The symptom scores from three rating scales were subjected to factor analysis. Four factors were found to explain the variance satisfactorily: one comprising psychopathological symptoms specific for schizophrenia, one relating to contact disturbances, one psychomotor activity and one representing neurotic symptoms. Analysis of these factors revealed certain differences between the treatment groups over time and demonstrated the effect of combination of psychotherapy and neuroleptic drugs in a subgroup of patients. This type of analysis of treatment results might contribute to improving our knowledge of rehabilitation of schizophrenic patients and help us to draw up giudelines for selection of suitable measures. | [
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PMID:24985 | Auricular tyrosine hydroxylase and dopamine-beta-hydroxylase activities and noradrenaline content in ischaemic heart disease. | Assessments were made of the tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities as well as the noradrenaline (NA) content of samples excised from right auricular tissue during cardiac surgery on a total of 55 patients with ischaemic heart disease (IHD), valvular heart disease (VHD), uncomplicated atrial septal defect (ASD) or congestive heart failure (CHF). The NA content was significantly higher in the IHD group than in the other three groups. The TH activity was highest in the IHD group although the difference was statistically significant only compared with the ASD and CHF groups. The DBH activity was also highest in the IHD group, but again the difference was statistically significant only compared with the ASD and CHF groups. In the whole material there was a significant positive correlation between the NA content and TH or DBH activity, as well as between TH and DBH activity. In the IHD group there was a significant positive correlation between heart volume and TH activity. The results suggest that at least compared with ASD and CHF, the sympathetic tone is relatively high in IHD, possibly involving an enhanced NA turnover. | Auricular tyrosine hydroxylase and dopamine-beta-hydroxylase activities and noradrenaline content in ischaemic heart disease. Assessments were made of the tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities as well as the noradrenaline (NA) content of samples excised from right auricular tissue during cardiac surgery on a total of 55 patients with ischaemic heart disease (IHD), valvular heart disease (VHD), uncomplicated atrial septal defect (ASD) or congestive heart failure (CHF). The NA content was significantly higher in the IHD group than in the other three groups. The TH activity was highest in the IHD group although the difference was statistically significant only compared with the ASD and CHF groups. The DBH activity was also highest in the IHD group, but again the difference was statistically significant only compared with the ASD and CHF groups. In the whole material there was a significant positive correlation between the NA content and TH or DBH activity, as well as between TH and DBH activity. In the IHD group there was a significant positive correlation between heart volume and TH activity. The results suggest that at least compared with ASD and CHF, the sympathetic tone is relatively high in IHD, possibly involving an enhanced NA turnover. | [
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PMID:24989 | Cyclic nucleotide metabolism in solid tumor tissues. | The examination of the regulation of the system of 3'-5' cyclic nucleotide monophosphates has only begun in cancer tissues. In human cancers, these studies are notably non-existent. However, in animal cancers, especially the Morris hepatomas, enough data has been gathered that, while risky, certain trends seem to begin to appear. Cyclic AMP is constant or lowered, while cyclic GMP is elevated in the fast growing hepatomas. Regulation of adenylate cyclase by protein hormones is reduced, while regulation by epinephrine may be increased. Binding of glucagon is decreased in the fast growing hepatomas. Guanylate cyclase, while being predominantly cytoplasmic in the normal liver, is predominantly membrane bound in the tumors. The liver enzyme is also readily stimulated by several chemical carcinogens. The cyclic GMP phosphodiesterases are decreased in these tumors; while the cAMP phosphodiesterases are increased. Although the cyclic nucleotide dependent protein kinases (histone as substrate) are altered in the hepatomas, observations of unique cyclic nucleotide binding proteins or cAMP independent protein kinases in cancer tissues may be of even greater significance for the development of or the maintenance of the neoplastic state of cells. | Cyclic nucleotide metabolism in solid tumor tissues. The examination of the regulation of the system of 3'-5' cyclic nucleotide monophosphates has only begun in cancer tissues. In human cancers, these studies are notably non-existent. However, in animal cancers, especially the Morris hepatomas, enough data has been gathered that, while risky, certain trends seem to begin to appear. Cyclic AMP is constant or lowered, while cyclic GMP is elevated in the fast growing hepatomas. Regulation of adenylate cyclase by protein hormones is reduced, while regulation by epinephrine may be increased. Binding of glucagon is decreased in the fast growing hepatomas. Guanylate cyclase, while being predominantly cytoplasmic in the normal liver, is predominantly membrane bound in the tumors. The liver enzyme is also readily stimulated by several chemical carcinogens. The cyclic GMP phosphodiesterases are decreased in these tumors; while the cAMP phosphodiesterases are increased. Although the cyclic nucleotide dependent protein kinases (histone as substrate) are altered in the hepatomas, observations of unique cyclic nucleotide binding proteins or cAMP independent protein kinases in cancer tissues may be of even greater significance for the development of or the maintenance of the neoplastic state of cells. | [
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PMID:24994 | Quantitative effects of salycylhydroxamic acid and glycerol on Trypanosoma brucei glycolysis in vitro and in vivo. | During anaerobic glycolysis in vitro in the presence of salicylhydroxamic acid, Trypanosoma brucei brucei converts glucose to equimolar amounts of glycerol and pyruvate as end products. Glycerol, whether generated endogenously and pyruvate as end products. Glycerol, whether generated endogenously or added exogenously, can inhibit anaerobic glycolysis sufficiently in vitro to result in cell death. The concomitant administration of salicylhydroxamic acid and glycerol to rats infected with T. brucei brucei results in a rapid clearance of parasitemia. Our results clearly demonstrate a new and approachable chemotherapeutic target for African trypanosomes. | Quantitative effects of salycylhydroxamic acid and glycerol on Trypanosoma brucei glycolysis in vitro and in vivo. During anaerobic glycolysis in vitro in the presence of salicylhydroxamic acid, Trypanosoma brucei brucei converts glucose to equimolar amounts of glycerol and pyruvate as end products. Glycerol, whether generated endogenously and pyruvate as end products. Glycerol, whether generated endogenously or added exogenously, can inhibit anaerobic glycolysis sufficiently in vitro to result in cell death. The concomitant administration of salicylhydroxamic acid and glycerol to rats infected with T. brucei brucei results in a rapid clearance of parasitemia. Our results clearly demonstrate a new and approachable chemotherapeutic target for African trypanosomes. | [
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PMID:24995 | Effect of beta-lapachone on hydrogen peroxide production in Trypanosoma cruzi. | beta-Lapachone, an antimicrobial agent, markedly increase the generation of H2O2 in intact Trypanosoma cruzi epimastigotes (Y strain). Increase in H2O2 was determined by the horseradish peroxidase-H2O2 Compound II formation as well as by a cytochemical technique. | Effect of beta-lapachone on hydrogen peroxide production in Trypanosoma cruzi. beta-Lapachone, an antimicrobial agent, markedly increase the generation of H2O2 in intact Trypanosoma cruzi epimastigotes (Y strain). Increase in H2O2 was determined by the horseradish peroxidase-H2O2 Compound II formation as well as by a cytochemical technique. | [
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PMID:24996 | [Data on the life cycle of Ribeiroia marini guadeloupensis n. ssp., a trematode sterilizing Biomphalaria glabrata in Guadeloupe]. | Data on the life cycle of Ribeiroia marini guadeloupensis n.ssp., Trematode sterilizing Biomphalaria glabrata in Guadeloupe. Maintenance of the life cycle with a view to an eventual control of the populations of Molluscs. In Guadeloupe (French West Indies), the definitive hosts of Ribeiroia marini guadeloupensis n.ssp. are the two species of rats: Rattus rattus and R. norvegicus. The first intermediate host is Biomphalaria glabrata, the vector of intestinal schistosomiasis. The second intermediate host is a fish (Tilapia mossambica, Poecilia reticulata). The different stages of the life cycle are described; the transmission is studied experimentally and in natural conditions. A method for producing eggs of this Trematode in large quantities is described. | [Data on the life cycle of Ribeiroia marini guadeloupensis n. ssp., a trematode sterilizing Biomphalaria glabrata in Guadeloupe]. Data on the life cycle of Ribeiroia marini guadeloupensis n.ssp., Trematode sterilizing Biomphalaria glabrata in Guadeloupe. Maintenance of the life cycle with a view to an eventual control of the populations of Molluscs. In Guadeloupe (French West Indies), the definitive hosts of Ribeiroia marini guadeloupensis n.ssp. are the two species of rats: Rattus rattus and R. norvegicus. The first intermediate host is Biomphalaria glabrata, the vector of intestinal schistosomiasis. The second intermediate host is a fish (Tilapia mossambica, Poecilia reticulata). The different stages of the life cycle are described; the transmission is studied experimentally and in natural conditions. A method for producing eggs of this Trematode in large quantities is described. | [
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PMID:24998 | Alteration of amicrofilaremia in Dipetalonema viteae infected hamsters with immunosuppressive drugs. | Dipetalonema viteae-infected hamsters with amicrofilaremic infections were subjected to immunosuppressive therapy. Methyl prednisolone acetate caused the most severe recrudescence of microfilariae while cyclophosphamide caused a low level, transient microfilaremia. Saline injected control hamsters remained amicrofilaremic. Neither drug influenced the number of adult worms recovered at necropsy in the treated hamsters compared with control hamsters. | Alteration of amicrofilaremia in Dipetalonema viteae infected hamsters with immunosuppressive drugs. Dipetalonema viteae-infected hamsters with amicrofilaremic infections were subjected to immunosuppressive therapy. Methyl prednisolone acetate caused the most severe recrudescence of microfilariae while cyclophosphamide caused a low level, transient microfilaremia. Saline injected control hamsters remained amicrofilaremic. Neither drug influenced the number of adult worms recovered at necropsy in the treated hamsters compared with control hamsters. | [
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PMID:24999 | Serodiagnosis of human cysticercosis by microplate enzyme-linked immunospecific assay (ELISA). | The micro-ELISA described in this report is simple and can give objective results for the serodiagnosis of human cysticercosis. The visual assessment of results was satisfactory. The ELISA results showed a remarkably good correlation with IHA. It gave good reproudcibility. Cross-reactions were eliminated by using whole worm antigen instead of the cysticercus. | Serodiagnosis of human cysticercosis by microplate enzyme-linked immunospecific assay (ELISA). The micro-ELISA described in this report is simple and can give objective results for the serodiagnosis of human cysticercosis. The visual assessment of results was satisfactory. The ELISA results showed a remarkably good correlation with IHA. It gave good reproudcibility. Cross-reactions were eliminated by using whole worm antigen instead of the cysticercus. | [
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PMID:25000 | Responses of Anopheles minimus to DDT residual spraying in a cleared forested foothill area in central Thailand. | Anopheles balabacensis balabacensis and Anopheles minimus are the main malaria vectors in Thailand. In a cleared forested foothill area in the central part of the country A. minimus was the most prevalent anopheline species found, only 6 specimens of A. b. balabacensis being collected over a 3-year period. Cattle were scarce in the area, tractors being largely used for working in the fields. This situation contributed to high man-vector contact. A minimus occurred throughout the year, with a major peak of density in the dry cool season and a smaller peak in the wet season. The contact of A. minimus with man was much higher outdoors than indoors, and studies showed the species to be an early biter, especially in the dry season, thus increasing the chance of man-vector contact. DDT spraying appeared to reduce considerably the estimated vectorial capacities, however, this effect was not maintained and malaria transmission was not interrupted. Trials with supplementary or alternative attack measures are therefore indicated in this particular ecological situation. | Responses of Anopheles minimus to DDT residual spraying in a cleared forested foothill area in central Thailand. Anopheles balabacensis balabacensis and Anopheles minimus are the main malaria vectors in Thailand. In a cleared forested foothill area in the central part of the country A. minimus was the most prevalent anopheline species found, only 6 specimens of A. b. balabacensis being collected over a 3-year period. Cattle were scarce in the area, tractors being largely used for working in the fields. This situation contributed to high man-vector contact. A minimus occurred throughout the year, with a major peak of density in the dry cool season and a smaller peak in the wet season. The contact of A. minimus with man was much higher outdoors than indoors, and studies showed the species to be an early biter, especially in the dry season, thus increasing the chance of man-vector contact. DDT spraying appeared to reduce considerably the estimated vectorial capacities, however, this effect was not maintained and malaria transmission was not interrupted. Trials with supplementary or alternative attack measures are therefore indicated in this particular ecological situation. | [
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PMID:25001 | [Studies on an isolated tribe in the central highlands of Irian-Jaya (Indonesian New Guinea) within the field of tropical medicine. I. Clinical studies]. | Reports on medical research examinations in the field of tropical medicine of 130 indigenous, who were examined in the central Highland of West-Irian during an interdisciplinare research project. The inhabitants of this markedly isolated area are pygmies of a strong, well proportioned build of the body and in a relative good general condition. No avitaminoses, nor symptoms of malnutrition, nor tuberculosis were discovered, in spite of an only moderate intake of albumine and carbohydrates. All examined indigenous show a distinct diastase of the musculi recti, 51.55% an enlargement of both glandulae parotes, 47% an enlargement of the lymph nodes in the differemt regions, and 11.52% an enlargement of the liver. Distinct was a violent endemy with intestinal worms and some extreme anaemia. A later publication will deal with the extensive laboratory examinations which are partly not yet completed. | [Studies on an isolated tribe in the central highlands of Irian-Jaya (Indonesian New Guinea) within the field of tropical medicine. I. Clinical studies]. Reports on medical research examinations in the field of tropical medicine of 130 indigenous, who were examined in the central Highland of West-Irian during an interdisciplinare research project. The inhabitants of this markedly isolated area are pygmies of a strong, well proportioned build of the body and in a relative good general condition. No avitaminoses, nor symptoms of malnutrition, nor tuberculosis were discovered, in spite of an only moderate intake of albumine and carbohydrates. All examined indigenous show a distinct diastase of the musculi recti, 51.55% an enlargement of both glandulae parotes, 47% an enlargement of the lymph nodes in the differemt regions, and 11.52% an enlargement of the liver. Distinct was a violent endemy with intestinal worms and some extreme anaemia. A later publication will deal with the extensive laboratory examinations which are partly not yet completed. | [
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PMID:25002 | Radioimmunoassay of influenza A virus haemagglutinin. I. Preparation and properties of radioactive 125I-labelled bromelain-released haemagglutinin. | Haemagglutinin released from influenza A virus recombinant MRC11 [antigenically identical to the strain A/Port Chalmers/1/73 (H3N2)] by bromelain treatment and purified by rate zonal centrifugation (further on B-HA) was examined for eventual contamination by neuraminidase. According to specific enzymatic activities corresponding to MRC11 virus and B-HA alone respectively, B-HA contained less than 0.1% of enzymatically active neuraminidase orginally present in the virus. Gel double diffusion tests, specifities of rabbit antisera induced by B-HA, as well as radioimmunoprecipitation experiments demonstrated that B-HA was devoid of any antigenically active neuraminidase. Precipitation of 125I-labelled B-HA with antisera to influenza virus recombinants with N2 neuraminidase has been evidently caused by antibodies to host antigenic determinaant(s) present in these sera. With respect to purity as well as radioimmunoprecipitation properties, B-HA is quite suitable for radioimmunoassay experiments. | Radioimmunoassay of influenza A virus haemagglutinin. I. Preparation and properties of radioactive 125I-labelled bromelain-released haemagglutinin. Haemagglutinin released from influenza A virus recombinant MRC11 [antigenically identical to the strain A/Port Chalmers/1/73 (H3N2)] by bromelain treatment and purified by rate zonal centrifugation (further on B-HA) was examined for eventual contamination by neuraminidase. According to specific enzymatic activities corresponding to MRC11 virus and B-HA alone respectively, B-HA contained less than 0.1% of enzymatically active neuraminidase orginally present in the virus. Gel double diffusion tests, specifities of rabbit antisera induced by B-HA, as well as radioimmunoprecipitation experiments demonstrated that B-HA was devoid of any antigenically active neuraminidase. Precipitation of 125I-labelled B-HA with antisera to influenza virus recombinants with N2 neuraminidase has been evidently caused by antibodies to host antigenic determinaant(s) present in these sera. With respect to purity as well as radioimmunoprecipitation properties, B-HA is quite suitable for radioimmunoassay experiments. | [
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PMID:25003 | Effect of 5-bromo-2'-deoxyuridine on the in vitro DNA synthesizing activity of polyoma virus-infected cells. | The in vitro synthesizing activity of uninfected and polyoma virus-infected mouse embryo (ME) cells was investigated by measuring the incorporation of 3H-thymidine (dTR) into acidinsoluble material in cell-free extracts. The character of the enzyme reaction was described in uninfected cells and an activating effect of 0.01 M dithiothreitol (DTT) was observed. A variation of the enzyme activity in the course of cultivation of ME cells in primary culture was demonstrated. The induction of the DNA synthesizing activity due to polyoma virus infection was markedly increased in the presence of 5-bromo-2-deoxyuridine (BUDR), what emphasizes the importance of the de novo synthesized viral and/or cellular DNA in the regulation of induction enzymes participating in DNA synthesis. | Effect of 5-bromo-2'-deoxyuridine on the in vitro DNA synthesizing activity of polyoma virus-infected cells. The in vitro synthesizing activity of uninfected and polyoma virus-infected mouse embryo (ME) cells was investigated by measuring the incorporation of 3H-thymidine (dTR) into acidinsoluble material in cell-free extracts. The character of the enzyme reaction was described in uninfected cells and an activating effect of 0.01 M dithiothreitol (DTT) was observed. A variation of the enzyme activity in the course of cultivation of ME cells in primary culture was demonstrated. The induction of the DNA synthesizing activity due to polyoma virus infection was markedly increased in the presence of 5-bromo-2-deoxyuridine (BUDR), what emphasizes the importance of the de novo synthesized viral and/or cellular DNA in the regulation of induction enzymes participating in DNA synthesis. | [
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PMID:25004 | Some properties of the adenosine triphosphatase associated with herpes simplex virus and nuclear membrane of host cells. | An enzyme capable to split adenosine triphosphate (ATP) was shown to be firmly associated with mature herpes simplex virus particles purified from infected rabbit lung (ZP) cells. The enzyme localized in the viral envelope was markedly activated by bivalent cations, to the largest degree by Mg2+ at a pH optimum of 7.8--8.0. Na+ and K+ ions neither separately nor together showed any activating effect. Enzyme activity was not sensitive to the action of ouabain. No adenosine diphosphatase (ADPase) and adenosine monophosphatase (AMPase) activities were observed. ATPase activity was competitively inhibited by ADP. AMP and inorganic phosphate were without effect. The ATPase of nuclear membranes isolated from ZP cells exhibited similar properties but behaved differently to the action of sodium dithionite, dinitrophenol, oligomycin and gramicidin, as well as on heat inactivation. The origin of the virus enzyme is discussed. | Some properties of the adenosine triphosphatase associated with herpes simplex virus and nuclear membrane of host cells. An enzyme capable to split adenosine triphosphate (ATP) was shown to be firmly associated with mature herpes simplex virus particles purified from infected rabbit lung (ZP) cells. The enzyme localized in the viral envelope was markedly activated by bivalent cations, to the largest degree by Mg2+ at a pH optimum of 7.8--8.0. Na+ and K+ ions neither separately nor together showed any activating effect. Enzyme activity was not sensitive to the action of ouabain. No adenosine diphosphatase (ADPase) and adenosine monophosphatase (AMPase) activities were observed. ATPase activity was competitively inhibited by ADP. AMP and inorganic phosphate were without effect. The ATPase of nuclear membranes isolated from ZP cells exhibited similar properties but behaved differently to the action of sodium dithionite, dinitrophenol, oligomycin and gramicidin, as well as on heat inactivation. The origin of the virus enzyme is discussed. | [
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PMID:25005 | Dengue viral antigens in host cell membranes. | Membranes from type 2 dengue virus (DEN-2) infected BHK cells, when used as immunogen, elicit antibodies detectable by complement fixation, hemagglutination inhibition and plaque reduction neutralization tests with suckling-mouse-brain-derived DEN-antigens. Membrane fractions from infected cells separated by sucrose density gradient centrifugation were employed as antigen in serological tests with anti-DEN-2 infected suckling mouse brain hyperimmune mouse serum and hyperimmune mouse ascitic fluid. Antigen (s) capable of fixing complement were associated with all membrane fractions, including the plasma membrane, whereas antigen capable of reacting with antihemagglutinin was largely confined to the two membrane bands consisting of (1) a mixture of rough and smooth endoplasmic reticulum (2) predominantly rough endoplasmic reticulum. | Dengue viral antigens in host cell membranes. Membranes from type 2 dengue virus (DEN-2) infected BHK cells, when used as immunogen, elicit antibodies detectable by complement fixation, hemagglutination inhibition and plaque reduction neutralization tests with suckling-mouse-brain-derived DEN-antigens. Membrane fractions from infected cells separated by sucrose density gradient centrifugation were employed as antigen in serological tests with anti-DEN-2 infected suckling mouse brain hyperimmune mouse serum and hyperimmune mouse ascitic fluid. Antigen (s) capable of fixing complement were associated with all membrane fractions, including the plasma membrane, whereas antigen capable of reacting with antihemagglutinin was largely confined to the two membrane bands consisting of (1) a mixture of rough and smooth endoplasmic reticulum (2) predominantly rough endoplasmic reticulum. | [
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PMID:25006 | Studies of cell-mediated immunity to Junín virus. | Junín virus is uniformly lethal in newborn mice, but fails to kill adult animals. But there is direct evidence that in older mice the immunological mechanism occurs when certain conditions are fulfilled. The present results showed that in Junín virus infection of mice, the development of the immunological mechanism occurs irrespectively of age. The induction of a regular cell-mediated immunity appears to be intimately related to multiple injections of the virus. These results were confirmed by the 51Cr release assay and by the effect of the transplanted sensitized cells. The extent of infection in the brain is another variable to be considered. Only when the virus has reached high titres and has been concentrated in the brain, the damage done by the immune attack is lethal. On the other hand the data obtained suggest that Junín virus-sensitized spleen cells do not possess the ability to transfer significant antiviral effects to recipient preinfected newborn mice. | Studies of cell-mediated immunity to Junín virus. Junín virus is uniformly lethal in newborn mice, but fails to kill adult animals. But there is direct evidence that in older mice the immunological mechanism occurs when certain conditions are fulfilled. The present results showed that in Junín virus infection of mice, the development of the immunological mechanism occurs irrespectively of age. The induction of a regular cell-mediated immunity appears to be intimately related to multiple injections of the virus. These results were confirmed by the 51Cr release assay and by the effect of the transplanted sensitized cells. The extent of infection in the brain is another variable to be considered. Only when the virus has reached high titres and has been concentrated in the brain, the damage done by the immune attack is lethal. On the other hand the data obtained suggest that Junín virus-sensitized spleen cells do not possess the ability to transfer significant antiviral effects to recipient preinfected newborn mice. | [
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PMID:25007 | Antiviral pyrimidine derivatives: binding with biopolymers and photosensitization. | Two antiviral pyrimidine derivatives, known to partially inhibit RNA dependent RNA polymerase of Mengo virus in a cell-free system, were found to bind with biopolymers. The antiviral compounds, at concentration of 100 and 50 muM and lower, showed complete inhibition of the virus-induced cytopathic effect and plaque reduction. Both compounds showed fluorescence emission with a maximum at about 500 nm under the influence of UV light of the wavelength of 366 nm. The fluorescence intensity increased upon addition of aqueous solutions of DNA, RNA and human serum albumin. This indicates that both compounds are capable of binding with nucleic acids and proteins. Based on the binding experiments alone it cannot be decided whether interference with nucleic acid template activity, enzyme function, or both are responsible for the virostatic action. Irradiation with violet light considerably enhances the virostatic activity, a fact that may be caused by photodynamic processes. | Antiviral pyrimidine derivatives: binding with biopolymers and photosensitization. Two antiviral pyrimidine derivatives, known to partially inhibit RNA dependent RNA polymerase of Mengo virus in a cell-free system, were found to bind with biopolymers. The antiviral compounds, at concentration of 100 and 50 muM and lower, showed complete inhibition of the virus-induced cytopathic effect and plaque reduction. Both compounds showed fluorescence emission with a maximum at about 500 nm under the influence of UV light of the wavelength of 366 nm. The fluorescence intensity increased upon addition of aqueous solutions of DNA, RNA and human serum albumin. This indicates that both compounds are capable of binding with nucleic acids and proteins. Based on the binding experiments alone it cannot be decided whether interference with nucleic acid template activity, enzyme function, or both are responsible for the virostatic action. Irradiation with violet light considerably enhances the virostatic activity, a fact that may be caused by photodynamic processes. | [
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] |
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