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PMID:27946 | [Actual knowledge on beta blocking agents in psychiatry (author's transl)]. | A new group of substances blocking central beta receptors, ie beta blocking agents among which oxprenol and pindolol, have been used in psychiatry, mainly in anxious or depressive-anxious patients. The anxiolytic effect, particularly on somatic anxiety, is interesting, and is present in double blind studies with benzodiazepines, where it is superior to these classical agents. The author has observed this therapeutic activity in series of one hundred patients and also a dynamising effect in some of these patients. Without having observed by himself and possibly because of the low doses experimented, the author states that these drugs have an antipsychotic activity. | [Actual knowledge on beta blocking agents in psychiatry (author's transl)]. A new group of substances blocking central beta receptors, ie beta blocking agents among which oxprenol and pindolol, have been used in psychiatry, mainly in anxious or depressive-anxious patients. The anxiolytic effect, particularly on somatic anxiety, is interesting, and is present in double blind studies with benzodiazepines, where it is superior to these classical agents. The author has observed this therapeutic activity in series of one hundred patients and also a dynamising effect in some of these patients. Without having observed by himself and possibly because of the low doses experimented, the author states that these drugs have an antipsychotic activity. | [
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PMID:27953 | Resonance Raman studies on the ligand-iron interactions in hemoproteins and metallo-porphyrins. | The resonance Raman spectra (RRS) were measured for various hemoproteins, as well as for free hemes, and analysed in terms of the interactions between the porphyrin ring and the heme iron and between the axial ligand and the heme iron. To establish vibrational assignments, the RRS of metallo-octae-thylporphyrin (M(OEP)), its 15N substituted and meso-deuterated derivatives were measured. It was found that the Raman line corresponding to the oxidation state marker of hemoproteins involves appreciable displacement of the pyrrolic nitrogen atoms toward metal ion but not that of methine bridges and that the frequencies of methine-bridge CC stretching vibrations are altered by the conjugation interaction between the porphyrin ring and the metal ion present. The prominent Raman lines of Ni(OEP) were assigned on the basis of the normal coordinate analysis. The Raman spectra of heme a bis-imidazole complex (Fe(A)(Im)2) in the presence of cyanide changed when pH was reduced to neutral. It implied formation of cyanhydrin at the peripheral formyl group of heme a. The Fe(A)(Im)2 formed an addition compound with NaHSO3 in a neutral solution but the added NaHSO3 was eliminated when the heme iron was reduced. The Raman spectra of hemoproteins were classified into four groups on the basis of the relative intensities and frequencies of the four key bands. It demonstrated the existence of two kinds of ferrous low-spin states. The difference between the two species was attributed to the difference in the nature of chemical bond between the heme iron and its sixth ligand (L). The Fe-L bonds of ferrous low-spin molecules in Groups A and C are mainly associated with the dz2(Fe)-lone pair and dz(Fe)-II(L) interactions, respectively. This interpretation of the Raman spectra appears consistent with the experimental facts that the ferrous low-spin molecules in Group C photodissociate upon illumination of light at the Soret band and also that the internal stretching frequencies of the sixth ligand are shifted to lower frequency upon coordination to the heme iron. The frequency of the oxidation state marker of reduced cytochrome P-450 (P-450cam) was unusually low in comparison with those of other hemoproteins. It was ascribed to delocalization of electrons from the thiolate anion to the porphyrin II*(ring) orbital through the pi-type molecular orbital (Eq.3). The RRS of reduced P-450cam.metyrapone adduct was quite close to that of reduced cytochrome b5. In conclusion, the Raman frequencies of hemoproteins may depend primarily upon the amount of electrons delocalized to the II* orbital of the porphyrin ring. The coordination of lone-pair electrons of the axial ligand to the iron dz2 orbital yields bond energy but scarcely affects the Raman frequencies. If the pi orbital of the axial ligand interacts with the iron dpi orbital, it perturbs the delocalization of the dpi(Fe) electrons to the II*(ring) orbital of porphyrin ring and thus affects the Raman frequencies. | Resonance Raman studies on the ligand-iron interactions in hemoproteins and metallo-porphyrins. The resonance Raman spectra (RRS) were measured for various hemoproteins, as well as for free hemes, and analysed in terms of the interactions between the porphyrin ring and the heme iron and between the axial ligand and the heme iron. To establish vibrational assignments, the RRS of metallo-octae-thylporphyrin (M(OEP)), its 15N substituted and meso-deuterated derivatives were measured. It was found that the Raman line corresponding to the oxidation state marker of hemoproteins involves appreciable displacement of the pyrrolic nitrogen atoms toward metal ion but not that of methine bridges and that the frequencies of methine-bridge CC stretching vibrations are altered by the conjugation interaction between the porphyrin ring and the metal ion present. The prominent Raman lines of Ni(OEP) were assigned on the basis of the normal coordinate analysis. The Raman spectra of heme a bis-imidazole complex (Fe(A)(Im)2) in the presence of cyanide changed when pH was reduced to neutral. It implied formation of cyanhydrin at the peripheral formyl group of heme a. The Fe(A)(Im)2 formed an addition compound with NaHSO3 in a neutral solution but the added NaHSO3 was eliminated when the heme iron was reduced. The Raman spectra of hemoproteins were classified into four groups on the basis of the relative intensities and frequencies of the four key bands. It demonstrated the existence of two kinds of ferrous low-spin states. The difference between the two species was attributed to the difference in the nature of chemical bond between the heme iron and its sixth ligand (L). The Fe-L bonds of ferrous low-spin molecules in Groups A and C are mainly associated with the dz2(Fe)-lone pair and dz(Fe)-II(L) interactions, respectively. This interpretation of the Raman spectra appears consistent with the experimental facts that the ferrous low-spin molecules in Group C photodissociate upon illumination of light at the Soret band and also that the internal stretching frequencies of the sixth ligand are shifted to lower frequency upon coordination to the heme iron. The frequency of the oxidation state marker of reduced cytochrome P-450 (P-450cam) was unusually low in comparison with those of other hemoproteins. It was ascribed to delocalization of electrons from the thiolate anion to the porphyrin II*(ring) orbital through the pi-type molecular orbital (Eq.3). The RRS of reduced P-450cam.metyrapone adduct was quite close to that of reduced cytochrome b5. In conclusion, the Raman frequencies of hemoproteins may depend primarily upon the amount of electrons delocalized to the II* orbital of the porphyrin ring. The coordination of lone-pair electrons of the axial ligand to the iron dz2 orbital yields bond energy but scarcely affects the Raman frequencies. If the pi orbital of the axial ligand interacts with the iron dpi orbital, it perturbs the delocalization of the dpi(Fe) electrons to the II*(ring) orbital of porphyrin ring and thus affects the Raman frequencies. | [
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PMID:27947 | [Flunitrazepam and memory (author's transl)]. | This work is based on the observation of memory troubles before sleep in patients with sleep problems treated with flunitrazepam. Eight subjects are tested in two sessions, flunitrazepam and placebo, in double blind, with memory tests given the evening after medication and controlled the next morning. One additional test is controlling vigilance. The results show that memory is significantly disturbed by flunitrazepam, both for direct and delayed memory, the next day. On the contrary, recognition is not altered, neither vigilance. | [Flunitrazepam and memory (author's transl)]. This work is based on the observation of memory troubles before sleep in patients with sleep problems treated with flunitrazepam. Eight subjects are tested in two sessions, flunitrazepam and placebo, in double blind, with memory tests given the evening after medication and controlled the next morning. One additional test is controlling vigilance. The results show that memory is significantly disturbed by flunitrazepam, both for direct and delayed memory, the next day. On the contrary, recognition is not altered, neither vigilance. | [
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PMID:27954 | Nuclear magnetic resonance studies of high-spin ferric hemoproteins. | 220 MHz proton Fourier transform (FT) NMR with quadrature phase detection (QPD) technique is applied to observe largely hyperfine-shifted signals of various hemoproteins and hemoenzymes in ferric high-spin state. The binding of F-, OCN-, SCN-, and CH3OH to the ferric heme iron in high-spin state in various hemoproteins has been studied by the use of FT/QPD technique at 220 MHz. The binding of formate ion to metmyoglobin (metMb) has also been studied. The spectrum of the formate complex was compared with that of hemoglobin M Milwaukee where carboxylate groups are bound to the hemes of the beta subunits. The acid-base transition of ferric myoglobin (Mb) was confirmed by monitoring the pH-dependent shift of the heme side methyl signals with the reflection point at pH 9.1. This finding is analyzed on the basis of rapid exchange between alkaline (low spin) and acidic (high spin) forms accompanied by the dissociation and association of one proton in the ferric Mb. The structure of the heme environment of ferric horseradish peroxidase (HRP) was studied. The pH-dependent features of NMR spectra of the ferric enzyme and its complexes with cyanide and azide were discussed in terms of heme environmental structures, comparing with the case of metMb. The results were interpreted as follows: There exists an ionizable amino group near the heme responsible for the ligand binding reactions of the enzyme, which modulates the entry of external azide to the heme iron through protolytic equilibrium of this group. The pK value of this group was determined to be 5.9 by monitoring the pH-dependent shift of the heme peripheral methyl signals of the native enzyme, indicating that the group is probably a histidyl residue. Acid-alkaline transition of metMb was confirmed to associate with the proton dissociation of an iron-bound water molecule, whereas in HRP, pH-dependent spin state change characterized by pK 11 is attributed not to the simple protolytic reaction of the iron-bound water but to the direct coordination of an amino acid residue of the polypeptide chain to the ferric heme iron. Histidyl imidazole is a possible candidate for the new sixth iron ligand in alkaline peroxidase above pH 11. Interaction of HRP with electron donor(indolepropionic acid, IPA) was also studied. The hyperfine-shifted proton signals of the heme peripheral groups of the enzyme showed a small but significant shift with stepwise additions of IPA, indicating that the donor binds at a specific site of HRP. There results are interpreted in terms of the interaction between the enzyme and the donor at the heme edge site. | Nuclear magnetic resonance studies of high-spin ferric hemoproteins. 220 MHz proton Fourier transform (FT) NMR with quadrature phase detection (QPD) technique is applied to observe largely hyperfine-shifted signals of various hemoproteins and hemoenzymes in ferric high-spin state. The binding of F-, OCN-, SCN-, and CH3OH to the ferric heme iron in high-spin state in various hemoproteins has been studied by the use of FT/QPD technique at 220 MHz. The binding of formate ion to metmyoglobin (metMb) has also been studied. The spectrum of the formate complex was compared with that of hemoglobin M Milwaukee where carboxylate groups are bound to the hemes of the beta subunits. The acid-base transition of ferric myoglobin (Mb) was confirmed by monitoring the pH-dependent shift of the heme side methyl signals with the reflection point at pH 9.1. This finding is analyzed on the basis of rapid exchange between alkaline (low spin) and acidic (high spin) forms accompanied by the dissociation and association of one proton in the ferric Mb. The structure of the heme environment of ferric horseradish peroxidase (HRP) was studied. The pH-dependent features of NMR spectra of the ferric enzyme and its complexes with cyanide and azide were discussed in terms of heme environmental structures, comparing with the case of metMb. The results were interpreted as follows: There exists an ionizable amino group near the heme responsible for the ligand binding reactions of the enzyme, which modulates the entry of external azide to the heme iron through protolytic equilibrium of this group. The pK value of this group was determined to be 5.9 by monitoring the pH-dependent shift of the heme peripheral methyl signals of the native enzyme, indicating that the group is probably a histidyl residue. Acid-alkaline transition of metMb was confirmed to associate with the proton dissociation of an iron-bound water molecule, whereas in HRP, pH-dependent spin state change characterized by pK 11 is attributed not to the simple protolytic reaction of the iron-bound water but to the direct coordination of an amino acid residue of the polypeptide chain to the ferric heme iron. Histidyl imidazole is a possible candidate for the new sixth iron ligand in alkaline peroxidase above pH 11. Interaction of HRP with electron donor(indolepropionic acid, IPA) was also studied. The hyperfine-shifted proton signals of the heme peripheral groups of the enzyme showed a small but significant shift with stepwise additions of IPA, indicating that the donor binds at a specific site of HRP. There results are interpreted in terms of the interaction between the enzyme and the donor at the heme edge site. | [
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PMID:27955 | Analysis of acid-base properties of peroxidase and myoglobin. | Two heme-linked groups of horseradish peroxidases, characterized by pKa = 5.8 (isoenzyme A) and 7.3 (isoenzyme C), are believed to be distal amino acid residues and, judging by their acid-base properties in various derivatives, influence the functions of these isoenzymes. In contrast, in myoglobin ionization of the distal histidine does not influence its reactivity. Accordingly, we conclude that the interaction of the distal base with a 6th ligand is weak in myoglobin but very strong in peroxidases. | Analysis of acid-base properties of peroxidase and myoglobin. Two heme-linked groups of horseradish peroxidases, characterized by pKa = 5.8 (isoenzyme A) and 7.3 (isoenzyme C), are believed to be distal amino acid residues and, judging by their acid-base properties in various derivatives, influence the functions of these isoenzymes. In contrast, in myoglobin ionization of the distal histidine does not influence its reactivity. Accordingly, we conclude that the interaction of the distal base with a 6th ligand is weak in myoglobin but very strong in peroxidases. | [
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PMID:27956 | Conformational change and cooperative ligand binding in hemoglobin. | Although many studies have been carried out on the cooperativityly of ligand binding to hemoglobin, its molecular mechanism is not yet completely confirmed. Various models have been proposed on one hand, but on the other hand the direct judgement of the validity of each model is confronted with experimental difficulties. With this situation in mind, we re-examine carefully various kinds of experimental data, with the intention of finding any hints for future studies on the molecular mechanism of the cooperativity of ligand binding not only to hemoglobin but also to other allosteric proteins composed of subunits. As a result of these re-examinations most of the experimental data can be consistently explained from the viewpoint that the strain due to ligation is transmitted to the interfaces of the subunits and the degree of the strain stored in the interfaces between the subunits controls the cooperativity of of ligand binding. The subjects selected to the present study are molecular structural differences between the deoxy- and oxy-hemoglobin, temperature dependence of oxygen equilibrium constants, and recombination curves of carbon monoxide in flash photolysis experiments. In the first section, the difference of the interfaces of the subunits between deoxy- and oxy-hemoglobin is investigated on the basis of the atomic coordinates determined by Perutz et al. and we examine energetically which of the segment's pairs contributes mainly to the difference in the molecular structure between the two forms. On the basis of this investigation, it is shown in the next section that the oxygen equilibrium constants of human adult hemoglobin under normal physiological conditions are well explained by the following sequence of the conformational changes. The local changes in the interfaces of the subunits are reflected directly on the small differences among the first three Adair constants and the succeeding rearrangement to the four subunits causes the outstandingly larger value of the fourth Adair constant. In more alkaline pH, this rearrangement begins to occur at the earlier stages of ligation. In the succeeding section, it is pointed out that the property of this rearrangement can be studied in more detail through the recombination curves followed by flash photolysis under special conditions. | Conformational change and cooperative ligand binding in hemoglobin. Although many studies have been carried out on the cooperativityly of ligand binding to hemoglobin, its molecular mechanism is not yet completely confirmed. Various models have been proposed on one hand, but on the other hand the direct judgement of the validity of each model is confronted with experimental difficulties. With this situation in mind, we re-examine carefully various kinds of experimental data, with the intention of finding any hints for future studies on the molecular mechanism of the cooperativity of ligand binding not only to hemoglobin but also to other allosteric proteins composed of subunits. As a result of these re-examinations most of the experimental data can be consistently explained from the viewpoint that the strain due to ligation is transmitted to the interfaces of the subunits and the degree of the strain stored in the interfaces between the subunits controls the cooperativity of of ligand binding. The subjects selected to the present study are molecular structural differences between the deoxy- and oxy-hemoglobin, temperature dependence of oxygen equilibrium constants, and recombination curves of carbon monoxide in flash photolysis experiments. In the first section, the difference of the interfaces of the subunits between deoxy- and oxy-hemoglobin is investigated on the basis of the atomic coordinates determined by Perutz et al. and we examine energetically which of the segment's pairs contributes mainly to the difference in the molecular structure between the two forms. On the basis of this investigation, it is shown in the next section that the oxygen equilibrium constants of human adult hemoglobin under normal physiological conditions are well explained by the following sequence of the conformational changes. The local changes in the interfaces of the subunits are reflected directly on the small differences among the first three Adair constants and the succeeding rearrangement to the four subunits causes the outstandingly larger value of the fourth Adair constant. In more alkaline pH, this rearrangement begins to occur at the earlier stages of ligation. In the succeeding section, it is pointed out that the property of this rearrangement can be studied in more detail through the recombination curves followed by flash photolysis under special conditions. | [
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PMID:27964 | The effect of inhibitors of cellular RNA synthesis on stimulation of mouse encephalomyocarditis virus reproduction by poliovirus in HeLa and MIO cells. | Inoculation of HeLa and MIO cells with a guanidine-dependent mutant of poliovirus (gd-polio) in the absence of guanidine resulted in stimulation of mouse encephalomyocarditis (EMC) virus reproduction. No stimulation was found to occur in the presence of actinomycin D, on pre-treatment of the cells with cordycepin, or on their UV irradiation or enucleation. In contrast to HeLa cells, the enhancement of EMC virus reproduction by gd-polio in MIO cells required no current synthesis of cellular RNAs: it occurred in the presence of actinomycin D, upon UV irradiation of the cells or their enucleation. The possible mechanisms of the stimulating effect of poliovirus in HeLa and MIO cells are discussed. | The effect of inhibitors of cellular RNA synthesis on stimulation of mouse encephalomyocarditis virus reproduction by poliovirus in HeLa and MIO cells. Inoculation of HeLa and MIO cells with a guanidine-dependent mutant of poliovirus (gd-polio) in the absence of guanidine resulted in stimulation of mouse encephalomyocarditis (EMC) virus reproduction. No stimulation was found to occur in the presence of actinomycin D, on pre-treatment of the cells with cordycepin, or on their UV irradiation or enucleation. In contrast to HeLa cells, the enhancement of EMC virus reproduction by gd-polio in MIO cells required no current synthesis of cellular RNAs: it occurred in the presence of actinomycin D, upon UV irradiation of the cells or their enucleation. The possible mechanisms of the stimulating effect of poliovirus in HeLa and MIO cells are discussed. | [
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PMID:27965 | Marked difference in electrophoretic migration rates between two influenza A viruses. | Comparative moving boundary electrophoresis revealed that influenza virus A/PR/8/34 (H0N1) has a 2.5 times higher electrophoretic migration rate at pH 7 than influenza virus A/Singpore/1/57 (H2N2). This difference was the same whether the compared viruses were purified first by either ammonium sulphate precipitation or adsorption onto and elution from red blood cells and then by density gradient centrifugation. The same electrophoretic methods was used for testing the homogeneity of influenza virus preparations purified by either method. | Marked difference in electrophoretic migration rates between two influenza A viruses. Comparative moving boundary electrophoresis revealed that influenza virus A/PR/8/34 (H0N1) has a 2.5 times higher electrophoretic migration rate at pH 7 than influenza virus A/Singpore/1/57 (H2N2). This difference was the same whether the compared viruses were purified first by either ammonium sulphate precipitation or adsorption onto and elution from red blood cells and then by density gradient centrifugation. The same electrophoretic methods was used for testing the homogeneity of influenza virus preparations purified by either method. | [
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PMID:27966 | Multiplication of herpes simplex virus types 1 and 2 in macrophages of NMRI and C57/BL mice. | The multiplication of 8 strains of herpes simplex virus of type 1 and 2 in normal and stimulated macrophages of NMRI and C57/bl mice was tested. Only 3 strains multiplied in normal NMRI macrophages, whereas all strains multiplied in stimulated cells. No multiplication except of one strain was observed in C57/bl macrophages. The multiplication rates of the virus strains correlated well with the determination of the acid-soluble and acid-insoluble thymidine (dTR) radioactivity and autoradiographic studies of infected (normal and stimulated) NMRI and C57/bl macrophages. The influence of the age of mice used for obtaining the macrophages was also studied. In stimulated macrophages more viral DNA was synthesised than in non-stimulated cells. | Multiplication of herpes simplex virus types 1 and 2 in macrophages of NMRI and C57/BL mice. The multiplication of 8 strains of herpes simplex virus of type 1 and 2 in normal and stimulated macrophages of NMRI and C57/bl mice was tested. Only 3 strains multiplied in normal NMRI macrophages, whereas all strains multiplied in stimulated cells. No multiplication except of one strain was observed in C57/bl macrophages. The multiplication rates of the virus strains correlated well with the determination of the acid-soluble and acid-insoluble thymidine (dTR) radioactivity and autoradiographic studies of infected (normal and stimulated) NMRI and C57/bl macrophages. The influence of the age of mice used for obtaining the macrophages was also studied. In stimulated macrophages more viral DNA was synthesised than in non-stimulated cells. | [
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PMID:27967 | Haemagglutination inhibition antibodies in nasal secretions of persons after natural parainfluenza virus infection. | In 7 adults and 7 children with upper respiratory illness of parainfluenza aetiology, the virus was isolated in the acute phase from nasal washings or nasal smears in spite of high titres of haemagglutination inhibition (HI) antibodies in serum. By contrast, secretory HI antibodies were not demonstrated at the onset of illness in any of the patients, but their formation started early and the antibodies reached maximal levels about 10 days after onset of illness. The individual patients showed considerable differences in the dynamics of secretory antibody formation and especially in their persistence. In some of the patients, secretory antibodies were demonstrated as late as 12 months after the illness. | Haemagglutination inhibition antibodies in nasal secretions of persons after natural parainfluenza virus infection. In 7 adults and 7 children with upper respiratory illness of parainfluenza aetiology, the virus was isolated in the acute phase from nasal washings or nasal smears in spite of high titres of haemagglutination inhibition (HI) antibodies in serum. By contrast, secretory HI antibodies were not demonstrated at the onset of illness in any of the patients, but their formation started early and the antibodies reached maximal levels about 10 days after onset of illness. The individual patients showed considerable differences in the dynamics of secretory antibody formation and especially in their persistence. In some of the patients, secretory antibodies were demonstrated as late as 12 months after the illness. | [
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PMID:27968 | Cell- and antibody-mediated responses to measles and mumps viruses in experimental animals. | Monkeys and guinea pigs were immunized with various doses of measles and mumps viruses. A cell-mediated response measured by leukocyte migration inhibition occured during the first two weeks after immunization. In case of measles virus, marked migration inhibition occurred already on the 7th day in monkeys and guinea pigs immunized with high virus doses. The response declined as early as 14 days after immunization in contrast to the group of guinea pigs inoculated with a lower virus dose. In these animals the response sustained for up to 50 days. Immunization of animals with various doses of mumps virus was similar and positive responses were obtained in the absence of detectable antibodies. Even 2.5 TCID50 of mumps virus induced the response although more irregularly than 250 or 2500 TCID50 virus. | Cell- and antibody-mediated responses to measles and mumps viruses in experimental animals. Monkeys and guinea pigs were immunized with various doses of measles and mumps viruses. A cell-mediated response measured by leukocyte migration inhibition occured during the first two weeks after immunization. In case of measles virus, marked migration inhibition occurred already on the 7th day in monkeys and guinea pigs immunized with high virus doses. The response declined as early as 14 days after immunization in contrast to the group of guinea pigs inoculated with a lower virus dose. In these animals the response sustained for up to 50 days. Immunization of animals with various doses of mumps virus was similar and positive responses were obtained in the absence of detectable antibodies. Even 2.5 TCID50 of mumps virus induced the response although more irregularly than 250 or 2500 TCID50 virus. | [
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PMID:27969 | Morphological characteristics of the infection of animals with tick-borne encephalitis virus persisting for a long time in cell cultures. | The pathogenicity of the Soph-K strain of tick-borne encephalitis (TBE) virus produced by the persistently infected HEp-2-Soph cell culture was investigated in monkeys, white mice and hamsters. The persistent infection of this culture with TBE virus has been maintained for 17 years. The Soph-K strain was shown to retain its pathogenic properties for mice of different ages and hamsters. Morphological examinations of the brains and spinal cords of these animals infected with the Soph-K strain revealed acute and subacute forms of encephalitis. Monkeys inoculated with the Soph-K strain intracerebrally showed an asymptomatic infection with the pathomorphological picture of subacute disseminated meningoencephalitis with a progredient course for 3 months of observation. This chronic TBE infection in monkeys offers an interesting model for investigations on progressive degenerative disease of the nervous system. | Morphological characteristics of the infection of animals with tick-borne encephalitis virus persisting for a long time in cell cultures. The pathogenicity of the Soph-K strain of tick-borne encephalitis (TBE) virus produced by the persistently infected HEp-2-Soph cell culture was investigated in monkeys, white mice and hamsters. The persistent infection of this culture with TBE virus has been maintained for 17 years. The Soph-K strain was shown to retain its pathogenic properties for mice of different ages and hamsters. Morphological examinations of the brains and spinal cords of these animals infected with the Soph-K strain revealed acute and subacute forms of encephalitis. Monkeys inoculated with the Soph-K strain intracerebrally showed an asymptomatic infection with the pathomorphological picture of subacute disseminated meningoencephalitis with a progredient course for 3 months of observation. This chronic TBE infection in monkeys offers an interesting model for investigations on progressive degenerative disease of the nervous system. | [
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PMID:27970 | Sepcific immunofluorescent IgG, IgM, and IgA antibodies in lymphocytic choriomeningitis. | In postnatally acquired lymphocytic choriomeningitis (LCM), specific immunofluorescent (IF) IgM antibody was found nearly in all the examined sera from 23 patients for 6-8 months after onset of the disease, IgA antibody in two-thirds of the patients and only during the first 5 weeks of the disease. In the first weeks, the titres of IF IgG and IgM antibodies reached values from 256-512 in some patients; IgA antibody titres were considerably lower. No specific IF IgM and IgA antibody was found in sera from 5 infants with prenatal LCM virus infection (3 infants with congenital hydrocephalus and chorioretinitis, 1 with cerebral palsy and chorioretinitis, and 1 with asymptomatic infection). IF IgM antibody in a titre of 4 was detected only in 2 specimens of the cerebrospinal fluid from one of the infants with hydrocephalus. It is suggested that in prenatal LCM virus infection the production of specific IgM antibody is more or less inhibited. | Sepcific immunofluorescent IgG, IgM, and IgA antibodies in lymphocytic choriomeningitis. In postnatally acquired lymphocytic choriomeningitis (LCM), specific immunofluorescent (IF) IgM antibody was found nearly in all the examined sera from 23 patients for 6-8 months after onset of the disease, IgA antibody in two-thirds of the patients and only during the first 5 weeks of the disease. In the first weeks, the titres of IF IgG and IgM antibodies reached values from 256-512 in some patients; IgA antibody titres were considerably lower. No specific IF IgM and IgA antibody was found in sera from 5 infants with prenatal LCM virus infection (3 infants with congenital hydrocephalus and chorioretinitis, 1 with cerebral palsy and chorioretinitis, and 1 with asymptomatic infection). IF IgM antibody in a titre of 4 was detected only in 2 specimens of the cerebrospinal fluid from one of the infants with hydrocephalus. It is suggested that in prenatal LCM virus infection the production of specific IgM antibody is more or less inhibited. | [
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PMID:27972 | Accurate determination of volumes injected intracerebrally into suckling mice. | Inoculum with 125I added as a marker was used to determine the volume actually administered to suckling mice on intracerebral (i.c.) inoculation. In 1-2 days old animals, this volume corresponded to approximately 75% of a 20 microliter dose. | Accurate determination of volumes injected intracerebrally into suckling mice. Inoculum with 125I added as a marker was used to determine the volume actually administered to suckling mice on intracerebral (i.c.) inoculation. In 1-2 days old animals, this volume corresponded to approximately 75% of a 20 microliter dose. | [
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PMID:27973 | Effect of interferon and poly I:C on replication of influenza virus in organ cultures of human origin. | Interferon and poly I : C inhibited the growth of influenza virus in organ cultures of foetal nasal mucosa, trachea, oesophagus and adult nasal mucosa. No antiviral effect was observed in decidua organ cultures. The combined use of interferon and poly I : C resulted in the enhancement of the antiviral effect. | Effect of interferon and poly I:C on replication of influenza virus in organ cultures of human origin. Interferon and poly I : C inhibited the growth of influenza virus in organ cultures of foetal nasal mucosa, trachea, oesophagus and adult nasal mucosa. No antiviral effect was observed in decidua organ cultures. The combined use of interferon and poly I : C resulted in the enhancement of the antiviral effect. | [
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PMID:27974 | Quantitative immunoelectrophoresis of human interferon. A new approach to characterization of interferon preparations. | The electroimmunoassay (quantitative "rocket" immunoelectrophoresis) method was adopted for analysis and characterization of interferon preparations. Ammonium sulphate-precipitated anti-interferon globulin also containing unknown antibodies against antigens that contaminate interferon preparations was used in the tests. By comparing the results of the electroimmunoassay of fractions obtained by polyacrylamide gel electrophoresis of human leukocyte interferon with the antiviral activity of the fractions, an excellent dissociation of molecules with interferon activity from the bulk of contaminating antigens was achieved. The method is extremely sensitive and requires very small volumes for assay. | Quantitative immunoelectrophoresis of human interferon. A new approach to characterization of interferon preparations. The electroimmunoassay (quantitative "rocket" immunoelectrophoresis) method was adopted for analysis and characterization of interferon preparations. Ammonium sulphate-precipitated anti-interferon globulin also containing unknown antibodies against antigens that contaminate interferon preparations was used in the tests. By comparing the results of the electroimmunoassay of fractions obtained by polyacrylamide gel electrophoresis of human leukocyte interferon with the antiviral activity of the fractions, an excellent dissociation of molecules with interferon activity from the bulk of contaminating antigens was achieved. The method is extremely sensitive and requires very small volumes for assay. | [
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PMID:27975 | Transmission of Kyasanur Forest disease virus by Rhipicephalus haemaphysaloides ticks. | Larvae of Rhipicephalus haemaphysaloides were infected with Kaysanur Forest disease (KFD) virus by feeding on viraemic rodents and reared into next generation larvae. Fed larvae, nymphs, unfed adults, fed adult males, and females after oviposition were found infected, while the larvae were found free from infection. Nymphs and adults transmitted the infection by bite to rodents and rabbits respectively. The virus was also passed through a second rodent-tick cycle. Adult ticks showed a titre of 3.1 to 4.5 dex mouse LD50/0.03 ml, and the virus was also detected 245 days after infection. | Transmission of Kyasanur Forest disease virus by Rhipicephalus haemaphysaloides ticks. Larvae of Rhipicephalus haemaphysaloides were infected with Kaysanur Forest disease (KFD) virus by feeding on viraemic rodents and reared into next generation larvae. Fed larvae, nymphs, unfed adults, fed adult males, and females after oviposition were found infected, while the larvae were found free from infection. Nymphs and adults transmitted the infection by bite to rodents and rabbits respectively. The virus was also passed through a second rodent-tick cycle. Adult ticks showed a titre of 3.1 to 4.5 dex mouse LD50/0.03 ml, and the virus was also detected 245 days after infection. | [
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PMID:27976 | Failure of 5-bromodeoxyuridine to influence the activation of latent herpex simplex virus infection in explants of the rabbit regional sensory ganglia. | The occurence of virus-specific antigens in explants of the Gasserian ganglia of rabbits with healed keratitis induced by the Kupka strain of human herpesvirus type 1 was tested by indirect immunofluorescence. In explants, the neurons and satellite cells revealed specific fluorescence from the 3rd day of culturing. The pattern of virus activation in the ganglion tissue was similar irrespective of whether the explants were cultured in the presence or absence of 5-bromo-2'-deoxyuridine. | Failure of 5-bromodeoxyuridine to influence the activation of latent herpex simplex virus infection in explants of the rabbit regional sensory ganglia. The occurence of virus-specific antigens in explants of the Gasserian ganglia of rabbits with healed keratitis induced by the Kupka strain of human herpesvirus type 1 was tested by indirect immunofluorescence. In explants, the neurons and satellite cells revealed specific fluorescence from the 3rd day of culturing. The pattern of virus activation in the ganglion tissue was similar irrespective of whether the explants were cultured in the presence or absence of 5-bromo-2'-deoxyuridine. | [
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PMID:27977 | Khasan virus, a new ungrouped bunyavirus isolated from Haemaphysalis longicornis ticks in the Primorie region. | Strain LEIV-776P, possessing no haemagglutinating activity was isolated in 1971 in the Primorie region (U.S.S.R.) from Haemaphysalis longicornis Neumann 1091 tick. Complement fixation (CF) tests revealed no antigenic relationship with 24 antigenic groups of arboviruses or 21 ungrouped viruses isolated from ticks. The virus isolate contains RNA and is relatively sensitive to ether and sodium deoxycholate; it is pathogenic for suckling mice and two-week-old white mice by the intracerebral route, and replicates in primary cultures of chick and duck fibroblasts and green monkey kidneys and in a continuous line of pig embryo kidney cells without any cytopathic effect. According to electron microscopy, its size is 90-110 nm. Its morphological properties permit to classify it as a member of the family Bunyaviridae. | Khasan virus, a new ungrouped bunyavirus isolated from Haemaphysalis longicornis ticks in the Primorie region. Strain LEIV-776P, possessing no haemagglutinating activity was isolated in 1971 in the Primorie region (U.S.S.R.) from Haemaphysalis longicornis Neumann 1091 tick. Complement fixation (CF) tests revealed no antigenic relationship with 24 antigenic groups of arboviruses or 21 ungrouped viruses isolated from ticks. The virus isolate contains RNA and is relatively sensitive to ether and sodium deoxycholate; it is pathogenic for suckling mice and two-week-old white mice by the intracerebral route, and replicates in primary cultures of chick and duck fibroblasts and green monkey kidneys and in a continuous line of pig embryo kidney cells without any cytopathic effect. According to electron microscopy, its size is 90-110 nm. Its morphological properties permit to classify it as a member of the family Bunyaviridae. | [
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PMID:27980 | Correlation between foetal pH, cord blood glucose level and Apgar score in a foetal intensive care unit--preliminary report. | The foetal pH (the term 'foetal pH' is used for the pH of foetal capillary blood obtained by making a small incision in the foetal scalp or buttocks) and the umbilical cord blood glucose levels in pregnant women with foetal distress were estimated in 19 babies as a prospective study in Ile-Ife, Nigeria. The Apgar Scores on delivery were also estimated. There was a significant correlation coefficient between foetal pH and Apgar Score r = 0.38 and the coefficient of correlation between umbilical artery blood glucose and foetal pH was 0.08. Estimation of the pH of blood taken from the foetal scalp is now well established as a diagnostic measure in the early diagnosis of foetal distress due to hypoxia. The results obtained from this small series of nineteen patients highlights the importance of the estimation of foetal pH, blood glucose and the Apgar Score. This is the first account in Ile-Ife, Nigeria. | Correlation between foetal pH, cord blood glucose level and Apgar score in a foetal intensive care unit--preliminary report. The foetal pH (the term 'foetal pH' is used for the pH of foetal capillary blood obtained by making a small incision in the foetal scalp or buttocks) and the umbilical cord blood glucose levels in pregnant women with foetal distress were estimated in 19 babies as a prospective study in Ile-Ife, Nigeria. The Apgar Scores on delivery were also estimated. There was a significant correlation coefficient between foetal pH and Apgar Score r = 0.38 and the coefficient of correlation between umbilical artery blood glucose and foetal pH was 0.08. Estimation of the pH of blood taken from the foetal scalp is now well established as a diagnostic measure in the early diagnosis of foetal distress due to hypoxia. The results obtained from this small series of nineteen patients highlights the importance of the estimation of foetal pH, blood glucose and the Apgar Score. This is the first account in Ile-Ife, Nigeria. | [
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PMID:27982 | Adjunctive drug use by methadone patients. | Clinical impressions, reinforced by reports in both professional journals and the lay press, suggested that use and abuse of minor tranquilizers and sedative-hypnotics was extensive among patients in our drug treatment clinics and required some change in our policies. We surveyed a randomly selected national sample of methadone program physicians and found they shared our assumptions concerning the use of these drugs. A pilot program of urine screening for the presence of adjunctive drugs was completed, and we found the incidence of use to be below expected levels, except for opiates and alcohol. These results suggest we should reconsider plans to alter clinic policies concerning the regulation of these substances. A rigorous examination of serum and/or urine in a national research program to determine both the incidence of adjunctive drug use by clients in drug treatment programs and correlations of such data with national surveys would be an expensive undertaking, but would provide a more rational basis for policy making at both local and national levels. | Adjunctive drug use by methadone patients. Clinical impressions, reinforced by reports in both professional journals and the lay press, suggested that use and abuse of minor tranquilizers and sedative-hypnotics was extensive among patients in our drug treatment clinics and required some change in our policies. We surveyed a randomly selected national sample of methadone program physicians and found they shared our assumptions concerning the use of these drugs. A pilot program of urine screening for the presence of adjunctive drugs was completed, and we found the incidence of use to be below expected levels, except for opiates and alcohol. These results suggest we should reconsider plans to alter clinic policies concerning the regulation of these substances. A rigorous examination of serum and/or urine in a national research program to determine both the incidence of adjunctive drug use by clients in drug treatment programs and correlations of such data with national surveys would be an expensive undertaking, but would provide a more rational basis for policy making at both local and national levels. | [
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PMID:27983 | Esophageal epithelial response to gastroesophageal reflux. A quantitative study. | Exposure of the distal esophageal mucosa to acid gastric juice was quantitated by 24-hr pH monitoring in 100 individuals and was correlated with morphologic data derived from esophageal biopsies. The degree of acid exposure to the distal esophagus correlated directly with increases in both relative and absolute length of the subepithelial papillae and to relative basal zone hyperplasia. Both papillary length and basal zone hyperplasia decreased after antireflux surgery had reduced acid exposure to normal. Reflux in the recumbent position resulted in prolonged exposure of the mucosa to acid because of poor acid clearing from the esophagus. This caused longer papillae than did upright reflux, where there were more frequent reflux episodes, but with rapid acid clearance. The presence of a hiatal hernia was associated with longer papillae, lower DES pressure, increased reflux frequency, and prolonged recumbent acid clearance. Twenty-four hour pH monitoring correlated better with papillary length than did symptoms or other clinical measures of gastroesophageal reflux. | Esophageal epithelial response to gastroesophageal reflux. A quantitative study. Exposure of the distal esophageal mucosa to acid gastric juice was quantitated by 24-hr pH monitoring in 100 individuals and was correlated with morphologic data derived from esophageal biopsies. The degree of acid exposure to the distal esophagus correlated directly with increases in both relative and absolute length of the subepithelial papillae and to relative basal zone hyperplasia. Both papillary length and basal zone hyperplasia decreased after antireflux surgery had reduced acid exposure to normal. Reflux in the recumbent position resulted in prolonged exposure of the mucosa to acid because of poor acid clearing from the esophagus. This caused longer papillae than did upright reflux, where there were more frequent reflux episodes, but with rapid acid clearance. The presence of a hiatal hernia was associated with longer papillae, lower DES pressure, increased reflux frequency, and prolonged recumbent acid clearance. Twenty-four hour pH monitoring correlated better with papillary length than did symptoms or other clinical measures of gastroesophageal reflux. | [
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PMID:27984 | NADPH-oxidation activities in subcellular fractions isolated from resting or phagocytozing human polymorphonuclears. | Using a fluorometric assay for the determination of oxidized pyridine nucleotides (NAD[P]+), total and cyanide-resistant NADPH-oxidative activities have been measured in subcellular fractions isolated from resting and phagocytosing human polymorphonuclears. Enzymatic activies responsible for the oxidation of the NADPH have been recovered in the heavy particles (15,000g/15 min), the low-density particles (100,000g/30 min), and the cytosolic fraction. Stimulation of the cells with opsonized zymosan had a different effect on the NADPH-oxidative activities of these subcellular fractions, which suggests the involvement of various types of enzymatic systems in the oxidation of NADPH. The cytosolic fraction interacted strongly with the enzymatic activities occurring in the sedimentable fractions and is therefore thought to play a central role in the regulation of the activation of the oxidative metabolism associated with phagocytosis. | NADPH-oxidation activities in subcellular fractions isolated from resting or phagocytozing human polymorphonuclears. Using a fluorometric assay for the determination of oxidized pyridine nucleotides (NAD[P]+), total and cyanide-resistant NADPH-oxidative activities have been measured in subcellular fractions isolated from resting and phagocytosing human polymorphonuclears. Enzymatic activies responsible for the oxidation of the NADPH have been recovered in the heavy particles (15,000g/15 min), the low-density particles (100,000g/30 min), and the cytosolic fraction. Stimulation of the cells with opsonized zymosan had a different effect on the NADPH-oxidative activities of these subcellular fractions, which suggests the involvement of various types of enzymatic systems in the oxidation of NADPH. The cytosolic fraction interacted strongly with the enzymatic activities occurring in the sedimentable fractions and is therefore thought to play a central role in the regulation of the activation of the oxidative metabolism associated with phagocytosis. | [
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PMID:27985 | Presence of arylsulfatase A (ARS A) in multiple sulfatase deficiency disorder fibroblasts. | Multiple deficiency disorder fibroblasts cultured in MEM-CO2 showed deficiencies of arylsulfatase A(ARS A) comparable to the deficiency in metachromatic leukodystrophy fibroblasts. However, the MSDD fibroblasts cultured in MEM-HEPES contained near normal levels of ARS A. Moreover, the enzyme from the latter fibroblasts was indistinguishable from ARS A of control fibroblasts on DEAE-cellulose chromatography, ratio of activity with several substrates, thermal inactivation, sensitivity to inhibitors, and precipitation by antiserum to human ARS A. These data support the conclusion that the ARS A genome is intact in MSDD fibroblasts and, by extension, in MSDD patients. Other sulfatases were present at levels ranging from mildly deficient to near normal but never as low as seen in the corresponding specific sulfatase deficient disorders. | Presence of arylsulfatase A (ARS A) in multiple sulfatase deficiency disorder fibroblasts. Multiple deficiency disorder fibroblasts cultured in MEM-CO2 showed deficiencies of arylsulfatase A(ARS A) comparable to the deficiency in metachromatic leukodystrophy fibroblasts. However, the MSDD fibroblasts cultured in MEM-HEPES contained near normal levels of ARS A. Moreover, the enzyme from the latter fibroblasts was indistinguishable from ARS A of control fibroblasts on DEAE-cellulose chromatography, ratio of activity with several substrates, thermal inactivation, sensitivity to inhibitors, and precipitation by antiserum to human ARS A. These data support the conclusion that the ARS A genome is intact in MSDD fibroblasts and, by extension, in MSDD patients. Other sulfatases were present at levels ranging from mildly deficient to near normal but never as low as seen in the corresponding specific sulfatase deficient disorders. | [
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PMID:27986 | Renal response of fetal lamb to complete occlusion of umbilical cord. | The renal response of the fetal lamb to repeated complete occlusion of the umbilical cord was studied in nine chronically instrumented animals. Five episodes of occlusion of the umbilical cord, each lasting for two minutes, produced a twofold rise in fetal urine osmolality and sodium, chloride, and potassium concentrations. Output of urine and glomerular filtration rate remained essentially unchanged while free water clearance decreased from a control of +0.10 to -0.02 ml. per kilogram per minute at the end of the fifth episode. Electrolyte concentrations in urine remained elevated for at least two hours following the occlusions. In addition to changes in urine composition, there was a 50- to 200-fold increase in the fetal plasma concentration of vasopressin. These studies indicate that complete interruption of the umbilical circulation, even though of short duration, produces disturbances in fetal renal function that can lead to loss of electrolytes in the urine. They provide an explanation for the low sodium levels reported in asphyxiated newborn infants in renal failure. | Renal response of fetal lamb to complete occlusion of umbilical cord. The renal response of the fetal lamb to repeated complete occlusion of the umbilical cord was studied in nine chronically instrumented animals. Five episodes of occlusion of the umbilical cord, each lasting for two minutes, produced a twofold rise in fetal urine osmolality and sodium, chloride, and potassium concentrations. Output of urine and glomerular filtration rate remained essentially unchanged while free water clearance decreased from a control of +0.10 to -0.02 ml. per kilogram per minute at the end of the fifth episode. Electrolyte concentrations in urine remained elevated for at least two hours following the occlusions. In addition to changes in urine composition, there was a 50- to 200-fold increase in the fetal plasma concentration of vasopressin. These studies indicate that complete interruption of the umbilical circulation, even though of short duration, produces disturbances in fetal renal function that can lead to loss of electrolytes in the urine. They provide an explanation for the low sodium levels reported in asphyxiated newborn infants in renal failure. | [
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PMID:27988 | Effects of pH, Ca, ADH, and theophylline on kinetics of Na entry in frog skin. | The short circuit current as a function of Na concentration in both solutions was found to obey Michaelis-Menten kinetics under a variety of experimental conditions. Values of maximal transport rate (Im) and half-maximal Na concentrations (Kt) were determined from these experiments. Three type of results were obtained: 1) Im and Kt both decreased by approximately the same fraction when the pH of both solutions was reduced by increasing PCO2, 2) Im decreased and Kt increased when the external pH was decreased, and 3) Im increased with ADH and theophylline, decreased with external Ca, and Kt remained unchanged. Various criteria were utilized to determine that these were properties of the entry barrier for Na into the "transport pool." The results are explained in terms of a model that separates three different types of actions on the entry barrier: 1) competition of Na with other ions in the external solution for entry, 2) modulation of the number of sites available for Na translocation by changing the cytoplasmic pH, and 3) alterations in the rate of Na translocation caused by changes in the Na permeability or the electrochemical gradient across the entry barrier. | Effects of pH, Ca, ADH, and theophylline on kinetics of Na entry in frog skin. The short circuit current as a function of Na concentration in both solutions was found to obey Michaelis-Menten kinetics under a variety of experimental conditions. Values of maximal transport rate (Im) and half-maximal Na concentrations (Kt) were determined from these experiments. Three type of results were obtained: 1) Im and Kt both decreased by approximately the same fraction when the pH of both solutions was reduced by increasing PCO2, 2) Im decreased and Kt increased when the external pH was decreased, and 3) Im increased with ADH and theophylline, decreased with external Ca, and Kt remained unchanged. Various criteria were utilized to determine that these were properties of the entry barrier for Na into the "transport pool." The results are explained in terms of a model that separates three different types of actions on the entry barrier: 1) competition of Na with other ions in the external solution for entry, 2) modulation of the number of sites available for Na translocation by changing the cytoplasmic pH, and 3) alterations in the rate of Na translocation caused by changes in the Na permeability or the electrochemical gradient across the entry barrier. | [
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PMID:27989 | Intracellular pH transients in rat diaphragm muscle measured with DMO. | Changes of the intracellular pH of rat diaphragm muscle were monitored at 30-min intervals with the weak acid DMO (5,5-dimethyl-2,4-oxazolidinedione). Transferring the muscle from a CO2-containing to a CO2-free solution caused intracellular pH (pHi) to rise by an average of 0.18 during the first 30 min and then to level off at a slightly lower value over the next 60-90 min. Transferring the muscle from a CO2-free to a CO2-containing solution caused pHi to fall by 0.18 during the first 30 min and then to recover by 0.05 over the next 90 min. Subsequent return to the CO2-free solution caused pHi to overshoot the control value by 0.10. Both the recovery and the overshoot can be accounted for by an acid-extruding pump. Intracellular acid loading with 118 mM DMO similarly caused pHi to fall initially, to recover slowly during the acid loading, and then to overshoot the control pHi on removal of the acid load. In the absence of HCO3-/CO2, acid extrusion was reduced by about a fifth. SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid) had no effect. The absence of either Na+ or Cl- from HCO3-/CO2- free solution reduced acid extrusion by about a half. | Intracellular pH transients in rat diaphragm muscle measured with DMO. Changes of the intracellular pH of rat diaphragm muscle were monitored at 30-min intervals with the weak acid DMO (5,5-dimethyl-2,4-oxazolidinedione). Transferring the muscle from a CO2-containing to a CO2-free solution caused intracellular pH (pHi) to rise by an average of 0.18 during the first 30 min and then to level off at a slightly lower value over the next 60-90 min. Transferring the muscle from a CO2-free to a CO2-containing solution caused pHi to fall by 0.18 during the first 30 min and then to recover by 0.05 over the next 90 min. Subsequent return to the CO2-free solution caused pHi to overshoot the control value by 0.10. Both the recovery and the overshoot can be accounted for by an acid-extruding pump. Intracellular acid loading with 118 mM DMO similarly caused pHi to fall initially, to recover slowly during the acid loading, and then to overshoot the control pHi on removal of the acid load. In the absence of HCO3-/CO2, acid extrusion was reduced by about a fifth. SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid) had no effect. The absence of either Na+ or Cl- from HCO3-/CO2- free solution reduced acid extrusion by about a half. | [
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PMID:27990 | Infection rates of Aedes triseriatus following ingestion of La Crosse virus by the larvae. | Infection rates ranged from 0-2.1% in adults of Aedes triseriaus reared from groups of larvae that had ingested La Crosse (LAC) virus (Clifornia encephalitis group) at dosages of 7.0-8.3 log 10 SMICLD50/ml. Females form orally infected larvae transmitted the virus to suckling mice. Larvae that devoured carcasses of transovarially infected larvae containing 3.0 log 10 SMICLD 50/ml failed to become infected. Ingestion by larvae of infected carcasses appears, therefore, to be unimportant as a method of horizontal amplification of LAC virus. | Infection rates of Aedes triseriatus following ingestion of La Crosse virus by the larvae. Infection rates ranged from 0-2.1% in adults of Aedes triseriaus reared from groups of larvae that had ingested La Crosse (LAC) virus (Clifornia encephalitis group) at dosages of 7.0-8.3 log 10 SMICLD50/ml. Females form orally infected larvae transmitted the virus to suckling mice. Larvae that devoured carcasses of transovarially infected larvae containing 3.0 log 10 SMICLD 50/ml failed to become infected. Ingestion by larvae of infected carcasses appears, therefore, to be unimportant as a method of horizontal amplification of LAC virus. | [
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PMID:27993 | [Effects of diazepam and flunitrazepam on the undesired postoperative side-effects of ketamine anaesthesia (author's transl)]. | 150 patients undergoing minor gynaecological procedures (curretages) were anesthetized with ketamine and either diazepam flunitrazepam or placebo in order to establish the best combination for the prevention of postoperative psychotomimetic effects. From observations, up to 24 h after operation, it was found and statistically proven that the combination of ketamine/flunitrazepam as compared to the combinations ketamine/diazepam and ketamine/placebo led to a remarkable reduction of psychotomimetic side reactions. | [Effects of diazepam and flunitrazepam on the undesired postoperative side-effects of ketamine anaesthesia (author's transl)]. 150 patients undergoing minor gynaecological procedures (curretages) were anesthetized with ketamine and either diazepam flunitrazepam or placebo in order to establish the best combination for the prevention of postoperative psychotomimetic effects. From observations, up to 24 h after operation, it was found and statistically proven that the combination of ketamine/flunitrazepam as compared to the combinations ketamine/diazepam and ketamine/placebo led to a remarkable reduction of psychotomimetic side reactions. | [
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PMID:28036 | [The use of naloxone in neuroleptoanalgesia]. | Naloxone was used in 20 patients divided into two series: series A consisted of 10 adults with an average age of 50.6 years (+/- 12.03) and series B 10 children with an average age of 8.5 years (+/- 5.16). Naloxone was given in the treatment of postoperative respiratory depression related to persistence of morphine impregnation, the patients having received either fentanyl (mean dose 0.04 mg/kg/h) or dextromoramide (mean dose 1.15 mg/kg/h). The mean dose of naloxone was 0.26 mg +/- 0.10, i.e. 3.9 microgram/kg in series A, and 0.13 mg +/- 0.11, i.e. 5.3 microgram/kg in series B. In both series, study of ventilatory function showed correction and stabilisation of the various parameters (F/min, Vt and V) up to 180 minutes after the injection. Recovery was rapid in both groups (7 to 10 min) and of good quality. Whilst it was accompanied in a number of cases by the recurrence of pain, the latter never required specific relief. The administration of naloxone was associated with an increase in heart rate (non-significant) at 10 min in series A and 30 min in series B. Apart an episode of nausea in one case of series A, no disagreeable side effects were observed. | [The use of naloxone in neuroleptoanalgesia]. Naloxone was used in 20 patients divided into two series: series A consisted of 10 adults with an average age of 50.6 years (+/- 12.03) and series B 10 children with an average age of 8.5 years (+/- 5.16). Naloxone was given in the treatment of postoperative respiratory depression related to persistence of morphine impregnation, the patients having received either fentanyl (mean dose 0.04 mg/kg/h) or dextromoramide (mean dose 1.15 mg/kg/h). The mean dose of naloxone was 0.26 mg +/- 0.10, i.e. 3.9 microgram/kg in series A, and 0.13 mg +/- 0.11, i.e. 5.3 microgram/kg in series B. In both series, study of ventilatory function showed correction and stabilisation of the various parameters (F/min, Vt and V) up to 180 minutes after the injection. Recovery was rapid in both groups (7 to 10 min) and of good quality. Whilst it was accompanied in a number of cases by the recurrence of pain, the latter never required specific relief. The administration of naloxone was associated with an increase in heart rate (non-significant) at 10 min in series A and 30 min in series B. Apart an episode of nausea in one case of series A, no disagreeable side effects were observed. | [
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PMID:28037 | [Antagonistic effects of naloxone against morphinomimetic agents. Apropos of 10 cases in gynecologic surgery]. | The object of this study was the use of naloxone to correct hypoventilation related to the use of morphinomimetics without suppressing the analgesic effect of these agents. The study involved ten patients undergoing gynaecological surgery under neuroleptanalgesia and who at the end of surgery had hypoventilation due to the use of fentanyl (average dose : 4.87 microgram/kg/h) or phenoperidine (average dose : 48.7 microgram/kg/h). Naloxone was administered intravenously in an average dose of 1.37 microgram/kg (in one or two injections) followed by an intramuscular injection of an average of 0.73 microgram/kg. Under these conditions, respiratory depression was completely corrected in all cases, the effect being durable. Good analgesia was retained and there was a normal return to consciousness without undesirable effects. | [Antagonistic effects of naloxone against morphinomimetic agents. Apropos of 10 cases in gynecologic surgery]. The object of this study was the use of naloxone to correct hypoventilation related to the use of morphinomimetics without suppressing the analgesic effect of these agents. The study involved ten patients undergoing gynaecological surgery under neuroleptanalgesia and who at the end of surgery had hypoventilation due to the use of fentanyl (average dose : 4.87 microgram/kg/h) or phenoperidine (average dose : 48.7 microgram/kg/h). Naloxone was administered intravenously in an average dose of 1.37 microgram/kg (in one or two injections) followed by an intramuscular injection of an average of 0.73 microgram/kg. Under these conditions, respiratory depression was completely corrected in all cases, the effect being durable. Good analgesia was retained and there was a normal return to consciousness without undesirable effects. | [
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PMID:28039 | [Electrophysiologic aspects of the effects of etomidate in man]. | Recordings were electroencephalographical (EEG with spectral analysis), polygraphical (EMG, EKG, breathing). Visual and Auditory Cerebral Evoked Responses were also recorded. The depth of narcosis was quantified upon EEG data. The reactivity during the narcosis and the mechanisms of action of Etomidate on the "non specific structures" are discussed. Cautions should be taken with the use of tomidate in anesthesiology with epileptic and arteriopathic patients. | [Electrophysiologic aspects of the effects of etomidate in man]. Recordings were electroencephalographical (EEG with spectral analysis), polygraphical (EMG, EKG, breathing). Visual and Auditory Cerebral Evoked Responses were also recorded. The depth of narcosis was quantified upon EEG data. The reactivity during the narcosis and the mechanisms of action of Etomidate on the "non specific structures" are discussed. Cautions should be taken with the use of tomidate in anesthesiology with epileptic and arteriopathic patients. | [
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PMID:28040 | [Effect of etomidate on cerebral blood flow and oxygen metabolism in man]. | The effects of Etomidate on cerebral blood flow (C.B.F.) and cerebral oxygen consumption (C.02 C.) were studied in 13 patients in a neuroradiology department. Induction of anaesthesia was ensured using a standard dose of 15 mg of Etomidate, followed by a constant rate infusion (2.8 mg/kg/hour). Seven subjects were considered to be normal whilst six were suffering from tumour pathology. Under the influence of Etomidate, C.B.F. in the normal subjects decreased by 34 p. 100 and C.02 C. by 46.7 p. 100. The relationship between C.B.F. and arterial PC01 was studied under the influence of Etomidate: cerebral vasoactivity to C02 was maintained. A special study was made of focal changes in flow in patients with tumour pathology. Under the influence of Etomidate, there were zones of adaptation of flow, indicative of vasoparalysis situated opposite the tumour. | [Effect of etomidate on cerebral blood flow and oxygen metabolism in man]. The effects of Etomidate on cerebral blood flow (C.B.F.) and cerebral oxygen consumption (C.02 C.) were studied in 13 patients in a neuroradiology department. Induction of anaesthesia was ensured using a standard dose of 15 mg of Etomidate, followed by a constant rate infusion (2.8 mg/kg/hour). Seven subjects were considered to be normal whilst six were suffering from tumour pathology. Under the influence of Etomidate, C.B.F. in the normal subjects decreased by 34 p. 100 and C.02 C. by 46.7 p. 100. The relationship between C.B.F. and arterial PC01 was studied under the influence of Etomidate: cerebral vasoactivity to C02 was maintained. A special study was made of focal changes in flow in patients with tumour pathology. Under the influence of Etomidate, there were zones of adaptation of flow, indicative of vasoparalysis situated opposite the tumour. | [
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PMID:28041 | [Hemodynamic effects of etomidate]. | A study of the haemodynamic effects of an injection of 0.3 mg/kg of Etomidate was carried out in 11 multiple trauma patients under constant controlled ventilation. At the 3 rd minute after injection there was a slight, but significant, increase in cardiac output and in the systolic index of the left ventricle, persisting at the 20th minute. It may be concluded that the injection of a dose of 0.3 mg/kg has no harmful haemodynamic effects in this type of patient. | [Hemodynamic effects of etomidate]. A study of the haemodynamic effects of an injection of 0.3 mg/kg of Etomidate was carried out in 11 multiple trauma patients under constant controlled ventilation. At the 3 rd minute after injection there was a slight, but significant, increase in cardiac output and in the systolic index of the left ventricle, persisting at the 20th minute. It may be concluded that the injection of a dose of 0.3 mg/kg has no harmful haemodynamic effects in this type of patient. | [
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PMID:28042 | [Constant flow anesthesia using a combination of etomidate and fentanyl]. | In 35 orthopaedic surgery patients (33 adults and 2 children), anaesthesia was obtained using an association of etomidate and fentanyl. Induction was obtained by injection from a syringe of a mixture of etomidate and fentanyl in an average dose of 21 mg for etomidate and 0,08 mg for fentanyl. Anaesthesia was maintained by constant dose of etomidate was 1.29 mg/kg/h and 4.96 microgram/kg/h for fentanyl. The mixture used for both induction and maintenance contained 1.3 mg of etomidate and 5 mg of fentanyl per ml. The results, value, indications and contraindications of this technique are described. | [Constant flow anesthesia using a combination of etomidate and fentanyl]. In 35 orthopaedic surgery patients (33 adults and 2 children), anaesthesia was obtained using an association of etomidate and fentanyl. Induction was obtained by injection from a syringe of a mixture of etomidate and fentanyl in an average dose of 21 mg for etomidate and 0,08 mg for fentanyl. Anaesthesia was maintained by constant dose of etomidate was 1.29 mg/kg/h and 4.96 microgram/kg/h for fentanyl. The mixture used for both induction and maintenance contained 1.3 mg of etomidate and 5 mg of fentanyl per ml. The results, value, indications and contraindications of this technique are described. | [
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PMID:28045 | [Choice of a local anesthetic in obstetrical analgesia]. | A local anaesthetic may be selected from amongst the two major groups of drugs of this type: amino-alcoyl-esters and amino-acylamides. In practice, three substances are available or will shortly be available in France: lignocaine, etidocaine and bupivacaine, thus limiting the choice. This choice is guided by the toxicity of the substance, its clinical effects and 1st side effects. 1-Toxicity depends upon the nature of the substance, the dose necessary to obtain analgesia and to prolong it for a sufficient time. 2-Amongst the clinical effects which should be noted in the choice of a local anaesthetic are the latent period before analgesia is obtained, the degree of sensory block, the degree of motor block and the duration of action. The three substances available are compared in relations to these parameters and in the light of the specific requirements of obstetric analgesia. The value of the addiction of adrenalin is discussed. 3-The side effects are those of the local anesthetic itself and of its possible association with adrenalin. On the basis of the various criteria mentioned, it would seem that the analgesic of choice for obstetric analgesia is bupivacaine used with or without adrenalin. | [Choice of a local anesthetic in obstetrical analgesia]. A local anaesthetic may be selected from amongst the two major groups of drugs of this type: amino-alcoyl-esters and amino-acylamides. In practice, three substances are available or will shortly be available in France: lignocaine, etidocaine and bupivacaine, thus limiting the choice. This choice is guided by the toxicity of the substance, its clinical effects and 1st side effects. 1-Toxicity depends upon the nature of the substance, the dose necessary to obtain analgesia and to prolong it for a sufficient time. 2-Amongst the clinical effects which should be noted in the choice of a local anaesthetic are the latent period before analgesia is obtained, the degree of sensory block, the degree of motor block and the duration of action. The three substances available are compared in relations to these parameters and in the light of the specific requirements of obstetric analgesia. The value of the addiction of adrenalin is discussed. 3-The side effects are those of the local anesthetic itself and of its possible association with adrenalin. On the basis of the various criteria mentioned, it would seem that the analgesic of choice for obstetric analgesia is bupivacaine used with or without adrenalin. | [
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PMID:28046 | [Effects of peridural analgesia on labor]. | A review of the effects during labour of epidural analgesia on dilatation, expulsion and delivery of the placenta. Uncertainties in knowledge of the precise organisation of uterine innervation and of the intrinsic innervation of the organ render the study of changes in uterine contraction and in cervical resistances difficult. At circulating levels higher than those found in clinical practice, local anaesthetics have a definite oxytocic e-fect, local anaesthetics have a definite oxytoci effect, whilst adrenalin is a powerfult tocolytic. By contrast, the indirect effects related to neurolysis in extradural analgesia are negligeable. Cervico-segmentary resistances are decreased. In practice, there is no increase in the period of dilatation in the absence of any haemodynamic disturbances and if mixtures containing adrenalin are avoided. Expulsion is favourised by muscular relaxation but impaired by the lack of voluntary expulsive effort, hence the choice of a local anaesthetic with the lowest possible motor effect. Delivery of the placenta, which involves only uterine contraction, which is not affected, may be accelerated by oxytocics. | [Effects of peridural analgesia on labor]. A review of the effects during labour of epidural analgesia on dilatation, expulsion and delivery of the placenta. Uncertainties in knowledge of the precise organisation of uterine innervation and of the intrinsic innervation of the organ render the study of changes in uterine contraction and in cervical resistances difficult. At circulating levels higher than those found in clinical practice, local anaesthetics have a definite oxytocic e-fect, local anaesthetics have a definite oxytoci effect, whilst adrenalin is a powerfult tocolytic. By contrast, the indirect effects related to neurolysis in extradural analgesia are negligeable. Cervico-segmentary resistances are decreased. In practice, there is no increase in the period of dilatation in the absence of any haemodynamic disturbances and if mixtures containing adrenalin are avoided. Expulsion is favourised by muscular relaxation but impaired by the lack of voluntary expulsive effort, hence the choice of a local anaesthetic with the lowest possible motor effect. Delivery of the placenta, which involves only uterine contraction, which is not affected, may be accelerated by oxytocics. | [
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PMID:28048 | [The use of Marcaine in obstetrical analgesia]. | Bupivacaine (Marcaine) is being used increasingly in obstetrics for epidural analgesia, by virtue of the good sensory block obtained and the minimum of side-effects on the mother and newborn infant. At a concentration of less than 0.5 p. 100, analgesia is excellent with a minimal effect on motor fibres. Side-effects and toxicity are limited by the use of fractionated doses from the beginning of labour or of a single dose during or at the end of labour calculated in relation to the effect sought. Any action on the newborn infant would appear to be exceptional, if dose recommendations are respected, the high percentage of Marcaine bound to proteins limiting its transplacental passage. | [The use of Marcaine in obstetrical analgesia]. Bupivacaine (Marcaine) is being used increasingly in obstetrics for epidural analgesia, by virtue of the good sensory block obtained and the minimum of side-effects on the mother and newborn infant. At a concentration of less than 0.5 p. 100, analgesia is excellent with a minimal effect on motor fibres. Side-effects and toxicity are limited by the use of fractionated doses from the beginning of labour or of a single dose during or at the end of labour calculated in relation to the effect sought. Any action on the newborn infant would appear to be exceptional, if dose recommendations are respected, the high percentage of Marcaine bound to proteins limiting its transplacental passage. | [
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PMID:28049 | [Experience of labor and obstetrical analgesia]. | A prospective study was undertaken at Strasbourg of the assessment of the patients of the techniques used by the obstetric team and of the general atmosphere in which labour and delivery took place. A questionnair of 115 items was analysed by computer using a Pastis-Pascal programme (see attached). The first results, concerning the analysis of 100 cases and taking into account approximately ten variables, gave the following findings: -the intolerable pain factor is related to the period of dilatation; -the analgesic or amnesic factor in the mother influences the satisfaction she experiences in relation to her child; -demand for epidural anaesthesia appeared the same, whether the woman had been prepared by a psychoprophylactic method or not; -psychoprophylactic preparation would not appear to influence the assessment of pain; -women having an epidural anaesthetic never considered their labour to have been intolerable. Discriminant analysis with study of correlations is not possible at present. Given the number of variables to be considered, the population analysed is inadequate. A multicentre study would improve the performance of this research. Our questionnaire is available to any teams who might wish to use it. | [Experience of labor and obstetrical analgesia]. A prospective study was undertaken at Strasbourg of the assessment of the patients of the techniques used by the obstetric team and of the general atmosphere in which labour and delivery took place. A questionnair of 115 items was analysed by computer using a Pastis-Pascal programme (see attached). The first results, concerning the analysis of 100 cases and taking into account approximately ten variables, gave the following findings: -the intolerable pain factor is related to the period of dilatation; -the analgesic or amnesic factor in the mother influences the satisfaction she experiences in relation to her child; -demand for epidural anaesthesia appeared the same, whether the woman had been prepared by a psychoprophylactic method or not; -psychoprophylactic preparation would not appear to influence the assessment of pain; -women having an epidural anaesthetic never considered their labour to have been intolerable. Discriminant analysis with study of correlations is not possible at present. Given the number of variables to be considered, the population analysed is inadequate. A multicentre study would improve the performance of this research. Our questionnaire is available to any teams who might wish to use it. | [
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PMID:28050 | [The organization of an obstetric center in relation to obstetrical analgesia]. | In order that continous epidural anaesthesia may be given safely in an obstetric centre, the permanent presence of an anaesthetist is necessary. Obstetricians and midwives must be familiar with the management of labour using this method and team spirit involving continous cooperation between the anaesthetist, obstetrician and midwives is essential. Training related to epidural anaesthesia is necessary for the members of the obsteric centre, as well as education of the patients. | [The organization of an obstetric center in relation to obstetrical analgesia]. In order that continous epidural anaesthesia may be given safely in an obstetric centre, the permanent presence of an anaesthetist is necessary. Obstetricians and midwives must be familiar with the management of labour using this method and team spirit involving continous cooperation between the anaesthetist, obstetrician and midwives is essential. Training related to epidural anaesthesia is necessary for the members of the obsteric centre, as well as education of the patients. | [
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PMID:28051 | [Economic and social problems posed by peridural anesthesia and obstetrical analgesia]. | It is impossible not to note the small number of epidural anaesthetics given for obstetrics in France. The rarity of centres where it is offered by a team of specially trained anaesthetists and obstetricians contrasts with the increase in demand from the patients themselves. Study of the number of epidural anaesthetics predictable in obstetrics according to the criteria of indication indicates that the procedure could be used in as many as 30 to 50 per cent of deliveries. This implies a need for an increase in the number of anaesthetists, i.e. an increase not so much in the total number as in those trained in obstetrics with experience of epidural anaesthesia. Similar changes are necessary in hospital organisation, in such a way that the place of the anaesthetist in the maternity unit is recognised officially, this recognition being strengthened by routine out-patient consultation with all patients during their pregnancy. The economic aspect of a possible increase in the number of epidural anaesthetics carried out in France and in the number of anaesthetists performing the procedure is envisaged in terms of salaries in the public hospital system, costing of the procedure by the Social Security and the true cost of epidural anaesthesia. | [Economic and social problems posed by peridural anesthesia and obstetrical analgesia]. It is impossible not to note the small number of epidural anaesthetics given for obstetrics in France. The rarity of centres where it is offered by a team of specially trained anaesthetists and obstetricians contrasts with the increase in demand from the patients themselves. Study of the number of epidural anaesthetics predictable in obstetrics according to the criteria of indication indicates that the procedure could be used in as many as 30 to 50 per cent of deliveries. This implies a need for an increase in the number of anaesthetists, i.e. an increase not so much in the total number as in those trained in obstetrics with experience of epidural anaesthesia. Similar changes are necessary in hospital organisation, in such a way that the place of the anaesthetist in the maternity unit is recognised officially, this recognition being strengthened by routine out-patient consultation with all patients during their pregnancy. The economic aspect of a possible increase in the number of epidural anaesthetics carried out in France and in the number of anaesthetists performing the procedure is envisaged in terms of salaries in the public hospital system, costing of the procedure by the Social Security and the true cost of epidural anaesthesia. | [
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PMID:28052 | [Study of a new respiratory analeptic: injectable almatrine. Apropos of 22 cases of acute hypoventilation: respiratory activity and electroencephalographic control]. | 2620 is a respiratory analeptic which acts by stimulation of peripheral chemoreceptors. It was administered intravenously in 22 patients in acute respiratory insufficiency. Doses during the first hour varied between 0.7 and 3 mg/kg. A careful study of the effects on respiration showed a significant increase in minute ventilation without any proportional increase in frequency for doses of between 1.7 and 3 mg/kg. Continuous recording of the electroencephalogram over a period of one hour revealed no convulsant effect even in particularly vulnerable patients. In seven patients, tracings showed a change in the sense of increased consciousness which corresponded with the clinical course of the diseases responsible for the state of hypoventilation. | [Study of a new respiratory analeptic: injectable almatrine. Apropos of 22 cases of acute hypoventilation: respiratory activity and electroencephalographic control]. 2620 is a respiratory analeptic which acts by stimulation of peripheral chemoreceptors. It was administered intravenously in 22 patients in acute respiratory insufficiency. Doses during the first hour varied between 0.7 and 3 mg/kg. A careful study of the effects on respiration showed a significant increase in minute ventilation without any proportional increase in frequency for doses of between 1.7 and 3 mg/kg. Continuous recording of the electroencephalogram over a period of one hour revealed no convulsant effect even in particularly vulnerable patients. In seven patients, tracings showed a change in the sense of increased consciousness which corresponded with the clinical course of the diseases responsible for the state of hypoventilation. | [
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PMID:28053 | [Apropos of complications following the use of methylmethacrylate. Possible prevention by betamethasone]. | The aim of this study was to determine whether the prior injection of betamethasone was capable of preventing blood pressure changes and the fall in arterial pO2 when following the fixation of total hip protheses with methyl metacrylate. It involved 54 patients in whom systolic, diastolic and mean blood pressure (BP), arterial pO2, pCO2 and heart rate were noted at different times: T1, 15 minutes after the beginning of the operation; T2 and T3, one minute and five minutes after application of the cement; T4, at the end of the operation. There was no significant difference between the various measurements at times T1, T2, and T3 as far as blood pressure and heart rate were concerned. By contrast, there was a fall in pO2 at times T2 and T2 in relation to times T1 and T4. This fall was significant (p is less than 0.01) but never theless remained moderate. The possible influence of betamethasone is discussed. | [Apropos of complications following the use of methylmethacrylate. Possible prevention by betamethasone]. The aim of this study was to determine whether the prior injection of betamethasone was capable of preventing blood pressure changes and the fall in arterial pO2 when following the fixation of total hip protheses with methyl metacrylate. It involved 54 patients in whom systolic, diastolic and mean blood pressure (BP), arterial pO2, pCO2 and heart rate were noted at different times: T1, 15 minutes after the beginning of the operation; T2 and T3, one minute and five minutes after application of the cement; T4, at the end of the operation. There was no significant difference between the various measurements at times T1, T2, and T3 as far as blood pressure and heart rate were concerned. By contrast, there was a fall in pO2 at times T2 and T2 in relation to times T1 and T4. This fall was significant (p is less than 0.01) but never theless remained moderate. The possible influence of betamethasone is discussed. | [
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PMID:28054 | [Comparative study of venous contamination with low FiO2 and with pure oxygen in disease-induced pulmonary edema]. | A comparative study of the venous contamination (Qs/Qt = (Cc'O2 - CaO2) / (Cc'O2 - C-vO2) under FIO2 = 0.45 - 0.6 and under FIO2 = 1, was realised in 9 patients with lesions of pulmonary oedema. Increasing the FIO2 lead to an increase in the venous contamination three times (average increase was 36 p. 100 of the initial value), to no change two times and a decrease four times (average decrease of 34 p. 100). The values of the venous contamination under average FIO2 are statistically lower in the group where it rises on increasing the FIO2 than in that in which it falls or remains unchanged (p is less than 0.005). | [Comparative study of venous contamination with low FiO2 and with pure oxygen in disease-induced pulmonary edema]. A comparative study of the venous contamination (Qs/Qt = (Cc'O2 - CaO2) / (Cc'O2 - C-vO2) under FIO2 = 0.45 - 0.6 and under FIO2 = 1, was realised in 9 patients with lesions of pulmonary oedema. Increasing the FIO2 lead to an increase in the venous contamination three times (average increase was 36 p. 100 of the initial value), to no change two times and a decrease four times (average decrease of 34 p. 100). The values of the venous contamination under average FIO2 are statistically lower in the group where it rises on increasing the FIO2 than in that in which it falls or remains unchanged (p is less than 0.005). | [
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PMID:28055 | [Biological tests as indirect indicators of the activity of drug metabolizing enzymes. Use of glucaric acid and gamma-glutamyltransferase]. | Laboratory tests are increasingly important in the surveillance of drug treatments. People in charge of clinical laboratory science must now become aware of a new development, the use of as indicators of the activity of drug-metabolizing enzymes, especially of the induction of such enzymes. Ideally, the activity of such enzymes should be measured in the tissues. In man, however, easier indirect methods of application are now most often used : measurement of antipyrine half-life, urinary and plasma drug metabolites, protein and specific enzyme levels in palsma, changes in endogenous substrates and endogenous metabolites, and enzymes in circulating blood cells. Of all these, two examinations are now widely performed, those for urinary glucaric acid and gamma-glutamyltrasferase. The value and limitations of these two tests are discussed. | [Biological tests as indirect indicators of the activity of drug metabolizing enzymes. Use of glucaric acid and gamma-glutamyltransferase]. Laboratory tests are increasingly important in the surveillance of drug treatments. People in charge of clinical laboratory science must now become aware of a new development, the use of as indicators of the activity of drug-metabolizing enzymes, especially of the induction of such enzymes. Ideally, the activity of such enzymes should be measured in the tissues. In man, however, easier indirect methods of application are now most often used : measurement of antipyrine half-life, urinary and plasma drug metabolites, protein and specific enzyme levels in palsma, changes in endogenous substrates and endogenous metabolites, and enzymes in circulating blood cells. Of all these, two examinations are now widely performed, those for urinary glucaric acid and gamma-glutamyltrasferase. The value and limitations of these two tests are discussed. | [
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PMID:28056 | [Gamma-glutamyltransferase. Human pathology and animal biology]. | Gamma-glutamyltransferase (GGT, EC 2.3.2.2) is in man and animals mainly a renal enzyme. It is also present in non-negligeable quantities in the liver except in certain rodents such as the rat. In the cells, the cytosoluble fraction of the enzyme is very low and most of the enzyme is linked to the microsomal fraction in vitro. This fraction permits its use in the diagnosis of liver and biliary disease by measurement of its serum activity and that of renal disease by measurement of its urinary activity. In biological research, the prospects offered by GGT both in human and animal cancers, and in pharmacology and toxicology makes it probably one of the most appreciated biological tests in the exploration of liver, biliary and renal function. | [Gamma-glutamyltransferase. Human pathology and animal biology]. Gamma-glutamyltransferase (GGT, EC 2.3.2.2) is in man and animals mainly a renal enzyme. It is also present in non-negligeable quantities in the liver except in certain rodents such as the rat. In the cells, the cytosoluble fraction of the enzyme is very low and most of the enzyme is linked to the microsomal fraction in vitro. This fraction permits its use in the diagnosis of liver and biliary disease by measurement of its serum activity and that of renal disease by measurement of its urinary activity. In biological research, the prospects offered by GGT both in human and animal cancers, and in pharmacology and toxicology makes it probably one of the most appreciated biological tests in the exploration of liver, biliary and renal function. | [
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PMID:28057 | [Neutral leucinamidasic activity of human serum. Semiautomatic method of analysis]. | Half automated method for determining a L-leucinamide splitting enzymatic activity in human sera. In normal and pathological human sera, two distinct L-leucinamide splitting enzymatic activities have been demonstrated. One of them has an optimal activity at pH 9 (alcaline leucine amidase activity) and shows the most properties of a classic leucinaminopeptidase (E.C. 3.4.11.1). The other (neutral leucine amidase activity) has an optimal activity at pH : 7,5--7,8 and is not activated by Mg2+ ions. In the present work a semi-automated method permitting the determination of the "neutral leucine amidase activity" is presented. The mean of the reference values for normal human sera are established to 31,54 mUI/ml, and the upper normal limit is 48 mUI/ml. The neutral leucine amidase activity is studied in pathological sera comparatively with two other aminopeptidase activities : "alcaline leucine amidase activity", and "leucine-arylamidase". Our study shows that in pathological sera, the neutral leucine amidase activity" varies often without any correlation with those parameters. | [Neutral leucinamidasic activity of human serum. Semiautomatic method of analysis]. Half automated method for determining a L-leucinamide splitting enzymatic activity in human sera. In normal and pathological human sera, two distinct L-leucinamide splitting enzymatic activities have been demonstrated. One of them has an optimal activity at pH 9 (alcaline leucine amidase activity) and shows the most properties of a classic leucinaminopeptidase (E.C. 3.4.11.1). The other (neutral leucine amidase activity) has an optimal activity at pH : 7,5--7,8 and is not activated by Mg2+ ions. In the present work a semi-automated method permitting the determination of the "neutral leucine amidase activity" is presented. The mean of the reference values for normal human sera are established to 31,54 mUI/ml, and the upper normal limit is 48 mUI/ml. The neutral leucine amidase activity is studied in pathological sera comparatively with two other aminopeptidase activities : "alcaline leucine amidase activity", and "leucine-arylamidase". Our study shows that in pathological sera, the neutral leucine amidase activity" varies often without any correlation with those parameters. | [
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PMID:28058 | Safety of therapy for allergic symptoms during pregnancy. | We undertook a literature review to document whether certain therapeutic measures could be considered safe during pregnancy in the allergic patient. With the possible exception of brompheniramine, the commonly used antihistamine drugs appear to be safe during pregnancy. The bronchodilators ephedrine and theophylline also appear to be safe, as does cromolyn. Corticosteroids do not appear to have adverse effects in pregnancy beyond those well recognized in nonpregnant patients. Because side effects are reduced when steroids are administered as aerosols in the nose or lung, these preparations seem well suited for use in pregnancy. The safety of allergic immunotherapy has been confirmed. For asthma, annual influenza vaccination is indicated. | Safety of therapy for allergic symptoms during pregnancy. We undertook a literature review to document whether certain therapeutic measures could be considered safe during pregnancy in the allergic patient. With the possible exception of brompheniramine, the commonly used antihistamine drugs appear to be safe during pregnancy. The bronchodilators ephedrine and theophylline also appear to be safe, as does cromolyn. Corticosteroids do not appear to have adverse effects in pregnancy beyond those well recognized in nonpregnant patients. Because side effects are reduced when steroids are administered as aerosols in the nose or lung, these preparations seem well suited for use in pregnancy. The safety of allergic immunotherapy has been confirmed. For asthma, annual influenza vaccination is indicated. | [
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PMID:28059 | Bilateral central retinal artery occlusions in polyarteritis nodosa. | The third reported case of bilateral central retinal artery occlusion associated with polyarteritis nodosa is presented. An alternative etiology of the frequently observed association of polyarteritis nodosa with optic atrophy is suggested. A plan of therapy is recommended. | Bilateral central retinal artery occlusions in polyarteritis nodosa. The third reported case of bilateral central retinal artery occlusion associated with polyarteritis nodosa is presented. An alternative etiology of the frequently observed association of polyarteritis nodosa with optic atrophy is suggested. A plan of therapy is recommended. | [
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PMID:28061 | beta-Blockers and the eye: an overview. | Some beta-adrenoceptor blocking drugs are exciting new ocular hypotensive compounds. Unlike pilocarpine, the mainstay of glaucoma treatment for the last 100 years, beta-blocking agents do not contract the pupil nor interfere with vision even in patients with central lens opacities. They also do not cause spasm of the ciliary muscle producing transient myopia and disturbance of accommodation. Paradoxically, one of these agents, timolol, causes a fall in intraocular pressure when administered locally even in patients responding to beta-agonists with a reduction in intraocular pressure. Concomitant administration of timolol with epinephrine seems to enhance its ocular hypotensive effect in many patients. The exact mode of action of beta-blockers in reducing intraocular pressure is unknown but appears to primarily reduce aqueous production. This new class of drugs seems destined to play an important role in the treatment as well as in the understanding of glaucoma. | beta-Blockers and the eye: an overview. Some beta-adrenoceptor blocking drugs are exciting new ocular hypotensive compounds. Unlike pilocarpine, the mainstay of glaucoma treatment for the last 100 years, beta-blocking agents do not contract the pupil nor interfere with vision even in patients with central lens opacities. They also do not cause spasm of the ciliary muscle producing transient myopia and disturbance of accommodation. Paradoxically, one of these agents, timolol, causes a fall in intraocular pressure when administered locally even in patients responding to beta-agonists with a reduction in intraocular pressure. Concomitant administration of timolol with epinephrine seems to enhance its ocular hypotensive effect in many patients. The exact mode of action of beta-blockers in reducing intraocular pressure is unknown but appears to primarily reduce aqueous production. This new class of drugs seems destined to play an important role in the treatment as well as in the understanding of glaucoma. | [
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PMID:28065 | Athlete exertion injuries. | Over a period of three years 829 cases of greater than or equal to 16-year-old athlete exertion injuries and syndromes were collected. There were 75 women and 754 men in the series. About 90% of the athletes had been training regularly for more than two years, and 75% of them trained 6 times a week or more. Approximately 52% of the injuries occurred in track and field athletics, about 17% in ball events, 13.6% in skiing, 7.4% in orienteering, and 4.7% in power events. Other sports were associated with fewer exertion injuries. 28.7% of the conditions occurred in the knee, 17% in the ankle, foot and heel, 14.8% in the leg, 8.2% in the back and trunk, 8.1% in the thigh, 7.4% in the achilles tendon. The rest were in the shoulder, neck and upper extremities. In 92% of the patients conservative treatment and rest were used. Only 8% of the cases were treated surgically. | Athlete exertion injuries. Over a period of three years 829 cases of greater than or equal to 16-year-old athlete exertion injuries and syndromes were collected. There were 75 women and 754 men in the series. About 90% of the athletes had been training regularly for more than two years, and 75% of them trained 6 times a week or more. Approximately 52% of the injuries occurred in track and field athletics, about 17% in ball events, 13.6% in skiing, 7.4% in orienteering, and 4.7% in power events. Other sports were associated with fewer exertion injuries. 28.7% of the conditions occurred in the knee, 17% in the ankle, foot and heel, 14.8% in the leg, 8.2% in the back and trunk, 8.1% in the thigh, 7.4% in the achilles tendon. The rest were in the shoulder, neck and upper extremities. In 92% of the patients conservative treatment and rest were used. Only 8% of the cases were treated surgically. | [
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PMID:28066 | A short review of techniques for the localisation of gamma-glutamyl transferase isoenzymes after electrophoresis. | The development of a sensitive method for the localisation of gamma-glutamyl transferase isoenzymes after electrophoresis on various media is described. Recommendations on final conditions are given for optimal concentrations of substrate, acceptor and buffer, and for pH of the reaction mixture. The reaction conditions are compared with other isoenzyme localisation techniques previously reported. | A short review of techniques for the localisation of gamma-glutamyl transferase isoenzymes after electrophoresis. The development of a sensitive method for the localisation of gamma-glutamyl transferase isoenzymes after electrophoresis on various media is described. Recommendations on final conditions are given for optimal concentrations of substrate, acceptor and buffer, and for pH of the reaction mixture. The reaction conditions are compared with other isoenzyme localisation techniques previously reported. | [
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PMID:28067 | Butanol extraction of serum and urinary gamma-glutamyltransferase and its application in clinical diagnosis. | Gamma-glutamyltransferase (gamma-GT) activity was measured in serum and urine before and after extraction with n-butanol. Residual gamma-GT activity after extraction of normal serum with butanol was more than 75%, whereas for normal urine the figure was less than 68%. The loss of activity from urine was not affected by prior dialysis, and the stabilisation which resulted from adding bovine serum albumin at a concentration of 40 g/l did not approach the residual activity with normal serum. In patients with a variety of renal diseases, residual gamma-GT activity in the urine after butanol extraction was inversely correlated with the creatinine clearance. Butanol extraction was performed on serum samples from 182 patients with a variety of diseases. Eighty-one per cent of patients with elevated gamma-GT activities caused by hepatobiliary disease had an increased loss of activity after butanol extraction. By contrast, only 34% of patients with increases gamma-GT activities in whom there was no clinical or other biochemical evidence of hepatic disease, had increased loss of gamma-GT activity after butanol. The reasons for differences between urinary and serum gamma-GT in response to butanol, and the implications in interpreting serum gamma-GT activities are discussed. | Butanol extraction of serum and urinary gamma-glutamyltransferase and its application in clinical diagnosis. Gamma-glutamyltransferase (gamma-GT) activity was measured in serum and urine before and after extraction with n-butanol. Residual gamma-GT activity after extraction of normal serum with butanol was more than 75%, whereas for normal urine the figure was less than 68%. The loss of activity from urine was not affected by prior dialysis, and the stabilisation which resulted from adding bovine serum albumin at a concentration of 40 g/l did not approach the residual activity with normal serum. In patients with a variety of renal diseases, residual gamma-GT activity in the urine after butanol extraction was inversely correlated with the creatinine clearance. Butanol extraction was performed on serum samples from 182 patients with a variety of diseases. Eighty-one per cent of patients with elevated gamma-GT activities caused by hepatobiliary disease had an increased loss of activity after butanol extraction. By contrast, only 34% of patients with increases gamma-GT activities in whom there was no clinical or other biochemical evidence of hepatic disease, had increased loss of gamma-GT activity after butanol. The reasons for differences between urinary and serum gamma-GT in response to butanol, and the implications in interpreting serum gamma-GT activities are discussed. | [
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PMID:28068 | Anomalous behaviour of control sera in automated versions of the Kind and King alkaline phosphatase method. | Differences in alkaline phosphatase activity of some commerical control sera were observed when comparing manual with AutoAnalyzer versions of the Kind and King procedure. This phenomenon was found to be associated with sera boosted with exogenous alkaline phosphatase and to be owing mainly to inadequate provision of buffer in some automated methods. It is suggested that a modification to the SMA procedure may lessen the problem, but the constraints of the system necessitate a compromise. There was better precision after the modification had been introduced. Awareness of this phenomenon is of paramount importance if commerical sera are to be used in any way in the calibration of automated systems for alkaline phosphatase assay. | Anomalous behaviour of control sera in automated versions of the Kind and King alkaline phosphatase method. Differences in alkaline phosphatase activity of some commerical control sera were observed when comparing manual with AutoAnalyzer versions of the Kind and King procedure. This phenomenon was found to be associated with sera boosted with exogenous alkaline phosphatase and to be owing mainly to inadequate provision of buffer in some automated methods. It is suggested that a modification to the SMA procedure may lessen the problem, but the constraints of the system necessitate a compromise. There was better precision after the modification had been introduced. Awareness of this phenomenon is of paramount importance if commerical sera are to be used in any way in the calibration of automated systems for alkaline phosphatase assay. | [
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PMID:28069 | A comparison of two methods of quality control of pH, Pco2, and Po2 measurements. | pH, Pco2, and Po2 measurements have been made over a three-week period on General Diagnostics Blood GAS Control Ampoules and on a tonometered buffer system. The latter seems adequate as a precision and accuracy control of pH, Pco2, and Po2 measurements in a single solution. The former seems adequate as a precision control of these measurements, but, on the particular batch provided, mean values need to be determined within the customer's laboratory. | A comparison of two methods of quality control of pH, Pco2, and Po2 measurements. pH, Pco2, and Po2 measurements have been made over a three-week period on General Diagnostics Blood GAS Control Ampoules and on a tonometered buffer system. The latter seems adequate as a precision and accuracy control of pH, Pco2, and Po2 measurements in a single solution. The former seems adequate as a precision control of these measurements, but, on the particular batch provided, mean values need to be determined within the customer's laboratory. | [
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PMID:28070 | A comparison between metoprolol and pindolol in the treatment of essential hypertension. | The antihypertensive effects on metoprolol and pindolol were compared in 50 patients with essential hypertension belonging to WHO stage 1 or 2. After four weeks of placebo treatment the patients were randomly allocated to treatment with metoprolol or pindolol. During the initial dose-titration period of six weeks the dose was individually adjusted, aiming at a diastolic blood pressure in the seated position less than 95 mm Hg. The maximum possible dosage for metoprolol was 50, 100 and 150 mg b.i.d. and for pindolol 5, 10 and 15 mg b.i.d. Thereafter followed a fixed-dose period of 20 weeks. Six patients did not complete the study. At the end of the study satisfactory blood pressure control, defined as a diastolic blood pressure in the seated position less than 95 mm Hg, was achieved in 15 of the 20 patients (75%) in the metroprolol group and in 13 out of 24 patients (54%) in the pindolol group. The average reduction in diastolic blood pressure was more pronounced with metoprolol than with pindolol, while no difference was found between the two beta-blockers with regard to the reduction of the systolic blood pressure. Generally, metoprolol and pindolol were both well tolerated by the patients. | A comparison between metoprolol and pindolol in the treatment of essential hypertension. The antihypertensive effects on metoprolol and pindolol were compared in 50 patients with essential hypertension belonging to WHO stage 1 or 2. After four weeks of placebo treatment the patients were randomly allocated to treatment with metoprolol or pindolol. During the initial dose-titration period of six weeks the dose was individually adjusted, aiming at a diastolic blood pressure in the seated position less than 95 mm Hg. The maximum possible dosage for metoprolol was 50, 100 and 150 mg b.i.d. and for pindolol 5, 10 and 15 mg b.i.d. Thereafter followed a fixed-dose period of 20 weeks. Six patients did not complete the study. At the end of the study satisfactory blood pressure control, defined as a diastolic blood pressure in the seated position less than 95 mm Hg, was achieved in 15 of the 20 patients (75%) in the metroprolol group and in 13 out of 24 patients (54%) in the pindolol group. The average reduction in diastolic blood pressure was more pronounced with metoprolol than with pindolol, while no difference was found between the two beta-blockers with regard to the reduction of the systolic blood pressure. Generally, metoprolol and pindolol were both well tolerated by the patients. | [
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PMID:28071 | Penbutolol, a new non-selective beta-adrenergic blocking compound in the treatment of hypertension. A comparision with propranolol. | The antihypertensive effect of a new non-selective beta-adrenergic blocking compound, penbutolol (40 mg b.i.d.), was compared with propranolol (160 mg b.i.d.) in a series of 20 hypertensive patients using a double-blind cross-over scheme. Both compounds reduced both the supine and the standing blood pressure significantly. The magnitude of the responses did not differ significantly and both compounds evoked a commensurate decrease in heart rate. No significant side-effects were noted and a series of laboratory tests did not disclose any biochemical changes. | Penbutolol, a new non-selective beta-adrenergic blocking compound in the treatment of hypertension. A comparision with propranolol. The antihypertensive effect of a new non-selective beta-adrenergic blocking compound, penbutolol (40 mg b.i.d.), was compared with propranolol (160 mg b.i.d.) in a series of 20 hypertensive patients using a double-blind cross-over scheme. Both compounds reduced both the supine and the standing blood pressure significantly. The magnitude of the responses did not differ significantly and both compounds evoked a commensurate decrease in heart rate. No significant side-effects were noted and a series of laboratory tests did not disclose any biochemical changes. | [
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PMID:28072 | Response of left ventricular myocardial perfusion and cavity size to beta-blockade by acebutolol. | The effect of beta-blockade by acebutolol on global and regional myocardial perfusion (133Xenon wash-out) was studied in 10 patients with coronary artery disease. Another group of 10 similar patients was used to study the effect of acebutolol on left ventricular cavity size (metal markers--spot film camera). Global perfusion responses roughly paralleled the changes in rate-pressure variable which decreased in 8 patients and increased in 2 who had spontaneous angina pectoris. Regional perfusion decreased more in areas distal to less than 75% stenoses than in those distal to less than 75% stenoses (29 vs 12%; p = 0.10 less than 0.20). Left ventricular asynergy did not modify the response, nor did the presence or absence of collateral vessels. No evidence was found to support the thesis that beta-blockade may evoke a redistribution in perfusion which favours the potentially ischaemic areas of myocardium. Left ventricular cavity size remained unchanged after acebutolol, a cardioselective beta-blocking compound with some degree of agonist activity. | Response of left ventricular myocardial perfusion and cavity size to beta-blockade by acebutolol. The effect of beta-blockade by acebutolol on global and regional myocardial perfusion (133Xenon wash-out) was studied in 10 patients with coronary artery disease. Another group of 10 similar patients was used to study the effect of acebutolol on left ventricular cavity size (metal markers--spot film camera). Global perfusion responses roughly paralleled the changes in rate-pressure variable which decreased in 8 patients and increased in 2 who had spontaneous angina pectoris. Regional perfusion decreased more in areas distal to less than 75% stenoses than in those distal to less than 75% stenoses (29 vs 12%; p = 0.10 less than 0.20). Left ventricular asynergy did not modify the response, nor did the presence or absence of collateral vessels. No evidence was found to support the thesis that beta-blockade may evoke a redistribution in perfusion which favours the potentially ischaemic areas of myocardium. Left ventricular cavity size remained unchanged after acebutolol, a cardioselective beta-blocking compound with some degree of agonist activity. | [
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PMID:28073 | Further characterization of bound measles-specific IgG eluted from SSPE brains. | Tissue residues from 3 SSPE brains extracted at neutral pH were thoroughly washed with phosphate-buffered saline and further extracted at acidic pH. The low-pH extracts had significant measles antibody titers, and their measles-specific IgG content ranged from 40 to 60% of total IgG. Agarose-gel electrophoretic analysis of the extracts showed oligoclonal IgG bands, most of which disappeared after suitable absorption with measles virus, demonstrating the presence of restricted measles antibody population. Ouchterlony analysis showed a reaction of identity between bound IgG and IgG extracted at neutral pH. Thus IgG extracted at low and neutral pHs is remarkably similar. | Further characterization of bound measles-specific IgG eluted from SSPE brains. Tissue residues from 3 SSPE brains extracted at neutral pH were thoroughly washed with phosphate-buffered saline and further extracted at acidic pH. The low-pH extracts had significant measles antibody titers, and their measles-specific IgG content ranged from 40 to 60% of total IgG. Agarose-gel electrophoretic analysis of the extracts showed oligoclonal IgG bands, most of which disappeared after suitable absorption with measles virus, demonstrating the presence of restricted measles antibody population. Ouchterlony analysis showed a reaction of identity between bound IgG and IgG extracted at neutral pH. Thus IgG extracted at low and neutral pHs is remarkably similar. | [
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PMID:28076 | Extracellular accumulation of a new amino acid, O-2-hydroxypropylhomoserine, from 1,2-propanediol by flavobacterium rigense. | During an investigation of microorganisms utilizing petrochemicals, a strain identified as Flavobacterium rigense was found to accumulate a new amino acid in a medium containing 1,2-propanediol as the sole carbon source. Cultural conditions for the accumulation of the product were investigated, and as a result, the yield was increased to 2.8 mg/ml after a 5-day incubation in a medium containing 8% 1,2-propanediol. The pure amino acid was isolated, and its structure was investigated. Elemental analysis and infrared, nuclear magnetic resonance, and mass spectral analyses indicated that the amino acids is O-2-hydroxypropylhomoserine. | Extracellular accumulation of a new amino acid, O-2-hydroxypropylhomoserine, from 1,2-propanediol by flavobacterium rigense. During an investigation of microorganisms utilizing petrochemicals, a strain identified as Flavobacterium rigense was found to accumulate a new amino acid in a medium containing 1,2-propanediol as the sole carbon source. Cultural conditions for the accumulation of the product were investigated, and as a result, the yield was increased to 2.8 mg/ml after a 5-day incubation in a medium containing 8% 1,2-propanediol. The pure amino acid was isolated, and its structure was investigated. Elemental analysis and infrared, nuclear magnetic resonance, and mass spectral analyses indicated that the amino acids is O-2-hydroxypropylhomoserine. | [
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PMID:28077 | Viral aggregation: quantitation and kinetics of the aggregation of poliovirus and reovirus. | The aggregation of poliovirus and reovirus was followed in buffers at various pH values by means of a single particle analysis (SPA) test. The SPA test used here was modified from the original test reported earlier to prevent disaggregation of virus clumps from invalidating the results. The modified SPA test demonstrated that the efficiency of aggregation, which is a measure of the percentage of collisions which are effective in producing an aggregate, may vary widely depending on the conditions in which the virus is placed. The modified SPA test was also used to demonstrate that the kinetic features of viral aggregation follow the classical laws of colloid particle aggregation, which in turn are solely dependent upon diffusion of the particles as caused by brownian motion. | Viral aggregation: quantitation and kinetics of the aggregation of poliovirus and reovirus. The aggregation of poliovirus and reovirus was followed in buffers at various pH values by means of a single particle analysis (SPA) test. The SPA test used here was modified from the original test reported earlier to prevent disaggregation of virus clumps from invalidating the results. The modified SPA test demonstrated that the efficiency of aggregation, which is a measure of the percentage of collisions which are effective in producing an aggregate, may vary widely depending on the conditions in which the virus is placed. The modified SPA test was also used to demonstrate that the kinetic features of viral aggregation follow the classical laws of colloid particle aggregation, which in turn are solely dependent upon diffusion of the particles as caused by brownian motion. | [
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PMID:28078 | Viral aggregation: effects of salts on the aggregation of poliovirus and reovirus at low pH. | As a first step toward the understanding of virus particle interactions in water, we have used the modified single particle analysis test to follow the aggregation of poliovirus and reovirus as induced by low pH in suspensions containing varying amounts of dissolved salts. Salts composed of mono-, di-, and trivalent cations and mono- and divalent anions were tested for their ability to reduce or increase the aggregation of these viruses in relation to that obtained by low pH alone. Mono- and divalent cations in concentrations covering those in natural waters were generally found to cause a decrease in aggregation, with the divalent cations having a much greater effectiveness than the monovalent cations. Trivalent ions (Al3+), in micromolar concentrations, were found to cause aggregation over that at low pH alone. Anions, whether monovalent or divalent, had little ability to produce inhibition of viral aggregation, and thus the overall effects were due almost exclusively to the cation. This was true regardless of whether the overall charge on the virus particle was positive or negative, as determined by the relation between the isoelectric point and the pH at which the tests were carried out. Thus, whereas virus particles conform to classical colloid theory in many respects, there are specific exceptions which must be taken into account in the design of any experiment in which viral aggregation is a factor. | Viral aggregation: effects of salts on the aggregation of poliovirus and reovirus at low pH. As a first step toward the understanding of virus particle interactions in water, we have used the modified single particle analysis test to follow the aggregation of poliovirus and reovirus as induced by low pH in suspensions containing varying amounts of dissolved salts. Salts composed of mono-, di-, and trivalent cations and mono- and divalent anions were tested for their ability to reduce or increase the aggregation of these viruses in relation to that obtained by low pH alone. Mono- and divalent cations in concentrations covering those in natural waters were generally found to cause a decrease in aggregation, with the divalent cations having a much greater effectiveness than the monovalent cations. Trivalent ions (Al3+), in micromolar concentrations, were found to cause aggregation over that at low pH alone. Anions, whether monovalent or divalent, had little ability to produce inhibition of viral aggregation, and thus the overall effects were due almost exclusively to the cation. This was true regardless of whether the overall charge on the virus particle was positive or negative, as determined by the relation between the isoelectric point and the pH at which the tests were carried out. Thus, whereas virus particles conform to classical colloid theory in many respects, there are specific exceptions which must be taken into account in the design of any experiment in which viral aggregation is a factor. | [
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PMID:28079 | Simple method for the isolation of astaxanthin from the basidiomycetous yeast Phaffia rhodozyma. | A method is described for the quantitative and, possibly, large-scale extraction of astaxanthin from the yeast Phaffia rhodozyma. The method utilizes extracellular enzymes produced by the bacterium Bacillus circulans WL-12, which partially digests the yeast cell wall and renders the carotenoid pigments extractable by acetone or ethanol. Complete recovery of astaxanthin from heat-killed P. rhodozyma cells was obtained after growing B. circulans WL-12 on these yeast cells for 26 h and then extracting the yeast-bacterium mixture with acetone. A bacteria-free lytic system, which gave quantitative extraction of astaxanthin from P. rhodozyma, was obtained by concentrating the culture broth from the growth of B. circulans WL-12 on P. rhodozyma cells. Hydrolytic enzyme activities detected in this concentrate included beta-(1 leads to 3)-glucanase, beta-(1 leads to 6)-glucanase, alpha-(1 leads to 3)-glucanase, xylanase, and chitinase. The lytic system was found to work most efficiently at pH 6.5 and with low concentrations of yeast. | Simple method for the isolation of astaxanthin from the basidiomycetous yeast Phaffia rhodozyma. A method is described for the quantitative and, possibly, large-scale extraction of astaxanthin from the yeast Phaffia rhodozyma. The method utilizes extracellular enzymes produced by the bacterium Bacillus circulans WL-12, which partially digests the yeast cell wall and renders the carotenoid pigments extractable by acetone or ethanol. Complete recovery of astaxanthin from heat-killed P. rhodozyma cells was obtained after growing B. circulans WL-12 on these yeast cells for 26 h and then extracting the yeast-bacterium mixture with acetone. A bacteria-free lytic system, which gave quantitative extraction of astaxanthin from P. rhodozyma, was obtained by concentrating the culture broth from the growth of B. circulans WL-12 on P. rhodozyma cells. Hydrolytic enzyme activities detected in this concentrate included beta-(1 leads to 3)-glucanase, beta-(1 leads to 6)-glucanase, alpha-(1 leads to 3)-glucanase, xylanase, and chitinase. The lytic system was found to work most efficiently at pH 6.5 and with low concentrations of yeast. | [
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PMID:28080 | Sulfide oxidation by spheroplasts of Thiobacillus ferrooxidans. | Thiobacillus ferrooxidans is an acidophilic organism important to metal leaching of low-grade ores. The aforementioned importance is related to the ability of the bacterium to oxidize reduced iron and sulfur, principally found in nature as pyrite (FeS2). The present study dealt with sulfide oxidation at low pH values and the involvement of the cell envelope in the process of the inorganic oxidations. Sulfide oxidation was noted in spheroplasts of T. ferrooxidans prepared by enzymatic and chemical treatments and partially purified by differential centrifugation. No enzyme activities were noted in membrane fractions containing enrichments of lipopolysaccharide symbolic of outer membrane material or in membrane vesicles containing (or associated with) higher levels of proteins. Results to date indicate that in an acid milieu the envelope structure containing both the outer membrane and the intact inner cytoplasmic membrane is required for sulfide oxidation. | Sulfide oxidation by spheroplasts of Thiobacillus ferrooxidans. Thiobacillus ferrooxidans is an acidophilic organism important to metal leaching of low-grade ores. The aforementioned importance is related to the ability of the bacterium to oxidize reduced iron and sulfur, principally found in nature as pyrite (FeS2). The present study dealt with sulfide oxidation at low pH values and the involvement of the cell envelope in the process of the inorganic oxidations. Sulfide oxidation was noted in spheroplasts of T. ferrooxidans prepared by enzymatic and chemical treatments and partially purified by differential centrifugation. No enzyme activities were noted in membrane fractions containing enrichments of lipopolysaccharide symbolic of outer membrane material or in membrane vesicles containing (or associated with) higher levels of proteins. Results to date indicate that in an acid milieu the envelope structure containing both the outer membrane and the intact inner cytoplasmic membrane is required for sulfide oxidation. | [
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PMID:28081 | Induction of colonial growth and replica plating of the white rot basidiomycete Phanaerochaete chrysosporium. | A medium containing L-sorbose and sodium deoxycholate was devised which induces colonial growth of Phanaerochaete chrysosporium in the presence of a variety of supplements. The restricted size and heavy conidial production of the colonies permits high plating densities and the use of a replica-plating technique for copying the pattern of colony growth. | Induction of colonial growth and replica plating of the white rot basidiomycete Phanaerochaete chrysosporium. A medium containing L-sorbose and sodium deoxycholate was devised which induces colonial growth of Phanaerochaete chrysosporium in the presence of a variety of supplements. The restricted size and heavy conidial production of the colonies permits high plating densities and the use of a replica-plating technique for copying the pattern of colony growth. | [
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PMID:28094 | Preliminary data on antiserotonin effects of oxatomide, a novel anti-allergic compound. | Oxatomide or R 35443, 1-(3-[4-(diphenylmethyl)-1-piperazinyl]propyl)-1,3-dihydro--2H-benzimidazol-2-one, a compound with potent antihistaminic and anti-anaphylactic activities, shows specific antiserotonin effects on isolated caudal arteries of the rat. In vivo it is a powerful antagonist of bronchospasm induced by serotonin and by histamine; it has no anticholinergic effects and does not affect blood pressure in spontaneously hypertensive rats. These antiserotonin properties of oxatomide may contribute significantly to its anti-allergic activity. | Preliminary data on antiserotonin effects of oxatomide, a novel anti-allergic compound. Oxatomide or R 35443, 1-(3-[4-(diphenylmethyl)-1-piperazinyl]propyl)-1,3-dihydro--2H-benzimidazol-2-one, a compound with potent antihistaminic and anti-anaphylactic activities, shows specific antiserotonin effects on isolated caudal arteries of the rat. In vivo it is a powerful antagonist of bronchospasm induced by serotonin and by histamine; it has no anticholinergic effects and does not affect blood pressure in spontaneously hypertensive rats. These antiserotonin properties of oxatomide may contribute significantly to its anti-allergic activity. | [
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PMID:28095 | Discriminable effects of antihistamine drugs. | Rats were trained to discriminate drug vs. no-drug in a shock-escape T-maze task; a right turn was required when rats were drugged and a left turn when undrugged. The three antihistamine drugs pyrilamine, dimenhydrinate (Dramamine) and diphenhydramine (Benadryl) were discriminated after an average of 20 training sessions indicating that their effects were only moderately discriminable. After criterion performance was achieved under the training conditions, substitution tests were conducted during which rats received a novel drug and were then run in the maze with both goals accessible. Rats trained with antihistamine drugs made drug choices during tests with other antihistamines. Rats trained with other types of drugs made no-drug choices during tests with antihistamines. The results suggest that the antihistamines share a discriminable effect which is relatively unique to that class of drugs. | Discriminable effects of antihistamine drugs. Rats were trained to discriminate drug vs. no-drug in a shock-escape T-maze task; a right turn was required when rats were drugged and a left turn when undrugged. The three antihistamine drugs pyrilamine, dimenhydrinate (Dramamine) and diphenhydramine (Benadryl) were discriminated after an average of 20 training sessions indicating that their effects were only moderately discriminable. After criterion performance was achieved under the training conditions, substitution tests were conducted during which rats received a novel drug and were then run in the maze with both goals accessible. Rats trained with antihistamine drugs made drug choices during tests with other antihistamines. Rats trained with other types of drugs made no-drug choices during tests with antihistamines. The results suggest that the antihistamines share a discriminable effect which is relatively unique to that class of drugs. | [
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PMID:28096 | Clobazam. A 1.5 benzodiazepine derivative: effects upon human psychomotor performance under different levels of task reinforcement. | Two dose levels of clobazam, a benzodiazepine derivative, were compared to placebo for their effects upon psychomotor performance in an acute dose daytime study with normals. An acute dose of 10 mg clobazam significantly reduced response latencies in the low reinforcement condition of a psychomotor performance task but not in the high reinforcement condition. However 20 mg clobazam did not produce any significant changes in performance under either low or high reinforcement. Response speed changes generally correlated positively with trait anziety and neuroticism scores at both doses of clobazam. | Clobazam. A 1.5 benzodiazepine derivative: effects upon human psychomotor performance under different levels of task reinforcement. Two dose levels of clobazam, a benzodiazepine derivative, were compared to placebo for their effects upon psychomotor performance in an acute dose daytime study with normals. An acute dose of 10 mg clobazam significantly reduced response latencies in the low reinforcement condition of a psychomotor performance task but not in the high reinforcement condition. However 20 mg clobazam did not produce any significant changes in performance under either low or high reinforcement. Response speed changes generally correlated positively with trait anziety and neuroticism scores at both doses of clobazam. | [
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PMID:28097 | Studies on the inhibition by beta adrenergic receptor agonists of cyclic AMP phosphodiesterase activity of rat heart. | Isoproterenol (10(-5) and 10(-4)M) inhibited a low affinity but not a high affinity form of rat heart cyclic AMP phosphodiesterase. The concentrations of isoproterenol required to produce inhibition of the isolated enzyme were 10,000 to 100,000 fold larger than those required to produce a positive chronotropic response in the isolated atria. Another beta adrenergic receptor agonist, soterenol, had no effect on any of the isolated forms of the enzyme. Theophylline produced inhibition of low and high affinity forms of phosphodiesterase at the same concentrations required to produce a positive chronotropic response in the isolated atria. Results from two experimental models failed to reveal any circumstances under which a contribution to the positive chronotropic response could result from isoproterenol-induced inhibition of cyclic AMP phosphodiesterase. | Studies on the inhibition by beta adrenergic receptor agonists of cyclic AMP phosphodiesterase activity of rat heart. Isoproterenol (10(-5) and 10(-4)M) inhibited a low affinity but not a high affinity form of rat heart cyclic AMP phosphodiesterase. The concentrations of isoproterenol required to produce inhibition of the isolated enzyme were 10,000 to 100,000 fold larger than those required to produce a positive chronotropic response in the isolated atria. Another beta adrenergic receptor agonist, soterenol, had no effect on any of the isolated forms of the enzyme. Theophylline produced inhibition of low and high affinity forms of phosphodiesterase at the same concentrations required to produce a positive chronotropic response in the isolated atria. Results from two experimental models failed to reveal any circumstances under which a contribution to the positive chronotropic response could result from isoproterenol-induced inhibition of cyclic AMP phosphodiesterase. | [
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PMID:28098 | The role of vanadium in green plants. IV. Influence on the formation of delta-aminolevulinic acid in Chlorella. | In a series of experiments, it is demonstrated that the trace element vanadium (4.10(-7) g-at/1 as NH4VO3) has a considerable positive influence on the synthesis of delta-aminolevulinic acid(delta-ALA) in the autotrophically growing green alga Chlorella pyrenoidosa, the effect being visible by an enhanced output of the amino acid into the culture medium in presence of levulinic acid (LA). The level of intracellularly accumulated delta-ALA, however, is not changed in presence of the metal. The V-effect on exogenous found delta-ALA is suppressed, when LA is added to the nutrient medium at low pH (pH5), although V-uptake into the algal cells is not disturbed by LA. As demonstrated in culture media with various nitrogen sources (urea, partially hydrolized urea, ammonium salts), the development of the pH during the cultivation time is important for the presentation of the V-effect on delta-ALA. It is suggested that vanadium acts as a catalyst in the conversion of 4,5-dioxovaleric acid to delta-ALA by transamination. | The role of vanadium in green plants. IV. Influence on the formation of delta-aminolevulinic acid in Chlorella. In a series of experiments, it is demonstrated that the trace element vanadium (4.10(-7) g-at/1 as NH4VO3) has a considerable positive influence on the synthesis of delta-aminolevulinic acid(delta-ALA) in the autotrophically growing green alga Chlorella pyrenoidosa, the effect being visible by an enhanced output of the amino acid into the culture medium in presence of levulinic acid (LA). The level of intracellularly accumulated delta-ALA, however, is not changed in presence of the metal. The V-effect on exogenous found delta-ALA is suppressed, when LA is added to the nutrient medium at low pH (pH5), although V-uptake into the algal cells is not disturbed by LA. As demonstrated in culture media with various nitrogen sources (urea, partially hydrolized urea, ammonium salts), the development of the pH during the cultivation time is important for the presentation of the V-effect on delta-ALA. It is suggested that vanadium acts as a catalyst in the conversion of 4,5-dioxovaleric acid to delta-ALA by transamination. | [
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PMID:28100 | [Endocrine data in cryptorchism]. | Endocrine evaluation with LH-RH (0.1 mg/m2) and chorionic gonadotrophin (HCG 3 X 1,500 I.U.) in 154 cryptorchid boys aged 1 month to 15 years showed a decrease of LH pituitary secretion and Leydig-cells response to HCG in prepubertal and early pubertal patients. These deficiencies were positively correlated. Partial and at least transient descent of cryptorchid testis or testes has been obtained in 87 of 265 patients treated with HCG (3 to 9 X 1,500 I.U.). Plasma testosterone after HCG 3 X 1,500 I.U. was less increased in patients whose cryptorchid testis or testes descended after 9 X 1,500 I.U. than in those whose testes remained undescended. These data suggest that a partial, early and transient deficiency of pituitary LH secretion may be responsible for testicular maldescent in part of cryptorchid boys. | [Endocrine data in cryptorchism]. Endocrine evaluation with LH-RH (0.1 mg/m2) and chorionic gonadotrophin (HCG 3 X 1,500 I.U.) in 154 cryptorchid boys aged 1 month to 15 years showed a decrease of LH pituitary secretion and Leydig-cells response to HCG in prepubertal and early pubertal patients. These deficiencies were positively correlated. Partial and at least transient descent of cryptorchid testis or testes has been obtained in 87 of 265 patients treated with HCG (3 to 9 X 1,500 I.U.). Plasma testosterone after HCG 3 X 1,500 I.U. was less increased in patients whose cryptorchid testis or testes descended after 9 X 1,500 I.U. than in those whose testes remained undescended. These data suggest that a partial, early and transient deficiency of pituitary LH secretion may be responsible for testicular maldescent in part of cryptorchid boys. | [
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PMID:28102 | Standard and long-acting depot neuroleptics in chronic schizophrenics: an 18-month open multicentric study. | The overall objective of this 18-month open study was to compare standard neuroleptics and long-acting depot neuroleptics following the current psychiatric practice in order to determine the best therapy. Thirty French psychiatrists from 15 different wards participated in this experiment. One hundred eighty-one chronic schizophrenic patients were randomly assigned to receive one of the following three treatments: standard neuroleptics, pipotiazine palmitate, or fluphenazine decanoate. Criteria used for evaluation were an overall clinical evaluation by a psychiatrist, a Brief Psychiatric Rating Scale, and a Nurse's Observation Scale for Inpatient Evaluation. No significant difference (P greater than .05) was observed between the three groups in drug effectiveness or tolerance. | Standard and long-acting depot neuroleptics in chronic schizophrenics: an 18-month open multicentric study. The overall objective of this 18-month open study was to compare standard neuroleptics and long-acting depot neuroleptics following the current psychiatric practice in order to determine the best therapy. Thirty French psychiatrists from 15 different wards participated in this experiment. One hundred eighty-one chronic schizophrenic patients were randomly assigned to receive one of the following three treatments: standard neuroleptics, pipotiazine palmitate, or fluphenazine decanoate. Criteria used for evaluation were an overall clinical evaluation by a psychiatrist, a Brief Psychiatric Rating Scale, and a Nurse's Observation Scale for Inpatient Evaluation. No significant difference (P greater than .05) was observed between the three groups in drug effectiveness or tolerance. | [
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PMID:28103 | Vestibular responses in schizophrenia. | In a study of vestibular responses to caloric stimulation that controlled opportunity for fixation and state of alertness, we evaluated previous findings of diminished nystagmus in schizophrenia. We failed to replicate earlier reports in these respects: (1) None of the psychotic patient groups, when compared with normal controls, showed lower response intensity, latency, or culmination time of the nystagmic response. (2) The schizophrenic groups did not manifest a prevalence of clinically significant asymmetry. We did, however, observe that chronic deteriorated schizophrenics and recent schizophrenics have significantly greater dysrhythmic responses. This diminished orderliness of nystagmus may explain previous reports of absent or diminished nystagmus in the schizophrenics. The results are not compatible with peripheral vestibular disease in schizophrenia, but they may reflect state-related phenomena consistent with disturbances in alertness, which are not necessarily voluntary or motivational in origin. | Vestibular responses in schizophrenia. In a study of vestibular responses to caloric stimulation that controlled opportunity for fixation and state of alertness, we evaluated previous findings of diminished nystagmus in schizophrenia. We failed to replicate earlier reports in these respects: (1) None of the psychotic patient groups, when compared with normal controls, showed lower response intensity, latency, or culmination time of the nystagmic response. (2) The schizophrenic groups did not manifest a prevalence of clinically significant asymmetry. We did, however, observe that chronic deteriorated schizophrenics and recent schizophrenics have significantly greater dysrhythmic responses. This diminished orderliness of nystagmus may explain previous reports of absent or diminished nystagmus in the schizophrenics. The results are not compatible with peripheral vestibular disease in schizophrenia, but they may reflect state-related phenomena consistent with disturbances in alertness, which are not necessarily voluntary or motivational in origin. | [
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PMID:28104 | [Proteolytic activities in mature human placenta. II. Neutral peptidases and PZ-peptidase (author's transl)]. | Continuing our contributions on proteases of human placenta we enriched some unidentified neutral peptidases by chromatographying freeze dried placenta extracts on CM-Sephadex, followed by preparative isoelectric focusing and chromatography on Ultrogel. By this procedure two Acetyl-aminoacyl-p-nitranilidases, three Ala-Ala-p-nitranilidases, one Benzyloxycarbonyl-Ala-Ala-p-nitranilidase, one Carbobenzoxy-Gly-Pro-Arg-p-nitranilidase and one PZ-peptidase could be characterized in greater detail. Here molecular weights, isoelectric points and pH-optima of these enzymes are reported. | [Proteolytic activities in mature human placenta. II. Neutral peptidases and PZ-peptidase (author's transl)]. Continuing our contributions on proteases of human placenta we enriched some unidentified neutral peptidases by chromatographying freeze dried placenta extracts on CM-Sephadex, followed by preparative isoelectric focusing and chromatography on Ultrogel. By this procedure two Acetyl-aminoacyl-p-nitranilidases, three Ala-Ala-p-nitranilidases, one Benzyloxycarbonyl-Ala-Ala-p-nitranilidase, one Carbobenzoxy-Gly-Pro-Arg-p-nitranilidase and one PZ-peptidase could be characterized in greater detail. Here molecular weights, isoelectric points and pH-optima of these enzymes are reported. | [
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PMID:28105 | Concept of paraneurons. | Paraneurons are those cells which have not been designated as neurons but are recognized as closely related to neurons on the basis of their fine structure (possession of neurosecretion-like and synaptic vesicle-like granules/vacuoles), metabolism (production of neurosecretion- and neurotransmitter-like substances) and origin (evidenced or proposed neuroectodermal). Some paraneurons are mainly endocrine in function, while others are sensory. Some should be called interneurons. There are graduations between these types of paraneurons; also a definite boundary between neurons and paraneurons can not be determined. Different types of paraneurons (together with some related neurons) are shown in Figure 1. Comments and discussions were given on the neuron-like characteristics of the individual paraneurons. | Concept of paraneurons. Paraneurons are those cells which have not been designated as neurons but are recognized as closely related to neurons on the basis of their fine structure (possession of neurosecretion-like and synaptic vesicle-like granules/vacuoles), metabolism (production of neurosecretion- and neurotransmitter-like substances) and origin (evidenced or proposed neuroectodermal). Some paraneurons are mainly endocrine in function, while others are sensory. Some should be called interneurons. There are graduations between these types of paraneurons; also a definite boundary between neurons and paraneurons can not be determined. Different types of paraneurons (together with some related neurons) are shown in Figure 1. Comments and discussions were given on the neuron-like characteristics of the individual paraneurons. | [
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PMID:28107 | Neuro-epithelial bodies in the lung of the rat and the mouse. | Histochemical and ultrastructural examinations were performed on neuroepithelial bodies (N. E. B.) in the lung of the mouse and rat. The N. E. B. were identified as specialized groups of pale, columnar cells. They were located throughout the intrapulmonary airway. These cells displayed some special cytochemical properties also seen in the APUD (Amine Precursors Uptake and Decarboxylation) endocrine system, such as cytoplasmic argyrophilia and the capability of selective uptake of amine precursors. Ultrastructrally the N. E. B. were composed of a kind of granulated cell which had concentrations of specific cored vesicles in the basal cytoplasm. It seemed likely that the cells released the contents of the cored vesicles into the extracellular space by exocytosis. These cells made extensive and intimate contact with the mitochondria-rich nerve terminals which occurred mainly at the level of the supranuclear portions of the granulated cells. In this contact area, the membrane of the nerve terminals were apposed to that of the granulated cells with a consistent gap of about 20 nm. Among these membrane appositions, some membrane thickenings were observed in which cored vesicles were closely associated in the granulated cell cytoplasm. From these observations, it was conceived that the lung N. E. B. function both as receptor and endocrine organs and that their specific cored vesicles may have an intimate correlation with these dual functions. | Neuro-epithelial bodies in the lung of the rat and the mouse. Histochemical and ultrastructural examinations were performed on neuroepithelial bodies (N. E. B.) in the lung of the mouse and rat. The N. E. B. were identified as specialized groups of pale, columnar cells. They were located throughout the intrapulmonary airway. These cells displayed some special cytochemical properties also seen in the APUD (Amine Precursors Uptake and Decarboxylation) endocrine system, such as cytoplasmic argyrophilia and the capability of selective uptake of amine precursors. Ultrastructrally the N. E. B. were composed of a kind of granulated cell which had concentrations of specific cored vesicles in the basal cytoplasm. It seemed likely that the cells released the contents of the cored vesicles into the extracellular space by exocytosis. These cells made extensive and intimate contact with the mitochondria-rich nerve terminals which occurred mainly at the level of the supranuclear portions of the granulated cells. In this contact area, the membrane of the nerve terminals were apposed to that of the granulated cells with a consistent gap of about 20 nm. Among these membrane appositions, some membrane thickenings were observed in which cored vesicles were closely associated in the granulated cell cytoplasm. From these observations, it was conceived that the lung N. E. B. function both as receptor and endocrine organs and that their specific cored vesicles may have an intimate correlation with these dual functions. | [
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PMID:28108 | Cimetidine, carbenoxolone sodium, and antacids for the prevention of experimental stress ulcers. | Cimetidine, an H2-receptor, antagonist, and carbenoxolone sodium, a drug used to stimulate gastric mucus synthesis and increase the life span of gastric epithelial cells, were studied to determine their possible prophylactic effect on the formation of stress ulcers, gastric transmucosal potential difference and gastric pH in rats, using a restraint stress model. The number of ulcers substantially decreased in the rat groups receiving either cimetidine or carbenoxolone pretreatment for two or more days before stress. When the drugs were used in combination, there was an additive effect, since there was a significant decrease in ulcer formation even after half a day of pretreatment. When antacids were used, there was also decreased ulcer formation with half a day of pretreatment. Gastric pH was significantly increased from control levels in all the groups treated with antacid, cimetidine and carbenoxolone. Both cimetidine and carbenoxolone, either alone or in combination, prevented the decrease in potential difference that was produced in the untreated stressed rats. This study suggests that either cimetidine or carbenoxolone, and particularly their combination, may be a useful prophylactic regimen for the prevention of stress ulceration in patients subjected to severe stress. | Cimetidine, carbenoxolone sodium, and antacids for the prevention of experimental stress ulcers. Cimetidine, an H2-receptor, antagonist, and carbenoxolone sodium, a drug used to stimulate gastric mucus synthesis and increase the life span of gastric epithelial cells, were studied to determine their possible prophylactic effect on the formation of stress ulcers, gastric transmucosal potential difference and gastric pH in rats, using a restraint stress model. The number of ulcers substantially decreased in the rat groups receiving either cimetidine or carbenoxolone pretreatment for two or more days before stress. When the drugs were used in combination, there was an additive effect, since there was a significant decrease in ulcer formation even after half a day of pretreatment. When antacids were used, there was also decreased ulcer formation with half a day of pretreatment. Gastric pH was significantly increased from control levels in all the groups treated with antacid, cimetidine and carbenoxolone. Both cimetidine and carbenoxolone, either alone or in combination, prevented the decrease in potential difference that was produced in the untreated stressed rats. This study suggests that either cimetidine or carbenoxolone, and particularly their combination, may be a useful prophylactic regimen for the prevention of stress ulceration in patients subjected to severe stress. | [
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PMID:28109 | [The effect of pelleting cereal straw with NaOH-addition on rumen fermentation in cows]. | Experiments with rumen-fistulated dairy cows were performed to study the effect of NaOH-addition to cereal pellets. Compared to straw-concentrate rations in which the straw pellets were free of NaOH, cereal straw pellets containing 2.4 kg NaOH per 100 kg straw caused the rumenal pH to go up from 6.21 to 6.47, the cellulotlytic activity to rise by some 20%, and the passage turnover rate of dry matter to increase from 0,039 to 0,056. The concentrations of volatile fatty acids and the fermentation patterns were not influenced by the NaOH-content of the pellets. It is concluded that NaOH-addition during straw pelleting has a favourable effect on digestion in the bovine rumen. | [The effect of pelleting cereal straw with NaOH-addition on rumen fermentation in cows]. Experiments with rumen-fistulated dairy cows were performed to study the effect of NaOH-addition to cereal pellets. Compared to straw-concentrate rations in which the straw pellets were free of NaOH, cereal straw pellets containing 2.4 kg NaOH per 100 kg straw caused the rumenal pH to go up from 6.21 to 6.47, the cellulotlytic activity to rise by some 20%, and the passage turnover rate of dry matter to increase from 0,039 to 0,056. The concentrations of volatile fatty acids and the fermentation patterns were not influenced by the NaOH-content of the pellets. It is concluded that NaOH-addition during straw pelleting has a favourable effect on digestion in the bovine rumen. | [
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PMID:28110 | [On the toxicology of carbromal. III. Role of active metabolites in humans acutely poisoned with carbromal-containing sedatives (author's transl)]. | Carbromal is metabolized extensively in humans. The major metabolites known to date are bromoethylbutyramide, ethylbutyrylurea and inorganic bromide. After ingestion of a therapeutic dose of 1.0 g carbromal (4.2 mmoles) by four healthy volunteers highest concentrations in serum were found to be for carbromal 30 mumoles/l, for bromoethylbutyramide up to 20 mumoles/l and for ethylbutyrylurea 2--3 mumoles/l. In patients acutely poisoned by carbromal-containing sedatives serum concentrations measured were in the range of 200 mumoles/l carbromal, 350 mumoles/l bromoethylbutyramide and 50 mumoles/l ethylbutyrylurea. These patients were comatose, apneic, had isoelectric encephalographic records and decreased body temperature. The degree of central nervous depression as judged by clinical signs was found to correlate with the serum concentrations of carbromal and of bromoethylbutyramide. Pharmacological activity and acute toxicity of carbromal and its two metabolites were examined in rats and compared with the activity of phenobarbitone. For intraperitoneal injection LD-50 values were found to be for carbromal 1.8 mmoles/kg, for bromoethylbutyramide 1.5 mmoles/kg, for ethylbutyrylurea 5.0 mmoles/kg and for phenobarbitone 0.9 mmoles/kg. Carbromal and bromoethylbutyramide severely decreased body temperature. The relative narcotic activity was estimated to be for carbromal = 100; bromoethylbutyramide = 66; ethylbutyrylurea = 33; phenobarbitone = 100. The anticonvulsive activity against pentetrazol-induced generalized seizures was nearly identical for carbromal, bromoethylbutyramide and phenobarbitone. Anticonvulsant activity of ethylbutyrylurea was two to three times less than that of carbromal. Inorganic bromide was found to increase the narcotic activity of carbromal and of bromoethylbutyramide. The findings show that the clinical signs of central nervous system depression seen in patients acutely poisoned with carbromal are caused mainly by unchanged carbromal and by its metabolite bromoethylbutyramide. | [On the toxicology of carbromal. III. Role of active metabolites in humans acutely poisoned with carbromal-containing sedatives (author's transl)]. Carbromal is metabolized extensively in humans. The major metabolites known to date are bromoethylbutyramide, ethylbutyrylurea and inorganic bromide. After ingestion of a therapeutic dose of 1.0 g carbromal (4.2 mmoles) by four healthy volunteers highest concentrations in serum were found to be for carbromal 30 mumoles/l, for bromoethylbutyramide up to 20 mumoles/l and for ethylbutyrylurea 2--3 mumoles/l. In patients acutely poisoned by carbromal-containing sedatives serum concentrations measured were in the range of 200 mumoles/l carbromal, 350 mumoles/l bromoethylbutyramide and 50 mumoles/l ethylbutyrylurea. These patients were comatose, apneic, had isoelectric encephalographic records and decreased body temperature. The degree of central nervous depression as judged by clinical signs was found to correlate with the serum concentrations of carbromal and of bromoethylbutyramide. Pharmacological activity and acute toxicity of carbromal and its two metabolites were examined in rats and compared with the activity of phenobarbitone. For intraperitoneal injection LD-50 values were found to be for carbromal 1.8 mmoles/kg, for bromoethylbutyramide 1.5 mmoles/kg, for ethylbutyrylurea 5.0 mmoles/kg and for phenobarbitone 0.9 mmoles/kg. Carbromal and bromoethylbutyramide severely decreased body temperature. The relative narcotic activity was estimated to be for carbromal = 100; bromoethylbutyramide = 66; ethylbutyrylurea = 33; phenobarbitone = 100. The anticonvulsive activity against pentetrazol-induced generalized seizures was nearly identical for carbromal, bromoethylbutyramide and phenobarbitone. Anticonvulsant activity of ethylbutyrylurea was two to three times less than that of carbromal. Inorganic bromide was found to increase the narcotic activity of carbromal and of bromoethylbutyramide. The findings show that the clinical signs of central nervous system depression seen in patients acutely poisoned with carbromal are caused mainly by unchanged carbromal and by its metabolite bromoethylbutyramide. | [
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PMID:28111 | Hepatotoxic effect of thioacetamide (TAM) on NADP-linked enzymes, aminotransferases and glutamate dehydrogenase. | NADP-linked dehydrogenases, glucose-6-P dehydrogenase (G 6PDH) 6-P gluconate dehydrogenase (6 PGDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase decarboxylating (ME) and aminotransferases GOT and GPT were analyzed in the soluble fraction of blood free homogenates. Glutmate dehydrogenase (GDH) was assayed in the mitochondrial fraction. TAM was i.p. administered to male albino rats (50 mg/kg/day) for 28 days. enzyme activities were determined as described by Bermeyer 1965 (Methods Enzymatic Analysis. Verlag Chemie. Acad. Press). | Hepatotoxic effect of thioacetamide (TAM) on NADP-linked enzymes, aminotransferases and glutamate dehydrogenase. NADP-linked dehydrogenases, glucose-6-P dehydrogenase (G 6PDH) 6-P gluconate dehydrogenase (6 PGDH), isocitrate dehydrogenase (ICDH), malate dehydrogenase decarboxylating (ME) and aminotransferases GOT and GPT were analyzed in the soluble fraction of blood free homogenates. Glutmate dehydrogenase (GDH) was assayed in the mitochondrial fraction. TAM was i.p. administered to male albino rats (50 mg/kg/day) for 28 days. enzyme activities were determined as described by Bermeyer 1965 (Methods Enzymatic Analysis. Verlag Chemie. Acad. Press). | [
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PMID:28112 | Changes in liver tyrosine aminotransferase after acute and chronic administration of morphine in the rat. | Acute administration of Morphine (20 mg/kg/s.c.) in the rat results in a rise of liver tyrosine aminotransferase (TAT) expressed as mumoles of p-hydroxyphenylpyruvate/100 mg/h. With chronic administration, a tolerance develops to this enzymatic effect. TAT induction is not evident in pregnant rats, given the narcotic, in which enzyme levels are already initially high. After delivery TAT returns to normal levels and it is possible to show both induction and tolerance developing to morphine. Enzyme activity in fetal livers is much lower than that of adult animals: after maternal administration of morphine only a modest TAT increase is seen which is not, however, statistically significant. TAT activity is fully evident in livers of offspring, with much higher mean levels in newborn rats from morphine-treated animals, as a possible consequence of morphine deprivation. In this latter group of newborn rats narcotic administration causes TAT activity to return to levels as high as those of naive animals. On the other hand, morphine administration to the prole of naive rats results in an induction of liver TAT. | Changes in liver tyrosine aminotransferase after acute and chronic administration of morphine in the rat. Acute administration of Morphine (20 mg/kg/s.c.) in the rat results in a rise of liver tyrosine aminotransferase (TAT) expressed as mumoles of p-hydroxyphenylpyruvate/100 mg/h. With chronic administration, a tolerance develops to this enzymatic effect. TAT induction is not evident in pregnant rats, given the narcotic, in which enzyme levels are already initially high. After delivery TAT returns to normal levels and it is possible to show both induction and tolerance developing to morphine. Enzyme activity in fetal livers is much lower than that of adult animals: after maternal administration of morphine only a modest TAT increase is seen which is not, however, statistically significant. TAT activity is fully evident in livers of offspring, with much higher mean levels in newborn rats from morphine-treated animals, as a possible consequence of morphine deprivation. In this latter group of newborn rats narcotic administration causes TAT activity to return to levels as high as those of naive animals. On the other hand, morphine administration to the prole of naive rats results in an induction of liver TAT. | [
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PMID:28113 | [Morphometric and electron microscopic study of the small intestine following total orthotopical auto- and allotransplantation]. | Total orthotopic autotransplantation of the small intestine was performed in 22 dogs, allotransplantation--in 13 dogs. Changes in the wall of the graft resulted from the effect of both nonspecific (ischaemia, blockage of lymph outflow, denervation) and specific factors connected with the reaction of tissue incompatibility. Changes caused by the nonspecific factors are demonstrated as lymphostasis, edema of the wall in the graft, atrophy of the villi with epithelial flattening, hyperplasy of the intestinal gland, macrophagal and plasmocytic reaction in the mucous lamina propria, drop in villous-cryptic coefficient and reduction of the absorbing surface of the villi. At autotransplantation, structural-functional changes in the intestine undergo three stages: the stage of acute morphological changes and pronounced functional disturbances (up to 1,5 months); the stage of relative structural stabilization and gradual functional restoration (up to 6 months); the stage of atrophic-hyperplastic changes in the wall and decrease in functional activity of the intestinal graft (followed-up for 15 months). At allotransplantation, depending on the degree of cellular reaction and vascular changes, as well as on the localization of the process in the wall of the graft, a "graft versus host" reaction and a "recipient versus graft" reaction is demonstrated. Peculiar rosettes of plasmocytes have been described as a possible index of the reaction "graft versus host". | [Morphometric and electron microscopic study of the small intestine following total orthotopical auto- and allotransplantation]. Total orthotopic autotransplantation of the small intestine was performed in 22 dogs, allotransplantation--in 13 dogs. Changes in the wall of the graft resulted from the effect of both nonspecific (ischaemia, blockage of lymph outflow, denervation) and specific factors connected with the reaction of tissue incompatibility. Changes caused by the nonspecific factors are demonstrated as lymphostasis, edema of the wall in the graft, atrophy of the villi with epithelial flattening, hyperplasy of the intestinal gland, macrophagal and plasmocytic reaction in the mucous lamina propria, drop in villous-cryptic coefficient and reduction of the absorbing surface of the villi. At autotransplantation, structural-functional changes in the intestine undergo three stages: the stage of acute morphological changes and pronounced functional disturbances (up to 1,5 months); the stage of relative structural stabilization and gradual functional restoration (up to 6 months); the stage of atrophic-hyperplastic changes in the wall and decrease in functional activity of the intestinal graft (followed-up for 15 months). At allotransplantation, depending on the degree of cellular reaction and vascular changes, as well as on the localization of the process in the wall of the graft, a "graft versus host" reaction and a "recipient versus graft" reaction is demonstrated. Peculiar rosettes of plasmocytes have been described as a possible index of the reaction "graft versus host". | [
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PMID:28114 | [Morphological characteristics of acute respiratory tract diseases of mixed etiology in children]. | The analysis of 30 etiologically deciphered (by the direct Coons method) autopsy observations of acute respiratory diseases in children under 8 is presented. Monoinfections were established only in 6 cases. Morphological examinations of respiratory organs in 24 cases of mixed acute respiratory diseases (associations of virus-bacteria and virus-Mycoplasma pneumoniae-diplostreptococcus) revealed marked circulatory disorders and desquamative, dystrophic, and inflammatory processes in segmental bronchi, bronchioles and alveoles. Morphometric studies demonstrated statistically significant differences in the cell composition of infiltrates of interalveolar septa in monoinfections and associated infections. | [Morphological characteristics of acute respiratory tract diseases of mixed etiology in children]. The analysis of 30 etiologically deciphered (by the direct Coons method) autopsy observations of acute respiratory diseases in children under 8 is presented. Monoinfections were established only in 6 cases. Morphological examinations of respiratory organs in 24 cases of mixed acute respiratory diseases (associations of virus-bacteria and virus-Mycoplasma pneumoniae-diplostreptococcus) revealed marked circulatory disorders and desquamative, dystrophic, and inflammatory processes in segmental bronchi, bronchioles and alveoles. Morphometric studies demonstrated statistically significant differences in the cell composition of infiltrates of interalveolar septa in monoinfections and associated infections. | [
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PMID:28115 | The effect of cryptorchidism on the quantitative histology, histochemistry and hydrolytic enzyme activity of the rat testis. | Cryptorchidism of the mature rat testis led to degeneration of the seminiferous tubules and changes in enzyme patterns and activities. Spermatogenic stages 1-4, containing pachytene primary spermatocytes in late meiotic prophase, and stage 5, containing recently formed round spermatids, were damaged by 48 h. Within 96 h stages showed a loss of germinal cells into the lumen and this was almost complete by 192 h. Acid phosphatase showed increased histochemical activity in the basal area of the seminiferous tubule up to 96 h of cryptorchidism, and at 192 h much of the activity was located in large lipidcontaining bodies within the remaining seminiferous epithelium. Total and free biochemical acid phosphatase decreased during cryptorchidism in parallel with cell loss; there were no significant changes in total cathepsin D activity but free enzyme activity was increased throughout the experimental period indicating increased lability of lysosomes in the Sertoli cell. Lactate dehydrogenase activity was mainly tubular but succinate dehydrogenase also showed interstitial activity. Lipoamide dehydrogenase (NADH) was found mainly in the interstitium. During cryptorchidism both lactate and succinate dehydrogenase activity decreased in the tubules parallel to the loss of germinal cells, whereas lipoamide dehydrogenase (NADH) activity increased in both interstitial and tubular areas. It is suggested that the initial lesion in the seminiferous epithelium, produced by cryptorchidism is in the Sertoli cell and that germ cell damage may result from reduced function of the Sertoli cell. | The effect of cryptorchidism on the quantitative histology, histochemistry and hydrolytic enzyme activity of the rat testis. Cryptorchidism of the mature rat testis led to degeneration of the seminiferous tubules and changes in enzyme patterns and activities. Spermatogenic stages 1-4, containing pachytene primary spermatocytes in late meiotic prophase, and stage 5, containing recently formed round spermatids, were damaged by 48 h. Within 96 h stages showed a loss of germinal cells into the lumen and this was almost complete by 192 h. Acid phosphatase showed increased histochemical activity in the basal area of the seminiferous tubule up to 96 h of cryptorchidism, and at 192 h much of the activity was located in large lipidcontaining bodies within the remaining seminiferous epithelium. Total and free biochemical acid phosphatase decreased during cryptorchidism in parallel with cell loss; there were no significant changes in total cathepsin D activity but free enzyme activity was increased throughout the experimental period indicating increased lability of lysosomes in the Sertoli cell. Lactate dehydrogenase activity was mainly tubular but succinate dehydrogenase also showed interstitial activity. Lipoamide dehydrogenase (NADH) was found mainly in the interstitium. During cryptorchidism both lactate and succinate dehydrogenase activity decreased in the tubules parallel to the loss of germinal cells, whereas lipoamide dehydrogenase (NADH) activity increased in both interstitial and tubular areas. It is suggested that the initial lesion in the seminiferous epithelium, produced by cryptorchidism is in the Sertoli cell and that germ cell damage may result from reduced function of the Sertoli cell. | [
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PMID:28118 | Rudimentary locus of Drosophila melanogaster: partial purification of a carbamylphosphate synthase--aspartate transcarbamylase--dihydroorotase complex. | Glutamine-dependent CPSase, ATCase, and DHOase from Drosophila, the first three enzymes in pyrimidine biosynthesis, show coordinate variation in activity throughout development. The three activities were highest in first instar larvae and decreased as development proceeded. The three activities cosediment in sucrose gradients as a single peak with a relative sedimentation coefficient of approximately 30S. CPSase, ATCase, and DHOase copurify during (NH4)2SO4 fractionation and during DEAE-cellulose and hydroxylapatite chromatography. | Rudimentary locus of Drosophila melanogaster: partial purification of a carbamylphosphate synthase--aspartate transcarbamylase--dihydroorotase complex. Glutamine-dependent CPSase, ATCase, and DHOase from Drosophila, the first three enzymes in pyrimidine biosynthesis, show coordinate variation in activity throughout development. The three activities were highest in first instar larvae and decreased as development proceeded. The three activities cosediment in sucrose gradients as a single peak with a relative sedimentation coefficient of approximately 30S. CPSase, ATCase, and DHOase copurify during (NH4)2SO4 fractionation and during DEAE-cellulose and hydroxylapatite chromatography. | [
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PMID:28119 | Genetics and physiological expression of beta-hydroxy acid dehydrogenase in Drosophila. | A mutant Hadnl was induced in Drosophila melanogaster and found to be deficient in beta-hydroxy acid dehydrogenase. This mutation was utilized to study the genetics and physiological expression of Had+ . Had+ was mapped to the X chromosome at 54.4 and seems to be the structural gene for the enzyme. Enzyme activity in male and female flies indicates that the gene shows both dosage compensation independent from dose effect and differential activity during ontogeny. Electrophoretic mobility data indicate that the enzyme is a dimer which forms by random association of subunits. The fact that the mutant shows no detrimental effect implies that the enzyme is dispensable, at least under laboratory conditions. The biological and technical implications of this gene--enzyme system are discussed. | Genetics and physiological expression of beta-hydroxy acid dehydrogenase in Drosophila. A mutant Hadnl was induced in Drosophila melanogaster and found to be deficient in beta-hydroxy acid dehydrogenase. This mutation was utilized to study the genetics and physiological expression of Had+ . Had+ was mapped to the X chromosome at 54.4 and seems to be the structural gene for the enzyme. Enzyme activity in male and female flies indicates that the gene shows both dosage compensation independent from dose effect and differential activity during ontogeny. Electrophoretic mobility data indicate that the enzyme is a dimer which forms by random association of subunits. The fact that the mutant shows no detrimental effect implies that the enzyme is dispensable, at least under laboratory conditions. The biological and technical implications of this gene--enzyme system are discussed. | [
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PMID:28133 | Pharmacokinetics of fazadinium in man. | The disposition of fazadinium was studied in 10 patients with normal hepatic and renal function undergoing abdominal surgery. The serum and urinary concentrations were determined fluorimetrically. A single dose of fazadinium 1.5 mg kg-1 was administered i.v. The plasma decay curve for fazadinium was found to be diphasic and the data were interpreted according to a two-compartment open model. The half-lives of the distribution and elimination phases were 12.3 and 76.4 min respectively. The total apparent volume of distribution averaged 234 ml kg-1 and the plasma clearance 132 ml min-1. From these results it is suggested that fazadinium should have a shorter duration of action than other non-depolarizing agents because of the more rapid decline of the serum concentration corresponding mainly to the short half-life of the beta phase. This rapid elimination phase of fazadinium did not correspond to an extensive biotransformation because fazadinium was excreted almost unchanged in the urine and this excretion accounted for 50% of the injected dose within 24 h. | Pharmacokinetics of fazadinium in man. The disposition of fazadinium was studied in 10 patients with normal hepatic and renal function undergoing abdominal surgery. The serum and urinary concentrations were determined fluorimetrically. A single dose of fazadinium 1.5 mg kg-1 was administered i.v. The plasma decay curve for fazadinium was found to be diphasic and the data were interpreted according to a two-compartment open model. The half-lives of the distribution and elimination phases were 12.3 and 76.4 min respectively. The total apparent volume of distribution averaged 234 ml kg-1 and the plasma clearance 132 ml min-1. From these results it is suggested that fazadinium should have a shorter duration of action than other non-depolarizing agents because of the more rapid decline of the serum concentration corresponding mainly to the short half-life of the beta phase. This rapid elimination phase of fazadinium did not correspond to an extensive biotransformation because fazadinium was excreted almost unchanged in the urine and this excretion accounted for 50% of the injected dose within 24 h. | [
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PMID:28128 | Pharmacokinetics of sulphamethoxazole in man: effects of urinary pH and urine flow on metabolism and renal excretion of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole. | A high performance liquid chromatography method for the determination of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole is described. The renal excretion rate and cumulative renal excretion of sulphamethoxazole is markedly influenced by urinary pH. With constant urinary pH, the renal excretion rate and the renal clearance of sulphamethoxazole is dependent on the urine flow. The renal clearance of the metabolite N4-acetylsulphamethoxazole is not influenced by urinary pH or urine flow. No clear acetylator phenotype could be detected in the group of volunteers studied. The extent of acetylation depends on the amount of sulphamethoxazole available for acetylation, thus indirectly on the urine pH and flow. | Pharmacokinetics of sulphamethoxazole in man: effects of urinary pH and urine flow on metabolism and renal excretion of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole. A high performance liquid chromatography method for the determination of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole is described. The renal excretion rate and cumulative renal excretion of sulphamethoxazole is markedly influenced by urinary pH. With constant urinary pH, the renal excretion rate and the renal clearance of sulphamethoxazole is dependent on the urine flow. The renal clearance of the metabolite N4-acetylsulphamethoxazole is not influenced by urinary pH or urine flow. No clear acetylator phenotype could be detected in the group of volunteers studied. The extent of acetylation depends on the amount of sulphamethoxazole available for acetylation, thus indirectly on the urine pH and flow. | [
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PMID:28134 | The use of chlorazepate for premedication on the night before surgery. | Chlorazepate, a long-acting benzodiazepine, allayed anxiety before operation, being superior to placebo in a double-blind study in which the drug was given the night before surgery. Long-term relief of apprehension before surgery by the administration of chlorazepate, combined with a narcotic analgesic when indicated, is advocated. | The use of chlorazepate for premedication on the night before surgery. Chlorazepate, a long-acting benzodiazepine, allayed anxiety before operation, being superior to placebo in a double-blind study in which the drug was given the night before surgery. Long-term relief of apprehension before surgery by the administration of chlorazepate, combined with a narcotic analgesic when indicated, is advocated. | [
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PMID:28135 | Comparative peripheral and coronary haemodynamic effects of rimiterol and isoprenaline. | 1. Rimiterol and isoprenaline produced significant dose-related increases in cardiac output. 2. These changes in cardiac output were accompanied by increases in heart rate and myocardial oxygen consumption which were similar for each drug and dose-related. 3. Isoprenaline in contrast with rimiterol produced direct coronary vasodilation, i.e. coronary vasodilation in excess of that required to meet increases in myocardial oxygen demands. 4. It is suggested that the beta-adrenergic receptors in the human coronary vasculature are mainly of the beta1 type. 5. Rimiterol, because it does not produce direct coronary vasodilation may be preferable to isoprenaline in the treatment of low-cardiac output syndrome where there is regional myocardial ischaemia, since it would be less likely to produce a "coronary steal" effect. | Comparative peripheral and coronary haemodynamic effects of rimiterol and isoprenaline. 1. Rimiterol and isoprenaline produced significant dose-related increases in cardiac output. 2. These changes in cardiac output were accompanied by increases in heart rate and myocardial oxygen consumption which were similar for each drug and dose-related. 3. Isoprenaline in contrast with rimiterol produced direct coronary vasodilation, i.e. coronary vasodilation in excess of that required to meet increases in myocardial oxygen demands. 4. It is suggested that the beta-adrenergic receptors in the human coronary vasculature are mainly of the beta1 type. 5. Rimiterol, because it does not produce direct coronary vasodilation may be preferable to isoprenaline in the treatment of low-cardiac output syndrome where there is regional myocardial ischaemia, since it would be less likely to produce a "coronary steal" effect. | [
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PMID:28142 | 13C nuclear magnetic resonance study of the cis-trans isomerism in X-Pro-Pro tripeptides. | 13C nuclear magnetic resonance has been used to characterize quantitatively the cis-trans isomerism about both peptide bonds in the tripeptides Ser-Pro-Pro and Arg-Pro-Pro. Detailed pH titration data indicate that the configuration about both peptide bonds is closely linked to titration of the terminal carboxyl group and, to a lesser extent, to titration of the terminal amino group. The Pro2 C-3 resonance has been found particularly useful for interpretation due to its sensitivity to the isomerization about both peptide bonds. Analysis of the probabilities of the trans-trans, cic-cis, cis-trans, and trans-cis isomers in aqueous solution indicates a stability decrease in the order given. Similarities in the isomerization behavior of the two peptides indicate that side chain interactions involving the first residue have very little effect on the observed cis/trans ratios. The sensitivity of the cis/trans ratio to titration of the terminal amino group is most readily explained on the basis of an indirect effect on carbonyl-carbonyl repulsion. | 13C nuclear magnetic resonance study of the cis-trans isomerism in X-Pro-Pro tripeptides. 13C nuclear magnetic resonance has been used to characterize quantitatively the cis-trans isomerism about both peptide bonds in the tripeptides Ser-Pro-Pro and Arg-Pro-Pro. Detailed pH titration data indicate that the configuration about both peptide bonds is closely linked to titration of the terminal carboxyl group and, to a lesser extent, to titration of the terminal amino group. The Pro2 C-3 resonance has been found particularly useful for interpretation due to its sensitivity to the isomerization about both peptide bonds. Analysis of the probabilities of the trans-trans, cic-cis, cis-trans, and trans-cis isomers in aqueous solution indicates a stability decrease in the order given. Similarities in the isomerization behavior of the two peptides indicate that side chain interactions involving the first residue have very little effect on the observed cis/trans ratios. The sensitivity of the cis/trans ratio to titration of the terminal amino group is most readily explained on the basis of an indirect effect on carbonyl-carbonyl repulsion. | [
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PMID:28146 | Enzymatic basis for the Ca2+-induced cross-linking of membrane proteins in intact human erythrocytes. | The accumulation of Ca2+ ions in intact human erythrocytes leads to the production of membrane protein polymers larger than spectrin. The polymer has a heterogeneous size distribution and is rich in gamma-glutamyl-epsilon-lysine cross-links. Isolation of this isodipeptide, in amounts as high as 6 mol/10(5) g of protein, confirms the idea [Lorand L., Weissmann, L.B., Epel, D.L., and Bruner-Lorand, J. (1976), Proc. Natl. Acad. Sci. U.S.A. 73, 4479] that the Ca2+-induced membrane protein polymerization is mediated by transglutaminase. Formation of the polymer in the intact cells is inhibited by the addition of small, water-soluble primary amines. Inasmuch as these amines are known to prevent the Ca2+-dependent loss of deformability of the membrane, it is suggested that transglutaminase-catalyzed cross-linking may be a biochemical cause of irreversible membrane stiffening. | Enzymatic basis for the Ca2+-induced cross-linking of membrane proteins in intact human erythrocytes. The accumulation of Ca2+ ions in intact human erythrocytes leads to the production of membrane protein polymers larger than spectrin. The polymer has a heterogeneous size distribution and is rich in gamma-glutamyl-epsilon-lysine cross-links. Isolation of this isodipeptide, in amounts as high as 6 mol/10(5) g of protein, confirms the idea [Lorand L., Weissmann, L.B., Epel, D.L., and Bruner-Lorand, J. (1976), Proc. Natl. Acad. Sci. U.S.A. 73, 4479] that the Ca2+-induced membrane protein polymerization is mediated by transglutaminase. Formation of the polymer in the intact cells is inhibited by the addition of small, water-soluble primary amines. Inasmuch as these amines are known to prevent the Ca2+-dependent loss of deformability of the membrane, it is suggested that transglutaminase-catalyzed cross-linking may be a biochemical cause of irreversible membrane stiffening. | [
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PMID:28148 | Effects of substituents on the rates of deacylation of substituted benzoyl papains. Role of a carboxylate residue in the catalytic mechanism. | The effect of ring substituents on the rates of deacylation of 8 meta- and para-substituted benzoyl papains was evaluated. The rate constants were found to depend upon a single ionizing group of pKa = 4.2--4.3, and to decrease by a factor of approximately 2.2 when measured in 94% D2O/H2O. The rates of deacylation are increased greatly by electron-withdrawing groups on the benzene ring. The Hammett rho value is 2.74 +/- 0.32. A plot of the rate constants for deacylation of the benzoyl papains against the corresponding constants for substituted benzoyl chymotrypsins generates a straight line of slope 1.0. This result suggests a very similar distribution of charge on the benzoyl moiety in the transition state for the two enzymes, which is interpreted in terms of the net charge of the transition state for the deacylation of nonspecific acyl papains being equal to--1 with the general base catalyzed assistance to the attack of water on the acyl enzyme being provided by the negatively charged Asp-158 rather than by the neutral Asn-175-His-159 hydrogen bond network. This result together with a survey of literature data suggests that the role of Asp-158 in papain catalysis has been underestimated. The evidence advanced to date in support of the proposition that an imidazolium-159-cysteine-25 thiolate ion pair exists in native papain is evaluated and considered to be insufficient to decide the issue. | Effects of substituents on the rates of deacylation of substituted benzoyl papains. Role of a carboxylate residue in the catalytic mechanism. The effect of ring substituents on the rates of deacylation of 8 meta- and para-substituted benzoyl papains was evaluated. The rate constants were found to depend upon a single ionizing group of pKa = 4.2--4.3, and to decrease by a factor of approximately 2.2 when measured in 94% D2O/H2O. The rates of deacylation are increased greatly by electron-withdrawing groups on the benzene ring. The Hammett rho value is 2.74 +/- 0.32. A plot of the rate constants for deacylation of the benzoyl papains against the corresponding constants for substituted benzoyl chymotrypsins generates a straight line of slope 1.0. This result suggests a very similar distribution of charge on the benzoyl moiety in the transition state for the two enzymes, which is interpreted in terms of the net charge of the transition state for the deacylation of nonspecific acyl papains being equal to--1 with the general base catalyzed assistance to the attack of water on the acyl enzyme being provided by the negatively charged Asp-158 rather than by the neutral Asn-175-His-159 hydrogen bond network. This result together with a survey of literature data suggests that the role of Asp-158 in papain catalysis has been underestimated. The evidence advanced to date in support of the proposition that an imidazolium-159-cysteine-25 thiolate ion pair exists in native papain is evaluated and considered to be insufficient to decide the issue. | [
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PMID:28149 | The status of tyrosyl residues in a Formosan cobra cardiotoxin. | Spectrophotometric titration of Formosan cobra cardiotoxin showed that two of the three tyrosyl residues were titrated freely with a normal apparent pKa of 9.6 whereas the remaining one ionized at pH above 11.0. Nitration of cardiotoxin in Tris . HCl buffer with tetranitromethane resulted in the selective nitration of tyrosine 11 and tyrosine 22. It also revealed that tyrosine 51 was the abnormal one in the spectrophotometric titration. Complete nitration occurred in the presence of 6.0 M guanidine hydrochloride. Compared with the conformation of native cardiotoxin, the peptide conformation of the partially nitrated cardiotoxin did not change significantly but the conformation of the completely nitrated cardiotoxin changed remarkably. The biological activity of cardiotoxin was indeed affected by nitration, but the immunological activity was nearly intact even when all the tyrosine residues were nitrated. | The status of tyrosyl residues in a Formosan cobra cardiotoxin. Spectrophotometric titration of Formosan cobra cardiotoxin showed that two of the three tyrosyl residues were titrated freely with a normal apparent pKa of 9.6 whereas the remaining one ionized at pH above 11.0. Nitration of cardiotoxin in Tris . HCl buffer with tetranitromethane resulted in the selective nitration of tyrosine 11 and tyrosine 22. It also revealed that tyrosine 51 was the abnormal one in the spectrophotometric titration. Complete nitration occurred in the presence of 6.0 M guanidine hydrochloride. Compared with the conformation of native cardiotoxin, the peptide conformation of the partially nitrated cardiotoxin did not change significantly but the conformation of the completely nitrated cardiotoxin changed remarkably. The biological activity of cardiotoxin was indeed affected by nitration, but the immunological activity was nearly intact even when all the tyrosine residues were nitrated. | [
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PMID:28150 | Spectroscopic studies on the tyrosine residues of canavalin. | Canavalin is a tetramer with 6 tyrosines per subunit. In the work presented here, we have classified these tyrosines by their spectrophotometric and fluorometric pH titration and their ability to be quenched I-. Of the 6 residues, 2 were found to be exposed to the solvent. One (pK = 10.2) contributes 28% of the total fluorescence intensity; the second has a pK of 11.50, and a lower quantum yield, contributing only 16% of the total intensity. The remaining 4 residues (pK = 12.5, contributing 54% of fluorescence intensity) are buried; their titration is irreversible, requiring protein denaturation. | Spectroscopic studies on the tyrosine residues of canavalin. Canavalin is a tetramer with 6 tyrosines per subunit. In the work presented here, we have classified these tyrosines by their spectrophotometric and fluorometric pH titration and their ability to be quenched I-. Of the 6 residues, 2 were found to be exposed to the solvent. One (pK = 10.2) contributes 28% of the total fluorescence intensity; the second has a pK of 11.50, and a lower quantum yield, contributing only 16% of the total intensity. The remaining 4 residues (pK = 12.5, contributing 54% of fluorescence intensity) are buried; their titration is irreversible, requiring protein denaturation. | [
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PMID:28152 | Proton NMR studies on soya bean lipoxygenase-1. | The 270 MHz 1H-NMR spectrum of soya bean lipoxygenase-1 (linoleate: oxygen oxidoreductase, EC 1.13.11.12) was investigated at 298 K and at several pH values. A large fraction of the protein (50%) was found to be effectively random coil. | Proton NMR studies on soya bean lipoxygenase-1. The 270 MHz 1H-NMR spectrum of soya bean lipoxygenase-1 (linoleate: oxygen oxidoreductase, EC 1.13.11.12) was investigated at 298 K and at several pH values. A large fraction of the protein (50%) was found to be effectively random coil. | [
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PMID:28153 | [Role of the electron acceptor properties of lysozyme and its substrate inhibitors in photosensitized electron transport in their complexes by the EPR method]. | The nature of electron-acceptor groups in the system of lysozyme with its substrate-inhibitors has been studied in a wide range of pH values by the method of photosensitized electron transfer. In the lysozyme molecule disulphide bonds and peptide groups are the electron--acceptor groups. The nature of radicals in irradiated lysozyme depends on pH. At complex-formation of lysozyme with oligomeres of N-acetylglucosamine the electron transfer from the enzyme molecule to N-acetyl group of the substrate-inhibitor molecule is realized. Under conditions ruling out complex-formation of lysozyme with the inhibitors (N-acetylglucosamine and its dimer) the electrons are localized on disulphide bonds of the protein molecules at alkaline pH and at pH less than or equal to 3 the radicals are observed which are due to the remove of hydrogen atom from the Calpha-atom of the protein polypeptide chain. | [Role of the electron acceptor properties of lysozyme and its substrate inhibitors in photosensitized electron transport in their complexes by the EPR method]. The nature of electron-acceptor groups in the system of lysozyme with its substrate-inhibitors has been studied in a wide range of pH values by the method of photosensitized electron transfer. In the lysozyme molecule disulphide bonds and peptide groups are the electron--acceptor groups. The nature of radicals in irradiated lysozyme depends on pH. At complex-formation of lysozyme with oligomeres of N-acetylglucosamine the electron transfer from the enzyme molecule to N-acetyl group of the substrate-inhibitor molecule is realized. Under conditions ruling out complex-formation of lysozyme with the inhibitors (N-acetylglucosamine and its dimer) the electrons are localized on disulphide bonds of the protein molecules at alkaline pH and at pH less than or equal to 3 the radicals are observed which are due to the remove of hydrogen atom from the Calpha-atom of the protein polypeptide chain. | [
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PMID:28158 | Sympathetic and parasympathetic control of heart rate in unanaesthetized fetal and newborn lambs. | Development of autonomic nervous control of basal heart rate was studied in unanesthetized fetal lambs (93 days to term) and newborn lambs (2--29 days), using atropine and/or propranolol blockade. Fetal lambs showed a progressive increase in parasympathetic restraint of heart rate; vagal influence in the newborn lamb was similar to the term fetus. Sympathetic stimulation of fetal heart rate declined toward term, possibly due to the strongly increasing parasympathetic influence. Sympathetic influence in the newborn was similar to the early-gestation fetus. Intrinsic heart rate was about 185 beats/min throughout the fetal and newborn life span studied. Thus changes in basal heart rate resulted from a different balance of the sympathetic and parasympathetic components of the autonomic nervous outflow. | Sympathetic and parasympathetic control of heart rate in unanaesthetized fetal and newborn lambs. Development of autonomic nervous control of basal heart rate was studied in unanesthetized fetal lambs (93 days to term) and newborn lambs (2--29 days), using atropine and/or propranolol blockade. Fetal lambs showed a progressive increase in parasympathetic restraint of heart rate; vagal influence in the newborn lamb was similar to the term fetus. Sympathetic stimulation of fetal heart rate declined toward term, possibly due to the strongly increasing parasympathetic influence. Sympathetic influence in the newborn was similar to the early-gestation fetus. Intrinsic heart rate was about 185 beats/min throughout the fetal and newborn life span studied. Thus changes in basal heart rate resulted from a different balance of the sympathetic and parasympathetic components of the autonomic nervous outflow. | [
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PMID:28154 | [Structural changes in cell nuclei in the physiologic pH range]. | Fluorescence of the suspension of cell nuclei from rat liver was investigated under neutral pH range. The pH decrease from 7 to 5 causes the quenching of protein fluorescence of nuclei and leads to an increase of the polarization degree of the fluorescence. Buffering properties of the nuclei in this range were detected. The use of 1-anilino-8-naphthalenesulfonate as the fluorescent probe permits to find the changes of nuclei surface properties with increasing the proton concentration in the solution. Circular dichroism spectra of nuclei were shown to depend on the pH solution too. It was suggested that structure state of the nuclei depends on the pH solution. The structural changes are reversible in the physiological pH range and were concluded to be in the envelope and chromatin of the nuclei. The role of histidine residues of nuclear proteins in the initiation of the structure changes was discussed. It was supposed that structure changes of the nuclei in the physiological pH range have an essential functional role. | [Structural changes in cell nuclei in the physiologic pH range]. Fluorescence of the suspension of cell nuclei from rat liver was investigated under neutral pH range. The pH decrease from 7 to 5 causes the quenching of protein fluorescence of nuclei and leads to an increase of the polarization degree of the fluorescence. Buffering properties of the nuclei in this range were detected. The use of 1-anilino-8-naphthalenesulfonate as the fluorescent probe permits to find the changes of nuclei surface properties with increasing the proton concentration in the solution. Circular dichroism spectra of nuclei were shown to depend on the pH solution too. It was suggested that structure state of the nuclei depends on the pH solution. The structural changes are reversible in the physiological pH range and were concluded to be in the envelope and chromatin of the nuclei. The role of histidine residues of nuclear proteins in the initiation of the structure changes was discussed. It was supposed that structure changes of the nuclei in the physiological pH range have an essential functional role. | [
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PMID:28159 | Fundamental aspects of antimony thin film electrodes for pH measurement. | This report concerns the investigation of the sensitivity, temperature dependence, accuracy, and the standard electrode potential EO of an antimony thin film pH electrode which was prepared with electron beam evaporation techniques. The air-formed oxide film on antimony thin film electrodes has been proved by both the cathodic reduction method and electron spectroscopy for chemical analysis (ESCA). The antimony thin film electrode responded rapidly to pH changes and its sensitivity was slightly changed depending on the buffer composition. The accuracy of this electrode was compared with that of the glass electrode. Temperature had some influence on the function of this electrode. The standard electrode potential of this electrode was discussed together with that of other forms of antimony electrodes. The structure and thickness of the surface oxide on antimony thin film electrodes was confirmed by cathodic reduction and ESCA. It was clear that the surface oxide governs the electrode reactions. Possible applications of the antimony thin film electrode are discussed stating some limitations in the use. | Fundamental aspects of antimony thin film electrodes for pH measurement. This report concerns the investigation of the sensitivity, temperature dependence, accuracy, and the standard electrode potential EO of an antimony thin film pH electrode which was prepared with electron beam evaporation techniques. The air-formed oxide film on antimony thin film electrodes has been proved by both the cathodic reduction method and electron spectroscopy for chemical analysis (ESCA). The antimony thin film electrode responded rapidly to pH changes and its sensitivity was slightly changed depending on the buffer composition. The accuracy of this electrode was compared with that of the glass electrode. Temperature had some influence on the function of this electrode. The standard electrode potential of this electrode was discussed together with that of other forms of antimony electrodes. The structure and thickness of the surface oxide on antimony thin film electrodes was confirmed by cathodic reduction and ESCA. It was clear that the surface oxide governs the electrode reactions. Possible applications of the antimony thin film electrode are discussed stating some limitations in the use. | [
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] |
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