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Relationship between use of diuretics and continence status in the elderly. Although diuretics have been implicated as a cause of urinary incontinence, no evidence has been presented prior to this report to confirm such a relationship. Our epidemiologic survey of 1,956 respondents sixty years of age and older in Washtenaw County, Michigan, revealed 24.6 percent of men and 36.9 percent of women were current users of a diuretic medication. Comparisons between users and non-users of diuretics and continence and incontinence status revealed no significant difference in the prevalence of incontinence in either gender. However, when male respondents who had cystometric examinations were analyzed, it was found that diuretic users who have uninhibited detrusor contractions (UDC) had a significantly higher prevalence of urinary incontinence (85.7%) when compared with non-users with UDC (25%) (p = 0.009). Among men who did not have UDC, use or non-use of diuretics showed a similar relationship but did not reach statistical significance (p = 0.085). There were too few female respondents with UDC to make meaningful analysis in this group. | 18 |
The syndrome of alcoholic ketoacidosis. To further elucidate the clinical spectrum of alcoholic ketoacidosis (AKA). A case series of 74 patients with AKA defined as a wide anion gap metabolic acidosis unexplained by any other disorder or toxin, including any patient with a history of chronic alcohol abuse. The setting was the Medical Emergency Department at Grady Memorial Hospital in Atlanta, Georgia, a university-affiliated inner-city hospital. AKA is a common disorder in the emergency department, more common than previously thought. The acid-base abnormalities are more diverse than just a wide-gap metabolic acidosis and often include a concomitant metabolic alkalosis, hyperchloremic acidosis, or respiratory alkalosis. Lactic acidosis is also common. Semiquantitative serum acetoacetate levels were positive in 96% of patients. Elevated blood alcohol levels were present in two thirds of patients in whom alcohol levels were determined, and levels consistent with intoxication were seen in 40% of these patients. Electrolyte disorders including hyponatremia, hypokalemia, hypophosphatemia, hyperglycemia, hypocalcemia, and hypomagnesemia were common on presentation. The most common symptoms were nausea, vomiting, and abdominal pain. The most common physical findings were tachycardia, tachypnea, and abdominal tenderness. Altered mental status, fever, hypothermia, or other abnormal findings were uncommon and reflected other underlying processes. AKA is a common disorder in chronic malnourished alcoholic persons. The acid-base abnormalities reflect not only the ketoacidosis, but also associated extracellular fluid volume depletion, alcohol withdrawal, pain, sepsis, or severe liver disease. Although the pathophysiology is complex, the syndrome is rapidly reversible and has a low mortality. | 15 |
Measurement of immunoreactive gastrin in gastric mucosa. A method for measurement of gastrin in gastric mucosa has been developed, and distribution of gastrin in the stomach of pig, dog, cat, rabbit, and man was examined. Measurable amounts of gastrin were found in corpus of all species, but the content in the antrum was considerably higher. The highest concentration of gastrin was seen in man. The borderline between corpus and antrum was abrupt, and in both parts of the stomach gastrin was evenly distributed. In 44 patients with duodenal ulcer the antral gastrin concentration was 21.3 mug eqv. per g mucosa, in 15 patients with prepyloric ulcer 23.0, in 10 patients with gastric ulcer 5.9, and in 16 patients with gastric carcinoma 7.9. The control group consisted of 10 healthy volunteers and 12 patients with minor abdominal complaints. Mean antral gastrin concentrations were 28.1 and 20.7 respectively. No significant relationship was observed between PAO and gastrin content of antral mucosa in any group. | 10 |
The visual perception of accelerated motion. The present research is an investigation of how changes in the rate of motion are percieved. Five separate experiments were performed with the use of filmed stimulus material and a variety of response measures, including both categorical judgments and reporduction techniques. It was found that (a) the smaller the ratio of terminal to initial velocity, the less frequent the judgments of acceleration or deceleration, (b) deceleration was significantly easier to perceive than acceleration, (c) the perception of acceleration was facilitated when the velocity of a lead-in segment was the same as the velocity at onset of motion, (d) a short tunnel centered in the motion path facilitated the perception of acceleration and deceleration, and (e) instantaneous changes in velocity were much more easily perceived than gradual changes. A one-event model for the perception of motion change in which there is a continuous interplay between earlier, later, and interpolated motion segments is favored over a two-event model in which earlier and later segments of velocity are compared. | 23 |
Conventional and color Doppler transvaginal sonography in gynecologic infertility. Current clinical applications. TVS affords accurate follicular monitoring and guidance for follicular aspiration. The role of TVS in assessing the adequacy of the endometrium is still undergoing investigation. Our studies suggest that there is a statistically significant difference in the pregnancy rate when the endometrium has a multilayered appearance. Infertility patients who successfully achieve pregnancy should be monitored with TVS because of a higher incidence of ectopic pregnancy, anembryonic gestation, and spontaneous abortion. TVS has a secondary role in evaluating certain uterine malformations and tubal disorders. With TV-CDS it is also possible to evaluate physiologic parameters such as adnexal and uterine blood flow. The role of TV-CDS in the anatomic and physiologic evaluation of early pregnancy is now being established. | 15 |
Kinetics of conformational changes in tRNA Phe (yeast) as studied by the fluorescence of the Y-base and of formycin substituted for the 3'-terminal adenine. The kinetics of the melting transitions of tRNA Phe (yeast) were followed by the fluorescence of the Y-base and of formycin substituted for the 3'-terminal adenine. As judged from differential UV absorbance melting curves the formycin label had virtually no influence on the conformation of the tRNA. A temperature jump apparatus was modified to allow the simultaneous observation of transmission and fluorescence intensities by two independent optical channels. The design of a temperature jump cell with an all quartz center piece is given. The cell is resistant to temperatures up to 90 degrees C; it provides high optical sensitivity, low stray light intensity and the possibility of measuring fluorescence polarization. The T-jump experiments allowed to discriminate between fast unspecific fluorescence quenching (r less than 5 musec) and slow cooperative conformational changes. In the central part of the temperature range of UV-melting (midpoint temperature 30 degrees C in 0.01 M Na+ and 39 degrees C in 0.03 M Na+, pH 6.8) two resolvable relaxation processes were observed. The corresponding relaxation times were 20 msec and 800 msec at 30 degrees C in 0.01 M Na+, and 4 msec and 120 msec at 39 degrees C in 0.03 M Na+. The Y-base fluorescence shows both of the relaxation effects, which almost cancel in equilibrium fluorescence melting, because their amplitudes have opposite signs. From this finding the existence of some residual tertiary structure is inferred which persists after the unfolding of the main part of tertiary structure during early melting (midpoint temperature 24 degrees C in 0.03 M Na+). In the fluorescence signal of the formycin also the two relaxation effects appear. Both of them are connected with a decrease of the fluorescence intensity. From the results a coupled opening of the anticodon and acceptor branches is concluded. | 16 |
Immunofluorescence localization of an adducin-like protein in the chromosomes of mouse oocytes. The mouse oocyte expresses a polypeptide of Mr 120,000 that cross-reacts with an antibody to the brain membrane skeletal protein adducin. Immunofluorescence localization showed a bright chromosomal staining reaction in metaphase I and metaphase II oocytes. Following in vitro fertilization the maternal chromosomes lost their immunoreactivity during pronuclear development. The fertilizing sperm chromatin and male pronucleus did not show any detectable staining reaction. Bright chromosomal fluorescence was again observed in the first mitotic metaphase when both maternal and paternal chromosomes gave a positive staining reaction. In contrast to the immunoreactivity of the maternal meiotic chromosomes, the meiotic chromosomes of male germ line cells failed to exhibit any detectable staining reaction and this difference was confirmed by immunolabeling of oocyte and spermatocyte karyotypes. Mitotic chromosomes in preimplantation embryos, fetal liver, adult intestinal epithelium, and MDCK cells also failed to show any detectable labeling reaction. The results suggest that expression of the immunoreactive chromosomal adducin may be a unique feature of oogenesis. | 17 |
Biosynthesis of oligosaccharide-lipid in Streptococcus sanguis. An oligosaccharide-lipid containing N-acetyl d-glucosamine (GlcNAc), l-rhamnose, and d-glucose was synthesized when the particulate enzyme from Streptococcus sanguis was incubated with UDP-GlcNAc, TDP-rhamnose, and UDP-glucose. The incorporation of d-glucose into the lipid was dependent on the preincorporation of l-rhamnose, which in turn was dependent on that of GlcNAc. This indicates that the order of sugar incorporation is GlcNAc, l-rhamnose, and d-glucose. The synthesis of GlcNAc-lipid was stimulated twofold by ATP and was inhibited strongly by UDP and slightly by UMP, CDP, and TDP, but not by all other nucleoside diphosphates and nucleoside monophosphates tested. A [gamma-(32)P]ATP labeling experiment indicated that some acceptor lipid was present in nonphosphorylated form. The acid and alkaline stabilities of the GlcNAc-lipid were similar to those of glycosyl undecaprenylphosphate, and the thin-layer chromatographic mobility of the lipid was slightly faster than that of the mannosylphosphorylundecaprenol. The molar ratio of phosphate to GlcNAc in purified GlcNAc-lipid was found to be 0.96:1. These results suggested that the GlcNAc was attached to the lipid moiety, presumably undecaprenol, by phosphodiester bonds. The incorporation of l-rhamnose into the lipid was inhibited by UDP and UMP, respectively, in a manner similar to the incorporation of GlcNAc. This suggested that the oligosaccharide was also linked to the lipid moiety by phosphodiester bonds. | 15 |
A review of the pharmacology of selegiline. Selegiline (1-deprenyl) is an irreversible inhibitor of monoamine oxidase (MAO) type B. Because in the human brain, dopamine is metabolised mainly by MAO-B, selegiline increases dopamine content in the central nervous system. Besides the inhibition of MAO-B, selegiline also inhibits the uptake of dopamine and noradrenaline into presynaptic nerve and increases the turnover of dopamine. Thanks to these properties, selegiline significantly potentiates the pharmacological effects of levodopa. These favourable characteristics have been applied in the treatment of Parkinson's disease using selegiline both with levodopa and alone. Unlike earlier MAO-inhibitors, selegiline does not potentiate the hypertensive effects of tyramine. This is due to the selectivity to MAO-B, leaving intestinal MAO-A intact, and also due to the fact that selegiline inhibits the uptake of tyramine into neurons. Selegiline can prevent the parkinsonism caused by MPTP in animals; similar findings have been reported with other toxins like 6-OHDA and DSP-4, that destroys noradrenergic nuclei. Furthermore, selegiline reduces oxidative stress caused by degradation of dopamine and increases free radical elimination by enhancing superoxide dismutase and catalase activity. These findings may be important when considering the possible neuroprotective effects of selegiline. Besides the basic pharmacology also the interactions and pharmacokinetics of selegiline are reviewed in this article. | 16 |
Ketopantoic acid and ketopantoyl lactone reductases. Stereospecificity of transfer of hydrogen from reduced nicotinamide adenine dinucleotide phosphate. The stereospecificity of hydrogen transfer from NADPH to the appropriate carbonyl substrate catalyzed by ketopantoic acid and ketopantoyl acid and ketopantoyl lactone reductases of yeast (Saccharomyces cerevisiae) and Escherichia coli has been determined. Yeast and E. coli ketopantoic acid reductases are B-specific enzymes which transfer hydrogen from [4B-3H]-NADPH to ketopantoic acid to form [3H]pantoic acid. In contrast to the usual observations on the stereospecificity of functionally similar dehydrogenases from different species, yeast and E. coli ketopantoyl lactone reductases exhibit opposite stereospecificities. Both of two forms of yeast ketopantoyl lactone reductases are A-specific enzymes which form [3H]pantoyl lactone from ketopantoyl lactone and [4A-3H]NADPH, whereas, two forms of E. coli ketopantoyl lactone reductases are B-specific enzymes. | 19 |
Major histocompatibility complex independent T cell receptor-antigen interaction: functional analysis using fluorescein derivatives. We have isolated T cell receptor (TCR) cDNAs from fluorescein (FL)-specific human T cell clones (alpha FL beta FL), and transferred them to TCR beta- Jurkat cells in order to study direct FL-binding to the TCR. Using either FL-conjugated polymers (FL-polymer) or FL-substituted Sepharose beads, we are able to demonstrate the direct binding of antigen to the T cell surface, and the functional activation of the T cell transfectants. We present evidence against the involvement of major histocompatibility complex (MHC) molecules or antigen presentation in the interaction of FL with the alpha FL beta FL transfectants. Additionally, we have examined the effect of ring substitutions on the FL molecule as well as specific alterations of substituents attached to the 5' position, and we have found that all of them interfere with the functional recognition of the alpha FL beta FL TCR. These experiments demonstrate that TCRs like antibodies have intrinsic affinities for antigen, even without the involvement of MHC molecules. | 20 |
Postischemic stunning--the case for calcium as the ultimate culprit. Two phases of the stunning phenomenon are proposed. The first causative phase occurs almost immediately with reperfusion and is thought to be associated with cytosolic calcium overload and an apparently normal or nearly normal mechanical function. Agents enhancing calcium influx, if introduced at this stage, may worsen subsequent stunning, whereas those inhibiting calcium influx may lessen the extent of subsequent stunning. The second phase, true stunning, is associated with established hypocontractility and responds favorably to agents enhancing calcium influx, whereas calcium antagonists further impair mechanical function when given at this stage. These patterns, derived from data obtained on isolated rat-heart studies, cannot directly be extrapolated to the large animal heart, such as that of the dog, where the presence of added circulating leukocytes may confound the issue and explain the apparently contradictory benefit of the late administration of calcium antagonists. The harmful effects of free radicals are not discounted but could be explained, at least in part, by multiple membrane damage, with a consequent rise of cytosolic calcium during the reperfusion period. | 18 |
The characteristics of early diagnostic hypotheses generated by physicians (experts) and students (novices) at one medical school. How hypotheses generated at the outset of a physician-patient encounter influence the physician's diagnostic reasoning has received relatively little attention in the literature. Yet, this activity modulates the efficiency and accuracy of the diagnostic process. The authors proposed the theory that physicians (experts) would generate less specific initial diagnostic hypotheses than would students (novices). In 1988 and 1989, the hypotheses generated by 32 practicing physicians and 39 third-year medical students at one medical school were analyzed for number, specificity, and breadth (i.e., range) of diagnoses, and for differences between those generated by the physicians and by the students. The hypotheses were formulated on the basis of the initially available data--chief complaint and its duration, and basic demographic descriptions--from patients in three clinical scenarios. Compared with the physicians, the students generated significantly more hypotheses and significantly more specific hypotheses. There was no significant difference between the groups in the breadths of the hypotheses they selected, that is, the numbers of broad categories of diagnosis covered by individuals' hypotheses. | 19 |
Influence of temperature and gas atmosphere on in-vitro fertilization and embryo development in domestic cats. The influence of culture temperature and gas atmosphere on in-vitro fertilization and embryo development was examined in the domestic cat. In Exp. 1, eggs were fertilized and cultured in 5% CO2 in air at 37, 38 or 39 degrees C. Experiment 2 evaluated the effects of 5% CO2 in air; 5% CO2, 5% O2 and 90% N2; and 10% CO2 in air. Fertilization (cleavage) and development to the morula/blastocyst stage were not influenced (P greater than 0.05) by variations in temperature and gas composition. Despite changing these culture conditions, egg cleavage averaged approximately 75% and greater than 80% of the 2-cell embryos proceeded to morulae in vitro. However, the partial in-vitro morula-to-blastocyst developmental block normally observed in this species was not removed. | 14 |
Experimental renal osteodystrophy. The response to 25-hydroxycholecalciferol and dicholomethylene diphosphate therapy. Bone mineral and matrix maturation in chronically uremic, nonacidotic rats were investigated after 25-hydroxcholecalciferol (25OHD) and/or dichloromethylene diphosphonate (C12MDP) therapy utilizing bromoform-toluene density gradient fractionation and X-ray diffraction analyses. The bromoform-toluene density gradient analyses demonstrated that the progressive accumulation of less dense, more immature bone characteristic of progressive uremia was reversed by 25OHD and/or C12MDP therapy for a 2-wk period, and that after 4 wk of therapy the maturational profile of bones from chronically uremic animals treated with 250HD and/or C12MDP was comparable to that from nonuremic littermates. X-ray diffraction analysis revealed that by the 4th wk of therapy with 25OHD and C12MDP both the degree of crystallinity and the crystal size/perfection parameters in the uremic bones were comparable to those of nonuremic, pair-fed control littermates. Treatment for 4 wk with 25OHD resulted in enlarged and/or more perfect apatite crystallites, while C12MDP alone slightly inhibited crystal growth and/or perfection after 2 wk of treatment. Soft tissue calcification was diminished in uremic animals treated for 4 wk with C12MDP or a combined C2MDP/25OHD regimen, the latter being much more effective in this regard. The accumulated data in this study support the premise that the attendant accelerated bone resorption, soft tissue calcification, and abnormal mineralization and maturation of the skeletal tissue, well documented to characterize experimental ranal insufficiency, may be alleviated with therapeutic dosages of 25OHD and/or C12MDP. | 23 |
Fully synthetic immunogens. Part III. Synthesis of hinge-peptide/gastrin conjugates and their immunological properties. As core molecule for the multiple attachment of antigenic peptides we have selected the human IgG1 hinge fragment 225-232/225'-232'. Two types of conjugates of this double-chain bis-cystinyl hinge-peptide were prepared i) by linking its C-termini to [NIe15]-human-little-gastrin-[2,17] and ii) by elongating the resulting hinge-peptide/[NIe15]-little-gastrin-[2-17] conjugate at the two N-termini with the human big-gastrin sequence 1-14 to produce the big-gastrin-[1-14]/hinge-peptide/little-gastrin-[2-17] conjugate. For the synthesis of these peptide structures both the route via the preformed double-chain bis-cystinyl peptide and the route via suitably protected monomeric bis-cysteinyl peptides were used. For the latter approach advantage was taken of the previous observation about the preferred oxidation of the bis-cysteinyl hinge-peptide 225-232 to the dimer in parallel alignment. Both synthetic routes led to identical products. Immunization experiments in guinea pigs with the synthetic hybrids led to surprisingly strong immune responses with anti-little-gastrin antibody titers comparable to those induced by the iso-1-cytochrome c/little-gastrin-[2-17] conjugate as carrier-hapten system. These findings show that the two gastrin constructs are fully competent immunogens. Additionally, the gastrin receptor-like specificity of the antibodies indicates that both the synthetic hybrids and the cytochrome c conjugate allow for expression of a little-gastrin-specific conformational epitope similar to the bioactive structure of this hormone. The usefulness of such synthetic hybrids is further confirmed by the observation that the bivalent immunogen, containing both the little-gastrin 2-17 and the big-gastrin 1-14 sequence, is capable of inducing an immune response against both antigenic sequences, although with different efficiency. These results fully confirm our expectations. | 16 |
Uterine artery blood flow studies in the pregnant monkey. Studies were performed in anesthetized monkeys in the third trimester of pregnancy, with continuous monitoring of maternal blood pressure and uterine artery blood flow by electromagnetic flow probe and with measurement of prostaglandin levels in uterine vein samples. Acute elevation of the systemic blood pressure by intravenous infusion of angiotensin II was associated with increased uterine artery blood flow and an increase in the levels of prostaglandin E measured in the uterine vein. An increase in PGE levels was also observed following the discontinuation of the angiotensin II infusion, when blood pressure and uterine artery blood flow returned to baseline levels. Intravenous administration of indomethacin was associated with a slight rise in maternal blood pressure. The changes in uterine artery blood flow following indomethacin treatment were variable, perhaps reflecting the stresses of surgery and anesthesia. In single experiments, intravenous diazoxide produced a profound hypotension, and intravenous furosemide induced a prompt and marked diuresis, associated with a very marked fall in uterine artery blood flow. | 20 |
[Frontobasal injuries and csf fistulas. Attempt at an anatomoclinical classification. Therapeutic incidence]. The authors present a classification of trauma to the cranial base, based on observation in 80 cases. There are five types. Type I : involves only the anterior wall of the frontal sinus. Type II : involves the face (craniofacial disjunction of the Lefort II type or crush face) and extend upward to the cranial base and, in occurency, to the anterior wall of the frontal sinus, because of the facial retrusion. Type III : ivolves frontal part of the skull and extend down to the cranial base. Type IV : is a combination of types II and III. Type V : involves only ethmoidal or sphenoidal bones. Cerebrospinal fluid leak is unfrequent in types II, and transitionnal, if it occurs ; but it often occurs in types III, IV and V which include in every case a dural tear. Correct diagnosis facilitates treatment. Fractures of types I and II can be fully treated by maxillo-facial surgeons, whereas for types III, IV, and V, they need the help of a neuro-surgeon. | 8 |
Different response of cellular DNA content to cardiac hypertrophy in human and rat heart myocytes. 1. Rat and human heart myocytes adapt to overload-induced hypertrophy differently. 2. Human myocyte nuclei respond with polyploidization and multinucleation, thus increasing the DNA content per myocyte from 20 to 40 pg. As a result, nuclear DNA content per 10,000 microns3 of cell volume decreases from 12 to 10 pg. 3. In rat hearts with aortic constriction nuclear DNA content remains constant (13 pg), and the DNA content per 10,000 microns3 of myocyte volume falls from 9 to 6 pg. 4. We hypothesize that "dilution" of nuclear DNA in the hypertrophied rat heart myocyte limits the capacity to hypertrophy (much less than 100%). 5. The human heart myocyte, which is able to compensate for dilution of nuclear DNA, may increase in size more than three-fold. 6. The lower limit of DNA content per unit of myocyte volume is 6 pg/10,000 microns3 in both species. | 7 |
The chromosomal order of genes controlling the major histocompatibility complex, properdin factor B, and deficiency of the second component of complement. The relationship of the genes coding for HLA to those coding for properdin Factor B allotypes and for deficiency of the second component of complement (C2) was studied in families of patients with connective tissue disorders. Patients were selected because they were heterozygous or homozygous for C2 deficiency. 12 families with 15 matings informative for C2 deficiency were found. Of 57 informative meioses, two crossovers were noted between the C2 deficiency gene and the HLA-B gene, with a recombinant fraction of 0.035. A lod score of 13 was calculated for linkage between C2 deficiency and HLA-B at a maximum likelihood value of the recombinant fraction of 0.04. 18 families with 21 informative matings for both properdin Factor B allotype and HLA-B were found. Of 72 informative meioses, three recombinants were found, giving a recombinant fraction of 0.042. A lod score of 16 between HLA-B and Factor B allotypes was calculated at a maximum likelihood value of the recombinant fraction of 0.04. A crossover was shown to have occurred between genes for Factor B and HLA-D, in which HLA-D segregared with HLA-A and B. These studies suggest that the genes for Factor B and C2 deficiency are located outside those for HLA, that the order of genese is HLA-A, -B, -D, Factor B allotype, C2 deficiency, that the genes coding for C2 deficiency and Factor B allotypes are approximately 3--5 centimorgans from the HLA-A and HLA-B loci, and that the apparent lack of recombinants between the Factor B gene and C2 deficiency gene suggests that these two genes lie in close proximity to one another. | 16 |
Two distinct sequences control the targeting and anchoring of the mouse P450 1A1 into the yeast endoplasmic reticulum membrane. We previously expressed mouse P450 1A1 in the yeast S. cerevisiae. In the present study, I describe experiments in which several deletions in the 5' end of the corresponding cDNA were created. The truncated forms were then expressed in yeast cells. Studies of microsomes obtained from transformed yeast show that the signal-sequence is not required in vivo for the integration of mouse P450 1A1 into the endoplasmic reticulum membrane. In addition, the cytochrome deleted for its hydrophobic signal-sequence appears to be enzymatically functional. These results strongly argue for the existence of a second determinant of membrane targeting and binding. | 13 |
[Electroencephalographic and cardiovascular effects of milnaciplan hydrochloride (TN-912), a novel antidepressant]. The electroencephalographic (EEG) and cardiovascular effects of milnaciplan hydrochloride (TN-912) were compared with those of imipramine (IMP) and maprotiline (MPT) in rats, guinea pigs and dogs. In conscious rats with chronic electrode implants, TN-912 (10-100 mg/kg, p.o.) had little effect on either the EEG activity or the EEG arousal response to auditory stimulation (2000 Hz). Both IMP (10-100 mg/kg, p.o.) and MPT (10-100 mg/kg, p.o.) tended to increase the drowsy EEG pattern period in the cortical and hippocampal EEG and inhibited the EEG arousal response to auditory stimulation. In conscious rats with a chronic arterial catheter, TN-912 (100 mg/kg, p.o.) slightly elevated the mean blood pressure (MBP) and decreased the heart rate (HR), while both IMP (10-100 mg/kg, p.o.) and MPT (10-100 mg/kg, p.o.) dose-dependently increased MBP and HR. In anesthetized dogs, i.v. injection of TN-912 (1-10 mg/kg), IMP (0.3-10 mg/kg) and MPT (1-20 mg/kg) produced a dose-dependent fall in MBP. IMP and MPT but not TN-912 dose-dependently increased HR. TN-912 did not show typical effects on femoral blood flow. TN-912 (30 mg/kg) had little effect on lead II electrocardiogram (ECG), while IMP and MPT markedly increased height of the T-wave on ECG. In the in vitro study with the isolated guinea pig atrium, TN-912 caused a slight positive inotropic and negative chronotropic effect, while both IMP and MPT showed marked negative inotropic and chronotropic actions. These results suggest that TN-912 has less EEG effect and cardiac toxicity, indicating that TN-912 may be safe in clinical use. | 10 |
[The distribution of various type of oncogenes products in the tumor tissue of malignant mesothelioma]. The distribution of various oncogenes in the tumor tissues of 8 cases of malignant mesothelioma related to asbestos exposure was evaluated by monoclonal antibodies against oncogenes. There was no staining for K-ras, H-ras and erb-B in all cases and C-abl slightly stained in only one case of a biphasic type of tumor. On the other hand, C-myc positively stained in epithelioid type and the epitheloidal portion of the biphasic type of tumors. C-neu, C-fos and N-myc positively stained in almost all cases. Of these 9 oncogenes, C-neu was most frequently stained in all cases. These results suggest that C-myc, N-myc, C-neu and C-fos oncogenes may have some role in the appearance of malignant mesothelioma related to asbestos exposure. | 14 |
[Antibacterial activity of rifampicin against the causative agents of suppurative, septic diseases]. The antibacterial activity of rifampicin was studied in comparison with other antibiotics with respect to clinical strains isolated from cases with various purulent inflammatory processes caused by Staphylococcus, E. coli, Ps. aeruginose, Proteus. The aim of the study was to define the role of rifampicin in the treatment of the above infections. No rifampicin resistant strains were found among staphylococci belonging to the phenotype carrying the determinants of resistance to 2-8 antibiotics. Rifampicin was less active against gramnegative organisms. High heterogeneity of the microbial population of rifampicin was shown with respect to all microbial strains tested. The rate of the spontaneous mutants was high. The average rate of the mutants was 1-7.7-10-8. The studies on the dynamics of the rifampicin resistance increase in the strains of Staphylococci, E. Coli, Ps. aeruginosa and Proteus showed that the resistance increased after 1-2 passages, which means that one-stage mutation was characteristic rifampicin. | 13 |
Quantitative magnetic resonance imaging and studies of degenerative diseases of the developing human brain. The Rett syndrome is a progressive disorder which is associated with regression of psychomotor development and precipitous deceleration of brain growth during the first year of life. General histopathological surveys in postmortem specimens have identified degeneration of subpopulations of neurons of the nigrostriatal system but no other evidence of degenerative process. Magnetic resonance imaging-based morphometry may usefully guide application of rigorous but demanding quantitative histologic search for evidence of neuronal degeneration. The volumes of the principal set of cortical and nuclear structures of principal interest in the disorder may be measured by currently available MRI-based methods. Optimized levels of precision now allow detection of volumetric changes over time in the same brain of approximately 10% at the 95% confidence level. | 19 |
Prolonged indomethacin therapy for the prevention of recurrences of patent ductus arteriosus. We tested the hypothesis that prolonged maintenance indomethacin therapy would allow more effective closure of patent ductus arteriosus (PDA) and thereby decrease the recurrence rate. Thirty-nine low birthweight neonates (less than 1500 gm) with confirmed PDA were randomly assigned in a double-blind fashion to receive standard indomethacin therapy (three doses), followed either by maintenance indomethacin therapy (0.2 mg/kg/day) for 5 days or by an equivalent volume of placebo for 5 days. Of the 20 infants who received maintenance indomethacin therapy, two (10%) required additional therapy and one of these required surgical ligation. Of the 19 infants who received only the first three indomethacin doses, nine (47%) required additional therapy for PDA (p less than 0.05) and seven of these had a ligation (p less than 0.05). We conclude that maintenance indomethacin therapy, in comparison with short-term indomethacin therapy, decreases the incidence of surgical PDA ligations, eliminates most PDA recurrences, and does not increase toxic effects of indomethacin in the low birth weight infant with PDA. | 21 |
Interferon-related cortical blindness. The term cortical blindness indicates loss of sight due to bilateral lesions in the occipital lobes. It is a rare but severe side effect produced by chemotherapeutic agents. Cortical blindness was diagnosed in a 75-year-old man who had been treated with alpha-interferon for metastatic renal-cell carcinoma. The absence of focal neurological signs and of abnormal findings as determined by two repeated computed tomography (CT) scans of the brain, which excluded structural damage to the occipital lobes, suggest that metabolic or toxic reactions may have caused the cortical blindness diagnosed in our patient. The temporal relationship between the treatment with alpha-interferon and the development of cortical blindness indicates that this substance may have been the causative agent for this phenomenon. | 15 |
Rapid vascular clearance of two strains of Junin virus in Calomys musculinus: selective macrophage clearance. Clearance of Junin (JUN) virus strains with different virulence for Calomys musculinus (Cm) was followed using the Candid #1 virulent and CbaFHA 5069 attenuated strains. In addition, virulent virus albino mice (AM) were included as control host and Venezuelan equine encephalitis (VEE-VI) virus as control virus. The virus inoculum (Vo) and the blood samples (Vt) obtained at different times post-inoculation (p.i.) were titrated on Vero cells and the cleared plaque forming-units (PFU) were calculated as the log Vt/Vo. In Cm both JUN virus strains were cleared rapidly (within 5 min the Candid #1 strain and within 10 min the CbaFHA 5069 strain); meanwhile, VEE-VI virus could be recovered from blood until 30 min p. i. Furthermore, JUN and VEE-VI viruses showed the same behaviour in Am as in Cm. We conclude that the JUN virus strains of different virulence for Cm did not show differences in their clearance from the blood of these animals. Moreover, the rapid clearance observed was independent of the animal host and viral dose. | 13 |
Laboratory model of membranous glomerulonephritis in rats induced by pronase-digested homologous renal tubular epithelial antigen. The laboratory counterpart of tubular antigen-mediated membranous glomerulonephritis in humans was produced in rats by a single injection of homologous nephritogenic tubular antigen with adjuvant. The rat developed membranous glomerulonephritis with typical clinicopathologic features of human nephritis mediated by the tubular antigen, i.e., massive proteinuria and diffuse thickening of glomerular basement membranes due to deposition of tubular antigen-antibody complexes which were demonstrated by immunofluorescent technique. The nephritogenic tubular antigen was solubilized by pronase digestion, further purified by gel filtration, and demonstrated to have the same physicochemical properties as the human tubular antigen which was found in the deposits together with beta1C- and immunoglobulins in the glomeruli of patients with membranous glomerulonephritis. | 28 |
Activating effect of light irradiation at various wavelength on the respiration in sperm of the echiuroid, Urechis unicinctus, in the presence of carbon monoxide. In sperm of the echiuroid, Urechis unicinctus, respiration in the presence of CO was reversibly augmented by light irradiation in an examined range of wavelengths between 350 and 650 nm. The respiratory rate of sperm in the presence of CO was enhanced by light irradiation in proportion to the light fluence rate. A sharp and large peak was obtained at the wavelength of 430 nm in the action spectrum of photo-activated respiration of sperm in the presence of CO. Broad and small peaks were also found at around 530 and 570 nm. This action spectrum is similar in its profile to the absorption spectrum of reduced cytochrome b. Absorption of photon energy by reduced b-type cytochrome probably activates the redox reaction of this cytochrome to enhance the respiratory rate. Photo-activated respiration in the presence of CO was inhibited by antimycin A and cyanide. In this respiratory system, an electron equivalent is probably transferred through the mitochondrial respiratory chain between cytochrome b and cytochrome c and finally to molecular oxygen in the reaction catalyzed by the CO-insensitive terminal oxidase. | 20 |
Enhanced GTPase activity of transducin when bound to cGMP phosphodiesterase in bovine retinal rods. The generation of the physiological response of a retinal rod cell to an incident photon involves activation of a cGMP phosphodiesterase (PDE) by a GTP-binding protein, transducin (T). This activation has been shown to occur by formation of a membrane-bound T alpha GTP-PDE complex (Clerc, A., and Bennett, N. (1992) J. Biol. Chem. 267, 6620-6627; Catty, P., Pfister, C., Bruckert, F., and Deterre, P. (1992) J. Biol. Chem 267, 19489-19493). The recovery of the response involves turning-off of T by its intrinsic GTPase activity. We show here that the formation of the membrane-bound T alpha GTP-PDE complex correlates with an enhanced rate of GTP hydrolysis. In vivo, this would provide an appropriate mechanism for fast turn-off of cGMP hydrolysis. | 10 |
Symposium on trauma for the general surgeon. 1. An accident health care program: the organization and development of regional trauma units. Fifteen thousand deaths, 3 million hospital bed--days and billions of dollars per year are the cost of dealing with accidents in Canada. Our present methods of caring for the seriously injured need revision. The available data on accidents, although extensive, are not sufficiently complete to allow clear definition of the Canadian accident profile. We are unable to explain why Canadians are subject to a 25% greater risk of motor vehicle accidents than are Americans. The development of a Canadian accident health care delivery and audit system is proposed that would provide an improved standard of health care and supply a data base for the advancement of effective programs for accident prevention. The system would include radio-equipped ambulance stations strategically located between regional trauma units, which would be equipped to care for the majority of injured patients. Those severely injured patients who could not be handled by the regional trauma units would be transferred to comprehensive trauma units established in the major referral centres. A trauma registry set up in every province would collect data on each patient and accident to provide an accurate provincial accident profile and a national trauma institute would correlate provincial data. | 15 |
Dietary effects on chemical carcinogenesis in animal models for colon and liver tumors. Studies of dietary effects on chemical carcinogenesis in rats have demonstrated that colon tumor induction is enhanced by increased dietary fat intake or dietary deficiency of vitamin A in some but not all cases. The enhancing effect of a high-fat diet is augmented by lipotrope deficiency. Induction of hepatic tumors by several different carcinogens also is enhanced in rats fed a high-fat diet marginally deficient in lipotropes. The dietary effects may be exerted through alteration of metabolism of carcinogens, which has been demonstrated in lipotrope-deficient rats, through immunological mechanisms, which influence induction of colon tumors, or through effects on gastrointestinal bacteria and bile acid metabolism. Demonstration of dietary effects on carcinogenesis may require utilization of combined dietary stresses that alter metabolic loads but do not seriously impair growth. | 19 |
Classical conditioning and protein kinase C activation regulate the same single potassium channel in Hermissenda crassicornis photoreceptors. The patch-clamp technique was used to study the effects of classical conditioning and protein kinase C (PKC) activation on K+ channels of identified neurons in the snail Hermissenda crassicornis. Here we present evidence that classical conditioning and PKC activation similarly modify the same K+ channel. K+ channels were recorded in cells from animals with different training experience. The 64-pS K+ channel appeared with significantly lower frequency in the conditioned group compared to the frequencies in control animals (naive and unpaired). In addition, when present, the 64-pS channel exhibited a lower percentage of open time and an increased interval between opening bursts in cells from conditioned animals. The 42-pS K+ channel was observed with about the same frequency in all three groups, and its percentage of open time was invariant, regardless of the animal's experience. Incubation of the photoreceptor with the PKC activator phorbol 12,13-dibutyrate (PDBu) led to a profound decrease in the percentage of open time of the 64-pS K+ channel, from 35.7% in the control group to 2.5% in the PDBu-treated group. The inactive phorbol 4 alpha-phorbol 12-myristate 13-acetate had no effect. The use of the PKC inhibitor H-7 significantly blocked the phorbol effect. Inside-out patches obtained from phorbol preincubated cells likewise showed the same effect of PDBu on K+ channels, but the effect was not observed when phorbol was added after the cell-free patches were obtained from nontreated cells. By contrast, the percentage of open time of the 42-pS K+ channel remained unchanged after phorbol treatment. | 16 |
Heat shock protein HSP90 and its association with the cytoskeleton: a morphological study. To investigate the cellular localization of the 90-kilodalton heat shock protein (HSP90) and its interaction with the cytoskeleton, we performed single- and double-staining immunofluorescence microscopy of cytoskeletal proteins and HSP90 in the absence and presence of cytoskeletal inhibitors. As a model, we used a human endometrial adenocarcinoma cell line (Ishikawa cells), which expresses HSP90. We confirmed the recently reported colocalization of HSP90 with microtubules. However, Ishikawa cells treated with 10(-5) M of the antimicrotubule agents colchicine or triethyl lead showed residual filamentous structures stained with anti-HSP90 antibodies, while no microtubules were visualized with anti-tubulin antibodies. In the presence of 10(-5) M cytochalasin B, the microfilament staining of the cells disappeared, while residual filamentous structures were labeled with anti-HSP90 antibodies. Furthermore, Ishikawa cells treated with 10(-5) M triethyl lead and stained with anti-HSP90 antibodies demonstrated residual filamentous structures, clearly different from those of reorganized vimentin intermediate filaments. Conversely, similar reorganized morphology of filamentous structures stained with both anti-HSP90 and anti-cytokeratins antibodies were observed when Ishikawa cells were treated with 2 x 10(-5) M cytochalasin B and 2 x 10(-5) M colchicine. HSP90 was also present in Ishikawa cell preparations of the Triton X-100 insoluble cytoskeleton. In addition, Triton-insoluble cytoskeleton treated with 10(-5). M triethyl lead and double stained with anti-HSP90 and anti-vimentin antibodies demonstrated clearly different filamentous patterns, when exposed on the same photographic plaque.(ABSTRACT TRUNCATED AT 250 WORDS) | 17 |
Macrophage reaction in rabbit lung following inhalation of iron chloride. Groups of eight rabbits were inhalation-exposed to iron, 1.4 +/- 0.7 mg/m3 (low Fe), or 3.1 +/- 1.8 mg/m3 (high Fe) as FeCl3 or to filtered air (controls) for 2 months, 5 days/week and 6 hours/day. The alveolar macrophages were increased in number in both exposed groups. Noduli of granular macrophages were found in lungs of all the rabbits in the high-Fe group, in one from the low-Fe group, and in one control rabbit. Especially in the high-Fe group there were prominent changes in the macrophages such as enlarged lysosomes containing fibrous-looking structures, iron-rich inclusions, and densely packed, 5-nm electron-dense granules. The number of cells filled with surfactant-like inclusions as well as a smooth surface was increased in the high-Fe group and the macrophages had enhanced phagocytic capacity. There was an increase in the phospholipid concentration and in the volume density of type II cells in the high-Fe group but the level of phosphatidylcholines was not significantly changed. The fact that Fe3+ affected mainly the alveolar macrophages might be due to the relatively high concentration of iron in these cells caused by the precipitation of iron in their lysosomes. | 16 |
Repair of tetralogy of Fallot in infancy. Effect of pulmonary artery size on outcome. The possible influence of small pulmonary artery size on the results following complete repair of tetralogy of Fallot has not been investigated in patients less than 1 year of age. We, therefore, reviewed our recent experience with infant repair to assess this. Between January 87 and October 90, repair was performed in 58 infants less than 1 year old (median, 6 months) with tetralogy of Fallot and pulmonary stenosis (n = 53) or pulmonary atresia without important aortopulmonary collaterals (n = 5). The McGoon ratio (diameter of the right pulmonary artery at the prebranching point plus that of the left divided by the diameter of the aorta at the diaphragm) by cineangiography (n = 48) was between 1.2 and 1.5 in 15 patients, 1.6 and 2.0 in 20, and greater than 2.0 in 13. Transannular patching was performed in 19 of the patients with pulmonary stenosis (36%). Muscle resection was avoided in 29 infants and was minimal in the remaining 29. A weak correlation, with considerable scatter, was found between the McGoon ratio and postrepair right ventricular/left ventricular pressure measured in the operating room (r = 0.4), and the relations were similar to those previously reported for children. Right ventricular/left ventricular pressure was 0.55 +/- 0.03 in infants with McGoon ratios of 1.2-1.5, 0.46 +/- 0.03 with ratios of 1.6-2.0, and 0.47 +/- 0.03 with ratios greater than 2.0 (p = 0.01). There were no hospital deaths, and the 3-year survivorship was 94%. Two infants underwent successful reoperation for residual right ventricular outflow tract obstruction. All other patients are free of significant hemodynamic residua.(ABSTRACT TRUNCATED AT 250 WORDS) | 14 |
Platelet storage in synthetic media lacking glucose and bicarbonate. The goal of these studies was to develop a cost-effective medium for the storage at 22 +/- 2 degrees C of platelets for transfusion. Platelet concentrates were prepared from platelet-rich plasma in a standard fashion and resuspended in 55 mL of medium. Residual plasma was 14.4 +/- 4.3 percent of the final suspending solution. The use of a simple solution containing electrolytes and citrate, but no glucose or bicarbonate, was associated with a drop in pH to the range of 6.0 to 6.6, as a result of the production of lactic acid from the platelet glycogen and glucose present in residual plasma. When 25 mM (25 mmol/L) sodium phosphate was included as a buffer, the drop in pH was retarded, but the range throughout storage was still 6.5 to 6.8. Nonetheless, platelets stored for 5 days in this phosphate-containing medium showed satisfactory maintenance of many in vitro variables. However, there was a 10 to 35 percent reduction of in vivo recovery after isotopic labeling. There was no significant reduction in subsequent mean cell life. Because of the in vivo abnormalities, these media are not recommended for use at the present time. However, the results are encouraging and suggest that further research may lead to a satisfactory, cost-effective medium. | 13 |
10 years of experience with intratympanally applied streptomycin (gentamycin) in the therapy of Morbus Menière. During the last 10 years a total of 83 patients with severe cases of unilateral Morbus Menière were treated in our clinic. The proposed therapy was to administer streptomycin (gentamycinsulfate) intratympanically by applying two different ways of procedure. In the first group of 40 patients we attempted to destroy the vestibular organ without harming the cochlea whereby we avoided surgical intervention. In the second group of 43 patients we integrated more recent findings in the pathophysiological mechanism underlying the pathogenesis of Morbus Menière into our therapeutic considerations and attempted to exclusively destroy the secretorial epithelium with minimal dosages of aminoclycoside antibiotics. The results after treatment were clearly better for the second group of patients. | 17 |
[Transient ischemic attacks and stroke]. The authors present some results of a study of 85 patients with brain strokes which were preceded by transient cerebral ischemic attacks. In most of the cases the brain stroke developed on the background of an ischemic cardiac diabetus, atheroscleorosis of the peripheral vessels, etc. It was established that in patients with atherosclerosis, the strokes developed at earlier periods after the first ischemic attack, than in the group of patients where atherosclerosis developed in combination with arterial hypertension. In disturbance of circulation in the basin of the carotid arteries, the strokes with preceding ischemic attacks developed not only more frequently, but earlier than those due to insufficiency of the circulation in the vertebro-basillar basin. It was also established that crude focal symptomatology appears as a rule in those cases when the stroke develops after the first ischemic attack. In frequent attacks which are repeated during several years, the appearing stroke is characterized by a more light focal symptomatology. | 16 |
Patterns of connectivity in the cat sensory-motor cortex: a light and electron microscope analysis of the projection arising from area 3a. Through its complex network of interconnections, each of the functionally specialized subdivisions in the cat primary somatosensory cortex may provide the motor cortex with different input and thus play a unique role in motor behavior. Areas 2 and 3a receive separate peripheral information. Cells in both regions project directly to the cat motor cortex but are thought to target different populations of neurons. In this study the morphology and distribution patterns of the area 3a projection to the motor cortex were compared to previous findings on the projection from area 2. Also, details of the projection from area 3a to area 2 were studied. Injections of Phaseolus vulgaris leucoagglutinin were made into area 3a and fixed brain tissue was processed for immunohistochemical staining of this anterograde tracer. Tissue was examined with the light microscope to determine the patterns of the 3a projections to area 2 and motor cortex, area 4. Axons arising from cells in area 3a terminated in multiple column-like clusters in both motor cortex and area 2. The small number of cells labeled at the injection sites suggested that multiple foci of the 3a fibers are formed by collateral axonal branches of the same neurons. The topography of the projection from area 3a to the motor cortex was more clearly defined than that from area 3a to area 2. Electron microscope analysis determined the laminar distribution and types of synapses formed between area 3a efferents and their target neurons. A high proportion of synapses was found in layer III in both target regions. However, unlike in area 4, labeled terminals were sparse in laminae I and II of area 2. Axospinous synapses were slightly more numerous than axodendritic synapses, but both were distributed similarly throughout the thickness of the cortex. In area 2 the axospinous synapses accounted for 63% of synapses and in area 4 for 57% of synapses. No axosomatic synapses were detected. | 14 |
[Two biotin-labeled probes of gentamicin resistance genes]. A 2.0 kb BamHI-HindIII fragment of pDG0103 from Australia containing gentamicin 2"-o-adenylytransferase [ANT(2")] gene and a 4.9 kb PstI-EcoRI fragment of pBY102 were recovered from low-temperature-melting agarose by the slot method. Both fragments were labeled with biotin-7-dATP by nick translation with a commercial kit. The result of colony and Southern hybridization was that: the 2.0 kb probe from Australia hybridized with that containing ANT(2") from America, while no hybridization occurred between the 2.0 kb probe and the 4.9 kb probe constructed in our lab. Furthermore, the above two fragments were used as probes for detection of 106 strains of gentamicin resistant Enterobacteriaceae. It revealed that there were more than one gentamicin resistance gene in the tested strains. | 15 |
Family planning services delivery. Danish experience. The purpose of this article is to give an overview of the Danish family planning services delivery based on a description of the country, the people, and their opinions. All laws and regulations about contraceptive services, including abortion and sterilization, are described in historical perspectives. It is concluded that the system has been developed on the basis of the health care system of the country to such a degree that it broadly covers the prevailing general attitudes of the population and that the expectations of the population to the system are reasonably met. What remains unsatisfactory is a relatively high proportion of induced abortions. Future possibilities for solving this problem could be: to improve the education of physicians, health nurses, midwives, teachers, and social workers with regard to family planning and sexuality; to revise teacher's guidelines on sex education and intensified sex education in the schools; to intensify information to risk groups such as teenagers and single women; and to accomplish general organisation of school class visits to family planning clinics. | 18 |
Escape rhythm in complete A-V block. The recovery phase after overdrive suppression from artificial ventricular suppression from artificial ventricular pacing. In 60 patients with third degree A-V block, recovery of escape rhythm from overdrive suppression after ventricular pacing has been studied. Implanted unipolar VVI pacemakers were inhibited by chest wall stimuli. A total of 165 rhythmograms were studied. In 37, the rate was irregular, in the other 128 the escape rate increased gradually, following an exponential curve until stabilization after 3 minutes. In 29 of these rhythmograms, a possible exit block of the first escape impulse was observed. In 99 rhythmograms without exit block, escape rhythm recovery time was an average 1.45 times basal escape RR intervals. Overdrive suppression was most marked in patients with a slow escape rhythm. | 12 |
Atypical large plasma cells in lymph node granulomas in cat-scratch disease. A histological variant of plasma cells found in the granulomas of cat-scratch disease (CSD) lymphadenitis is reported. Though the lesion shows the typical features of suppurative granulomatous lymphadenitis, many atypical giant cells which have abundant basophilic cytoplasm and bizarre nuclei with occasional multinucleated forms are noted among epithelioid histiocytes. The diagnosis of CSD lymphadenitis was confirmed by comparing clinical; histopathological, and histochemical (Warthin-Starry silver impregnation stain) studies on lymph node sections from five cases with features typical of the disease. Histochemical (methyl green-pyronine stain) and immunohistochemical examination provided several lines of evidence indicating that the atypical giant cells in our case were plasmacytic and confirmed that its proliferation was reactive, not neoplastic. Multinucleated giant cells were also occasionally present in the other five cases, but they had histological and immunohistochemical features of Langhans' type giant cells. We stress the importance of distinguishing such atypical large plasma cells from neoplastic cells. | 18 |
Cytogenetics of fleas (Siphonaptera: Pulicidae). 1. Rat fleas of the genus Xenopsylla. Five populations of Xenopsylla cheopis exhibit a chromosome complement of 2n = 17, X1X2Y (male), and 2n = 18, X1X1X2X2 (female). A detailed analysis of populations of X. astia from Bombay and Trivandrum led to the identification of two distinct cytotypes which hybridisation studies indicated were sibling species. These are referred to as X. astia with a diploid chromosome number of 2n = 18, X1X2X3Y (male), and 2n = 20, X1X1X2X2X3X3 (female) and X. prasadii with 2n = 10, X1X2Y1Y2 (male), and 2n = 10 X1X1X2X2 (female). It is proposed that X. prasadii is derived from X. astia through translocation/fusion events since the average total chromosome lengths are remarkably similar in all three species. | 13 |
Antigens of Mycobacterium leprae in the cerebrospinal fluid of leprosy patients: detection by monoclonal-antibody-based sandwich immunoradiometric assay and avidin/biotin immunoblotting. Mycobacterium leprae antigens could be detected in the cerebrospinal fluid (CSF) of patients with leprosy, using a monoclonal-antibody-based sandwich immunoradiometric assay (SIRMA). Antigens of 12 kD, 35 kD and 30-40 kD were detected using ML06, ML04, and ML34 monoclonal antibodies, respectively. The 30-40-kD polysaccharide antigen, although present in larger amounts in M. leprae than the 12-kD and 35-kD protein antigens, was found in the CSF of comparatively fewer subjects. The antigen capture assay has been found sensitive to the level of nanograms. Avidin-biotin-based immunoblotting using pooled leprosy sera detected a larger number of antigens than using anti-M. leprae antisera raised in rabbits. The immunoblotting of CSF samples revealed about three antigens in the region of 100-160 kD and three more in the region of 45-60 kD as probed by leprosy sera. This study has for the first time revealed the presence of M. leprae antigens in the CSF of leprosy patients and the probable involvement of the central nervous system in leprosy. | 16 |
Profiles of periodontal conditions in adolescents measured by CPITN. Results of more than 100 CPITN surveys from over 60 countries for the age group 15-19 years, stored in the WHO Global Oral Data Bank as of 1 August 1990, are assembled. They are presented in the form of graphs showing the mean number of sextants affected per person and arranged by country according to WHO regions. It is hoped that these overviews provide a frame of reference for the evaluation of periodontal conditions in populations and population subgroups. The most frequently observed condition in adolescents was score 2 (calculus with or without bleeding). Calculus seems to be much more prevalent in non-industrialized than in industrialized countries. Although some shallow pocketing of 4 or 5 mm was present in two-thirds of all populations observed, it affected mostly only a minority of the sample and then only in one or two sextants. However, a few surveys showed a relatively high prevalence of pocketing. As the surveys were carried out in adolescents, such high figures indicate serious problems ahead. | 13 |
Long-term prognosis of duodenal ulcer: follow-up study and survey of doctors' estimates. In 1976 we reviewed a randomly selected cohort of 227 patients with duodenal ulcer first diagnosed in 1963. The cohort comprised cases diagnosed in both hospitals and general practice. Fifty patients had died, 12 had emigrated, and 154 (93%) of the remaining patients were interviewed. Fifty-seven medically treated patients had no symptoms, 44 had mild symptoms, and 19 had more severe symptoms. The remaining 34 patients had been treated surgically. Cases diagnosed in hospital had a more severe prognosis than those diagnosed in general practice. A random sample of 65 general practitioners and 78 medical and surgical gastroenterologists tried to predict the results of this study. The range of the predictions was very wide showing that individual prognostic estimates were highly unreliable. The mean prediction by all doctors differed little from the actual result, suggesting that the collective experience of the medical profession is more reliable. The predictions of general practitioners, physicians, and surgeons showed small systematic differences, presumably reflecting the different types of patients they treat. | 13 |
[Accumulation mechanism of 111In in malignant tumor (author's transl)]. In order to clarify the accumulation mechanism of 111In in maligant tumor, subcellular distribution of 111In was quantitatively determined. Buffalo rats bearing Morris hepatoma 7316A were injected intraperitoneally 111In-chloride and tumor tissues were removed 24 hours later. Subcellular fractionation of tumor tissues were carried out according to the method of C. de Duve, et al. and radioactivity of each fraction was counted. Most of the total radioactivity was distributed among the soluble, nuclear and lysosomal fractions. On account of its low protein content, the relative specific radioactivity was the highest in the lysosomal fraction. The lysosomal fraction was solubilized gradually and the resultant stepwise release of 111In and acid phosphatase activity were measured. There was a close relationship between them. From these results it was concluded that 111In accumulated especially in the lysosomes. In the electron micrography the tumor lysosomes had already engulfed many foreign materials, so that the lysosomal function would be depressed. | 13 |
Refinement of the Modified Navy Plaque Index to increase plaque scoring efficiency in gumline and interproximal tooth areas. To improve the assessment of plaque present on teeth, a new index, based on the original Modified Navy Plaque Index, has been developed. The primary modifications to the original Modified Navy Plaque Index were: (1) extending areas F (distal) and D (mesial) into the region just below the interproximal contact point, and (2) extending areas C and A so as to increase the gumline (or marginal gingiva) region. The new index assesses the amount of plaque in the tooth area bounded by the tooth contact, the free gingival margin, and mesial or distal line angles. The use of this new index enables the examiner to evaluate and record both the gumline (or marginal areas) and interproximal areas of the tooth, thus giving these an anatomical areas an increased importance. A pilot clinical assessment study was conducted to utilize this new index in evaluating the plaque removal efficacy of five manual toothbrushes. The results from this pilot study indicated that, when the new plaque scoring index was used, significant differences between pre-toothbrushing and post-toothbrushing plaque scores (as well as among toothbrush groups) could be demonstrated. Further, these differences (plaque removal efficacy) were demonstrated on an interproximal (mesial and distal) basis and a gumline (or gingival margin) basis, as well as on a whole mouth basis. | 18 |
Anxiety disorders of childhood and adolescence: a critical review. The 1980s were a decade of advancement in the knowledge of anxiety disorders in children and adolescents; this sets the stage for research achievements in the 1990s. This review examines the anxiety disorders of childhood and adolescence (separation anxiety disorder, overanxious disorder, and avoidant disorder), including prevalence rates, demographic profiles, comparisons of clinical presentations in different developmental age groups, and comorbidity patterns. Fears and simple phobias, obsessive-compulsive disorder, post-traumatic stress disorder, and panic disorder in children and adolescents are also evaluated. The controversy of whether panic attacks occur in prepubertal children is addressed. A brief review of behavioral and pharmacological treatment studies is included. Future directions for research are suggested. | 16 |
The quantitative effects of maternal dietary energy intake on pregnancy and lactation in rural Gambian women. The quantitative relationships between dietary energy intake and weight gain in pregnancy, birthweight and lactation performance during the first three months of infancy have been studied in such a way as to take account of major differences in the patterns of heavy manual labour at different times of the year in a subsistence farming community. Maternal weight gain and the accumulation of subcutaneous fat were significantly lower when the last trimester of pregnancy fell during the time of heaviest farm work and lowest energy intakes. The birth-weight of babies was also significantly correlated with differences in energy intake throughout the year. During early lactation breast milk yields were significantly related to concomitant alterations in the subcutaneous fat stores. Evidence has been produced which suggests that in undernourished nursing women there could be a competition for dietary energy between the repleting maternal subcutaneous fat organs and the mammary glands at the expense of milk production. | 19 |
Changes in rat epiphyseal cartilage after treatment with dexamethasone and glycosaminoglycan-peptide complex. In 3-month-old rats, systemic administration of glucocorticosteroids induced regressive changes in the epiphyseal plate cartilage. Dexamethasone treatment resulted in inhibition of both chondrocyte proliferation and cartilage matrix production. The inhibition of chondrocyte proliferation was determined histologically from the thickness of the epiphyseal plate, the number of cell columns and the ratio of proliferating to hypertrophied chondrocytes. The decrease in cartilage matrix production was measured autoradiographically by incorporation of radioactive 35S-sulphate. Concomitant treatment with glycosaminoglycan-peptide complex (GP-C = RUMALON) overcame the negative effect of dexamethasone. The values in the dexamethasone + GP-C group approached those of the control group and differed significantly from the group given dexamethasone alone. | 17 |
Structure of the altered oligosaccharide present in glycoproteins from a clone of Chinese hamster ovary cells deficient in N-acetylglucosaminyltransferase activity. Clone 15B cells, derived from Chinese hamster ovary cells and deficient in a specific UDP-N-acetylglucosamine:glycoprotein N-acetylglucosaminyltransferase activity, synthesize glycoproteins with altered oligosaccharide units. Glycopeptides prepared from these glycoproteins contain large quantities of a glycopeptide with the composition (Man)5(GlcNAc)2-Asn whereas parent cells have only small amounts of this glycopeptide. The structure of the glycopeptide was determined by the combination of methylation analysis, acetolysis, Smith periodate degradation, and alpha- and beta-mannosidase digestion. Its complete structure is Manalpha 1 leads to 6[Manalpha1 leads to 3]-Manalpha1 leads to 6[Manalpha 1 leads to 3]-Manbeta1 leads to 4 GlcNAcbeta1 leads to 4 GlcNAc leads to Asn-peptide. The structures of two other glycopeptides found in smaller quantities in clone 15B but not detected in the parent cells were determined and are Manalpha 1 leads to 6 [Manalpha 1 leads to 3]-Manalpha1 leads to 6Manbeta 1 leads to 4 GlcNAcbeta 1 leads to 4GlcNAc-Asn-peptide and Manalpha 1 leads to 3 Manalpha 1 leads to 6[Manalpha 1 leads to 3] Manbeta 1 leads to 4GlcNAcbeta 1 leads to 4GlcNAc-Asn-peptide. It is proposed that the (Man)5(GlcNAc)2-Asn unit is the physiologic acceptor for the particular N-acetylglucosaminyltransferase which is deficient in clone 15B cells and that this reaction is necessary for complex oligosacchari-e biosynthesis. | 22 |
Ischemic injury to rat forebrain mitochondria and cellular calcium homeostasis. The three-vessel occlusion model of Kameyama et al. (Kameyama, M., Suzuki, J., Shirane, R. and Ogawa, A. (1985) Stroke 16, 489-493) was adapted with modifications to induce complete reversible rat forebrain ischemia. A fast and simple procedure for the isolation and purification of rat brain mitochondria, which provides high yield, is described. Mitochondria isolated from ischemic brain (12-30 min ischemia) exhibited decreases in State 3 respiratory rates of approx. 70% with NAD-linked respiratory substrates. Less effect was observed with succinate and rotenone. The State 4 respiratory activity remained near control levels except at 15 min of ischemia (25% increase) with NAD-linked substrates. Similarly, with succinate and rotenone, an approx. 30% increase in State 4 activity was observed at 20 min of ischemia. Consequently, the respiratory control indices (RCIs) were decreased. Both the respiratory rates and RCIs could be restored to near control levels upon the addition of EGTA(EDTA) or ruthenium red to the assay mixture. Analysis employing fura-2 as a Ca2+ probe, indicated a great decrease in the first order rate constant for Ca2+ uptake of ischemic mitochondria and a significant increase in Ca2+ homeostasis with an increase in the cytosolic Ca2+ concentration which results in excessive association of Ca2+ on the mitochondrial membrane and an inhibition of the respiratory chain-linked oxidative phosphorylation and Ca(2+)-transport activity of forebrain mitochondria. These deficits are proportional to the duration of ischemia. | 14 |
[Psychiatric aspects of low back pain (author's transl)]. Chronic low back pain is more significant from the psychiatric point of view than the acute pain. As a persistent pain of organic origin it leads to typical psychopathological symptoms ("algogenic psychosyndrome"). The algogenic psychosyndrome must be differentiated diagnostically from neurotic developments and masked depressions. Psychosomatic low back pain is a warning of failure in the accomplishment of professional or family duties and chronic and chronic inhibited aggression. - An interdisciplinary study of the courses of 50 patients operated on for prolapse of the lumbar intervertebral disk showed that the psychopathological picture and the pain syndrome are usually determined by several factors. The majority of neurotic disordered personalities developed symptoms of new syndromes after the operation. | 15 |
Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Immunoglobulin kappa chain gene formation involves site-specific somatic recombination between one of several hundred germ-line variable region genes and a joining site (or "J segment") encoded close to the constant region gene. We have cloned and determined the nucleotide sequence of major portions of the recombination region of the mouse kappa gene and discovered a series of five such J segments spread out along a segment of DNA 2.4 kilobases from the kappa constant region gene. These J segments encode the 13 COOH-terminal amino acids of the variable region, probably including amino acids involved in the antigen combining site and in heavy/light chain contacts. The J segments also display striking sequence homology to one another in both their coding and immediately flanking sequences. Major elements of a short palindrome--CAC(TA)GTG--are preserved adjacent to the recombination sites of both variable and J region genes and constitute inverted repeats at both ends of the sequences to be joined. These palindromes can be written as a hypothetical stem structure that draws variable and J regions together, providing a possible molecular basis for the DNA joining event. Four of the J segments that we have discovered encode amino acid sequences already found in myeloma proteins. By altering the frame of recombination, we can account for additional light chain amino acid sequences, suggesting that the V/J joining event might generate antibody diversity somatically both by using different combinations of variable and J region genes and by using alternative joining frames. | 19 |
Allergic contact dermatitis to underwear elastic. Chemically transformed by laundry bleach. Six subjects, allergic to the elastic in their undergarments, were patch test-negative to the rubber components and new elastic from the suppliers. However, washing the rubber with sodium hypochlorite gave the subjects allergic responses due to the effect of bleach on the rubber accelerator, zinc dibenzyldithiocarbamate (ZDC). To identify the allergen, ZDC was reacted with the sodium hypochlorite, and the resultant gum was extracted with diethyl ether. Eight compounds were identified in the reaction mixture by gas chromatography-mass spectrometry. The individual components were tested on volunteers after sensitization to the reaction mixture was produced in 14 of 25 volunteers. One component, N,N-dibenzylcarbamyl chloride produced an allergic response in each sensitized volunteer. | 14 |
The effects of clonazepam on rolandic discharge of benign epilepsy of children with centro-temporal EEG foci. 1) CZP had marked effects on RD. RD disappeared in 8 (73%) of 11 patients treated with CZP alone and 6 (43%) of 14 treated with CZP in combination with other drugs. Even when RD persisted, its amplitude and frequency decreased in some patients. 2) In the group treated with CZP in combination with other drugs, RD disappeared in all 5 patients with the persistent RD, of whom 2 had arachnoid cyst. Of the 6 patients with frequent seizures, 2 were subsequently diagnosed as having CPS and SPS, respectively. Patients who did not respond to CPZ included those in whom the diagnosis of BECCT should be reconfirmed, and electro-clinical response may be also useful for diagnosing RD. 3) In patients treated with CZP alone for a short-term treatment of BECCT, the drug administration could be discontinued only in one. A longer follow-up study is necessary to reach a conclusion in future. | 11 |
Conformational change and localization of calpactin I complex involved in exocytosis as revealed by quick-freeze, deep-etch electron microscopy and immunocytochemistry. Calpactin I complex, a calcium-dependent phospholipid-binding protein, promotes aggregation of chromaffin vesicles at physiological micromolar calcium ion levels. Calpactin I complex was found to be a globular molecule with a diameter of 10.7 +/- 1.7 (SD) nm on mica. When liposomes were aggregated by calpactin, quick-freeze, deep-etching revealed fine thin strands (6.5 +/- 1.9 [SD] nm long) cross-linking opposing membranes in addition to the globules on the surface of liposomes. Similar fine strands were also observed between aggregated chromaffin vesicles when they were mixed with calpactin in the presence of Ca2+ ion. In cultured chromaffin cells, similar cross-linking short strands (6-10 nm) were found between chromaffin vesicles and the plasma membrane after stimulation with acetylcholine. Plasma membranes also revealed numerous globular structures approximately 10 nm in diameter on their cytoplasmic surface. Immunoelectron microscopy on frozen ultrathin sections showed that calpactin I was closely associated with the inner face of the plasma membranes and was especially conspicuous between plasma membranes and adjacent vesicles in chromaffin cells. These in vivo and in vitro data strongly suggest that calpactin I complex changes its conformation to cross-link vesicles and the plasma membrane after stimulation of cultured chromaffin cells. | 18 |
Measurement of radiation doses in the most frequent simple examinations in paediatric radiology and its dependence on patient age. Radiation doses to patients were measured in four X-ray rooms specifically devoted to paediatric radiology, from two hospitals. The study was performed for the most frequent simple examinations, namely abdomen, hip and pelvis, skull, spine and chest. Patients were classed into four different age groups: 0.1-1 year, greater than 1-5 years, greater than 5-10 years and greater than 10-14 years. Operating X-ray generator parameters and entrance surface doses were recorded for all groups. Representative values were obtained for standard working conditions prior to any correcting action being taken. Dose values are reported, and some of the differences between the results found in the rooms for each examination are discussed. Without attempting to relate adult and paediatric radiology, the entrance surface doses measured and the provisionally recommended CEC values for similar examinations in adult patients are compared. | 14 |
Allosteric modulation of N-methyl-D-aspartate receptors. In this review we have attempted to describe the basis for current models of the NMDA receptor, and justify the need for the various binding sites that have been proposed. The NMDA receptor is clearly a complex molecule with a number of modulatory sites, any of which may have great functional significance. From the data presented above it is apparent that the NMDA recognition site is closely coupled with the glycine site, and can also be regulated by Zn2+. The glycine site is reciprocally coupled to the NMDA site, and may also be coupled to a divalent-cation site outside the channel. However, the glycine site is insensitive to Zn2+. The Zn2+ site is probably not inside the channel to any degree, but can profoundly affect the ability of NMDA site ligands to operate the channel. However, the determination of reciprocal effects at the Zn2+ site await the development of a suitably potent and selective ligand for this site. Several lines of evidence suggest that the phencyclidine and channel-blocking Mg2+ site are located within the NMDA-operated ion channel. Glutamate, glycine, and Zn2+ alter the binding of ligands to these sites. However, this is most likely to be due to alteration of access of the ligands to their sites rather than a direct allosteric coupling. It does appear that phencyclidine site drugs and Mg2+ bind to separate sites within the channel, and that these separate sites are allosterically coupled. This complex series of interactions, many of which are mediated by endogenous agents, may allow very fine control over the expression of NMDA receptor-mediated synaptic transmission. In addition to these ligand-produced modulatory effects, there may also be covalent modification of the channel by receptor phosphorylation. Furthermore, the voltage sensitivity of some of the effects allows control of NMDA receptor-mediated signaling by alteration of the membrane potential in the postsynaptic cell, which can be achieved in a wide variety of ways. The level of sophistication possible in adjusting the responsiveness of this receptor seems entirely appropriate given its central involvement in a wide variety of fundamental neurobiological events, and underscores the deleterious pathological sequelae of the system tilting out of balance. At the same time, the wide array of possible therapeutic targets raises hopes that it may soon be possible to treat effectively some severely debilitating and currently untreatable diseases. | 16 |
Importance of endogenous tumor necrosis factor alpha and gamma interferon in host resistance against Pneumocystis carinii infection. C.B-17 scid/scid (SCID) mice that have acquired natural pulmonary infection with Pneumocystis carinii clear these organisms by 19 days after reconstitution with spleen cells from immunocompetent mice and therefore serve as a model for studying the pathogenesis of and immunity to P. carinii pneumonia. The present study examined the importance of endogenous tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in the clearance of P. carinii by treatment of reconstituted SCID mice with anti-TNF-alpha and anti-IFN-gamma immunoglobulin G (IgG). Treatment of reconstituted mice with monospecific rabbit anti-TNF-alpha IgG almost completely inhibited the clearance of P. carinii from the lungs. In contrast, treatment with either anti-IFN-gamma antibody (polyclonal or monoclonal) or control IgG had no detectable effect on the clearance of P. carinii. The importance of endogenous TNF-alpha in the clearance of P. carinii was further supported by the finding of TNF-alpha but not IFN-gamma in lung homogenate supernatants from reconstituted SCID mice. Further study revealed that for the complete clearance of P. carinii, TNF-alpha must be present at the early stage of reconstitution, since clearance could be blocked by a single injection of anti-TNF-alpha IgG into SCID mice at day 0 but not at day 6 and/or day 12 after reconstitution. These results strongly suggest that, in reconstituted SCID mice, endogenous TNF-alpha is important in host resistance against P. carinii infection, whereas IFN-gamma appears not to play a significant role. | 21 |
Inhibition of cytokine synthesis by peritoneal dialysate persists throughout the CAPD cycle. The current study focused on the effect of continuous ambulatory peritoneal dialysis (CAPD) dialysate obtained following different intraperitoneal dwell periods on the release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha) from mononuclear leukocytes (PBMC). Aliquots of 5 x 10(6)/ml healthy peripheral PBMC were exposed to fresh or spent CAPD dialysate (10-240 min of intra-peritoneal dwell) and stimulated with Escherichia coli endotoxin (10 micrograms/ml, 2h). IL-6 and TNF alpha in cell supernatants were determined by specific enzyme immunoassays. Control PBMC in physiological buffer released 361 +/- 70 pg/ml IL-6 and 717 +/- 147 pg/ml TNF alpha (mean +/- SEM, n = 8), whereas exposure to fresh dialysis fluids severely suppressed cytokine release from PBMC (less than 30 pg/ml IL-6 and less than 15 pg/ml TNF alpha). A significant inhibition of IL-6 and TNF alpha release was also observed in PBMC exposed to spent dialysate. The inhibitory capacity of the spent fluids was pronounced with increasing intra-peritoneal dwell time (10 min: 183 +/- 45 pg/ml IL-6 and 538 +/- 109 pg/ml TNF alpha; 240 min: 26 +/- 5 pg/ml IL-6 and 105 +/- 30 pg/ml TNF alpha; mean +/- SEM, n = 16). These data indicate that the impairment of cell responsiveness following exposure of PBMC to peritoneal dialysate is not restricted to the unused fluids, but is also observed following intra-peritoneal equilibration. Moreover, our findings suggest the presence of cytokine inhibitory factors in the peritoneal dialysate of CAPD patients which appear to accumulate in the peritoneal effluent during the CAPD cycle. | 20 |
Immune electron microscopic characterization of monoclonal antibodies to Alzheimer neurofibrillary tangles. Characterization of eleven monoclonal antibodies (MAbs), raised to isolated sodium dodecyl sulfate (SDS)-treated Alzheimer's neurofibrillary tangles (ANT), has revealed the presence of at least two different epitopes. MAbs were tested for reactivity to ubiquitin and paired helical filaments (PHF) isolated by three different procedures. The effect of protease and/or alkaline phosphatase pretreatment on the reactivity of the MAbs with isolated PHF was also examined. All MAbs that had reacted strongly in the ELISA with sonicated SDS-treated ANT also immune decorated isolated PHF to varying degrees. Two MAbs exhibited a high reactivity to PHF: 3-39 and 5-25. MAb 3-39 was found to recognize a protease sensitive epitope. In contrast MAb 5-25 was found to consistently decorate isolated PHF in all preparations and exhibited a strong reactivity to ubiquitin, and the epitope in isolated PHF was not protease sensitive. Thus structural PHF after protease treatment and detergent treatment contain an antigenic site that is present in ubiquitin. | 16 |
Molecular analysis of structural protein genes of the Yamagata-1 strain of defective subacute sclerosing panencephalitis virus. II. Nucleotide sequence of a cDNA corresponding to the P plus M dicistronic mRNA. The nucleotide sequence of a cloned cDNA corresponding to the P + M dicistronic mRNA of a subacute sclerosing panencephalitis (SSPE) virus was determined and compared with data of measles virus (MV). The dicistronic mRNA of the SSPE virus consisted of the 3' proximal 626 nucleotides of P mRNA, intercistronic trinucleotides, a full length of M mRNA, and 75 poly A nucleotides. The part encoding the P protein had a high homology to MV, except at the noncoding region. The terminating consensus sequence of the P gene and the intercistronic trinucleotides of the SSPE virus were CTAC(A)6 and CCT; in MV they are TTAT(A)6 and CTT, respectively. In the M gene, the starting consensus sequence was exactly the same as MV, but at the 5' proximal end, one third of this gene was different: The first ATG codon of the MV M gene signaling opening of the reading frame was changed to ACG in the SSPE virus and one long open reading frame started from the third ATG codon. The stop codon (TAG) of the MV M gene was also changed to CAG in the SSPE virus. Thus, the deduced SSPE-virus M protein lacked 50 amino acids at the amino terminal and had 15 extra amino acids at the carboxyl end when compared with the MV M protein. | 15 |
Pleural fluid complement, complement conversion, and immune complexes in immunologic and nonimmunologic diseases. Forty-four pleural fluids and 41 blood specimens from patients with various diseases were examined for concentration of whole complement, C4, C3, conversion products of C3 and C3PA, and immune complexes. C3 conversion was found in all eight pleural fluids from patients with rheumatoid arthritis, five of seven with lupus erythematosus, two of six with congestive heart failure, and nine of 23 with malignant diseases. Conversion of C3PA correlated closely with C3 conversion and both were significantly inversely related to whole complement, C4, and C3. Concentration of immune complexes was highest in patients with rheumatoid arthritis. Pleural fluid immune complex concentrations correlated positively with conversion of C3 and C3PA. These findings suggest that the reduced levels of pleural fluid complement in rheumatoid arthritis and lupus erythematosus may be secondary to complement conversion by immune complexes. | 16 |
[Changes in electrical potentials of gastric mucosa during various types of experimental hypoxia]. In experiments performed on anaesthetized male and female Wistar rats the effects of different types of hypoxia on the electrical potential difference (PD) between the inner and the outer sides of the gastric wall were examined. The PD was determined by mean of the Digital Multimeter VC-10T, Unitra, and the calomel electrodes connected with the KCl-agar bridges. There were four series of experiments carried out in which hypoxia was produced by: I--low atmospheric pressure (hypobaric hypoxia) corresponding with the altitudes of 2500, 5500, 8500 and 10,500 m above sea level, II--1 min. nitrogen breathing (anoxic anoxia), III--bleeding ca. 1% of the body weight (anemic hypoxia), IV--the gastric vessels ligation (ischemic hypoxia). There were also performed the adequate control experiments of each series. In all types of hypoxia (I--IV) a decrease in the PD was observed. The value and rate of this decrease were dependent on the type, grade, duration and rate of hypoxia. In the conditions of the hypobaric hypoxia simulated altitude 10,500 m only evoked the statistically significant PD drops, by 31%. The nitrogen breathing caused the PD decrease by 23% and the anemic hypoxia by 18%. In the ischemic hypoxia the total disappearance of the potential difference (PD = 0 mV) was observed. In the control experiments small non significant fluctuations, not exceeding 4%, occurred only. The decrease in the PD of the gastric wall observed during hypoxia could be explained by the changes in the membrane transport e.g. the back-diffusion of Na+, Cl-, and H+ ions. | 14 |
Progesterone and 20 alpha-dihydroprogesterone in sheep: a model of their distribution and metabolism. The rates of metabolism of progesterone and 20alpha-dihydroprogesterone (20alpha-diHP) in sheep have been measured during and after the infusion of tracer amounts of [3H]progesterone. There were significant differences in the blood concentration of [3H]progesterone between experiments, but these were not attributable to the stage of gestation or to the difference between pregnant and non-pregnant animals. The mean (+/- S.E.M.) metabolic clearance rate of progesterone was 3-277 +/- 0-239 litres blood/min. The simplest model of the distribution of progesterone was one containing two pools, V1[P] and V2[P], where [p] is the blood concentration of progesterone, and in 23 experiments on 7 sheep the mean pool dimensions were 7-8[P] mug and 70[P] mug, respectively. This model was developed to include the formation of 20alpha-diHP from progesterone. Progesterone appeared to be the major source of 20alpha-diHP, though this did not seem to be an obligatory metabolite. The parameters obtained gave comparably low residual deviations for both labelled steroids and were consistent with other observations made on progesterone clearance. | 15 |
Aminopropylidine diphosphonate (APD) in mild primary hyperparathyroidism: effect on clinical status. Mild hypercalcaemia associated with primary hyperparathyroidism has been increasingly recognized with the use of automated biochemical screening. Management is often difficult as symptoms are often absent or non-specific. Accordingly, we employed the hypocalcaemic effect of the diphosphonate APD to assess the effect of an acute fall in plasma calcium on indices of general well being, blood pressure, and vasoactive hormones in patients with mild primary hyperparathyroidism. Ten patients were studied in a randomized single blind, placebo-controlled cross-over study, using 30 mg APD intravenously or control saline infusion, over 2 h. Metabolic measurements, formal tests of muscle strength and cognitive function, and a standardized questionnaire were assessed 7 days after infusions. Albumin corrected plasma calcium was significantly lower (mean 2.49 +/- 0.04 SEM mmol/l) after APD when compared to control values (2.70 +/- 0.06 mmol/l, P less than 0.001). Twenty-four-hour urinary calcium, plasma magnesium and absolute monocyte count decreased significantly, whereas plasma parathyroid hormone increased after APD (P less than 0.05). There was no significant change in hypercalcaemic symptoms, muscle strength or cognitive function, and blood pressure, renin, aldosterone and atrial natriuretic peptide did not change. Side-effects, when they occurred, were mild. It is concluded that APD is a safe and effective means of lowering plasma calcium in mild primary hyperparathyroidism, but these acute reductions are associated with little or no improvement in clinical status in these patients. | 17 |
Casein kinase II is associated with neurofibrillary tangles but is not an intrinsic component of paired helical filaments. Neurofibrillary tangles (NFT) are pathological cytoskeletal structures composed of paired helical filaments (PHF), and are found in neurons of patients afflicted with many neurodegenerative disorders, including Alzheimer's disease (AD). We previously found that an antiserum against casein kinase II (CK-II) stained NFT intensely in the brain tissue of AD patients. In the current study, we found that the anti-CK-II antiserum stains NFT and neuronal inclusions in many other neurodegenerative diseases as well, including Guam-Parkinson dementia complex, chromosome 18 deletion syndrome, progressive supranuclear palsy, Kufs' disease, and Pick's disease. This antiserum reacted, in crude brain homogenates, with both a doublet of Mr 43,000 and a Mr 27,000 Da protein which could correspond to the alpha, alpha', and beta chains of CK-II. The staining of these bands was adsorbed by preincubating anti-CK-II antiserum with purified CK-II. Preincubation of brain sections with purified CK-II strongly intensified the immunostaining of NFT with anti-CK-II, suggesting that NFT may bind CK-II. In the AD brain homogenates, the particulate CK-II levels are increased whereas the cytosolic levels are decreased without a change in total CK-II levels, consistent with the idea that CK-II binds to the particulate PHF, a major constituent of NFT. In accord with these findings, purified PHF bound CK-II, but purified PHF did not contain CK-II as its component. These results suggest that CK-II might be an extraneously deposited component of NFT. Thus, the altered CK-II compartmentalization might have significant consequences in the pathogenesis of AD. | 16 |
Antagonism by guanosine 3',5'-cyclic monophosphate derivatives against the action of adrenaline on the automaticity of isolated rat heart muscle cells in culture. Spontaneously and rhythmically beating single cells from the ventricles of new-born rats were cultured on coverslips for 3 to 4 days and transferred to a small perfusion chamber for photoelectric recording of their contractions. The cells responded to 3 - 10(-7) M adrenaline with a pronounced increase and to 1.7 - 10(-5) M carbamylcholine with a mode-rate decrease in the rate of beat. Carbamylcholine nearly abolished the beat-accelerating effect of adrenaline. 8-Bromo cyclic GMP and N2-2'-O-'DIBUTYRYL CYCLIC GMP, in concentrations of 4.2 to 8.4 - 10(-4) M, exerted only very slight depressant effects on the basal rate of beat, but strongly antagonized, and in the majority of experiments with 8-bromo cyclic GMP completely suppressed, the positive chronotropic action of adrenaline. Cyclic GMP, 5'-GMP, and 5'-guanylylimidodiphosphate were without effect. 8-Bromo cyclic AMP caused a marked acceleration of beating. In view of the mediator roles that cyclic AMP and cyclic GMP have been assigned in the cardiac actions of beta-adrenergic and of cholinergic agents, respectively, the present results may be interpreted as being indicative of an adrenergic-cholinergic antagonism at the level of these two cyclic nucleotides. | 18 |
[Allergy: the pressing need for public education]. Data collected using a self-questionnaire filled out by the families of 294 children under 12 years of age seen in a pneumoallergology clinic showed widespread lack of information on the role of environmental factors in allergic diseases. Parents ascribed their child's disease to the environment at home only when they were dissatisfied by their housing conditions. Parents who were satisfied with their home failed to perceive that indoor factors with detrimental effects may nevertheless be present. This lack of information was seen across the spectrum of enrolled patients, including in those with hypersensitivity to house mites. The need for health education of the public at large aimed at promoting preventive strategies is underlined. | 14 |
Simultaneous estimation of blood flow rate and tissue temperature. A new method for simultaneously estimating blood flow rate and tissue temperature under a RF hyperthermia treatment is presented. In this method the finite element method is used to solve the two-dimensional Laplace equation for a specific absorption rate (SAR) distribution and the two-dimensional bioheat transfer equation for a tissue temperature distribution from the SAR pattern over a cross-section of a patient-specific model input from computer tomography images. Blood flow rates used in the temperature distribution computation are determined from basal values given for respective types of tissues and tissue temperatures through an assumed function that is intended to represent the temperature dependence of the blood flow rate. The tissue temperature computation procedure is iterated until the estimated temperature at a given sampling point matches a measured value at that point. This iterative procedure allows one to simultaneously estimate blood flow rate and tissue temperature. This paper describes the numerical method along with results of rudimentary in vivo measurements made in a human brain, where blood flow rate was measured by the single photon emission computed tomography (SPECT) imaging technique and tissue temperature was measured by an invasive probe technique. | 20 |
[The possibility of the incorporation of macromolecules, including exogenous DNA, into the germ cells of male mice. The liposome method and Ca-P coprecipitation method]. Liposomes loaded with FITC-labeled albumin in the presence of PEG-1,500 are actively sorbed on the membranes of mature spermatozoa and remain attached even after thorough washing. Immature sperm cells are able to incorporate alien DNA carried by liposomes. In contrast, the mature spermatozoa could not incorporate plasmid DNA loaded with positively charged liposomes. Chlortetracycline in Ca-P coprecipitate crystals is tightly fixed in the postacrosomal region of mature sperms. Intensity of staining of chlortetracycline is stimulated by DNA load in Ca-P coprecipitate as well as by DMSO or EDTA. The method of Ca-P coprecipitation could not provide for plasmid DNA incorporation into taure sperms. Foreign DNA incorporation in postacrosomal regions of sperm heads seems quite possible in experiments with dimethylsulphoxide (DMSO). | 13 |
Laser laparoscopic herniorraphy: a clinical trial preliminary results. Laser laparoscopic inguinal herniorraphy represents an extension of current technology. Based on the principles of preperitoneal inguinal herniorraphy, it is performed by internal incision of the peritoneum and identification of the musculofascial defect through a laparoscope. Polypropylene mesh is then passed down the laparoscope, placed into the defect to obliterate the space, and the edges of the peritoneum are then reapproximated. Results in 20 patients with an 11 month followup indicates success in nineteen exhibiting early resumption of activity (3.3 days) and minimal pain (2.1 Tylenol #3 tablets per patient). One early recurrence suggests that anatomic identification of a direct space hernia may be difficult and that routine support of this area with additional mesh may be a requirement of a complete inguinal hernia repair. | 18 |
[The comparative characteristics of the hemodynamic and biochemical indices of the postischemic period in relation to the regimens of brain autohemoperfusion]. In anesthetized cats, comparative characteristics of hemodynamics and biochemical indications of postischemic period in respect to autohemoperfusion with stable blood volume and perfusion pressure, were determined. Cerebral ischemia was caused by the 15-min stop of the perfusing pump or flowmeter and a decrease of systemic arterial blood pressure to 40 ml Hg. In the autohemoperfusion of brain vessels in stable volume or stable arterial pressure, a phasic postischemic phenomenon becomes obvious. The regularity of modifications of the glucose and oxygen consumption by the brain, concentration of lactate and pyruvate under different conditions of autohemoperfusion, was found. | 19 |
Molecular analysis of an esterase-encoding gene from a lipolytic psychrotrophic pseudomonad. An esterase gene (estA) from a lipolytic psychotroph (Pseudomonas sp. LS107d2), was cloned in Escherichia coli and its nucleotide sequence was determined, revealing an ORF encoding a polypeptide of 389 amino acid residues, with a molecular mass of 42276 Da. Labelling of plasmid-encoded proteins with [35S]methionine, using the maxicell procedure, gave a single polypeptide of molecular mass 42 kDa, consistent with that calculated from the ORF. Colonies of E. coli cells containing estA produced a clear halo when grown on solid media containing tributyrin; no clearance was produced when cells were grown on media containing triolein. Extracts of cells containing estA also hydrolysed water-soluble nitrophenol esters, but were unable to cleave water-insoluble substrates. The preference for water-soluble substrates indicates that the gene product is an esterase. | 16 |
Pharmacy computer prescription databases: methodologic issues of access and confidentiality. To examine methodologic issues of access and confidentiality regarding the use of pharmacy computer prescription databases (PCPDs) for participant selection to receive mailed, self-administered, hypertensive quality-of-life survey outside a primary-care setting. Two separate PCPD searches by pharmacist owners for patients prescribed at least one of 130 potential antihypertensive medications. The first PCPD used a nonrandom sample of all patients (n = 635); the second PCPD used a random sample (n = 100) of three specific antihypertensive drug groups. Research protocol was approved by the investigators' institutional review board. Two independent, privately owned PCPDs. Individuals prescribed at least 1 of 130 PCPD medications potentially used in antihypertensive treatment. Individually addressed cover letter on pharmacy letterhead signed by a pharmacist requesting voluntary completion of the enclosed, self-administered, opinion survey on quality of life. Anonymous survey return to off-site post office box in envelope provided. Favorable or no opposition to PCPD methodology from pharmacist or participants. Ethical opposition was encountered when incorporating PCPD sampling technique into grant proposal. The American Pharmaceutical Association Code of Ethics is used as a basis to provide recommendations to examine and justify PCPD investigative use. Increasing availability of PCPD technology encourages more efficient and easier methods of research strategy. PCPD use, however, demands identical stringent guidelines used in traditional research and raises potential issues regarding pharmacist-patient confidentiality as well as the right of PCPD use by others. | 16 |
Effect of subacute intoxication with some heavy metals on hexobarbital sleep and metabolism. In experiments on albino rats it is found that cobaltous dichloride, cadmium nitrate, nickel sulphate, copper sulphate and lead acetate, applied subcutaneously for 7 days, potentiate hexobarbital anaesthesia, while mercury dichloride and iron dichloride have no effect on it. A higher hexobarbital content is found in the blood serum of rats, treated with cobaltous dichloride, cadmium nitrate, nickel sulphate, copper sulphate and lead acetate, compared with the control animals. Treatment for 7 days with cobalt dichloride, cadmium nitrate, copper sulphate and nickel sulphate inhibits the activity of the liver microsomal hexobarbital-oxidizing enzyme system. The prolonged hexobarbital sleep in rats subjected to subacute intoxication with cobalt, cadmium, nickel, copper and lead is probably due to a considerable extent to the inhibition of the hexobarbital metabolism by these metals. | 20 |
Gas chromatographic determination of micro amounts of cyanide residues in wines, distilled liquors, and other alcoholic beverages. A gas chromatographic method for the determination of cyanide residues in alcoholic beverages has been developed from procedures previously reported for application to water samples. Quantitatively isolating HCN from alcoholic beverages presented difficulties not encountered with aqueous solutions, particularly in the presence of S02 in the sample. HCN was liberated from the acidified sample by heating at 70 degrees C, flushed into an NaOH absorber solution, converted to cyanogen bromide (CNBr), extracted into diisopropyl ether, chromatographed on a Porapak Q column, and detected by an electron capture detector. S02 that is present in most wines interfered with the bromination step and caused low recoveries. This interference was eliminated by initially converting any cyanide present in the sample to the stable mercuric cyanide salt and then purging the acidified sample solution of all S02. The Hg(CN)2 present was then dissociated by adding KI and the analysis proceeded as previously described. Mean recoveries of 80-97% were obtained for 2-20 mug cyanide from replicate analyses of spiked samples of distilled liquors free of S02. The relative standard deviations ranged from 6.1 to 11.1%. Mean recoveries of 65 to 91% were obtained in the same range of cyanide from replicate analyses of spiked wine samples known to contain S02, with relative standard deviations ranging from 0.8 to 10.2%. The limit of detection was 0.2 mug HCN. | 17 |
Potassium transport in dispersed mucosal cells from guinea pig stomach. Dispersed mucosal cells (approx. 70% parietal cells) prepared from guinea pig stomach maintained their cellular concentration of potassium (65--80 nmol potassium/10(6) cells) for at least 5 h in vitro. Uptake of 42K by dispersed gastric mucosal cells depended on temperature, H+ concentration and oxidative metabolism. Carbachol and, in some instances, gastrin caused a 40--50% increase in cellular uptake of 42K as a consequence of the ability of these agents to increase 42K influx. Ouabain reduced uptake of 42K by 70% but did not alter the effect of carbachol. Cellular uptake of 42K was not altered by histamine, prostaglandin, E1, glucagon, secretin, vasoactive intestinal peptide or C-terminal octapeptide of cholecystokinin. Uptake of 42K was also increased by dibutyryl cyclic AMP or dibutyryl cyclic GMP but not by cyclic AMP, cyclic GMP or their 8-bromo derivatives. Theophylline caused a small (10--15%) increase in 42K uptake and potentiated the increase caused by submaximal concentrations of carbachol. The increase in 42K uptake caused by either dibutyryl cyclic nucleotide and carbachol was additive. | 14 |
Stressor-induced alterations of natural killer cell activity and central catecholamines in mice. Natural killer (NK) cell cytotoxicity was determined at various intervals (0.5, 24 or 48 h) following exposure to uncontrollable footshock in 3 strains of mice. Stressor application provoked reductions of NK activity, but the time course of the NK changes varied across strains. Whereas NK cytotoxicity was markedly reduced in C57BL/6J mice 0.5-48 h following stressor exposure, this effect was delayed in C3H/HeJ mice, being evident 24-48 h following stressor application. In BALB/cByJ mice, NK activity was significantly reduced 24 h after footshock, but in contrast to the other strains returned to control levels within 48 h of stressor exposure. Central NE and DA concentrations and activity were influenced by the stressor treatment in a strain-dependent fashion. However, the relationship between the central amine variations and the alterations of NK cytotoxicity associated with the stressor was limited. | 16 |
Interaction of digitalis and spironolactone with human sex steroid receptors. Spironolactone and digitoxin have previously been shown to interact with cytosol androgen and estrogen receptors, respectively, in the rat. The interaction of digitoxin with human uterine cytosol estrogen binding protein and spironolactone with human prostate and newborn prepuce cytosol dihydrotestosterone (DHT) binding protein has been analyzed in this study. Specific estradiol binding was found only in premenopausal uteri. The dissociation constant for estradiol binding was 0.6--2.3 X 10(-9) M (n - 12). Digitoxin in concentrations varying between 0.5--2.0 X 10(-6) M inhibited specific estradiol binding with a Ki of 2.0--7.3 X 10(-7) M (n = 9). The dissociation constants for DHT and the human androgen cytosol binding protein in prostate and newborn prepuce were 0.27--3.0 X 10(-8) M (n = 12) and 0.6--2.0 X 10(-8) M (n = 5), respectively. Spironolactone at concentrations of 0.3--2.0 X 10(-6) M competitively inhibited this binding with an affinity about one order of magnitude less than that of DHT. Digitoxin and spironolactone did not displace estradiol and DHT, respectively, from testosterone-estrogen binding globulin in male or female plasma. The interaction of digitoxin with the human uterus estrogen binding protein and spironolactone with the human prostate and prepuce androgen binding protein is similar to our previous observations in the rat, and may explain the weak estrogenic effects of digitoxin and spironolactone in man. | 17 |
Organization of amygdaloid projections to brainstem dopaminergic, noradrenergic, and adrenergic cell groups in the rat. The distribution of amygdaloid axons in the various brainstem dopaminergic, noradrenergic, and adrenergic cell groups was examined. This was accomplished by means of the Phaseolus vulgaris leucoagglutinin lectin (PHA-L) anterograde tracing technique combined with glucose-oxidase immunocytochemistry to catecholamine markers (i.e., tyrosine hydroxylase, dopamine beta hydroxylase, and phenylethanolamine N-methyltransferase). Injections of PHA-L in the medial part of the central amygdaloid nucleus resulted in axonal and terminal labeling in most catecholamine cell groups in the brainstem. Amygdaloid terminals appeared to contract catecholaminergic cells in several brainstem regions. The most heavily innervated catecholaminergic cells were the A9 (lateral) and A8 dopaminergic cell groups and the C2/A2 adrenergic/noradrenergic cell groups in the nucleus of the solitary tract. The medial part of the A9 and adjacent A10 dopaminergic cell groups was moderately innervated. A moderate innervation by amygdaloid terminals was observed on rostral locus coeruleus noradrenergic cells (A6 rostral) and adrenergic cells of the rostral ventrolateral medulla (C1). Noradrenergic cells of the A5, main body of the locus coeruleus (A6), A7, and subcoeruleus were sparsely innervated. Amygdaloid axons were not observed on noradrenergic neurons of the A4 cell group, area postrema, and A1 cells of the ventrolateral medulla. The results demonstrate that the amygdala primarily innervates the dopaminergic cells of midbrain (i.e., A8 and lateral A9 cells) and the adrenergic cells (C2) and noradrenergic (A2) cells in the nucleus of the solitary tract. The possible functional significance of amygdaloid innervation of catecholaminergic cells is discussed. | 19 |
Prediction of free phenytoin levels based on [total phenytoin]/[albumin] ratios. Potential errors with hypoalbuminemia. Therapeutic monitoring of the pharmacologically active (free drug) fraction of protein-bound medications (e.g., phenytoin) represents a major diagnostic challenge in clinical and laboratory medicine. While free drug levels may be beneficial in many clinical situations, current methods for predicting free phenytoin concentrations are unreliable and not recommended for general use. The authors have demonstrated a linear relationship (r2 = 0.98) between serum levels of total and bound phenytoin in 56 patients with seizure disorders. No significant correlations were observed when total phenytoin and albumin levels were compared independently to measured concentrations of free phenytoin or percent free phenytoin. A good correlation (r2 = 0.89) existed between free phenytoin levels and [total phenytoin]/[albumin] ratios in patients with normal or elevated albumin levels, but significantly weaker correlations were found in patients with hypoalbuminemia. Thus, [total phenytoin]/[albumin] ratios may have clinical value in predicting free phenytoin levels in uncomplicated patients without hypoalbuminemia. | 18 |
Pyruvate kinase isozymes in man. I. M type isozymes in adult and foetal tissues, electrofocusing and immunological studies. Anti human M2 type and anti human L type pyruvate kinase sera allowed us to distinguish two groups of pyruvate kinase in man. Erythrocyte and liver (L type) enzymes on the one hand were inhibited by anti L and not all by anti M2 serum; pyruvate kinase from all the other tissues on the other hand were inhibited by anti M2 and not at all by anti L serum. This latter group represent the M type pyruvate kinase isozymes. The M type isozymes have been studied by electrofocusing in thin layer acrylamide-ampholine gel. In adult tissues 4 types of isozymes were found, designated, from acid to alkaline pH, as M2 (predominant form in spleen, leukocytes, lung...), M3, M4 and M1 (predominant form in muscle and brain). In foetal tissues an extra band M2, called M2f, more anodic than M2, was added to the previously described isozymes. Except in brain (in which the isozymes M2, M3, M4 and M1 were found), the most anodic bands (M2f, M2 and M3) were predominant in all the foetal tissues. The isozymes M2f and M2 seem therefore to be the original M type pyruvate kinase forms from which the other isozymes issue. The rate of each isozyme seems to depend on tissue factors characterizing the state of differentiation of some tissues, as indicated by the ability of adult muscle extracts to change the isozymes M2 and M3 into more cathodic forms. | 14 |
Cell partition: a study of parameters affecting the partition phenomenon. Critical mixtures of aqueous solutions of polymers can be separated into two or more immiscible phases. Particulate materials are distributed in such phase systems generally between one bulk phase and the interface between bulk phases. The distribution is described by a simple partition law and is quantitatively determined by temperature, interfacial tensions, the electromotic potential difference between phases and the nature of the particle surface. The effects on transfacial potential differences of varying polymer, NaCl and sodium phosphate concentrations in dextran/polyethylene glycol systems were studied: increase of polyethylene glycol concentration increased the potential; addition of up to 40 mM NaCl progressively reduced the potential to zero: very small (less than 10 mM) concentrations of sodium phosphate buffer increased the potential, but further increase caused a fall in potential, which was less marked than that caused by equivalent concentrations of NaCl. The partition properties of a variety of cells, native or modified by treatment with trypsin, neuraminidase or maleic anhydride, were studied. In systems containing greater than 40 mM NaCl no difference in partition patterns for modifications of each cell type was observed. In systems containing no NaCl the partition pattern was highly dependent on the nature of the modification. From the behaviour of such models, polymer-electrolyte phase systems suitable for study of cell surface modification involving change, or no change, in net surface have been identified. | 19 |
Modification of vagal depressor reflex by CO2 in spontaneously breathing rabbits. The control of hindlimb and renal vascular beds by vagal afferents was studied, in anesthetized spontaneously breathing rabbits in which the carotid sinus and aortic depressor nerves were cut, by measuring the increase in vascular resistance (constant-flow perfusion with autologous blood) during bilateral vagal cold block (VCB). The effect of hypercapnia was studied with both increased ventilation (caused by inspiration of mixtures of CO2 in O2) and decreased ventilation (caused by infusion of gallamine during O2 breathing). The increase in hindlimb resistance with VCB was correlated with respiratory minute volume but not with PCO2; the reverse was true for the increase in renal resistance. Without VCB the renal vessel constriction caused by the hypercapnia was markedly attenuated, provided that there were minimal respiratory movements; the resistance increased dramatically when these movements were abolished or with VCB. Thus, the powerful central effect of CO2 on the renal vessels can be counteracted by vagal afferents activated by lung movement; even minimal respiratory activity can cause this effect. | 20 |
Involvement of supraspinal and spinal segmental alpha-2-adrenergic mechanisms in the medetomidine-induced antinociception. The effect of systemically administered medetomidine, a selective alpha-2-adrenoceptor agonist, was studied by electrophysiological recordings of the peripherally evoked responses of three different types of sensory neuronal populations in the rat: medial thalamic neurons exclusively responding to mechanical cutaneous stimuli at noxious intensities, spinothalamic tract neurons of the spinal cord responding exclusively or differentially to mechanical cutaneous stimuli at noxious intensities, and low-threshold mechanoreceptive spinal dorsal horn neurons with ascending projections. The neuronal effects were compared with the behavioral data obtained in mechanically and thermally induced nociceptive tail reflex tests in intact and spinal rats. A reversal of the antinociceptive effects was attempted by systemically (1.5 mg/kg, i.p.) or intrathecally (25 micrograms) administered atipamezole, a selective alpha-2-adrenoceptor antagonist. Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons. A lower dose of medetomidine was needed to suppress significantly (half-maximally) evoked responses of the nociceptive medial thalamic neurons (100 micrograms/kg) than those of the nociceptive spinothalamic tract neurons (300 micrograms/kg). The decrease of evoked responses of the nociceptive spinothalamic tract neurons was accompanied by a decrease in spontaneous activity. The responses of the low-threshold mechanoreceptive projection neurons of the spinal cord were not influenced by medetomidine (30-300 micrograms/kg). The reflex studies with a (anesthetic) medetomidine dose of 300 micrograms/kg indicated that in intact and otherwise drug-free rats, medetomidine produced a significant prolongation of the nociceptive reflex response latency to a tail-pinch and heat; these antinociceptive effects of systemic medetomidine were reversed by systemically and intrathecally applied atipamezole. In spinal rats systemically applied medetomidine (300 micrograms/kg) also produced a significant prolongation of the tail-flick latency, which was reversed by systemically applied atipamezole. The results suggest that a high anesthetic dose of systemically applied medetomidine (300 micrograms/kg) can suppress nociceptive sensory neuronal and reflex responses due to spinal segmental mechanisms through an action on alpha-2-adrenoceptors. This spinal effect is selective to responses of nociceptive neurons, and at least partly postsynaptic as indicated by the concomitant decrease in spontaneous activity. At a lower, subanesthetic (but sedative) dose (100 micrograms/kg) the antinociceptive effect of systemically applied medetomidine can be explained by supraspinal alpha-2-adrenergic mechanisms. | 23 |
In situ transformation of striatal glia into cerebellar-like glia after brain transplantation. Transplants of striatum from rabbit embryo were implanted into the colliculus posterior of newborn mice. After 4 weeks, astroglial cells derived from the transplant had migrated into the cerebellum of the host. Whenever they had settled in the cerebellum they presented forms similar to local glia. Some migrated glial cells were found to transform into forms of glia, such as radial-like glia, which are not present in the striatum. This observation confirms that glial precursor cells are highly plastic. It is an in vivo demonstration that local conditions alone define the morphology of glial cells. After grafting in an heterotopic location they take on forms that they were not destined to express in the region of origin. | 11 |
Determination of individual bile acids in serum by high performance liquid chromatography. A high performance liquid chromatographic (HPLC) method for analysis of 4 free and 8 conjugated bile acids in submicromolar quantities in serum is described using precolumn derivatization with 4-bromomethyl-7-methoxycoumarin (BMC) and fluorescence detection. Bile acids were extracted from serum with 0.4 M sodium bicarbonate, adsorbed onto a Sep-Pak C18 cartridge and eluted with methanol. The extract was derivatized with BMC in acetonitrile using 18-crown-6 crown ether as catalyst and the BMC labelled glycine conjugates and free bile acids were analysed using acetonitrile + methanol + water gradient elution and detection at 320/385 nm. Using a novel and simple approach, taurine conjugates were isolated by extracting the dried, derivatized material with water, in contrast to previous methods which required column chromatography cleanup to isolate the taurine conjugates prior to derivatization. The isolated taurine conjugates were then hydrolysed enzymatically, extracted, derivatized and analysed as free-bile acids. Recoveries of individual bile acids varied from 83-96% for free and glycine conjugates and 72-83% for taurine conjugates. Coefficients of variation were in the range of 5.1-12.5%. In addition to the simpler and shorter procedure for taurine conjugates, this method has increased sensitivity over most other procedures and improved HPLC separation for the various bile acids and conjugates with equivalent recovery and reproducibility compared with other published methods. | 20 |
Carbon dioxide-related changes in cerebral blood volume and cerebral blood flow in mechanically ventilated preterm neonates: comparison of near infrared spectrophotometry and 133Xenon clearance. Carbon dioxide-induced changes in near infrared spectrophotometry recordings were compared with changes in cerebral blood flow estimated by 133Xenon clearance (global cerebral blood flow (infinity)) at serial measurements in 24 mechanically ventilated preterm infants (mean gestational age 30.2 wk). In all infants, three measurements were taken at different arterial carbon dioxide tension levels (mean 4.4 kPa, range 2.1-7.8) obtained by adjustment of the ventilator settings. Mean arterial blood pressure changed spontaneously, whereas arterial oxygen tension was kept within normal range. At all wavelengths (904, 845, 805, and 775 nm), the OD increased at higher arterial carbon dioxide tension levels, indicating cerebral vasodilation. This conclusion was supported by conversion of the data to changes in oxygenated and deoxygenated Hb concentration. A parallel increase in cerebral blood volume index and global cerebral blood flow (infinity) was found (p less than 0.0001). The oxygenation level of cytochrome aa3 increased with increases in oxygen delivery (p less than 0.0001). This observation, however, may have been artifactual due to cross-talk between the oxidized cytochrome aa3 and the oxygenated Hb signals, as these signals were closely interrelated in the present experimental design. We suggest that near infrared spectrophotometry may be used for estimation of the cerebral blood volume index/cerebral blood flow-CO2 reactivity within a wide range of arterial carbon dioxide tension. Knowledge of the light path length would put this estimation on a quantitative basis. | 17 |
The muscarinic receptor gene expressed in rabbit parietal cells is the m3 subtype. To investigate the nature of the muscarinic receptors present on parietal cell membranes, binding studies and polymerase chain reaction (PCR) amplification of parietal cell messenger (m) RNA were undertaken. Displacement of N-[3H]methylscopolamine by various muscarinic antagonists showed displacement with a single affinity. The apparent dissociation constant values were as follows: atropine (nonselective), 1.95 +/- 0.28 nmol/L; pirenzepine (M1), 169 +/- 24 nmol/L; AF-DX 116 (M2), 1542 +/- 33 nmol/L; and hexahydrosiladifenidol (M3), 29 +/- 3.4 nmol/L. These data confirmed the existence of only an M3 receptor linked to acid secretion as defined pharmacologically. PCR amplification of parietal cell mRNA with primers designed for detection of all known muscarinic receptor subtypes showed that only m3 fragments were produced from parietal cell mRNA, whereas m1 and m2 products could be detected in brain or cardiac mRNA. The m3 nature of the PCR product was confirmed by Southern blotting with 32P-labeled human m3 complementary DNA. Hence the two carbachol affinities and the separable cellular responses following muscarinic activation are caused by separate coupling pathways of the M3 receptor. | 18 |
Specificity of the inhibition of DNA synthesis by extracts from cloned normal, sarcoma-virus-transformed and revertant 3T3 cells. Extracts containing tissue-specific DNA-inhibitory activity were prepared from normal FL (Swiss) and BALBc3T3 cells, from these cells transformed with sarcoma virus and from revertants cloned from the transformed cell lines. By testing all extracts on all cell lines we found that (1) production of and susceptibility to the inhibitors were decreased in transformed BALB/c cells (2) specificity varied with expression of the transforming genome, as an extract from a given cell line inhibited the growth of its cell of origin, e.g. revertant, more than normal or transformed cells, and (3) there was also a DNA-synthesis stimulator. | 18 |
[Significance of renal dopamine on pathogenesis of essential hypertension]. In order to clarify the role of renal dopaminergic activity in renal sodium-water metabolism, the effects of oral administration of L-DOPA (400 mg), were studied on blood pressure (BP), plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary volume (UV), urinary excretion of sodium and lithium (UNa and ULi) in 11 normal subjects (N) and 32 patients with essential hypertension (EH). EH were divided into the salt sensitive (SS) and non salt-sensitive (NSS) groups by response of mean blood pressure (10% increase) after administration of NaCl. The change of UNa, PRA, and PAC after administration of NaCl were lower in SS than in NSS. After administration of L-DOPA, BP falled and UV, UNa, FENa, FELi and Ccr increased in both N and EH. The change of these factors were greater in SS as compared with those in NSS. These results suggest that in SS patients the suppression of water-sodium handling in the kidney might be due to depression of renal dopaminergic activity. Renal dopaminergic activity may play an important role in the pathogenesis of EH. | 15 |
Lead poisoning in adults from renovation of an older home. Presented is the case of a group exposure to lead occurring during the removal of lead-based paint from an older home. One patient had symptoms from the time of exposure to the time of presentation, when he was acutely ill and encephalopathic. The patient was treated successfully with an initial course of British Anti-Lewisite agent and calcium disodium versenate (CaEDTA) chelation, and two subsequent chelations with CaE-DTA alone. The other two patients had elevated lead levels but were asymptomatic. They were followed closely, and their lead levels steadily declined over several months. The evaluation and treatment of lead poisoning and excessive lead levels in adults is discussed, as is the need for physicians and the lay public to become aware of the hazards of renovating older homes. | 14 |
Visken as supplementary drug in the treatment of pemphigus. Results of combined treatment with low doses of steroids (50-10-5 mg) and Visken (7.5-15 mg) in 5 cases of pemphigus erythematosus and 5 cases of pemphigus vulgaris are presented. Treatment lasted from 30 days to 1.5 years. Some of the patients had been previously treated with steroids and immunosuppressive drugs, but had active lesions or frequent recurrences. In pemphigus erythematosus, very good results were obtained in 3 of 5 cases, and failure in 2 cases was probably related to insufficient dosage of steroids, or no treatment with steroids at all. In pemphigus vulgaris results were not satisfactory. Visken can serve as a supplementary drug in the treatment of pemphigus erythematosus. No complications were observed, and the drug may be regarded as safe. | 11 |
The effects of low-pass filtering on the flash visual evoked potential of the albino rat. Flash visual evoked potentials (FVEPs) were recorded from the rat in order to determine the effects of low-pass filtering on the wave form. The low-frequency (high pass) filter remained fixed at 3.2 Hz while the setting of the high-frequency (low-pass) filter was progressively raised from 32 Hz to 3.2 kHz. The amplitude of the primary cortical potential (P30) steadily increased while its latency decreased until asymptotic values were recorded with a low-pass cut-off of 320 Hz. Thereafter, there was little additional change in wave form. It is concluded that a bandpass of 3.2-320 Hz is optimal to record the primary cortical response of the FVEP, and this is consistent with the theory that the P30 potential is generated by comparatively slow post-synaptic activity. In a second experiment the effects of low-pass filtering were examined on the later and more labile secondary components of the FVEP wave form. These were found to be less responsive to low-pass filtering than the early components and assumed a near optimal configuration when the high-frequency cut-off was raised to 80 Hz. The high-frequency filter setting which is most appropriate to record the primary component of the FVEP therefore appears to be more than adequate also to record the secondary responses. It is also shown that the same principles of low-pass filtering on the FVEP will apply irrespective of whether the subject is awake or anaesthetised. | 16 |
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