Biomedical subjects
Publications and source records attributed to S Vyas.
In 24 red cell isoimmunized pregnancies the fetal middle cerebral artery mean blood velocity increased with anemia. The blood velocity was not related to fetal blood PO2 and the relation of increased velocity to anemia was not affected by the pulsatility index. These findings suggest that the hyperdynamic circulation is a consequence of decreased blood viscosity.
In 81 small-for-gestational age fetuses (SGA) colour flow imaging was used to identify the fetal middle cerebral artery for subsequent pulsed Doppler studies. Impedence to flow (pulsatility index; PI) was significantly lower, and mean blood velocity was significantly higher, than the respective reference ranges with gestation. Fetal blood sampling by cordocentesis was performed in all SGA fetuses and a significant quadratic relation was found between fetal hypoxaemia and the degree of reduction in the PI of FVWs from the fetal middle cerebral artery. Thus, maximum reduction in PI is reached when the fetal PO2 is 2-4 SD below the normal mean for gestation. When the oxygen deficit is greater there is a tendency for the PI to rise, and this presumably reflects the development of brain oedema.
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To elucidate the role of the diacylglycerol-protein kinase C (PKC) pathway in beta-endorphin synthesis and secretion in anterior pituitary corticotrope tumor cells (AtT-20), a procedure for down-regulating PKC activity in the cells was developed. Treatment of AtT-20 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) led to an increase in [3H]phorbol 12,13-dibutyrate binding to PKC in the membrane fraction of these cells 30 s after its addition to the culture medium. Thereafter, a decrease in both [3H]phorbol 12,13-dibutyrate binding and PKC-specific phosphotransferase activity occurred in a time- and dose-dependent manner in both the cytosolic and membrane fractions. For example, treatment of the cells with 100 nM TPA for 24 h resulted in an almost complete depletion of PKC activity. Immunoreactive beta-endorphin secretion was found to be stimulated two- to fourfold in the control cells after incubation with corticotropin-releasing factor (10(-7) M), forskolin (10(-6) M), or TPA (10(-7) M) for 4 h. In cells rendered PKC deficient, TPA-stimulated immunoreactive beta-endorphin release was abolished, forskolin-stimulated release was unaffected, and corticotropin-releasing factor-stimulated release was depressed. Treatment of control cells with any one of the three stimulatory agents led to an increase in proopiomelanocortin mRNA levels, and these responses were also depressed after TPA pretreatment. The results suggest that physiological processes thought to be entirely cyclic AMP dependent, such as corticotropin-releasing factor-elicited secretion, may be partially dependent on PKC-mediated biochemical events.
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Color flow mapping was used to identify the fetal renal artery and to obtain flow-velocity waveforms. A reference range of the fetal renal artery pulsatility index with gestation was constructed from a cross-sectional study of 114 appropriate for gestational age fetuses of 17 to 43 weeks' gestation. The pulsatility index decreased linearly with gestation, indicating a fall in impedance to flow, and presumably an increase in renal perfusion. The renal artery pulsatility index was also determined in 18 small-for-gestational-age fetuses and was higher than the appropriate-for-gestational-age group. The small-for-gestational-age fetuses also had fetal blood sampling performed by cordocentesis. A significant, direct correlation was found between blood oxygen deficit and increased renal artery pulsatility index.
Color Doppler imaging could easily and rapidly detect the absence of an umbilical artery, despite the presence of oligohydramnios in one case and multiple cord loops involving a normal cord in the other case. In the third case, which on gray-scale imaging appeared as an indeterminate cystic structure of the cord, color Doppler imaging demonstrated a complex abnormal vascular pattern suggestive of an angiomyxoma.
Serial measurements of fetal bladder volume were obtained by real-time ultrasonography at 2- to 5-minute intervals, and the hourly fetal urine production rate was calculated. The mean hourly fetal urine production rate increased from 5 ml/hr at 20 weeks' gestation to 51 ml/hr at 40 weeks. These values are double those reported in previous studies that measured fetal bladder volumes at 15- to 30-minute intervals because the cycle length is shorter than previously thought.
A postal survey among families of 63 children attending two BDA educational holidays studied their expectations before (Questionnaire 1) and experiences 3 months afterwards (Questionnaire 2). Of 47 families replying to both questionnaires (22M, 25F; mean age 8.4 years, range 5-13.8 years), expectations expressed by parents for their children were that they gain in confidence and independence (n = 36), mix with other diabetic children (n = 32), learn to self-inject (n = 27), improve diet (n = 23), and have a good holiday (n = 10). Thirty-five families subsequently reported that their expectations had been met. After the holiday, although there was no change in frequency of blood or urine testing, there was an increase in children doing tests on their own (Q1: 15, Q2: 28, p = 0.003); more parents reported confidence in their child recognizing a hypoglycaemic episode (Q1: 29, Q2: 39, p = 0.001); and there was a sustained increase in independence with insulin injections (Q1: 29, Q2: 35, p = 0.042). This study provides evidence that BDA holidays benefit parents and their children, and do so mainly by increasing the children's confidence and independence in diabetic care.
The amino acid content of Torpedo synaptosomes was investigated. It was found that glutamate and taurine were particularly enriched, their concentration exceeding that of acetylcholine by 50-60%. Other amino acids such as alanine, gamma-aminobutyric acid (GABA), glycine, leucine and phenylalanine were also present, but in smaller quantities. The neurotransmitter-releasing agents gramicidin, calcium ionophore A23187, High K+ and Glycera venom all released acetylcholine, as shown previously. However, both glutamate and taurine were found to be released by these agents together with acetylcholine. The efflux of all 3 compounds was found to be largely calcium dependent.
Treatment of old rats, for two to three weeks, with pyrithioxin led to an increase in the levels of endogenous acetylcholine (ACh) in the cortex and the striatum but not in the hippocampus. Pretreatment of old rats with pyrithioxin also increased the resting release and the K+ stimulated release of radioactive ACh from brain slices in vitro.
Advantage was taken of a preparation of proteoliposomes made using Torpedo presynaptic membranes in which both the internal and external media can be controlled to investigate the effects of membrane potential and the Na+ gradient on choline transport activity. Under control conditions, Na+ outside and K+ inside, choline was concentrated by proteoliposomes and this phenomenon was sensitive to hemicholinium-3 and high levels of external choline. While proteoliposomes showed no permeability towards K+ spontaneously, in the presence of valinomycin a transmembrane potential was developed. The rate of transport was higher, the greater the inside negative potential. Both the affinity and the maximal velocity of high affinity transport rose in the presence of a potential. Likewise, the affinity and velocity of this transporter increased with increasing external Na+. Increasing internal Na+, on the other hand, caused a decrease in affinity and had little effect on the maximal velocity. The low affinity component was much less, if at all, affected by these changes. These results are consistent with a model of high affinity choline transport in which Na+ binds before choline and the carrier-Na+-choline complex is positively charged. However, these results do not provide a direct explanation for choline transport activation by nerve activity, underlining the need to study the effects of parameters other than membrane potential and the Na+ gradient on choline transport activity.
Proteoliposomes made by a butanol-sonication technique from electric organ presynaptic membranes showed choline transport activity. In contrast to intact nerve terminals, the uptake of choline was dissociated from its conversion to acetylcholine in this preparation. The kinetics of choline uptake by proteoliposomes was best described by two Michaelis-Menten components. At a low concentration of choline, uptake was inhibited by hemicholinium-3 and required external Na+ and, thus, closely resembled high-affinity choline uptake by intact cholinergic nerve terminals. Choline transport could be driven by the Na+ gradient and by the transmembrane potential (inside negative) but did not directly require ATP. External Cl-, but not a Cl- gradient, was needed for choline transport activity. It is suggested that internal K+ plays a role in the retention of choline inside the proteoliposome. Proteoliposomes should prove a useful tool for both biochemical and functional studies of the high-affinity choline carrier.
Mice initially infected with single and repeated doses of Hymenolepis nana deshelled eggs produced rapid and significant expulsion of challenged Ancylostoma caninum larvae. Absolute protective response was observed 8 days after initial infection (at 96 hours after challenge) in both singly and repeatedly infected groups probably due to high titres of heterologous reacting antibodies.
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1. Cimetidine produced dose-dependent contractions in isolated guinea pig ileum and these responses were not blocked by mepyramine the H1-receptor antagonist. 2. Atropine competitively inhibited the cimetidine-induced contractions in the guinea pig ileum. 3. Cimetidine-induced responses were potentiated in the presence of eserine. Magnesium ions non-competitively inhibited the contractions due to cimetidine. Our findings suggest that cimetidine excites the guinea pig ileum through muscarinic receptors by releasing acetylcholine.
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