Brain morphological changes in 1st episode cases of schizophrenia: are they progressive?
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Biomedical subjects
Publications and source records attributed to A Anand.
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A hydropic premature infant with intrauterine growth retardation died at 4 days of age and was found at necropsy to have advanced liver disease. Clinical and serologic findings in mother and infant were consistent with recent parvovirus B19 infection. Parvovirus can cause fetal liver disease in animals, and some instances of congenital hepatic dysfunction in man may be due to intrauterine parvovirus B19 infection.
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1. An attempt has been made to reconcile differing observations, made by different groups of investigators, on the responses of aortic chemoreceptors of cats during normoxia, hypoxia and hypercapnia. 2. In cats anaesthetized with sodium pentobarbitone it was observed that during hypoxic stimulation of twelve chemoreceptors, an intravenous injection of about 20 mg sodium pentobarbitone produced hypotension which was accompanied by an initial fall in chemoreceptor activity instead of the expected increase that invariably occurred in all the receptors when hypotension was produced mechanically by distending a balloon in the right atrium (twenty-six during normoxia, eleven during hypoxia and eight during hypercapnia). 3. In twelve receptors a reflex fall in blood pressure produced by injecting 8-25 micrograms veratridine (Bezold-Jarisch reflex) yielded results qualitatively similar to those following injection of sodium pentobarbitone. 4. In sixteen out of twenty-five chemoreceptors it was observed that ventilating the cat with 5.6-6.7% CO2 produced either no or little increase in activity; in nine receptors there was a clear increase in activity, which fell initially or was abolished after injecting a single dose of 20 mg sodium pentobarbitone. 5. In all seven chemoreceptors tested in seven deeply anaesthetized cats it was found that a larger dose (about 50-60 mg) of sodium pentobarbitone had no direct depressant effect on aortic chemoreceptor activity. It followed that the initial depressant effect of the much smaller doses of sodium pentobarbitone observed during hypoxic and hypercapnic stimulation (see above) must be due to reduction in the sympathetic outflow to the aortic bodies. This conclusion was supported by the results following injections of veratridine. 6. By comparing the present results with those reported previously it was concluded that the variations in the responses of aortic chemoreceptors during hypoxia and hypercapnia reported by different investigators could be partly due to variations in the level of sympathetic activity prevailing under different experimental conditions.
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Human parvovirus is the causative agent of erythema infectiosum, a mild epidemic illness. In a recent outbreak in northeast Scotland, six women had serologic evidence of having contracted human parvovirus infection during pregnancy. Two of the women had midtrimester abortions, and both abortuses were grossly hydropic with anemia. They had similar microscopical histopathological features--a pronounced leukoerythroblastic reaction, hepatitis, excessive iron pigment in the liver, and eosinophilic changes in the hematopoietic cell nuclei. Dot hybridization with radiolabeled human parvovirus DNA probes revealed viral DNA in several tissues from both fetuses, indicating that they had been infected by the virus in utero. The remaining four women had uncomplicated pregnancies and delivered apparently healthy babies, none of whom had human parvovirus-specific IgM antibody at delivery. We conclude that this common virus may pose a serious risk to the fetus after maternal infection.
In whatever mammalian receptor system Merkel cells are found, they are always associated with a characteristic slowly adapting response. The role of Merkel cells in the transduction process of slowly adapting Type I cutaneous mechanoreceptors (SAI receptors or touch domes) of rats and cats was investigated by mechanical and electrical stimulation of SAI receptors and their afferent fibers in an O2-depleted environment. Circulatory hypoxia was produced either by ventilating animals with N2 or by recirculating venous blood around a limb. In both these experimental preparations, the results obtained were identical. For receptor failure to occur, it was found necessary to have an O2-depleted environment on the limb surface. This was achieved by passing N2 into a gas-tight polythene sock placed over the limb. Replacement of N2 within the polythene sock with O2 was sufficient to bring about receptor recovery, irrespective of arterial blood PO2 levels. There was an inverse linear relationship between receptor response and time when touch domes were stimulated with N2 around the limb. In contrast, the replacement of N2 around the limb with O2 produced an exponential increase in the response with time. Correlated with receptor failure was a significant reduction in the number of dense-cored vesicles normally found in the Merkel cell cytoplasm adjacent to the nerve ending innervating the cell. Receptor recovery was associated with a return in the number of dense-cored vesicles back to that found in control cells. Hypoxia had no effect on the level of electrical stimulation necessary to initiate an action potential in the afferent fiber, even though the response of SAI receptors to mechanical stimulation had ceased. The results indicate that Merkel cell dense-cored vesicles are necessary for the characteristic slowly adapting response of SAI mechanoreceptors and that this may be due to the secretion of a transmitter substance stored within the vesicles.
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The rate constants and lumped constants (LCs) for [18F]fluorodeoxyglucose ([18F]FDG) and [11C]deoxyglucose ([11C]DG) were determined in humans for the glucose metabolic rate kinetic model used to measure local cerebral glucose consumption. The mean values (+/- SE) of the LCs for [18F]FDG and [11C]DG are 0.52 +/- 0.028 (n = 9) and 0.56 +/- 0.043 (n = 6), respectively. The mean values (+/- SE) of the rate constants k*1, k*2, k*3, and k*4 for [18F]FDG for gray matter are 0.095 +/- 0.005, 0.125 +/- 0.002, 0.069 +/- 0.002, and 0.0055 +/- 0.0003, respectively. The corresponding values for white matter are 0.065 +/- 0.005, 0.126 +/- 0.003, 0.066 +/- 0.002, and 0.0054 +/- 0.0006, respectively. Using these values and previously published values for the rate constants for [11C]DG, the average whole-brain metabolic rates for glucose in normal subjects measured with [18F]FDG and [11C]DG are 5.66 +/- 0.37 (n = 6) and 4.99 +/- 0.23 (n = 6) mg/100 g/min, respectively. These values are not significantly different (t = 1.56, p greater than 0.10) and agree well with reported values in the literature determined by means of the Kety-Schmidt technique.
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Cardiovascular control during asthma and other forms of obstructed breathing has not been extensively investigated. Previous studies in dogs have shown that obstructed breathing or an inspiratory effort against a blocked airway (Mueller maneuver) provoke large oscillations in blood pressure. During the inspiratory phase transmural systolic pressure relative to atmosphere drops initially, but transmural systolic pressure relative to intrathoracic pressure can remain unchanged or even increase. Because the carotid baroreceptors are located in the extrathoracic circulation, whereas the aortic baroreceptors are located in the intrathoracic circulation, and each responds to local transmural arterial pressure, simultaneous baroreceptor output from these two areas was measured in the anesthetized cat during normal and obstructed breathing and during Mueller maneuvers. Both whole-nerve and single-fiber preparations showed a significantly decreased output from the carotid baroreceptors during obstructed inspiratory efforts, whereas aortic baroreceptor output decreased significantly less or not at all. Transmural systolic pressure decreased significantly less in the aorta than in the carotid regions. Further, the aortic baroreceptors were more sensitive to changes in pulse pressure than were the carotid baroreceptors. These results suggest a mechanism for stabilizing the cardiac responses to precipitous falls in blood pressure that occur in obstructed breathing.
1. Experiments carried out on anaesthetized cats showed that increasing blood flow, through the lobes of a lung, by 133% (S.E. 33%) generated an average of 0.75 impulses/sec (S.E. 0.3) in ten almost silent J receptors. Equivalent activity was produced by injecting 12-18 micrograms phenyl diguanide/kg into the right atrium. Such activity caused marked reflex effects, i.e. apnoea, rapid shallow breathing and reduction in the knee jerk. 2. The reflex effects of J receptors were studied after blocking the activity from cardiac receptors by intrapericardial injections of xylocaine. This was necessary because left atrial injections of phenyl diguanide produced reflex respiratory effects and inhibition of the knee jerk. 3. Hypoxia, but not hypercapnia, attenuated the reflex effects of J receptors, apnoea being abolished if the Pa,O2 fell below 35 mmHg. This was a central effect as it occurred in spite of increased activity of J receptors following phenyl diguanide, and effects of hypoxia persisted after cutting both carotid nerves. 4. The only invariable reflex effect of J receptors was a reduction in the total number and the average frequency of phrenic impulses in each breath. The changes in inspiratory time (ti) and expiratory time (te) following apnoea were variable although most frequently both were reduced. In about half the observations the first effect before the apnoea was a reduction in ti, in the other half it was a reduction in te. It was concluded that an input from J receptors inhibits inspiratory and expiratory mechanisms directly. 5. In some cats apnoea and rapid shallow breathing produced by J receptors continued after interrupting their activity by vagotomy and this did not diminish the reduction in ti or te; in other cats it did. The reduction in te was at times quite independent of changes in ti, i.e. pulmonary stretch receptor activity. 6. It was concluded that J receptors must be stimulated during moderate exercise to levels that produce marked respiratory reflex effects and inhibition of muscles.
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Impulses were recorded in single afferent fibres of aortic chemoreceptors of cats anaesthetized with chloralose. As expected raising the blood pressure (BP) passively by occluding the abdominal aorta, consistently reduced or abolished the activity of the chemoreceptors. This reduction persisted for as long as the BP remained high. Stimulating the sensory receptors of the small intestines increased the activity of 10 aortic chemoreceptors. The increased activity persisted after bilateral adrenalectomy but it was abolished by blocking the nerves of the mesentery with xylocaine. The increased activity was noteworthy because it occurred in spite of the rise in blood pressure (that always occurred when the intestines were squeezed) which by itself would tend to reduce the activity of the chemoreceptors. It was concluded that stimulating the intestinal receptors produces a reflex increase in the activity of aortic chemoreceptors by causing a reduction of glomeral blood flow through impulses in the sympathetic fibres.
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An Ala322Asp mutation in the GABRA1 gene was recently reported to be responsible for causing the autosomal dominant (AD) form of juvenile myoclonic epilepsy (JME) in a French-Canadian family. To study if JME families from India exhibiting the AD mode of inheritance carry the Ala322Asp mutation, we examined 35 unrelated JME-affected individuals from such families for the Ala322Asp mutation in GABRA1. Ala322Asp mutation was not observed in any of these JME-affected individuals, suggesting that this mutation is unlikely to be a predominant mutation involved in causation of epilepsy. To evaluate the possibility of other mutation(s) in and around GABRA1 that may predispose to JME, we compared the allele frequencies at two marker loci, D5S2118 and D5S422, flanking GABRA1, in probands and 100 matched population controls. One of the allele frequencies at D5S422 shows a significant difference between the cases and controls (chi-square = 11.44, d.f. = 1, P = 0.0007), suggesting genetic association between JME and genes located in the proximity of the DNA marker.