The structure of HPr and site-directed mutagenesis.
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Biomedical subjects
Publications and source records attributed to S Sharma.
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To study the effect of T-cell-derived BCGF-12kD on human B-cell autocrine growth-associated functions, we cultured Epstein Barr virus (EBV)-transformed normal B cells (LCL 72285) and Burkitt's lymphoma cells (Raji) in the presence or absence of BCGF-12kD. When cultured in media supplemented only with fetal calf serum, the LCL and Raji cell lines maintained relatively high levels of episomes. Although a similar level of proliferation could be maintained under defined culture conditions in media supplemented with BCGF-12kD, these conditions resulted in a time-dependent reduction of EBV sequences, as detected with EBV nuclear antigen (EBNA-1 and EBNA-2) gene probes. These results suggest that stimulation with T-cell-derived BCGF-12kD can alter a regulatory step which may be involved in the EBV transformation of B cells.
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The production and electrophoretic expression of endoglucanase(s) were compared in the wild-type and three developmental mutants of Aspergillus nidulans. In the wild type, the production of endoglucanase and its distribution in extracellular and intracellular fractions varied with the age of the culture and the yield was better in stable cultures (production of conidia and cleistothecia) as compared with shake cultures (vegetative hyphae only). Two developmental mutants, aco-T69 and aco-40, which lack the development of conidia and cleistothecia, produced low levels of endoglucanase enzymes as compared with the wild type grown under similar conditions. On the other hand, in aco-90, a mutant capable of producing cleistothecia but no conidia, endoglucanase production was better. The results indicate a correlation between cleistothecial development and endoglucanase level. The electrophoretic studies revealed the presence of three forms of endoglucanase, i.e., EGI, EGII, and EGIII. The first two were detectable in the wild type as well as in mutant strains when grown under various experimental conditions and at all the stages of development. However, the third form could be observed only during cleistothecial development, indicating that this isozyme is developmentally regulated.
Adult rats handled (H) daily for the first 3 weeks of life show a dramatically altered adrenocortical response to stress. We found that H animals secreted less ACTH and corticosterone (B) during and following the termination of stress than did nonhandled (NH) controls. In contrast, H and NH animals did not differ in basal B secretion at any point in the diurnal cycle, nor in adrenocortical responses to exogenously administered oCRF or ACTH. Moreover, the clearance rate for B was similar in H and NH animals. H animals were more sensitive than NH animals to the inhibitory effects of either B or dexamethasone on stress-induced adrenocortical activity. In a dose-response study, both glucocorticoids administered 3 h prior to testing suppressed the adrenocortical response to a 20-min restraint stress to a greater extent in the H animals. Handling increased type II, glucocorticoid receptor binding capacity in the hippocampus of adult animals (approximately 50% increase in capacity, with no change in affinity). There were no handling-induced changes in type II receptor binding capacity in the hypothalamus or pituitary, nor in type I receptor binding capacity in the hippocampus. Following chronic (5 mg/kg/day) treatment with B, hippocampal type II receptor binding capacity was significantly reduced in the B-treated H animals, compared with saline-treated H animals, and indistinguishable from saline-treated NH animals. Down-regulated H animals, like NH animals, hypersecreted B following the termination of stress in comparison to the saline-treated H animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal biopsies from 45 children with idiopathic nephrotic syndrome were analysed. A clinicopathologic correlation has been attempted in 19 children with mesangioproliferative glomerulonephritis. Mesangial hypercellularity is found to have a direct correlation with the clinical presentation, response to therapy and final outcome. The presence of diffuse mesangial IgM or IgM with C3 is of no significance and lacks specificity.
Previous studies have revealed that the regional accumulation of ischemic metabolites including hydrogen ion (H+) and PCO2 diminish after repeated occlusions. We postulated that this diminution reflects a blunted metabolic response that is related to the severity of ischemic injury and, hence, may be most pronounced in subendocardial (ENDO) regions. To investigate this hypothesis, the left anterior descending coronary artery was serially occluded three times in 51 dogs for a period of either 3 minutes (n = 15), 5 minutes (n = 18), or 15 minutes (n = 18). Each occlusion was separated by 45 minutes of reperfusion. Myocardial [H+] was measured in the endomyocardium and in the epimyocardium of the ischemic anterior wall by use of miniature pH glass electrodes. Accumulation of H+ during occlusion (delta [H+]) in the ENDO region was significantly less during the second occlusion when compared with the first occlusion (3-minute occlusions: 28.2 +/- 3.7 nM/l vs. 39.4 +/- 5.4 nM/l, p less than 0.002; 5-minute occlusions: 49.8 +/- 5.0 nM/l vs. 72.1 +/- 6.5 nM/l, p less than 0.0002; 15-minute occlusions: 132.3 +/- 14.6 nM/l vs. 225.6 +/- 27.7 nM/l, p less than 0.0003). A similar trend was noted for delta [H+] in the subepicardial (EPI) regions. During occlusion, the rise in [H+] occurred sooner, and delta [H+] was consistently greater in the ENDO when compared with the EPI regions (p less than 0.05). Regional myocardial blood flow did not change during the three occlusions, indicating that the diminution in H+ accumulation stemmed from a decrease in H+ production and not from an increase in collateral flow. The decrement in H+ accumulation between the first and second occlusions (delta [H+]1-delta [H+]2) 1) was greater in the ENDO than in the EPI regions (p less than 0.05); 2) correlated with the duration of occlusion (ENDO: r = 0.66, p less than 0.001; EPI: r = 0.82, p less than 0.0001); and 3) was related to the impairment of anterior wall systolic shortening after the first reperfusion period. These findings suggest that the diminution in H+ production that follows serial coronary occlusions reflects a blunted metabolic response that is related to both the duration of ischemia and the degree of systolic dysfunction. Moreover, though attenuation of ischemic metabolite production occurs transmurally, it is most pronounced in the deep ENDO regions.
We have studied 40 patients with non-specific aorto-arteritis (Takayasu's disease) using intravenous digital subtraction angiography (DSA). The aorta, its major branches and (in 18 patients) pulmonary arteries were evaluated to determine the degree and extent of involvement. No complications related to the procedure were encountered. Good quality diagnostic images were obtained in 39 out of 43 instances. The unsuccessful examinations were in patients with congestive cardiac failure, and in one patient who would not co-operate. Aortic wall thickness and mild involvement of the descending aorta in the region of the diaphragm could not be assessed. Intravenous DSA is acceptable for the diagnosis and follow-up of aorto-arteritis in suitable patients.
We have analysed the ability of prior intravenous Buscopan (hyoscine butylbromide) injection to influence the incidence and severity of adverse reactions to intravascularly administered, iodinated, ionic contrast medium in 258 consecutive digital subtraction angiographic (DSA) examinations. Adverse reactions were seen in 7.9% of the intravenous and 2.4% of the intra-arterial DSA examinations. The incidence of adverse reactions with and without prior Buscopan injection during intravenous DSA examinations was 8.2% and 7.1%, respectively and during intra-arterial DSA examinations was 5.6% and 1.5%, respectively. This difference is not statistically significant (chi 2-test). We conclude that prior intravenous injection of Buscopan has no influence on the incidence or severity of adverse reactions to intravascular contrast media.
During the last 25 years, 20 patients with cirrhosis of liver with severe cyanosis and gross clubbing simulating congenital cyanotic heart disease were subjected to cardiac catheterization and angiography, splenography, liver function tests, and liver biopsy. No portopulmonary fistulas could be demonstrated. The cyanosis and clubbing were secondary to right to left intrapulmonary shunting across multiple tiny pulmonary arteriovenous fistulas. In 15 cases, selective pulmonary angiography revealed discrete arteriovenous fistulas. In five cases, the angiogram did not reveal any convincing evidence of pulmonary arteriovenous fistulas. In two of these five cases, peripheral vein contrast echocardiography demonstrated right to left intrapulmonary shunting and seems a sensitive investigation. Open lung biopsy in one case showed evidence of pulmonary arteriovenous fistulas.
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Two staining techniques for conjunctival impression cytology (CIC) were evaluated in both eyes of 106 subjects with either early clinical signs of xerophthalmia (17%) or without any obvious ocular disease (83%). One technique consisted of eleven steps of staining while the other of two steps. The slides were evaluated independently in a masked fashion by two readers using three criteria for evaluation of CIC, viz., goblet cells, mucin spots and epithelial cells. By either method, both readers had greatest agreement in evaluation of the goblet cells, the percentage difference being statistically not significant. Errors in interpretation of CIC can be minimized if goblet cells alone are considered as the major criterion of evaluation.
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The isolation and sequencing of three transcripts for the precursor of the cerebral amyloid of Alzheimer disease have greatly facilitated understanding the relationship of the amyloid precursor protein (APP) to its 42 amino acid residue fragment (beta-protein or A4) which composes amyloid fibrils. In this study, we have used the 695 amino acid residue sequence described by Kang and co-workers to prepare antisera to synthetic peptides corresponding to various regions of APP in order to identify localized concentrations of this protein in cerebral cortex in cases of Alzheimer disease. We found that antisera to APP regions outside those of the amyloidogenic beta protein recognize diffuse non-congophilic plaques. While these antisera did not recognize the congophilic senile plaque core, they did recognize a halo surrounding them. Interestingly, cell processes were often identified in this halo region. In contrast, those antisera raised to sequences contained within beta-protein recognized both congophilic amyloid cores as well as non-congophilic diffuse plaques. Our findings suggest that accumulation of APP precedes development of and probably defines the senile plaque and the site of APP processing.
A 1-year old girl having a giant pigmented nevus over trunk and widespread smaller pigmented nevi presented with focal motor seizures. This combination of features is rate.
Effect of epidural steroid injection has been studied in 107 cases (50 males and 57 females, mostly above 20 years of age) with non-specific low backache. Out of 42 cases with acute syndrome 20(47.6%) showed good response, 10(23.8%) showed fair response and 12(28.6%) showed poor response, whereas similar responses were found in 5(7.7%), 10(15.4%) and 50(76.9%) cases respectively among 65 cases of chronic syndrome (p less than 0.001). Agewise, 23(32.9%), 9(12.9%) and 38(54.2%) cases among 70 patients below 40 years of age and 2(5.4%), 11(29.8%) and 24 (69.8%) cases among 37 patients above 40 years of age showed good, fair and poor responses to epidural steroid respectively (p less than 0.001). Hence epidural steroid injection has been shown to be a useful adjunct to conservative treatment of low backache in young patients with acute syndrome.
Humoral and cell mediated immune responses were studied in control, infected and immunized-infected mice at different time intervals. The levels of antiporin antibodies were found to be higher throughout the study period in immunized-infected group in which 87.5% protection was observed by mouse potency test. A significant increase in stimulation index of lymphocyte blast transformation as well as delayed type hypersensitivity response was observed in the same group as compared to infected and control group when porins were used as antigens. Using nonspecific mitogens like PHA and Con A the lymphocyte proliferation was maximum in control group whereas a significant depression was observed in infected mice. It is indicated from this study that porins are excellent antigens interacting efficiently with both arms of the host immune systems which could play a role in providing protection against the disease.
Forty-four patients of meralgia paraesthetica presented with combination of symptoms mainly of numbness with loss of superficial sensation on the anterolateral aspect of a thigh were selected for the study. They responded well to local infiltration of hydrocortisone acetate and lignocaine hydrochloride which not only helped in diagnosis but also prevented the recurrence of symptoms in majority of cases.