Biomedical subjects
Publications and source records attributed to S Joshi.
PURPOSE: This study was conducted to report a rare cause of colonic bleeding. METHODS: Case report. CONCLUSION: Surgical resection of congenital colonic varices is associated with a low incidence of morbidity and mortality, and a favorable long-term prognosis can be expected when there is no evidence of hepatocellular disease (portal hypertension).
Control of sympathetic preganglionic neurons appears to be mediated, in part, through polysynaptic pathways using spinal interneurons. To identify spinal interneurons antecedent to adrenal sympathetic preganglionic neurons, we injected herpes simplex virus type 1 into the adrenal gland of hamsters as this virus is an effective trans-synaptic tracer of neural pathways. After a three day survival period, immunocytochemistry was used to visualize virus-infected spinal cord cells. Infected sympathetic preganglionic neurons with somata that were either kite-shaped, elliptical or fusiform and that had extensive dendrite arbors were identified as well as a group of smaller round cells with finer processes. For comparison, in additional hamsters, labelling with the retrograde tracer Fluoro-Gold and histochemical reactions for the enzyme nicotinamide adenine dinucleotide phosphate-diaphorase were used to identify sympathetic preganglionic neurons. Sympathetic preganglionic neurons identified with Fluoro-Gold or herpes virus were present mostly in the nucleus intermediolateralis, pars intermediolateralis and nucleus intermediolateralis, pars funicularis of the spinal cord. The smaller herpes virus-infected cells were found mostly medial to the preganglionic neurons in lamina VII and also dorsally in lamina V of the spinal cord. Assessing immunoreactivity for glial fibrillary acidic protein demonstrated that the smaller herpes virus-infected cells were not reactive astrocytes. Furthermore, these cells were immunoreactive for two neuronal markers, neuron-specific enolase and for microtubule-associated protein 2. These findings suggest that these smaller round cells with finer processes are distinct from sympathetic preganglionic neurons and astrocytes and may be interneurons antecedent to the sympathetic preganglionic neurons.
Studies to establish the structure/function relationships of oligomycin sensitivity-conferring protein (OSCP) of mitochondrial ATP synthase were carried out using genetic engineering and biochemical approaches. A full-length cDNA clone encoding OSCP was isolated from a bovine heart cDNA library, and the mature form of OSCP was expressed in Escherichia coli using plasmid expression vector pKP1500. Recombinant OSCP was found to accumulate in the cytoplasmic inclusion bodies, by virtue of which the recombinant protein could be purified to greater than 85% purity by simple low speed centrifugation of cell lysates. Recombinant OSCP was found to be indistinguishable from OSCP isolated from mitochondria with respect to (i) apparent molecular mass on sodium dodecyl sulfate gel electrophoresis, (ii) immunological reactivity to anti-OSCP serum, (iii) biological activity in restoring oligomycin-sensitive ATPase and Pi-ATP exchange activities to OSCP-depleted ATP synthase complexes, and (iv) insensitivity of the biological activity to sulfhydryl-directed alkylating reagents. The amino-terminal sequence of the recombinant protein revealed that the initiating methionine was not removed by E. coli, although that apparently did not affect protein folding or its biological activity. Data on nested deletion mutations starting from the carboxyl terminus in OSCP demonstrated that, in each instance, the mutant form was expressed and the protein product was sequestered in cytoplasmic inclusion bodies, similar to the wild-type form. However, none of the variants, including the one in which only the last 10 residues were deleted, was able to restore cold-stable oligomycin-sensitive ATPase or Pi-ATP exchange activity in OSCP-depleted complexes. Taken together, these data suggest that amino acid residues 181-190 (or some of the residues in this region) in the OSCP sequence may be important for OSCP-F1 interactions.
The Dissociative Disorders Interview Schedule was administered to a random sample of 502 adults in the general population of Winnipeg, a midwestern Canadian city. Results showed that paranormal/extrasensory experiences were common in the general population. They were linked to a history of childhood trauma and to other dissociative symptom clusters. A factor analysis of the paranormal experiences identified three factors which together accounted for 44.0% of the combined variance of the scores. A model is proposed in which paranormal experiences are conceptualized as an aspect of normal dissociation. Like dissociation in general, paranormal experiences can be triggered by trauma, especially childhood physical or sexual abuse. Such experiences discriminate individuals with childhood trauma histories from those without at high levels of significance.
A total of 619 clinical specimens from cases of pulmonary and extrapulmonary tuberculosis were processed by smear, culture and biochemical tests. Acid fast bacilli could be demonstrated in 93 samples (15.02%) by Z.N. staining method. Culture yielded positive growth in 95 samples (15.35%) M. tuberculosis human type was the most predominient pathogen obtained from 82 cultures (13.40%) M tuberculosis bovine type was isolated from 2 cases of ascitic fluids (0.32%). Atypical Mycobacteria were isolated from 11 samples (1.73%). 5 turned out to be M. scrofulacium, 4 were M. Kansasii, 1 was M. phlei and 1 was M. smegmatis.
Attempts were made to show that periodic measurements are important for evaluating impact of feeding programmes as considerable "within variation" in increments exists which cannot be overlooked. From two socio-economic classes two kindergartens were selected one of which was implementing a feeding programme while the other was not. A total of 273 children were measured for weight and height, three times during the period of 7 months. Normal children showed significant gain in weight while malnourished children showed significant gain in height. The significance in weight (or height) increment at the end of the feeding programme did not necessarily mean that the significance could be obtained in each period even of equal time interval. Simple and cross correlations in increment revealed that weight increment in one period was significantly associated with height increment in the following period suggesting alternating priorities of the body for growth. Carefully planned longitudinal growth studies are therefore necessary for better understanding of growth process and thereby for proper evaluation of feeding programmes.
The requirement of bovine heart mitochondrial oligomycin sensitivity conferring protein (OSCP) in conferring dicyclohexylcarbodiimide (DCCD)-sensitivity to membrane-bound F1 was investigated by using OSCP-depleted membrane fraction (UF0) of ATP synthase. The ATPase activity of UF0-F1 was completely insensitive to DCCD while that of UF0-F1-OSCP was inhibited 95% by 16 microM DCCD. Both UF0-F1 and UF0-F1-OSCP complexes bound 5 nmol [14C]DCCD/mg UF0, and all the radioactivity was found to be associated with the DCCD-binding proteolipid. The data suggest that OSCP may be necessary for transmitting not only energy-linked signals, but also signals induced by F0 inhibitory ligands in mitochondrial energy transduction.
A case-control study was carried out in the state of Tamil Nadu, southern India, to examine the association between the risk of visually disabling cataract and a lifetime history of severe diarrhea (including cholera). A series of 421 subjects, aged 35 to 65 years, meeting case (n = 181) and control (n = 240) eligibility criteria were enrolled from 19 rural cataract-screening camps. Ninety case-control pairs were postmatched for (reported) age (+/- 2 years), sex, and area of residence. A history of diarrhea was obtained by using an algorithm developed by other investigators in India who have reported a strong association between cataract and diarrhea. An odds ratio of 0.8 (95% confidence limits: 0.0, 3.2) was obtained from matched pairs analysis, and an odds ratio of 1.3 (95% confidence limit: 0.6, 2.7) was obtained among all subjects (n = 392) from a logistic analysis that adjusted for age, sex, occupation, area of residence, and caste. Findings of this study do not support the hypothesis of an increased risk of visually disabling cataract in persons with a positive history of severe diarrhea.
An alternative approach is described for cloning 'silent' or poorly expressed genes that might be activated as a result of proviral DNA integration. Generally, proviral DNA integrates randomly, in a single copy per cell, although some preferred integration sites exist. Thus, each cell infected by a retroviral vector should represent a different clone. These clones would have different phenotypes depending on the site of proviral DNA integration. Those expressing a desired phenotype would be screened for by using an assay system that depends on the gene of interest. The 5' and 3' flanking cellular DNA sequences, responsible for the observed phenotype in such mutants, could be cloned. Screening of these clones should be relatively simple due to the presence of a selectable marker in the proviral DNA. These sequences would then be used to isolate the wild type (wt) copy of the insertionally activated gene. Packaging retroviral vectors could lead to insertional activation of cellular genes and packaging of insertionally activated RNAs into vector particles. RNA extracted from the particles released into the culture medium would greatly facilitate cDNA cloning of 'silent' genes activated as a result of proviral DNA integration.
A number of methods for categorization of carcinogens, including classification and ranking, have been examined and applied to 13 carcinogenic chemicals. Compounds known to be carcinogenic to humans ranked highly in the ranking systems. The TD50 approach was a satisfactory ranking system. The examination of the classification system of the International Agency for Research on Cancer, and the studies of the ranking systems revealed the importance of considering the underlying mechanisms of carcinogenesis. Some of the important problems of categorizing carcinogens are discussed.
Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4+ lymphocytes and macrophages and causes AIDS in humans. Retroviral vectors allowing neomycin phosphotransferase (npt) gene expression were engineered to express 5' sequences of HIV-1 RNA in the antisense or sense orientation and used to transform the human CD4+ lymphocyte-derived MT4 cell line. Cells expressing antisense or sense RNA to the HIV-1 tat mRNA leader sequence, as part of the 3' untranslated region of the npt mRNA, remained sensitive to HIV-1 infection. In contrast, resistance to HIV-1 infection was observed in cells expressing antisense RNA to the HIV-1 primer-binding site or to the region 5' to the primer-binding site as part of the 3' region of the npt mRNA. Cells expressing the tat mRNA leader sequence in the sense orientation as a precise replacement of the 5' untranslated region of npt mRNA were also resistant to HIV-1. These results indicate that sense and antisense approaches can be used to interfere with HIV-1 multiplication.
Toward gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in AIDS, Moloney murine leukemia virus-derived retroviral vectors were engineered to allow constitutive and tat-inducible expression of an HIV-1 5' leader sequence-specific ribozyme (Rz1). These vectors were used to infect the human CD4+ lymphocyte-derived MT4 cell line. The stable MT4 transformants expressing an HIV-1 RNA-specific ribozyme, under the control of the herpes simplex virus thymidine kinase (tk) promoter, were found to be somewhat resistant to HIV-1 infection as virus production was delayed. In cells allowing ribozyme expression under control of the simian virus 40 or cytomegalovirus promoter, the rate of HIV-1 multiplication was slightly decreased, and virus production was delayed by about 14 days. The highest level of resistance to HIV-1 infection was observed in MT4 cells transformed with a vector containing a fusion tk-TAR (trans activation-responsive) promoter to allow ribozyme expression in a constitutive and tat-inducible manner; no HIV-1 production was observed 22 days after infection of these cells. These results indicate that retroviral vectors expressing HIV-1 RNA-specific ribozymes can be used to confer resistance to HIV-1 infection.
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The 28-item Dissociative Experiences Scale was administered to a stratified cluster sample of 1,055 respondents in the general population of Winnipeg. Dissociative experiences were common in the sample and were not related to socioeconomic status, sex, education, religion, or place of birth, although they declined with age in both sexes. A principal components analysis identified three factors accounting for 47.1 percent of the combined variance of the scores. The first factor, absorption-imaginative involvement, is composed of common, benign experiences, such as missing part of a conversation and being able to ignore pain. The other two factors, activities of dissociated states and depersonalization-derealization, composed of less common experiences such as not recognizing friends or family members and not recognizing one's reflection in a mirror, may be powerful predictors of DSM-III-R dissociative disorders.
Pulmonary complications encountered in 67 patients undergoing upper abdominal surgery in our unit in one year period are analysed. Pulmonary function tests and their post-operative reduction, as also the risk factors are discussed. Pathophysiology responsible for pulmonary complications is outlined.
Sixty five breast milk samples were subjected to bacteriological studies; each sample thrice (in fresh state, after heating at 1000C and freezing for 5 days at -20 degrees C). In fresh State, Staphylococci and diphtheroids were predominant organisms. After heating, none of the samples showed any micro-organisms while after freezing for 5 days, all the samples showing presence of micro-organisms earlier, showed decrease in colony counts. None of the milk samples showed inclusions of cytomegalovirus. Serum samples of mothers tested for Hepatitis B surface antigen and human immunodeficiency virus antibodies gave negative results. Such studies i.e. screening of breast milk samples are important if human milk is to be stored in banks and supplied to premature (high risk group) children.
The nearest neighbor relationships of bovine mitochondrial H(+)-ATPase subunits were investigated by the chemical cross-linking approach using the homobifunctional cleavable reagents dithiobis(succinimidyl propionate) and disuccinimidyl tartrate. Cross-linked proteins were resolved by one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Individual subunits were detected by silver staining or by Western blotting and staining with subunit-specific antisera. Products larger than 80,000 daltons were not analyzed. Interactions between F1 subunits included cross-links between gamma and delta as well as gamma and epsilon subunits. Among F0 subunit interactions were observed cross-links of (i) coupling factor 6 (F6) with 8-, 20-, and 24-kDa proteins, (ii) oligomycin sensitivity-conferring protein (OSCP) with 24-kDa protein, and (iii) 20-kDa protein with 24-kDa protein. In addition, several cross-links among subunits involving F1 and F0 sectors were detected. These included cross-links between F6 and alpha, F6 and gamma, OSCP and alpha/beta, and 24-kDa protein and alpha/beta. Thus, OSCP, F6, and the 24-kDa protein were found to form cross-links with both F1 and F0 subunits. The surface accessibility of F0 subunits was investigated by subjecting aliquots of F0 to trypsin treatment. Our data demonstrated that the rate of degradation was in the order OSCP greater than 24-kDa protein greater than or equal to F6 greater than subunit 6. The degradation of subunits of F0 was prevented in intact or reconstituted F1-F0. Based on our present and previously published observations, a model of H(+)-ATPase has been proposed wherein OSCP, F6, and the 24-kDa protein are placed in the stalk region and the alpha and beta subunits of F1-ATPase have been extended down to the membrane surface to enclose the stalk segment.