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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 1,117 records · Page 62Linked to original sources
PubMed1992

Analysis of hepatocellular proliferation: study of archival liver tissue is facilitated by an endogenous marker of DNA replication.

Assessment of liver regeneration with endogenous genes that are expressed during DNA replication is physiological, specific and direct. To determine whether H3 histone messenger RNA expression (which is tightly coupled with DNA synthesis) could be used for this purpose, we initially examined liver regeneration in a mouse model. After partial hepatectomy, RNA transblot studies showed induction of H3 histone messenger RNA expression in regenerating mouse livers. In situ molecular hybridization demonstrated that the overall pattern of H3 histone messenger RNA expression correlated with [3H]thymidine labeling of hepatocytes. After partial hepatectomy, H3 histone messenger RNA expression in hepatocytes peaked at 48 hr (greater than 60 times greater than at 24 hr; p less than 0.001) and then rapidly declined. Although hepatocyte labeling with [3H]thymidine showed similar kinetics of liver regeneration, use of this parameter resulted in overestimation of the proliferative compartment when it was compared with H3 histone messenger RNA expression. Next we determined whether H3 histone messenger RNA expression could be used to study hepatocellular proliferation in archival human material. H3 histone messenger RNA-expressing hepatocytes were identified on in situ hybridization in patients with acute or chronic active hepatitis and active cirrhosis, but not inactive cirrhosis. These studies demonstrate that H3 histone messenger RNA is expressed in a phasic manner during liver regeneration. Use of H3 histone messenger RNA expression to evaluate hepatocellular proliferation should facilitate clinical studies and greatly advance our understanding of the pathophysiology of liver regeneration.

Adolescent↗
PubMed1992

Macronodular adrenal hyperplasia causing Cushing's syndrome: report of two cases and an overview.

Of the various entities producing adrenal hyperfunction, nodular adrenal hyperplasia is rarely described, however, recent reports have established it as a distinct cause of Cushing's syndrome. Although the etiology of this disease remains uncertain, two distinct forms are recognised, namely: macronodular hyperplasia and micronodular dysplasia. Establishing the diagnosis preoperatively is difficult but essential to ensure the correct treatment is performed. Two cases of macronodular hyperplasia are reported herein followed by a review of the available literature on this subject.

Adrenal Glands↗
PubMed1992

Psychosis in Asian immigrants from the Indian sub-continent: preliminary findings from a follow-up study including a survey of general practitioners.

The paper presents preliminary findings from a follow-up study of 86 first-generation immigrants to the United Kingdom from the Indian sub-continent, and a matched indigenous English-born control group. All subjects had originally been seen at the Bethlem Royal and Maudsley Hospitals and had been diagnosed as suffering from a functional psychosis. Attempts to locate the patients 5-20 years later revealed that a significantly higher proportion of the immigrant group could not be traced to a general practitioner within the United Kingdom, or otherwise accounted for. Possible explanations for this finding are advanced; the fact itself has important implications for those concerned with the provision of care and services for mentally ill immigrants in this country.

Bangladesh↗
PubMed1992

Cross-national differences in the frequency and outcome of schizophrenia: a comparison of five hypotheses.

Measures of morbid risk for schizophrenia derived from the WHO Determinants of Outcome of Severe Mental Disorders Study showed large correlations with the following: an occupational index, a measure of urbanicity, geographical and climatic variables, a dietary measure, and the infant mortality rate. The same variables were also correlated with a measure of outcome derived from the International Pilot Study of Schizophrenia. Nearly all of the correlations were significant. The postulated "explanatory" variables were themselves highly intercorrelated.

Cross-Cultural Comparison↗
PubMed1992

Preferential expression and activity of multidrug resistance gene 1 product (P-glycoprotein), a functionally active efflux pump, in human CD8+ T cells: a role in cytotoxic effector function.

The multidrug resistance gene 1 (mdr 1) product, the P-glycoprotein (Pgp), is a 170-kD transmembrane transport protein, whose overexpression is associated with multidrug resistance in cancer cells and in chloroquine-resistant Plasmodium falciparum infection. In this study we show that normal freshly isolated human lymphocytes express low levels of mdr 1 mRNA and membrane Pgp. Although Pgp is expressed in both CD4+ and CD8+ T cells, it is preferentially expressed in CD8+ T cells. Activation of T lymphocytes with phytohemagglutinin leads to an amplification of both mdr 1 mRNA and membrane Pgp in T cells. P-glycoprotein in T cells is a functionally active efflux pump as demonstrated by decreased retention of rhodamine-123 and its increased accumulation by cyclosporin A, an inhibitor of Pgp function. In addition, MRK-16 antibody increased accumulation of Rh123 in CD8+ T cells. Furthermore, MRK16 anti-P-glycoprotein monoclonal antibody, in a concentration-dependent manner, inhibited T lymphocyte-mediated cytotoxicity. These data suggest a physiologic role of P-glycoprotein in cytotoxic T-lymphocyte effector function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Effect of cereal-legume chapati diets on absorption and retention of calcium.

Wheat chapati, wheat + Bengal gram (80:20 and 70:30) chapatis and casein diets, at 10 percent protein level, were fed to rats for 12 weeks to study the effect on calcium utilization. The supplementation of Bengal gram to wheat diets significantly improved the calcium absorption. The urinary calcium excretion in wheat + Bengal gram chapati diets was significantly less than that of wheat chapati diet fed group. The in vivo 45Ca absorption (CPM/100 microliters serum) was also less in wheat chapati group as compared to wheat + Bengal gram chapati diets fed groups. The supplementation of legumes to cereals improved the calcium utilization and it may be concluded that there will be no risk of occurrence of protein induced hypercalciuria.

Absorption↗
PubMed1992

Ancylostoma ceylanicum infection in female hamsters: an observation on altered reproductive function.

Reproductive performances of female hamsters were investigated during Ancylostoma ceylanicum (hookworm) infection. Animals having the highest levels of infection (34.96 +/- 1.11 worms) showed degenerative changes in the reproductive system. Ovaries of infected animals contained a few primary or secondary follicles. On cocaging with males of proven fertility, only 7-8% (80% in controls) of the infected females mated but did not conceive as evidenced by the absence of corpora lutea or implantation sites on day 10 postcoitum. Animals with low worm burdens (5.94 +/- 0.65 worms), however, showed almost normal fertility. The uterine weight bioassay and compensatory ovarian hypertrophy suggest strong suppression of pituitary gonadotrophin contents in infected females. Resorptive effects on the pregnancy outcome of infected female hamsters were also recorded.

Ancylostoma↗
PubMed1992

Host resistance assays as predictive models in styrene immunomodulation.

Three infection models namely an oncogenic virus Encephalomyocarditis (EMCV), a rodent strain of malaria, Plasmodium berghei, and a rodent hookworm parasite, Nippostrongylus brasiliensis, were used to confirm the in vivo immunotoxic potential of styrene reported in our previous communication. The altered host resistance to these challenge infections was evaluated in rodents pre-treated with 0, 0.02, 0.03 or 0.05 x LD50 dose of styrene (5 days/week) for 4 weeks. Significantly increased mortality in mice was observed at the various tested dose levels of styrene when challenged with EMCV. Similarly the results obtained in the malaria infection model indicated increased blood parasitaemia as well as significantly enhanced mortality in styrene-treated animals. Also the rejection of N. brasiliensis was also found to be significantly impaired in animals treated with a higher dose of styrene. These results indicate that the exposure of rodents to styrene can markedly impair host resistance which may have biological significance.

Adjuvants, Immunologic↗
PubMed1992

Epidermoid cyst in association with subcutaneous meningioma.

A 17-year-old female presented with a non-tender, firm and fixed swelling in the right frontal region. Skull x-rays revealed soft tissue shadow and mild hyperostosis of the underlying frontal bone. Histopathological examination after excision showed it to be a meningioma with an epidermoid cyst.

Adolescent↗
PubMed1992

Population genetics and dynamics of Plasmodium falciparum: an ecological view.

Molecular characterization of the Plasmodium falciparum genome has led to identification of polymorphic loci and the mechanisms generating genetic diversity in this parasite. This information has resulted in the development of molecular methods to type parasite diversity in the field. Consequently, we are now in a position to describe the population genetics and dynamics of P. falciparum. The limited number of field studies that have been conducted to date have revealed an extraordinary degree of genetic diversity in natural parasite populations. Heterozygous recombination which occurs during meiosis appears to be one mechanism for generating genetic diversity. The rate at which such recombination occurs in natural parasite populations defines the genetic structure of the parasite population and can influence the ability of the parasite to respond to selection pressure. The high frequency of single genotype infections and the female-biased gametocyte sex ratios found in hyperendemic malaria areas suggest that self-fertilization occurs frequently. Population-wide surveys of allele frequencies in endemic areas have, however, shown no evidence of linkage disequilibrium and are consistent with a panmictic population structure. We argue that these studies have only sampled symptomatic infections, within which rare or recombinant genotypes may be disproportionately represented. They also take no account of the spatial structure of P. falciparum populations. Systematic investigations of the amount of heterozygosity in small areas as part of population-wide surveys are required to define the genetic structure of P. falciparum populations. Population dynamic studies which consider genetic heterogeneity of P. falciparum have shown fluctuations of different serotypes in space and time. The host immune response appears to play an important role in generating these dynamics. Integrated field and laboratory studies, which consider the interaction between population genetics and dynamics, will be necessary to describe the population biology of P. falciparum.

Animals↗
PubMed1992

Interactions of LDL and modified LDL with mesangial cells and matrix.

Hyperlipidemia may play a role in the progression of diabetic and other renal diseases. Low density lipoprotein (LDL) and other proteins including extracellular matrix components undergo nonenzymatic glycation in vivo. We examined the effects of glycation of LDL as occurs in diabetes (4 to 8%) on binding and uptake by mesangial cells and their proliferation. The glycation of LDL (g-LDL) significantly decreased its binding and uptake by mesangial cells by 15 to 20%, indicating that glycated LDL binds to the LDL receptor, but with lower affinity than LDL. Both LDL and g-LDL modestly stimulated [3H] thymidine incorporation into mesangial cells at 5 to 10 micrograms/ml. Native, oxidized (Ox-LDL) and glycated LDL all bound to the extracellular matrix generated by rat mesangial cells in culture. The binding of LDL, Ox-LDL and g-LDL to mesangial matrix was two to four times higher than to mesangial cells. Binding of LDL and g-LDL was significantly higher to glycolaldehyde modified matrix, which serves as an in vitro model for nonenzymatic glycation end-product cross-linking of matrix which occurs in long-standing diabetes. Based on these findings, we propose that glycation of LDL decreases its binding and uptake by the LDL receptor of mesangial cells and may slow its catabolism. Furthermore, LDL bound to extracellular mesangial matrix can undergo oxidation and generate cytotoxic LDL components. This process may be further enhanced by advanced glycation of the mesangial matrix in diabetes, contributing to glomerular pathology.

Animals↗
PubMed1992

Hepatocyte transplantation: development of new systems for liver repopulation and gene therapy.

Following recent advances in molecular and cell biology, development of hepatocyte transplantation has been considerably invigorated. To study the fate of hepatocytes transplanted into the liver, new strategies have included the use of endogenously marked transgenic hepatocytes. Release of peripherally quantifiable marker proteins by transgenic hepatocytes has provided noninvasive ways to determine hepatocyte engraftment and prolonged survival. Further characterization of intrasplenic hepatocyte transplantation has established this to be the most suitable method for targeting hepatocytes to the liver. Advances in gene cloning, retrovirology, and gene transfer technology have provided further tools for accomplishing gene therapy. Practical strategies for ex vivo gene therapy involving hepatocytes have been developed by exploiting these new technologies. The potential value of hepatocyte transplantation in acute hepatic failure has begun to be reexamined. Therefore, hepatocyte transplantation can be predicted to provide new ammunition for continuing our assault on untreatable disorders. Resolution of outstanding issues should accelerate this process.

Animals↗
PubMed1992

Substituted methyl benzimidazole carbamate: efficacy against experimental cysticercosis.

Methyl [5-([4-(2-pyridinyl)-1-piprazinyl] carbonyl)-1H benzimidazole-2-yl] carbamate, a broad spectrum anthelmintic, was tested against Cysticercus fasciolaris in rats and the cysticercoids of Hymenolepis nana in beetles. A dose of 50 mg kg-1, given intraperitoneally (i.p.) to infected rats on 10 alternate days, was found most effective, killing all mature cysticerci. The same dose, given on each of five days, either from the fifth day prior to infection or the sixth day following infection, fully arrested the establishment of cysticerci. A single prophylatic dose of 500 mg kg-1, given intramuscularly (i.m.), protected rats against challenge with Taenia taeniaeformis eggs for 10 days. The test compound, mebendazole and praziquantel were all totally ineffective against mature cysticercoids in grain beetles but, of the beetles fed the drugs in flour, 66.3%, 50% and 83.8%, respectively, failed to support the development of immature cysticercoids. The effective cysticidal action of the compound makes it a candidate medical anthelmintic.

Animals↗
PubMed1992

Characterization of Staphylococcus aureus isolates with decreased susceptibility to vancomycin and teicoplanin: isolation and purification of a constitutively produced protein associated with decreased susceptibility.

"Derivative isolates" with 4- to 8-fold and 8- to 16-fold increases in MICs of vancomycin and teicoplanin, respectively, were selected from 2 susceptible clinical isolates of Staphylococcus aureus by serial incubation in low-level vancomycin. A protein of approximately 39 kDa was demonstrable in the cytoplasmic fraction and occasionally in the membrane fraction by SDS-PAGE of both derivatives. This protein was purified by DEAE chromatography, preparative SDS-PAGE, and electroelution. Derivative bacteria were larger on transmission electron microscopy, had thicker cell walls, and had changes in colony morphology on solid media. Further evidence for cell wall reorganization included loss of phage and capsular typing, decreased susceptibility to lysostaphin/lysozyme killing, and changes in condition for detection of optimal coagulase activity. The mechanism of decreased susceptibility to glycopeptide antibiotics among S. aureus derivative isolates is uncertain. The production of the approximately 39-kDa cytoplasmic protein and cell wall reorganization may mediate changed affinity of glycopeptide-peptidoglycan binding or impairment of glycopeptide access to its cell wall target.

Bacterial Proteins↗
PubMed1992

Immune tolerance to a defined heterologous antigen after intrasplenic hepatocyte transplantation: implications for gene therapy.

Development of a host immune response against gene products expressed by genetically modified cells could be a serious limitation for gene therapy. During examination of whether site-specific differences in antigen presentation could regulate the host immune response, we observed an absence of antibodies against hepatitis B virus surface antigen (HBsAg) when HBsAg producing transgenic hepatocytes were transplanted into the spleen. Intrasplenic transplantation resulted in translocation of a large number of cells into the portal vascular bed and liver sinusoids. In these recipients, HBsAg secreted by the transplanted hepatocytes circulated indefinitely in the blood. In contrast, subcutaneous or intraperitoneal transplantation of the transgenic hepatocytes induced an anti-HBs response, followed by clearance of serum HBsAg. Rechallenge with HBsAg in a highly immunogenic form failed to break the tolerance in intrasplenic hepatocyte recipients even though these animals responded to another antigen (keyhole limpet hemocyanin). Immunization with HBsAg in intraperitoneal recipients of HBsAg producing hepatocytes further elevated anti-HBs titers. Our results indicate that hepatocyte transplantation into the portal vascular bed via injection into the spleen can confer immune tolerance to secreted heterologous antigens. This finding should have important implications for human gene therapy as well as for analyzing the mechanisms of immune tolerance.

Animals↗