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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 559 records · Page 31Linked to original sources
PubMed1996

Free radical scavengers & lipid peroxidation in acute aluminium phosphide poisoning.

Free radicals scavengers superoxide dismuatase (SOD) and catalase and lipid peroxidation were studied in 45 patients of aluminium phosphide poisoning irrespective of age and sex admitted to a hospital in north India during the January 1992 to December 1993. Serial serum superoxide dismutase (SOD), catalase and MDA (malonyldialdehyde) were estimated on days 1, 2 and 5 post-admission depending on the survival of the patients. Serum SOD levels were significantly higher (P < 0.001) but serum catalase was significantly lower (P < 0.001) in patients than controls (patients of peripheral circulatory failure and normals) on days 1 and 2 which suggested stimulation of SOD and inhibition of catalase by phosphine resulting in excessive hydrogen peroxide (H2O2) load. Significantly higher levels of MDA (P < 0.001) in patients than controls on days 1 and 2 indicated enhanced lipid peroxidation in this poisoning. Twenty four patients died constituting a mortality rate of 53.3 per cent. The significantly high levels of SOD and MDA in non-survivors suggested their direct relation to mortality while catalase levels had an inverse relationship. Return of SOD and catalase and MDA to normal or near normal levels in survivors by day 5 suggested abolition of an oxidative stress due to elimination of phosphine.

Acute Disease↗
PubMed1996

Arthroscopic lavage treatment in rheumatoid arthritis of the knee.

OBJECTIVE: To assess the efficacy of outpatient arthroscopic lavage in rheumatoid arthritis (RA) of the knee. METHODS: 9 patients with RA and active synovitis of at least one knee were selected. All patients were taking disease modifying antirheumatic drugs and nonsteroidal antiinflammatory drugs and had failed intraarticular corticosteroid injection of the knee. Using the 1.9 mm office arthroscope and strict sterile technique the affected knee was lavaged with at least 750 cc of normal saline. At the end of the procedure 40 mg triamcinolone acetonide was injected through the arthroscope. Assessment was done at baseline and 4, 8, and 12 weeks after the lavage using a visual analog scale for pain and 50 foot walk time. RESULTS: 8 of the 9 patients showed marked improvement in their pain and walk time. This effect was maintained at least 12 weeks after the procedure. CONCLUSION: Office arthroscopic lavage treatment is beneficial in a selected group of patients. This procedure is simple and well tolerated without major complications, and may be an option when more conservative therapies have failed.

Activities of Daily Living↗
PubMed1996

Effect of plumbagin on gonadotrophic cycle of the housefly, Musca domestica L.

Topical treatment of the phytochemical plumbagin in doses ranging 0.005-5 micrograms prevented oocyte development and affected fecundity and fertility in M. domestica. The treatment to wandering larvae was less effective as the compound could only effect the fertility to a significant level whereas the fecundity was not significantly reduced. The effect of the compound was more pronounced in adult treatments where both fecundity and fertility reduced drastically. The compound also effected the oocyte maturation as it arrested the development of vitellogenic oocyte at stage six. As the juvenile hormone analogue methoprene and moulting hormone 20-hydroxyecdysone or the mixture of these hormones could not restore the development of the oocyte in ovaries of plumbagin treated flies, it is concluded that the compound does not effect the female houseflies through hormonal pathways, instead in all probability it acts like a cytotoxic compound.

Animals↗
PubMed1995

A 26 kDa yeast DNA topoisomerase I fragment: crystallographic structure and mechanistic implications.

BACKGROUND: Type I DNA topoisomerases, divided mechanistically into two subfamilies, are ubiquitous enzymes that participate in replication and transcription. In addition to its role in these fundamental processes, the biological importance of eukaryotic DNA topoisomerase I is underscored by its identification as the target of the antitumor alkaloid camptothecin. An understanding of the mechanism of catalysis and interactions with camptothecin and other drugs has been hampered by a lack of detailed structural information. RESULTS: The three-dimensional structure of a 26 kDA fragment (residues 135 to about 363) of Saccharomyces cerevisiae DNA topoisomerase I has been determined at 1.9 A resolution. The fragment has a novel architecture comprising a concave platform and a pair of outlying V-shaped helices. Photocrosslinking and protein footprinting experiments show that the positively charged concave surface and the junction region of the V-shaped pair of helices contact DNA in the enzyme-DNA complex. CONCLUSIONS: Crystallographic, biochemical and genetic data indicate that this 26 kDa fragment of yeast DNA topoisomerase I is involved in complex formation between the enzyme and DNA, and probably also in camptothecin-enzyme-DNA ternary complex formation. A molecular model for protein-DNA interaction based on these data is proposed. The bipartite DNA-binding regions of the 26 kDa fragment may enable eukaryotic DNA topoisomerase I to adapt to sequence-dependent structural variations in its DNA substrates.

Camptothecin↗
PubMed1995

Reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to a supraphysiologic glucose concentration is associated with loss of STF-1 transcription factor expression.

Chronic exposure of HIT-T15 beta cells to elevated glucose concentrations leads to decreased insulin gene transcription. The reduction in expression is accompanied by diminished binding of a glucose-sensitive transcription factor (termed GSTF) that interacts with two (A+T)-rich elements within the 5' flanking control region of the insulin gene. In this study we examined whether GSTF corresponds to the recently cloned insulin gene transcription factor STF-1, a homeodomain protein whose expression is restricted to the nucleus of endodermal cells of the duodenum and pancreas. We found that an affinity-purified antibody recognizing STF-1 supershifted the GSTF activator complex formed from HIT-T15 extracts. In addition, we demonstrated a reduction in STF-1 mRNA and protein levels that closely correlated with the change in GSTF binding in HIT-T15 cells chronically cultured under supraphysiologic glucose concentrations. The reduction in STF-1 expression in these cells could be accounted for by a change in the rate of STF-1 gene transcription, suggesting a posttranscriptional control mechanism. In support of this hypothesis, no STF-1 mRNA accumulated in HIT-T15 cells passaged in 11.1 mM glucose. The only RNA species detected was a 6.4-kb STF-1 RNA species that hybridized with 5' and 3' STF-1-specific cDNA probes. We suggest that the 6.4-kb RNA represents an STF-1 mRNA precursor and that splicing of this RNA is defective in these cells. Overall, this study suggests that reduced expression of a key transcriptional regulatory factor, STF-1, contributes to the decrease in insulin gene transcription in HIT-T15 cells chronically cultured in supraphysiologic glucose concentration.

3T3 Cells↗
PubMed1995

CD28-mediated signaling in vivo prevents activation-induced apoptosis in the thymus and alters peripheral lymphocyte homeostasis.

Activation of T lymphocytes can result in a functional immune response, anergy or apoptosis. Functional T cell activation requires the interaction of the TCR with Ag presented by MHC molecules on APC concurrent with appropriate interactions between cell surface accessory molecules. Interestingly, the level of CD28 expression is regulated during T cell development as well as during T cell activation and proliferation, suggesting that CD28 could play a role in determining the outcome of activation of TCR during T cell ontogeny. We identify, herein, a novel function of murine CD28 in the regulation of activation-induced apoptosis in thymocytes. In vivo, or combined in vivo and in vitro treatment with mAbs to CD28 prevents apoptosis of CD4+CD8+ thymocytes induced by Abs to the TCR complex. Prolonged administration of anti-CD28 Abs increased the number of both CD4+CD8- and CD4-CD8+ T cells in the thymus, while the number of CD4+CD8+ T cells is relatively unchanged. Furthermore, this treatment leads to a dramatic enlargement of peripheral lymphoid organs characterized primarily by the expansion of B cells. The number of CD4+CD8- T cells in the spleen of anti-CD28-treated mice is also moderately increased, while the number of CD4-CD8+ cells is relatively unchanged.

Animals↗
PubMed1995

Decreased plasma glutathione in cancer of the uterine cervix.

Plasma total glutathione (GSH) content (reduced plus oxidized) was estimated in varying grades of cervical intraepithelial neoplasia (CIN) and in invasive cervical cancer. The values were compared with age-matched control women. The results show significantly lower level of plasma GSH in CIN III and invasive cancer compared to controls (0.724 versus 1.082 and 0.622 versus 1.082 mumol/ml of plasma, P < 0.05). Further, the odds ratio analysis showed high plasma GSH content was found to be protective against the development of cervical cancer. The results suggest a plausible association of plasma GSH with cervical carcinogenesis. The quantitative changes occurring in plasma total glutathione during cervical carcinogenesis is a useful finding and might represent a systemic biochemical marker for precancerous and cancerous lesions of the uterine cervix.

Adult↗
PubMed1995

Cyclodextrins as protein folding aids.

Aggregation of proteins is a frequent occurrence during their transition from random coil to native structure. The influence of cyclodextrins in the refolding of carbonic anhydrase under aggregating conditions was studied. Cyclodextrin prevented formation of protein aggregates during renaturation of carbonic anhydrase. In addition, over 90% of active enzyme was recovered even at protein concentrations as high as 67 microM. The enhanced protein reactivation by cyclodextrins may be due to their ability to bind to hydrophobic sites in protein folding intermediate(s) followed by their subsequent removal as the protein refolds.

Animals↗
PubMed1995

DNA fingerprinting in silkworm Bombyx mori using banded krait minor satellite DNA-derived probe.

The genomic DNA from thirteen different ecotypes and inbred lines of silkworm, Bombyx mori, were analyzed by digesting with BstNI and HinfI restriction enzymes followed by hybridization with banded krait minor satellite DNA (Bkm)-2(8) minisatellite probe. The DNA fingerprinting revealed 9-31 discrete intense bands, some of which were ecotype/inbred line-specific. Individual specific DNA fingerprints in two representative genotypes and their F1 hybrid offspring were also obtained. Individuals of a given parental line showed very similar profiles and the hybrid offspring showed the combined profile of both parents. The presence of bands specific to diapausing and nondiapausing strains and to particular genotypes indicate their potential use for marker-assisted breeding and varietal identification.

Animals↗
PubMed1995

Fermentation of rice-bengal gram dhal blends with whey: changes in phytic acid content and in vitro digestibility of starch and protein.

Whey fermentation of various rice and bengal gram dhal blends prepared by mixing them in different proportions at 35 degrees C for 18 h brought about a significant decline in phytic acid content. Phytic acid content in various blends decreased to the extent of 23 to 36 per cent over the control values. Whey incorporation as well as fermentation improved the starch and protein digestibility (in vitro) of all the rice-bengal gram dhal mixtures. Improvement in starch and protein digestibility is related to the reduction in phytic acid content, as this antinutrient is known to inhibit amylolysis and proteolysis. A significant negative correlation found between phytic acid and digestibility of starch and protein strengthens our findings.

Animals↗
PubMed1995

Antitumor efficacy of taxane liposomes on a human ovarian tumor xenograft in nude athymic mice.

Taxanes such as paclitaxel (Taxol) and docetaxel (Taxotere) are promising agents for use against ovarian cancer and other malignancies. Recently, SB-T-1011, a semisynthetic taxane, has been prepared from 14-hydroxy-10-deacetylbaccatin III. SB-T-1011 shows similar or greater in vitro cytostatic activity than paclitaxel, depending on the tumor cell line. The administration of taxanes is problematic due to their low solubility in most pharmaceutically acceptable solvents; formulations used clinically contain Cremophor/ethanol (diluent 12) or polysorbate 80/ethanol, excipients which may cause serious adverse effects. To eliminate these vehicles, we have prepared paclitaxel liposome formulations. The objective of the present work was to evaluate the antitumor activity of paclitaxel and two semisynthetic analogs in Cremophor-based and liposomal formulations. Antitumor activity was evaluated against A121a, a taxane-sensitive human ovarian tumor, growing as subcutaneous xenografts in athymic nude mice. Free and liposomal formulations of each taxane showed similar antitumor effect. The antitumor activity of paclitaxel and SB-T-1011 was similar, and docetaxel was more potent than either paclitaxel or SB-T-1011. Overall, taxane liposomes were better tolerated and more easily administered iv than taxane formulated in Cremophor/ethanol.

Animals↗
PubMed1995

Human recombinant IL-2 augments immunoglobulin and induces rheumatoid factor production by rheumatoid arthritis lymphocytes engrafted into severe combined immunodeficient mice.

Recombinant (r) human IL-2 was administered in vivo to improve homing and engraftment of rheumatoid arthritis (RA) patients' peripheral blood mononuclear cells (PBMC) into severe combined immunodeficient (SCID) mice. Human rIL-2 treatment resulted in augmented human Ig production and induced IgM rheumatoid factor (RF) of human origin in SCID-RA chimeras. The increment of human serum IgG in SCID-RA chimeras after IL-2 treatment ranged between 15 and 43% and for IgM between 50 and 98% during 2-8 weeks postengraftment. Human IgM-RF was detectable after 1 to 2 weeks after engraftment and persisted over a period of 10-13 weeks. No RF was produced in SCID mice engrafted with PBMC from healthy individuals with or without exogenous rIL-2 administration. Thus, human rIL-2 expanded autoreactive clones involved in the production of RF in the SCID-RA chimeras. The present study provides a novel approach to establish an in vivo SCID-RA model to study the cellular and molecular mechanisms involved in the production of RF and development of a RA-like lesion.

Adult↗
PubMed1995

In situ quantification of hsp70 and alpha-beta transcripts at 87A and 87C loci in relation to hsr-omega gene activity in polytene cells of Drosophila melanogaster.

The hsp70-coding duplicate loci at the 87A and 87C sites (the 87C site also carries heat-inducible alpha-beta repeats) in polytene nuclei are known to puff to different levels under conditions in which heat shock does not induce the non-protein-coding hsr-omega gene at the 93D site. To understand the basis of this unequal puffing, the levels of hsp70 and alpha-beta transcripts at the 87A and 87C heat shock loci in polytene chromosomes of Drosophila melanogaster were quantified in situ by hybridization of antisense RNA probes after treatment with heat shock, benzamide, colchicine, heat shock followed by benzamide or heat shock in the presence of colchicine in salivary glands of late third instar larvae. Heat shock, resulting in equal puffing of the 87A and 87C loci, increased the hsp70 transcripts at both sites in proportion to the numbers of hsp70 gene copies at the two loci; levels of alpha-beta transcripts were also elevated at the 87C site following heat shock. Heat shock followed by benzamide treatment, which results in a larger puff at 87A, caused an increase in hsp70 transcripts per gene copy at 87A and a decrease at 87C without any effect on the alpha-beta transcripts; heat shock in the presence of colchicine, which causes the 87C puff to be larger than 87A, resulted in a decrease in hsp70 RNA at 87A but an increase in the levels of hsp70 as well as alpha-beta transcripts at the 87C site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

RNA metabolism in situ at the 93D heat shock locus in polytene nuclei of Drosophila melanogaster after various treatments.

Quantitative in situ hybridization to RNA on polytene chromosome spreads, using the 93D exon-, intron- and repeat-specific 35S-labeled antisense RNA probes, revealed treatment- (heat shock, benzamide, colchicine, heat shock followed by benzamide and heat shock in the presence of colchicine) specific differences in the metabolism (synthesis and/or accumulation at the puff site) of the various hsr-omega transcripts, namely hsr-omega-nuclear (omega-n), omega-pre-cytoplasmic (omega-pre-c) and omega-cytoplasmic (omega-c). While heat shock increased the levels of all the three transcripts at the 93D puff site in a coordinated manner, benzamide led to a significant increase in the levels of hsr-omega-n and pre-c; on the other hand, colchicine caused increased levels of the omega-n and omega-c RNA species at 93D. The results also suggested splicing of hsr-omega-pre-c RNA at the site of synthesis with the spliced-out 'free' intron (hsr-omega-fi) accumulating at the puff site. The rate of splicing and/or turnover of the hsr-omega-fi varied in a treatment-specific manner. Although a combined treatment to salivary glands with heat shock and benzamide or colchicine is known to inhibit puffing and [3H]uridine incorporation at 93D, the two treatments resulted in a treatment-specific increase in the in situ levels of different hsr-omega transcripts at the 93D site, suggesting a reduced turnover of specific transcripts from the site under these conditions. We suggest that the different 93D transcripts have roles in turnover and/or transport of RNA in nucleus as well as some role in cytoplasmic translation.

Animals↗
PubMed1995

Isolation of a melibiose-binding protein from human spleen.

A melibiose-binding protein was isolated from human spleen by serial affinity chromatography on lactose-, mannose-, and melibiose-Sepharose. The purified protein agglutinated rabbit erythrocytes and re-bound to melibiose, but did not bind to murine nor human laminin. The protein was composed of approximately 58 kDa and 26 kDa polypeptides. The polypeptides were detected in buffy coat cell extracts and they were synthesized in vitro by B lymphoblastoid cells. The polypeptides did not react with anti-galaptin, anti-C-reactive protein, anti-amyloid P, anti-keratin, and anti-rat lung lectin 29 sera. The 58 kDa polypeptide reacted very weakly with anti-core-specific lectin serum and reacted with anti-IgG serum. The data suggest that the major protein isolated is an anti-Ga1 alpha 1-->6 immunoglobulin.

Animals↗