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Biomedical subjects

M Verma

Publications and source records attributed to M Verma.

At least 19 recordsLinked to original sources
PubMed1992

Liposome-mediated modulation of multidrug resistance in human HL-60 leukemia cells.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in cancer treatment. Resistance of cultured tumor cells to major classes of cytotoxic drugs is frequently due to expression of a plasma membrane P-glycoprotein encoded by MDR genes. We have demonstrated that liposome-encapsulated doxorubicin is more toxic than the free drug and that it modulates MDR in Chinese hamster LZ cells and human colon cancer cells. PURPOSE: To investigate further the association between expression of P-glycoprotein and modulation of MDR by liposome-encapsulated doxorubicin, we studied vincristine-resistant HL-60/VCR leukemia cells, which express P-glycoprotein, and doxorubicin-resistant HL-60/ADR leukemia cells, which do not. METHODS: Cells were exposed to various concentrations of free doxorubicin and liposome-encapsulated doxorubicin. The cellular content of doxorubicin was determined by fluorescence analysis, and cytotoxicity was determined by cell growth inhibition. Photoaffinity-labeling studies of P-glycoprotein binding were performed on HL-60/VCR and HL-60/ADR cells and KB-GSV2 cells transfected with the MDR1 gene (also known as PGY1). RESULTS: The concentrations that caused 50% inhibition of growth (IC50) for free doxorubicin in HL-60, HL-60/ADR, and HL-60/VCR cells were 30 nM, 9 microM, and 0.9 microM, respectively. The values for liposome-encapsulated doxorubicin in parental HL-60 cells and HL-60/ADR cells were 20 nM and 9 microM, respectively, indicating little or no sensitization. In contrast, HL-60/VCR cells were fivefold more sensitive to liposome-encapsulated doxorubicin than to free doxorubicin, and IC50 was reduced to 0.17 microM. In HL-60 cells exposed to liposome-encapsulated doxorubicin, intracellular doxorubicin accumulation was less than that seen with free drug. In contrast, in HL-60/VCR cells, accumulation was twofold to threefold higher than that with free doxorubicin. Liposome-encapsulated doxorubicin completely inhibited the photoaffinity labeling of P-glycoprotein by azidopine in membrane vesicles of HL-60/VCR cells, with a potency comparable to that of azidopine, suggesting that circumvention of MDR by liposomes is related to their specific interaction with P-glycoprotein. The studies with KB-GSV2 cells indicated that blank liposomes can directly inhibit photoaffinity labeling of P-glycoprotein. CONCLUSIONS: These results demonstrate the effectiveness of liposome-encapsulated doxorubicin in overcoming resistance in the multidrug-resistant phenotype of HL-60/VCR cells by direct interaction with P-glycoprotein. Furthermore, they indicate that liposome-encapsulated doxorubicin may be an effective treatment for human cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Decreased access to medical care for girls in Punjab, India: the roles of age, religion, and distance.

Risk factors that increase the likelihood of discrimination against girls in India have not been well studied. In this study of hospitalized children in Punjab, India, girls were less likely to be in the newborn or infant age groups, to be of the Sikh religion, or to come from far away than were boys. These differences suggest that these factors are significant risk factors for denied access to medical care for girls living in Punjab, India.

Adolescent↗
PubMed1991

Analytical procedures for a cryptic messenger RNA that mediates translational control of prostaglandin synthase by glucocorticoids.

Expression of the enzyme prostaglandin H synthase in cultured vascular smooth muscle cells required epidermal growth factor (EGF) and type beta transforming growth factor (TGF-beta) and was inhibited by cycloheximide but not actinomycin D. Preincubation with the glucocorticoid dexamethasone (0.5 microM) blocked the EGF-induced expression of prostaglandin H (PGH) synthase. Following dexamethasone addition, levels of hybridizable mRNA for PG synthase were reduced by over 90% within 1 h. After dexamethasone was removed, PG synthase mRNA recovered within 3 h by a process that was not inhibited by actinomycin D. These observations, together with other findings, suggested that the mRNA was being converted into some nonextractable and nontranslated form, probably by binding of a glucocorticoid-induced protein to the conserved 3' untranslated region. In order to investigate further the nature of this phenomenon, seven different literature procedures were evaluated for extracting and determining the PG synthase mRNA. Five of the seven procedures failed to detect hybridizable PG synthase mRNA in glucocorticoid-treated cells. Two procedures, however, recovered mRNA in both glucocorticoid-treated and control cells. A comparison of the protocols indicated that only those methods that incorporate a cationic detergent (sodium N-lauroylsarcosine), instead of anionic detergents in the lysis or homogenization buffers, successfully extract the glucocorticoid-suppressed PG synthase mRNA. Based upon these results two procedures are described, one that optimizes the extraction and determination of the glucocorticoid-suppressed (cryptic) form of the mRNA, and another which optimizes the analysis of normal mRNA without extracting the cryptic form. The results indicate that translational control of PG synthase by glucocorticoids is regulated by converting the mRNA into a cryptic form that is more firmly tissue bound than normal mRNA.

Animals↗
PubMed1991

Measurement of neonatal skinfold thickness--is it of any clinical relevance?

The skinfold thickness (SFT) was measured in 750 Punjabi newborns at triceps and subscapular sites using a Harpenden's Caliper. It was correlated with various maternal and neonatal factors. SFT increased with increasing gestation but showed a decline after 40 weeks. There was a positive correlation of SFT with birth weight and length of the baby in both sexes. The correlation co-efficient for all these parameters was 0.9. The female babies had a higher SFT at all weight and length groups. Increasing maternal age, parity, weight and height all influenced the neonatal SFT positively. Mothers with higher SFT produced babies with more skinfold thickness. Similar relationship was observed between birth weight and these maternal factors. While severe pre-eclampsia and eclampsia led to a significant fall in SFT, hypertension alone did not affect it. A higher than normal SFT was seen among infants of diabetic mothers. It was concluded that the SFT does not give any additional information than that provided by the commonly measured parameters like birth weight and length.

Adult↗
PubMed1991

Hydatid disease.

Explore the source record for details and available documents.

Child↗
PubMed1990

Expression of DNA sequences containing neuron specific enolase gene in Escherichia coli.

There is evidence that the gene for gamma-gamma enolase (neuron specific enolase, NSE) is regulated during cell differentiation and development, conserved in a variety of organisms and contains mRNA destabilizing sequences. In order to investigate further the mechanisms of these processes and to obtain large quantity of this protein, the NSE gene was isolated from neuroblastoma cells and cloned in E. coli using standard molecular biology techniques. The NSE gene expression was studied and the expressed protein (recombinant NSE) was characterized extensively. The recombinant NSE behaves like parental NSE in antisera specificity, resistance for chaotropic agents like urea, thermal stability at higher temperatures etc. The physical parameters like secondary structure, hydrophilicity, antigenic index and flexibility of the expressed protein were studied. The results of the present investigation collectively form the basis for initial investigations of how the expression of NSE gene is regulated. This is the first report where the recombinant NSE gene has been characterized so extensively.

Amino Acids↗
PubMed1990

Aetiology of bacterial diarrhoea in north Indian children with special reference to Campylobacter jejuni.

A total of 184 cases of acute diarrhoea, in patients aged 1-36 months, were studied clinicobacteriologically. Enteropathogens were isolated in 22.28% cases. Campylobacter jejuni was isolated from 2.17% cases only. Salmonellae were isolated from 7.6% cases and 64.28% of them were S typhimurium. More than 75% of all isolates of salmonellae, shigellae, Esch coli and Campylobacter jejuni were sensitive to gentamicin and cephaloridine. Secondary lactose intolerance was noted in 6.52% cases only.

Campylobacter↗
PubMed1978

The forensic laboratory evaluation of evidence in alleged rape.

Serial vaginal fluid samples were obtained for laboratory analysis in 15 couples after voluntary intercourse. These samples were analyzed to determine the rate of decay of sperm and prostatic acid phosphatase as it pertains to alleged rape. An attempt was made to identify the male partner by laboratory examination of pubic hair combings and for foreign ABO antigens in vaginal fluid. If consideration is given to proper laboratory controls, examination for spermatozoa and prostatic acid phosphatase remains the primary test in alleged rape.

ABO Blood-Group System↗
PubMed1975

Substituted thiazolidones: selective inhibition of nicotinamide adenine dinucleotide-dependent oxidations and evaluation of their CNS activity.

Eight 2-arylimino-3-(3-N-morpholinopropyl) thiazolid-4-ones were synthesized from the corresponding 1-aryl-3-(3-N-morpholinopropyl) thiocarbamides, characterized, and tested for their effects on the cellular respiratory activity of rat brain homogenates. All substituted 4-thiazolidones selectively inhibited nicotinamide adenine dinucleotide (NAD)-dependent oxidations of pyruvate, citrate, DL-isocitrate, alpha-ketoglutarate, malate, beta-hydroxybutyrate, L-glutamate, and NADH, while the NAD-independent oxidation of succinate remained unaltered. All thiazolidones possessed some degree of anticonvulsant activity against pentylenetetrazol-induced convulsions, and the protection afforded by these compounds at a dose of 100 mg/kg ranged from 30 to 80%. The low toxicity possessed by most of these thiazolidones was reflected by their approximate LD-50 values from 300 mg/kg to greater than 1000 mg/kg. In the present study, the anticonvulsant activity possessed by these substituted 4-thiazolidones was unrelated to their ability to inhibit selectively the NAD-dependent oxidations by rat brain homogenates. These thiazolidones exhibited depression of the CNS activity which, in some cases, was associated with the increase in respiration. All thiazolidones potentiated pentobarbital (sodium) sleeping time in mice when administered in a dose of 100 mg/kg.

Animals↗