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Biomedical subjects

R Gupta

Publications and source records attributed to R Gupta.

At least 757 records · Page 42Linked to original sources
PubMed1987

Fertility in cryptorchidism: further development of an experimental model.

Further development of an experimental model for evaluating fertility in cryptorchidism led to studies of unilateral cryptorchidism, endocrinological cryptorchidism, and the effects of treatment. The results demonstrate that rats with unilateral mechanical cryptorchidism have a significant diminution in the ability to impregnate females (impregnation rate, 45%) when compared with sham-operated controls (84%) and rats undergoing unilateral orchiectomy (88%). In addition, we demonstrated that lower doses of estradiol caused cryptorchidism and resulted in infertility of approximately the same degree as higher doses (impregnation rates, 18% and 0%, respectively), but avoided obvious side effects. Treatment of estradiol-induced cryptorchidism with human chorionic gonadotropin resulted in testicular descent, but did not significantly improve the ability to bear offspring (10% with hCG vs. 0% without). Surgical orchiopexy after surgically induce mechanical cryptorchidism resulted in improved fertility (30% vs. 0%); however, the improvement was still significantly less than the control rate. In summary, this experimental model demonstrates the effects of various aspects of cryptorchidism and its treatment on fertility and can easily be adapted to evaluate important clinical problems.

Animals↗
PubMed1987

Were the original eubacteria thermophiles?

Thermotoga maritima is one of the more unusual eubacteria: It is highly thermophilic, growing at temperatures higher than any other eubacterium; its cell wall appears to have a unique structure and its lipids a unique composition; and the organism is surrounded by a loose-fitting sheath of unknown function. Its phenotypic uniqueness is matched by its phylogenetic position; Thermotoga maritima represents the deepest known branching in the eubacterial line of descent, as measured by ribosomal RNA sequence comparisons. T. maritima also represents the most slowly evolving of eubacterial lineages. The fact that the two deepest branchings in the eubacterial line of descent (the other, the green non-sulfur bacteria and relatives, i.e. Chloroflexus, Thermomicrobium, etc.) are both basically thermophilic and slowly evolving, strongly suggests that all eubacteria have ultimately arisen from a thermophilic ancestor.

Bacteria↗
PubMed1987

Unusual finger tip injury in children.

We report two children with finger tip ischaemia resulting from woollen mittens. Ischaemia has progressed to gangrene and required amputation of the affected finger.

Amputation, Surgical↗
PubMed1987

Etoposide (VP16) and teniposide (VM26): novel anticancer drugs, strongly mutagenic in mammalian but not prokaryotic test systems.

The mutagenic effect of the antineoplastic drugs VP16 (etoposide; 4'-demethylepipodophyllotoxin-ethylidene-beta-D-glucopyranoside) and VM26 (teniposide; 4'-demethylepipodophyllotoxin-thenylidene-beta-D-glucopyr ano side) in mammalian and prokaryotic test systems have been compared. Both VP16 and VM26 which interact with mammalian DNA topoisomerase II, are strongly mutagenic in Chinese hamster ovary cells as indicated by the induction of mutations at the hypoxanthine-guanine phosphoribosyl transferase and adenosine kinase loci, and production of DNA strand breaks and sister-chromatid exchanges. Mouse L cells treated with these drugs also show a large dose-dependent (0.05-0.2 microgram/ml for VM26 and 0.5-1.5 micrograms/ml for VP16) increase in the frequency of 6-thioguanine-resistant mutants and extensive fragmentation of cellular DNA. In contrast to the results obtained with mammalian cells, VP16, which was extensively investigated, showed no increase in revertant frequencies in the Salmonella typhimurium strains TA98 and TA100 at concentrations up to greater than 500 micrograms/plate, in either the absence or presence of an exogenous rat liver activation system. However, a very weak mutagenic response to VP16 and VM26 (less than 2-fold increase in revertant frequency) at very high drug concentrations was observed in the strain TA102. VP16 also failed to show any mutagenic response (up to greater than 500 micrograms/ml) in an excision repair-proficient Escherichia coli strain 113/143 employing two different forward mutation detection systems [viz. ability to grow in galactose (Gal+) or in presence of 5-methyltryptophan], which are capable of detecting various types of genetic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Genes for immunodominant protein antigens are highly homologous in Mycobacterium tuberculosis, Mycobacterium africanum, and the vaccine strain Mycobacterium bovis BCG.

The relatedness of immunodominant protein antigens in Mycobacterium tuberculosis, M. africanum, and M. bovis BCG was investigated by comparing the genes that encode major protein antigens in M. tuberculosis with their counterparts in the other two mycobacteria. Genes encoding homologs of M. tuberculosis major protein antigens were isolated from M. africanum and M. bovis BCG by constructing lambda gt11 recombinant DNA expression libraries and screening them with murine monoclonal antibodies and DNA probes. The antibodies were directed against four major protein antigens of M. tuberculosis with molecular masses of 71, 65, 19, and 14 kilodaltons. The isolated M. africanum and M. bovis BCG DNA clones were mapped with restriction endonucleases, and the maps of the mycobacterial genes were confirmed by Southern analysis of mycobacterial genomic DNA. The restriction maps of DNA containing the four genes in M. tuberculosis, M. africanum, and M. bovis BCG are identical, indicating that the immunodominant proteins that they encode are highly homologous in the three mycobacteria. Thus, the immunity against tuberculosis engendered by M. bovis BCG vaccination could be provided, at least in part, by the immune response to these homologous antigens.

Antigens, Bacterial↗
PubMed1987

Plasma alpha fetoprotein reference ranges in infancy: effect of prematurity.

The dearth of plasma alpha fetoprotein reference ranges for preterm infants often impairs the clinical interpretation of plasma alpha fetoprotein data collected from ill babies. This study tested our hypothesis that meaningful plasma reference ranges could be established for preterm infants by a simple correction of patient age at sampling date for gestational age deficit at birth. Using a modified radioimmunoassay kit method, determinations of alpha fetoprotein were performed on capillary and venous blood samples collected from 56 babies aged from birth to 5 months with gestational ages ranging from 26 weeks to 43 weeks. Unmodified plasma alpha fetoprotein values were grouped according to patient age and examined statistically using established normal theory methods, but these yielded excessively wide reference intervals and non-Gaussian distribution parameters. Acceptable reference ranges were derived using logarithmic transformation of plasma alpha fetoprotein values and rearrangement against patient age corrected for gestational age deficit. These provisional reference ranges for plasma alpha fetoprotein in preterm (and term) infants are applied to groups of previously meaningless alpha fetoprotein results and used to test the potential usefulness of plasma alpha fetoprotein determination as a diagnostic marker in biliary atresia, hepatitis, and yolk sac derived tumours.

Female↗
PubMed1987

A genetic study among the Lepchas of the Darjeeling area of eastern India.

A total of 215 Lepchas (75 Buddhists and 140 Christians) living in the Kalimpong subdivision, Darjeeling district, West Bengal, India, were investigated for the distribution of haemoglobin, serum proteins and red cell enzymes. The gene frequencies were as follows: HbE = 0.02; Hp1 = 0.18; TfB = 0.007; TfDChi = 0.005; Gc2 = 0.22; pa = 0.18; pc = 0.03; PGM2(1) = 0.18; PGM6(1) = 0.002; PGDc = 0.17; AK2 = 0.02; GLO1 = 0.21. The most striking features were the complete lack of G6PD deficiency and very high frequency of PGDC. The remaining loci (serum albumin, lactate dehydrogenase, malate dehydrogenase and glucose-6-phosphate dehydrogenase, phosphohexose isomerase and superoxide dismutase) were monomorphic. The gene frequencies were similar in the Buddhist and Christian Lepchas. The observed average heterozygosity (9 loci) was 0.20 in the entire sample.

Acid Phosphatase↗
PubMed1987

Oxalate metabolism in thiamine-deficient rats.

Male weanling rats were maintained on a thiamine-deficient diet for 4 weeks, and compared with ad libitum and pair-fed controls. Thiamine deficiency led to slow growth and finally a decrease in body weight. Liver and kidney weights of the deficient rats were low, but appropriate to the body weight. Thiamine deficiency also caused a significant decrease in erythrocyte transketolase levels. The decarboxylation of glyoxylate both via the glyoxylate oxidation cycle and alpha-ketoglutarate:glyoxylate (alpha-KG:GA) carboligase was significantly lower in the liver and kidney mitochondria, leading to accumulation of glyoxylate in the tissues and its excretion in the urine. Part of the accumulated glyoxylate is converted to oxalate, causing hyperoxaluria.

Aldehyde-Ketone Transferases↗
PubMed1987

Mediation of multi-drug resistance in a Chinese hamster ovary cell line by a mutant type II topoisomerase.

Identification of DNA topoisomerase II as the intracellular target for the DNA cleavage activity of the epipodophyllotoxins and several intercalating agents is well established. In contrast, definite correlation of cleavable complex formation with eventual cell death has been more difficult to document. Our studies with an epipodophyllotoxin resistant cell line not only provide additional evidence that the enzyme is a multi-drug target, but also implicate drug-stimulated cleavage activity as a critical component of cytotoxic effect. When compared to WT (wild type) cells, the mutant Chinese hamster ovary cell line, VpmR-5, exhibits marked resistance to both the cytotoxic and DNA cleavage activity of etoposide as well as various intercalating agents. Steady state concentrations of these drugs in both cell lines is identical. Enzyme content as measured by immunoblot and by total decatenation activity in crude nuclear extracts is equal. Catalytic activity is also equally sensitive to inhibition by etoposide. In contrast, cleavage activity in purified enzyme from VpmR-5 cells is profoundly resistant to stimulation by drug. These data indicate that a multi-drug resistant phenotype may be acquired by a qualitative change in the enzyme that alters its interaction with drug. Further, the data strongly support a direct role for cleavable complex formation in cell death.

Amsacrine↗
PubMed1987

Synthesis and structure-activity relationships among glycosidic derivatives of 4'-demethylepipodophyllotoxin and epipodophyllotoxin, showing VM26- and VP16-213-like activities.

We have synthesized acetal and ketal derivatives of 4'-demethylepipodophyllotoxin-beta-D-glucoside (DMEPG) and epipodophyllotoxin-beta-D-glucoside (EPG) with a number of different aldehydes (viz. acetaldehyde, propionaldehyde, 2-thiophenecarboxaldehyde, 3-thiophenecarboxaldehyde, 2-furancarboxaldehyde, benzaldehyde, phenylacetaldehyde, hydrocinnamaldehyde) and acetone. The cross resistance of these compounds towards a set of Chinese hamster ovary cell mutants resistant to either podophyllotoxin (PodR mutants) or VM26 (VpmR mutants) which exhibit mutually exclusive cross-resistance patterns toward compounds that show either podophyllotoxin- or VM26-like activities have been examined. Results of our studies show that, with the exception of 2-furan derivatives, all the remaining acetals and ketals of DMEPG and EPG showed similar cross-resistance patterns towards the VpmR and the PodR mutants, as seen with VM26 and VP16-213. These results provide strong suggestive evidence that all of these derivatives (except 2-furan) possess biological activities similar to VM26 and VP16-213, and that their cellular toxicities were due to this type of activity. The VM26-like behavior of different EPG derivatives, which lack the free 4'-OH group, provide evidence that a free 4'-OH group is not essential for VM26-like activity. However, in comparison to the EPG derivatives, the corresponding DMEPG compounds showed 10- to 30-fold higher activities, indicating an enhancing effect of the free 4'-OH group on this kind of activity. Some of the newly synthesized DMEPG and EPG derivatives show higher activity in comparison to VM26 and VP16-213, and structure-activity relationship among this group of compounds is discussed.

Antineoplastic Agents↗