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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 1,801 records · Page 100Linked to original sources
PubMed1988

Comparative metabolism of phenanthrene and benzo[f]quinoline by rat liver microsomes.

The metabolism of benzo[f]quinoline (BfQ) and its carbon analog phenanthrene has been compared in incubations with liver microsomes from control, 3-methylcholanthrene (3-MC)- and phenobarbital (PB)-pretreated rats. The rates of phenanthrene metabolism by the three types of microsomes were 0.7, 4.1 and 1.5 nmol/mg protein per min, respectively; the values for BfQ were 0.5, 3.7 and 2.5, respectively. Besides N-oxidation, the metabolism of BfQ by all the above microsomes was almost exclusively at the benzo-ring (49-69%) while that of phenanthrene was predominantly at the K-region (50-71%). Phenanthrene-1,2-dihydrodiol, a precursor of the bay-region diol epoxide of phenanthrene, was produced many times more than phenanthrene-3,4-dihydrodiol by both 3-MC- and PB-induced microsomes. While BfQ-7,8-dihydrodiol, the precursor of the bay-region diol epoxide of BfQ, was the predominant metabolite with 3-MC-induced microsomes, it was a minor metabolite with PB-induced microsomes. The benzo-ring oxidation of BfQ, but not of phenanthrene, was position-specific, i.e. predominantly 7,8-oxidation by 3-MC-induced microsomes and 9,10-oxidation by PB-induced microsomes, and implies that aza-substitution results in a site-specific attack by different cytochromes P-450.

Animals↗
PubMed1988

Hepatic DNA adduct formation in rats treated with benzo[f]quinoline.

The formation of hepatic DNA adducts in male Sprague-Dawley rats following i.p. administration of benzo[f]quinoline (BfQ) was examined using a 32P-post-labeling assay. BfQ exhibited a low binding (11-27 amol adducts/microgram DNA) to liver DNA. Two BfQ-nucleoside adducts (one major and one minor) were detected. The BfQ-DNA adducts formed in vivo were chromatographically distinct from the adducts formed by the reaction of calf thymus DNA in vitro with BfQ-5,6-oxide, syn-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydroBfQ, anti-9 alpha,10 beta-dihydroxy-7 alpha,8 alpha-epoxy-7,8,9,10-tetrahydroBfQ, or anti-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydroBfQ-N- oxide. These results suggest that the bay-region diol epoxide of BfQ, unlike the bay-region diol epoxide derivatives of polynuclear aromatic hydrocarbons, is not involved in the covalent binding of BfQ to DNA.

Animals↗
PubMed1988

Limited immunological recognition of critical malaria vaccine candidate antigens.

Current vaccine development strategies for malaria depend on widespread immunological responsiveness to candidate antigens such as the zygote surface antigens and the sporozoite coat protein, the circumsporozoite (CS) protein. Since immunological responsiveness is controlled mainly by genes mapping within the major histocompatibility complex (MHC), the humoral immune response to the zygote surface antigens and the cytotoxic T lymphocyte (CTL) response to the CS protein were examined in MHC-disparate congenic mouse strains. Only two of six strains responded to the 230-kilodalton zygote surface antigen and another two strains responded to the 48/45-kilodalton surface antigen. From two mouse strains, expressing between them five different class I MHC molecules, there was recognition of only a single CTL epitope from the CS protein, which was from a polymorphic segment of the molecule. The restricted CTL response to this protein parallels the restricted antibody response to this protein observed in humans and mice. These findings suggest that subunit malaria vaccines now being developed may be ineffective.

Animals↗
PubMed1988

Almost total conversion of pancreas to liver in the adult rat: a reliable model to study transdifferentiation.

Study of transdifferentiation provides an excellent opportunity to investigate various factors and mechanisms involved in repression of activated genes and derepression of inactivated genes. Here we describe a highly reproducible in vivo model, in which hepatocytes are induced in the pancreas of adult rats that were maintained on copper-deficient diet containing a relatively non-toxic copper-chelating agent, triethylenetetramine tetrahydrochloride (0.6% w/w) for 7-9 weeks and then returned to normal rat chow. This dietary manipulation resulted in almost complete loss of pancreatic acinar cells at the end of copper-depletion regimen, and in the development of multiple foci of hepatocytes during recovery phase. In some animals, liver cells occupied more than 60% of pancreatic volume within 6-8 weeks of recovery. Northern blot analysis of total RNA obtained from the pancreas of these rats revealed the expression of albumin mRNA. Albumin was demonstrated in these pancreatic hepatocytes by immunofluorescence. The advantages of this model over the previously described models are: a) low mortality (10%), b) depletion of acinar cells, and c) development of multiple foci of hepatocytes in 100% of rats.

Animals↗
PubMed1988

Cytotoxic T cells specific for the circumsporozoite protein of Plasmodium falciparum.

Malaria is initiated by the inoculation of a susceptible host with sporozoites from an infected mosquito. The sporozoites enter hepatocytes and develop for a period as exoerythrocyte or hepatic stage parasites. Vaccination with irradiated sporozoites can provide protective immunity and a recent study shows that this can also be conferred by immunization with a recombinant salmonella expressing only the circumsporozoite protein that normally covers the sporozoites. Protection against infection is likely to be mediated by cytotoxic CD8+ cells, as depletion of CD8+ T cells in a sporozoite-immunized animal can completely abrogate immunity. Here we demonstrate directly the existence of CD8+ cytotoxic T lymphocytes (CTL) that recognize the circumsporozoite protein. B10.BR mice immunized with sporozoites or with recombinant vaccinia virus expressing the CS protein of Plasmodium falciparum contain CTL that specifically kill L cell fibroblasts transfected with the gene encoding the same CS protein. The peptide epitope from the CS protein that is recognized by CTL from this strain of mice is from a variant region of the protein.

Amino Acid Sequence↗
PubMed1988

Tamm-Horsfall protein is a marker of renal and extra-renal rhabdoid tumours.

A monoclonal antibody (MAb) to Tamm-Horsfall protein (THP) was used to stain 6 renal rhabdoid tumours (RRT) and 2 primary extra-renal rhabdoid tumours (E-RRT). One of the E-RRT was a tumour from the posterior fossa of a 3-year-old child and the other was a lump from the right side of the neck in an 18-month-old girl. Five of 6 RRT and both cases of E-RRT were positive for THP. Both cases of E-RRT also reacted with vimentin and cytokeratin MAbs. On electron microscopy, cells from both E-RRT were seen to contain concentric whorls of intermediate filaments characteristic of rhabdoid tumours. Viable tissues from one RRT and one E-RRT (the posterior fossa tumour) were available for tissue culture. Ninety-five percent of the cells growing out of both tumours were polygonal and approximately 5% of these cells were THP-positive.

Biomarkers, Tumor↗
PubMed1988

Structure of 3-isoadenosine.

3-beta-D-Ribofuranosyladenine, C10H13N5O4, Mr = 267.25, orthorhombic, P2(1)2(1)2(1), a = 13.470 (4), b = 16.054 (6), c = 5.141 (2) A, V = 1111.8 (7) A3, Z = 4, Dx = 1.596 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 1.18 cm-1, F(000) = 560, T = 298 K, R = 0.043, wR = 0.042 for 1136 reflections. The tautomeric form present in the crystal is 6-NH2. The adenine moiety is nearly planar and the torsional angle of the glycosidic linkage O(4')-C(1')-N(3)-C(4) is -161.5 degrees. All N and O atoms except N(3) and O(4') participate in a three-dimensional hydrogen-bonding system.

Adenosine↗
PubMed1988

The effect of a native collagen gel substratum on the synthesis of collagen by bovine brain capillary endothelial cells.

Cultured capillary endothelial cells, derived from bovine brain, and maintained on a plastic substratum synthesized predominantly interstitial collagens of which approximately 75 per cent were secreted into the medium. When grown on a native hydrated collagen type I gel, although no marked alteration in the 'collagen synthetic pattern' was observed, the overall level of collagen synthesis was increased by approximately 100 per cent. More dramatic, however, was the alteration in the distribution of these molecules between medium and cell layer. Interstitial collagens produced by cells grown on collagen gels were almost exclusively associated with the cell layer or collagenous gel. These studies, thus, demonstrate that an extracellular matrix may exert a considerable influence on the cellular synthetic activities and possibly cellular polarity of capillary endothelial cells.

Animals↗
PubMed1988

A monoclonal antibody stains blastemal but not tubular components of Wilms' tumour.

The monoclonal antibody PAL-E is specific for endothelial cells in a wide variety of normal and tumour tissue. In normal kidney, PAL-E reacts exclusively with the endothelium of non-glomerular blood vessels. In Wilms' tumour, binding of PAL-E was not restricted to the endothelium; staining of blastemal cells was observed in seven out of eight cases examined. Mesenchymal and tubular components, if present in Wilms' tumour, were negative. In contrast, a monoclonal antibody to Factor VIII-related antigen (RFF-8-R-1) bound only to endothelial cells in these tumours. In fetal kidney, PAL-E binding showed a wider distribution than in adult kidney and both stromal and glomerular capillaries were stained. Tubules and non-endothelial stromal cells were negative. These results indicate that the reactivity of the monoclonal antibody, PAL-E, is not restricted to cells of endothelial origin in all tissues. The implications of these findings for the differentiation of Wilms' tumour are discussed.

Adult↗
PubMed1988

Evaluation of carcinogenic effect of jute batching oil (JBO-P) fractions following topical application to mouse skin.

Jute batching oil (JBO-P), a mineral oil fraction used in the processing of jute fibers, was, as reported in our earlier studies, found to be tumorigenic following repeated topical application to mouse skin. In the present investigation an attempt has been made to identify the carcinogenic constituents of this oil. The JBO was fractionated into (1) PAH free fraction, (2) fraction containing two- and three-ring PAHs and (3) more than three-ring PAH fractions by an enrichment procedure. These three JBO fractions along with unfractionated and reconstituted oil were then subjected to the in vivo assay of complete carcinogenic activity of JBO-P and its fractions following its topical application to mouse skin. The results showed that only unfractionated and reconstituted JBO-P samples per se were able to produce benign skin tumours, while all the other three fractions, i.e. PAH-free fraction, two- and three-ring PAH-containing fraction and more than three-ring PAH-containing fraction failed to produce tumours up to 40 weeks after application. In an extended study, mice belonging to the groups exposed to various fractions of JBO were promoted with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a potent skin tumour promoter, for the two stage initiation-promotion protocol for skin carcinogenesis. After 14 weeks of promotion with TPA, all the surviving animals exposed to the fraction having more than three-ring PAHs developed benign tumours on their backs, while the other two fractions failed to do so.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1988

Role of cutaneous GSH in 12-O-tetradecanoyl-phorbol 13-acetate-induced mouse skin tumor promotion.

The role of glutathione (GSH) in skin tumor promotion was ascertained in the present study by investigating the effect of the GSH depletor, diethyl-maleate (DEM), on the tumor-promoting ability of TPA in DMBA-initiated mouse skin. DEM lowered the tumor yield and the tumor incidence by 80% (p less than 0.001) in the DMBA + TPA treated group. The rate of tumor formation was also found to be influenced by DEM. The results suggest that clonal expansion of tumor-initiated cells, stimulated by TPA, depends upon the availability of reduced GSH in the tissue. The mechanism by which depletion of reduced GSH could result in inhibition of skin tumor promotion is not known. However, inactivation of GSH and thus blockage of the physiological function of reduced GSH in the biochemical events obligatory to tumor-cell proliferation in mouse skin could be the possible mechanisms providing effective control over proliferation of tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Template-directed oligomerization of 3-isoadenosine 5'-phosphate.

Template-directed oligomerization of an activated derivative of 3-isoadenosine 5'-phosphate (piA) on polyuridylic acid [poly(U)] was studied. The reaction of ImpiA is more efficient than the corresponding reaction of ImpA, and produces 3'-5'-linked oligomers while the reaction of ImpA gives only 2'-5'-linked oligomers. The base pairing between piA and poly(U) in this system is probably of the Hoogsteen type (involving the 6-amino group and N7 of 3-isoadenosine) rather than of the Watson-Crick type.

Adenosine Monophosphate↗
PubMed1988

Isometric and isokinetic back and arm lifting strengths: device and measurement.

This study was conducted to measure isometric (static) and isokinetic (dynamic) back and arm lifting strengths at 20, 60 and 100 cm s-1 of young adults. Ten male and ten female volunteers without a history of back pain participated. The isokinetic lifting task was achieved by controlled motorized dynamic strength tester (DST). A regression analysis and analysis of variance was carried out on the strength data. The peak static strength values were significantly greater from the peak dynamic strength values. The peak dynamic strength was inversely related to the speed of motion. There were significant differences between the dynamic strengths at different stages of lift.

Adult↗

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