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Biomedical subjects

S Mahajan

Publications and source records attributed to S Mahajan.

At least 73 records · Page 4Linked to original sources
PubMed1992

Cross-linking of surface immunoglobulin activates src-related tyrosine kinases in WEHI 231 cells.

Crosslinking of sIgM on the B cell line WEHI 231 with anti-sIgM antibody induces protein tyrosine phosphorylation, implicating protein tyrosine kinases (PTKs) in sIg-mediated signal transduction. We have analyzed this cell line for members of the src family of PTKs and have evaluated whether these PTKs might be involved in the process of sIgM-mediated signaling. Our results show that Blk, Lyn, Lck, and Hck are detectable in WEHI 231 cells. Addition of antibodies to sIgM were found to variably stimulate the activities of Blk, Lyn, Lck, and Hck as measured by immune-complex protein kinase assays. Autophosphorylation of these src PTKs, as assessed by reaction with anti-phosphotyrosine antibodies, increased over the time course of sIgM-mediated activation. Co-immunoprecipitation studies to investigate the potential physical interaction of src PTKs with the sIgM receptor complex revealed that, under digitonin and Brij 96 lysis conditions Lyn, Lck, Hck, but not Blk associated with sIgM.

Animals↗
PubMed1992

Conversion of monocyte chemoattractant protein-1 into a neutrophil attractant by substitution of two amino acids.

The small cytokine monocyte chemoattractant protein-1 has structural similarity to the neutrophil chemoattractant interleukin-8, but each protein is specific in attracting its own target cell. To investigate the structural basis of this cell type specificity, we have developed an Escherichia coli expression system for the monocyte chemoattractant and mutagenized selected amino acid residues to ones found at the corresponding positions of interleukin-8. We find that a double mutation of tyrosine 28 and arginine 30 to leucine and valine, respectively, causes a drastic decrease in chemotactic activity toward monocytes with the appearance of a novel (interleukin-8-like) neutrophil chemotactic activity. Computer graphic analysis predicts that, with the double substitution, a putative receptor binding groove of the monocyte chemoattractant protein would become topographically similar to that of interleukin-8. We therefore postulate that one or both of these amino acid residues are part of the binding contact of these small cytokines and their receptors.

Amino Acid Sequence↗
PubMed1991

Morphine-induced modulation of sciatic nerve stimulation evoked blood pressure responses.

Effect of i.v. morphine (1-2 mg/kg) on blood pressure changes evoked by sciatic nerve stimulation (SNS) were studied in chloralose anaesthetised cats. SNS gave a depressor, pressor or a biphasic BP response generally linked to the parameters of stimulation. Morphine produced marked attenuation of depressor and some facilitation of pressor response, suggesting a possible reciprocal relationship between depressor and pressor responses. Depressor response has been correlated with deep tissue or visceral pain mediated through A delta fibres and pressor response to cutaneous nociception involving C fibres or non nociceptive input via group II fibres. Involvement of medullary regions in differential modulation of these depressor and pressor response has been suggested.

Anesthesia↗
PubMed1990

Isolation, characterization, and host-cell-binding properties of a cytotoxin from Campylobacter jejuni.

A 68,000-molecular-weight protein was isolated by polyacrylamide gel electrophoresis from the organism-free filtrate of a fully virulent clinical strain of Campylobacter jejuni. The eluted protein was heat labile, was inactivated at either pH 3.0 or 9.0, was sensitive to trypsin, and was lethal for fertile chicken eggs. It also had toxic effects on chicken embryo fibroblast, Chinese hamster ovary (CHO), and intestinal 407 (Int407) cells. A monoclonal antibody (CETPMAb4) raised to this eluted toxic protein (ETP) from C. jejuni abolished these toxic activities. Homology between C. jejuni ETP and Vibrio cholerae toxin was not observed in that specific antisera to each did not block their respective toxic activities. In enzyme-linked immunosorbent assays, ETP, unlike chlorea enterotoxin, did not bind to GM1 ganglioside. Furthermore, the C. jejuni toxin had cytotoxinlike properties and induced rounding of CHO cells. Binding of ETP to Int407 and primary chicken embryo fibroblast cells was maximal after 2 h as assessed by enzyme-linked immunosorbent assay, and this toxin adherence to host cell membranes was significantly reduced by prior treatment of the cells with proteolytic enzymes, neuraminidase, or glutaraldehyde but not by treatment with beta-galactosidase, lipase, Nonidet P-40, or sodium metaperiodate. In competitive binding assays, sugars, lectins, or GM1 ganglioside did not adversely influence uptake of ETP by these cells. These results suggest that the ETP produced by C. jejuni is a cytotoxin which binds to Int407 cells via a protein- or glycoproteinlike receptor on cell membranes and possesses properties dissimilar to those of V. cholerae toxin.

Animals↗
PubMed1990

Variations in the life span, enzymes and lipid peroxide levels in ageing Caryedon serratus (Coleoptera: Bruchidae).

In the bruchid Caryedon serratus, life span of males was longer than that of females. Catalase showed an increasing trend with age in both the sexes but the increase was higher in males. However, an opposite trend was observed for lipid peroxide levels. A rapid decline of NADH and succinate dehydrogenases in females is indicative of early depletion of food reserves due to the higher metabolic rate. Thus, in C. serratus, the factors contributing to relatively higher life span of males are efficient homeostatic defence mechanisms and low oxidative damage in males, early maturity and more reproductive demands in females.

Aging↗
PubMed1989

Studies on the purified, lipid-reconstituted (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B membranes. Dependence of enzyme activity on lipid headgroup and hydrocarbon chain structure.

The purified (Na+ + Mg2+)-ATPase from Acholeplasma laidlawii B membranes was successfully reconstituted with a number of different phospho- and glycolipids, and the ability of these lipids to support the function of this enzyme was evaluated by their ability to increase the specific activity of the purified enzyme and by their ability to restore its lipid-phase state-dependent properties which were lost during purification. The incorporation of this ATPase into liposomes composed of the endogenous membrane lipids of the organism, or of zwitterionic phospholipids such as phosphatidylcholine or phosphatidylethanolamine, results in a full reconstitution of its activity and its lipid-phase state-dependent properties. In contrast, anionic phospholipids alone, or in combination with zwitterionic phospholipids at concentrations higher than 10 mol % of the anionic phospholipid, cause an irreversible inhibition of this ATPase. However, when combined with neutral glycolipids, larger amounts of anionic phospholipid can be tolerated without enzyme inhibition. Phosphatidylcholines with acyl chains of 14-24 linear carbon atoms and varying degrees of branching and unsaturation successfully reconstitute the enzyme, in marked contrast to the shorter chain homologues, which were ineffective. Our results indicate that the full expression of the activity of the A. laidlawii B ATPase requires a host lipid bilayer membrane of low to moderate negative surface charge which is predominantly liquid-crystalline and of a minimal bilayer thickness. Once such requirements are met, the enzyme exhibits considerable flexibility regarding the nature of the lipids which can effectively support its function. In particular, the activity of the A. laidlawii B ATPase is not very sensitive to lipid "fluidity" in the liquid-crystalline state.

Acholeplasma laidlawii↗
PubMed1989

Virulence of Campylobacter jejuni for chicken embryos.

The pathogenicity of Campylobacter jejuni was examined in chicken embryos. In this system, mortality data and histopathological findings induced by organisms and by bacterium-free filtered broth were identical. The absence in chicken embryo tissues both of organisms and of an inflammatory infiltrate suggests a toxin etiology.

Animals↗
PubMed1988

Taste acuity and zinc metabolism in captopril-treated hypertensive male patients.

Hypogeusia is a reported side effect of captopril. Linkage of hypogeusia to zinc deficiency has been suggested. We objectively assessed taste acuity using Henkin's three-drop stimulus technique and measured plasma zinc (PZn) level and urinary zinc excretion in 31 hypertensive patients. Of these, 11 were long-term, high-dose captopril recipients (more than 6 months, 266 +/- 34 mg/day), six were short-term captopril recipients (less than 6 months, 104 +/- 40 mg/daily dose), and the remaining 14 served as noncaptopril controls. Compared to controls, the long-term captopril group had significantly higher taste detection and recognition thresholds, lower PZn (91 +/- 3 vs. 100 +/- 3 micrograms/dl, P less than 0.05) and higher urinary zinc excretion (1017 +/- 89 vs. 609 +/- 76 micrograms/day, P less than 0.005). The short-term captopril group did not differ significantly from the noncaptopril group except for higher taste-recognition thresholds for NaCl and sucrose (P less than 0.05). Discontinuing captopril improved taste acuity and almost normalized zinc parameters in two patients on long-term captopril. These results suggest that abnormalities of taste are commonly associated with captopril therapy and may be related to changes in zinc metabolism. This is especially true in patients on long-term, high-dose captopril therapy.

Captopril↗
PubMed1988

Characterization of sodium transport in Acholeplasma laidlawii B cells and in lipid vesicles containing purified A. laidlawii (Na+-Mg2+)-ATPase by using nuclear magnetic resonance spectroscopy and 22Na tracer techniques.

The active transport of sodium ions in live Acholeplasma laidlawii B cells and in lipid vesicles containing the (Na+-Mg2+)-ATPase from the plasma membrane of this microorganism was studied by 23Na nuclear magnetic resonance spectroscopic and 22Na tracer techniques, respectively. In live A. laidlawii B cells, the transport of sodium was an active process in which metabolic energy was harnessed for the extrusion of sodium ions against a concentration gradient. The process was inhibited by low temperatures and by the formation of gel state lipid in the plasma membrane of this organism. In reconstituted proteoliposomes containing the purified (Na+-Mg2+)-ATPase, the hydrolysis of ATP was accompanied by the transport of sodium ions into the lipid vesicles, and the transport process was impaired by reagents known to inhibit ATPase activity. At the normal growth temperature (37 degrees C), this transport process required a maximum of 1 mol of ATP per mol of sodium ion transported. Together, these results provide direct experimental evidence that the (Na+-Mg2+)-ATPase of the Acholeplasma laidlawii B membrane is the cation pump which maintains the low levels of intracellular sodium characteristic of this microorganism.

Acholeplasma laidlawii↗
PubMed1985

Cerulenin inhibition of lipid synthesis and its reversal by exogenous fatty acids in Mycobacterium smegmatis ATCC 607.

Cerulenin inhibited the lipid synthesis of Mycobacterium smegmatis ATCC 607 over the range of 0.5-1.8 microgram/mL with complete inhibition at 1.8 microgram/mL, as monitored by [14C]glycerol incorporation into lipids. Exogenous fatty acids failed to restore the lipid synthesis at 1.8 microgram/mL; however, the addition of palmitic acid to the growth medium partially restored the lipid synthesis when cerulenin concentration was decreased to 1.6 microgram/mL. Fatty acid analysis of cerulenin plus palmitic acid supplemented cultures revealed that exogenously supplied fatty acid was incorporated into cellular phospholipids. Further investigations with 1.6 microgram/mL of cerulenin and [14C]acetate and [32P]orthophosphoric acid showed that cerulenin inhibited the synthesis of saturated plus unsaturated fatty acids and phospholipids. Pulse-chase studies with [14C]acetate revealed decreased synthesis and degradation of each of the phospholipid components.

Antifungal Agents↗
PubMed1984

Cerulenin effect on phospholipid metabolism in Mycobacterium smegmatis ATCC 607.

Phospholipid metabolism in the presence of a subinhibitory concentration of cerulenin was studied in Mycobacterium smegmatis ATCC 607 by pulse labelling and subsequent chasing of radioactivity in phospholipids using [32P]orthophosphate. Cerulenin inhibited biosynthesis of total phospholipids to a significant level which is reflected equally in all the phospholipid components (phosphatidylethanolamine, phosphatidylinositol mannosides and cardiolipin) within the time of exposure. On chase, alteration in degradation of all phospholipid components was observed on cerulenin treatment, in comparison with control cells. Differences seen in the metabolism of phospholipids in cerulenin-treated and control cells are discussed.

Antifungal Agents↗