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Biomedical subjects

S Agarwal

Publications and source records attributed to S Agarwal.

At least 235 records · Page 13Linked to original sources
PubMed1994

Platelet functions & lipid profile within 24 hours following an attack of TIA, thrombotic & haemorrhagic stroke.

The present study was undertaken to evaluate comparatively the lipid profile and platelet functions within 24 h of the three most frequent types of stroke encountered in clinical practice. Twenty patients of transient ischaemic attacks, 22 of thrombotic stroke and 26 of haemorrhagic stroke (hypertensive putaminal haemorrhage), all within 24 h of the acute event, and 21 control subjects were studied. Spontaneous platelet aggregation, platelet aggregation induced with adenosine diphosphate (2.5, 3.75 and 5.0 microM) and lipid profile (serum cholesterol, triglycerides, high density lipoprotein, low density lipoprotein and very low density lipoprotein) estimations were performed in all the subjects. Mean platelet aggregation values were significantly lower in haemorrhagic stroke patients as compared to controls. Serum cholesterol, triglycerides and very low density lipoprotein levels in ischaemic groups i.e., transient ischaemic attacks and thrombotic stroke patients, were significantly elevated, more so in the former group. It appears that platelet hypofunction has a role in the pathogenesis of hypertensive putaminal haemorrhage while in patients of transient ischaemic attack and thrombotic stroke, lipids may be a contributing factor in cerebral atherogenesis.

Adult↗
PubMed1993

Biochemical correlates of longevity in two closely related rodent species.

The objective of this study was to explore the basis of variations in the life span and metabolic potential, i.e., total amount of energy consumed during life, between different species, in context of the free radical hypothesis of aging. A comparison was made between the house mouse (Mus musculus) and the white-footed mouse (Peromyscus leucopus): the latter has > 2-fold greater life span and metabolic potential than the former. Longer life span and higher metabolic potential of Peromyscus were associated with low rates of mitochondrial O2.- and H2O2 generation, higher activities of catalase and glutathione peroxidase and low levels of protein oxidative damage as well as low susceptibility to oxidative damage in response to experimental oxidative stress. Results support the role of oxidative stress in aging.

Aging↗
PubMed1993

Relationship between aging and susceptibility to protein oxidative damage.

The objective of this study was to determine if the susceptibility of tissues to experimental oxidative damage is altered during the aging process. Adult houseflies were X-irradiated at different dosages, when they had reached 0.25 and 0.70 of their average life expectancy. Protein carbonyl content and activity of glucose-6-phosphate dehydrogenase were used as indices of oxidative damage. Fly homogenates as well as the live flies were more susceptible to oxidative damage at the older than at the younger age.

Aging↗
PubMed1993

Protein oxidative damage is associated with life expectancy of houseflies.

The objective of this study was to test some of the predictions of the oxidative-stress hypothesis of aging, which postulates that aging is causally associated with the molecular damage inflicted by reactive oxygen species. Protein carbonyl content was used as an index of molecular oxidative modifications. The carbonyl content was found to be associated with the physiological age or life expectancy of flies rather than with their chronological age. Exposure of flies to sublethal hyperoxia (100% oxygen) irreversibly enhanced the carbonyl content of the flies and decreased their rate of oxygen consumption. Results of this study indicate that protein carbonyl content may be a biomarker of aging and support the general concept that oxidative stress may be a causal factor in the aging process.

Animals↗
PubMed1993

Raf-1 and p21v-ras cooperate in the activation of mitogen-activated protein kinase.

Mitogen-activated protein (MAP) kinases Raf-1, pp60src, and p21ras all play important roles in the transfer of signals from the cell surface to the nucleus. We have used the baculovirus/Sf9 insect cell system to elucidate the regulatory relationships between pp60v-src, p21v-ras, MAP kinase (p44erk1/mapk), and Raf-1. In Sf9 cells, p44erk1/mapk is activated by coexpression with either v-Raf or a constitutively activated form of Raf-1 (Raf22W). In contrast, p44erk1/mapk is activated to only a limited extent by coexpression with either Raf-1 or p21v-ras alone. This activation of p44erk1/mapk is greatly enhanced by coexpression with both p21v-ras and Raf-1. Since we have previously shown that p21v-ras stimulates Raf-1 activity, the activation of p44erk1/mapk by p21v-ras may occur exclusively via a Raf-1-dependent pathway. However, a dominant-inhibitory mutant of Raf-1 (Raf301) does not block the activation of p44erk1/mapk by p21-v-ras. Further, pp60v-src, which activates Raf-1 at least as effectively as p21v-ras, fails to enhance p44erk1/mapk activity greatly when coexpressed with Raf-1. These data suggest that activation of p44erk1/mapk by p21v-ras may occur via both Raf-1-dependent and Raf-1-independent pathways.

Amino Acid Sequence↗
PubMed1993

A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials.

A comparative evaluation was made of the conventional spectrophotometric procedure and three published high performance liquid chromatographic (HPLC) procedures for the determination of malondialdehyde (MDA) as the thiobarbituric acid (TBA) derivative when applied to liver, fish meal, serum, and urine. Except for urine, spectrophotometric analysis overestimated MDA content. Purification of the TBA-MDA complex obtained from liver and fish meal on reverse phase cartridges was found to entail a loss of complex bound to residual peptides in the trichloracetic acid (TCA) extract. Mincing as opposed to homogenizing liver samples led to a doubling of values for MDA content. Hexanal was a major TBA reactant, in addition to MDA, in all the samples. Acid hydrolysis and heat were necessary for the release of MDA bound to the amino groups of proteins and other amino compounds. Methods for free MDA have limited application to biological materials except short term in vitro preparations such as peroxidizing microsomes, in which free MDA accumulates. On the basis of these and other observations, a modified HPLC procedure for the determination of MDA as the TBA-MDA complex is proposed.

Animals↗
PubMed1993

Direct in vivo gene transfer to airway epithelium employing adenovirus-polylysine-DNA complexes.

Adenovirus-polylysine-DNA complexes were evaluated for their capacity to accomplish direct in vivo gene transfer to airway epithelium employing a rodent model. Binary complexes containing transferrin or adenovirus, or combination complexes containing both transferrin and adenovirus, were evaluated. The highest in vitro gene transfer efficiency in primary cultures of airway epithelial cells was accomplished by the combination complexes. This result was paralleled in vivo. Transient gene expression of up to 1 week was observed with localization of the transduced cells to the region of the small airways. These results establish the feasibility of this type of approach for gene therapy applications.

Adenoviridae↗
PubMed1993

Receptor-mediated gene transfer to airway epithelial cells in primary culture.

A variety of methods have been utilized for gene transfer to the cells of the airway epithelium. These have included DNA-mediated mechanisms of gene transfer as well as recombinant viral vectors. Despite the availability of these methods, limitations in their utility warrant the development of alternate systems. As an alternative, receptor-mediated endocytosis using transferrin-polylysine conjugates has been shown to transduce immortalized airway epithelial cells efficiently via a physiologic pathway. When transferrin-polylysine conjugates were used to transduce airway epithelial cells grown in primary culture, however, gene transfer occurred inefficiently. Investigation into this relative inefficiency centered on endosomal entrapment of the conjugate-DNA complex. Pretreatment of the cells with chloroquine, which causes vacuolization and disruption of the endosome, or co-delivery of adenoviral particles, which serves to lyse the endosomal membrane, were both associated with greatly improved gene transfer efficiency. These studies established that the relative refractory state of the airway epithelial cells in primary culture was secondary to the retention of the internalized material within the endosome. We thus explored the efficiency of conjugates that possessed a mechanism to escape this endosomal entrapment; adenovirus-polylysine conjugates and transferrin-polylysine/adenovirus-polylysine conjugates were thus employed. Gene transfer efficiency improved significantly with the adenovirus-containing conjugates. These data support the concept that conjugates can be synthesized that mediate highly efficient gene transfer to airway epithelial cells in primary culture via the receptor-mediated endocytosis pathway.

Adenoviridae↗
PubMed1993

A clinico-hematological profile of hemolytic-uremic syndrome.

Hemolytic uremic syndrome (HUS) is defined as microangiopathic hemolytic anemia, thrombocytopenia and uremia. It is an important cause of acute renal failure (ARF) in children all over the world. The present study was carried out to assess the incidence, clinical presentation, hematological and biochemical profile of children presenting with HUS from 1987 to 1990. Out of the 100 cases who presented with ARF 22 had HUS. A majority of these children were males below 1 year of age, and had a prodromal phase of mainly gastrointestinal manifestations lasting for about a week. Anemia was a constant feature followed by bleeding diathesis, mainly melena and purpura. Neurological manifestations included altered sensorium, irritability, coma, hypertensive encephalopathy and convulsions. Renal problems mainly included oliguria, hypertension, hematuria and edema. Investigations revealed thrombocytopenia and microangiopathic hemolytic anemia in all cases. Evidence of disseminated intravascular coagulation (DIC) was observed in 3 cases as decreased fibrinogen levels, increased fibrinogen degradation products and deranged clotting studies. Blood biochemistry revealed azotemia in all cases, hyponatremia in 5 cases, hypernatremia in 3 cases and hyperkalemia in 12 cases. Stool culture showed the presence of Shigella in 8, E. coli in 6 and Klebsiella in 4 cases. Out of 22 cases of HUS, 15 were treated conservatively; of these 2 died. Both of these deaths were due to DIC 7 children were put on peritoneal dialysis; only 1 child died in this group. Factors affecting the outcome were duration of oliguria, levels of blood urea and presence of encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1993

Serum enzyme abnormalities in protein energy malnutrition.

Six serum enzymes, alkaline phosphatase, cholinesterase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase were studied in 30 cases of protein energy malnutrition (PEM). The mean serum values of alkaline phosphatase, cholinesterase and lactate dehydrogenase in cases of PEM were significantly lower than the controls, lowering being maximum in PEM Grade IV. The mean serum values of aspartate aminotransferase and alanine aminotransferase in patients with PEM were significantly higher than the controls. The mean serum values of gamma-glutamyl transpeptidase showed similar significant rise in all but PEM Grade IV. The degree of increase in the serum values of these three enzymes were maximum in cases with PEM Grade I. These findings suggest that abnormalities in blood levels of these enzymes occur in any form of PEM and these are related to the severity of the disease.

Adolescent↗
PubMed1992

Phosphatase inhibitors modulate the growth-regulatory effects of human tumor necrosis factor on tumor and normal cells.

Tumor necrosis factor alpha (TNF-alpha) has been shown to inhibit the growth of tumor cells and stimulate the growth of certain normal cells in vitro. The mechanism by which TNF exerts its cell growth-regulatory effects is not known. In this report, we investigated the effects of phosphatase inhibitors on the cell growth-inhibitory effects of TNF on L-929, a highly sensitive murine connective tissue tumor cell line, and on the growth-stimulatory effects of TNF on normal human fibroblasts. The antiproliferative effects of TNF on L-929 cells were inhibited by orthovanadate, an inhibitor of phosphotyrosine phosphatases, in a dose-dependent manner. Okadaic acid, which is a specific inhibitor of phosphoserine- and phosphothreonine-specific phosphatases, also blocked the growth-inhibitory effects of TNF, suggesting that TNF may function through the activation of certain phosphatases. These inhibitors had no effect on TNF receptors. Addition of phosphatase inhibitor, even 12 h after the treatment of cells with TNF, was sufficient to block the antiproliferative effects of the cytokine, suggesting that the inhibitor is acting at a late event in the pathway of action of TNF. Cells were protected by orthovanadate from the cytotoxic effects of TNF even in the presence of actinomycin D or cycloheximide, thus indicating the lack of a requirement for de novo protein synthesis. Orthovanadate altered the cell morphology from flat spindle shapes to rounded ones. Besides anticellular effects, a phosphatase inhibitor also suppressed the proliferative effects of TNF on human fibroblasts. These results thus suggest that phosphatases may be needed for both proliferative and antiproliferative effects of this cytokine. This is the first report to suggest that phosphatases play a role in the growth-regulatory action of TNF.

Animals↗
PubMed1992

Breakage and binding of DNA by reaction products of hypochlorous acid with aniline, 1-naphthylamine, or 1-naphthol.

Hypochlorous acid (HOCl) is a chemically reactive oxidant and a potent microbicidal agent that is synthesized in phagosomes of inflammatory neutrophils and released into extracellular spaces. Besides reducing pathogenicity by reacting with phagocytized infectious agents, HOCl may damage tissues and yield toxic products upon reaction with various other molecules, including xenobiotics. As model xenobiotics, the substituted aryl compounds aniline, 1-naphthylamine, and 1-naphthol (1-NOH) were investigated herein for their potential to react with HOCl and the transformed into genotoxic products. The compounds were first exposed to HOCl (25-150 microM) in phosphate buffer and afterward used to treat human fibroblasts or purified DNA. DNA single-strand breaks in cells and the binding of HOCl-reacted 1-[14C]NOH to purified DNA were assessed by DNA alkaline elution and scintillation spectrometry, respectively. It was found that neither HOCl nor compounds alone could break cellular DNA. But HOCl-reacted compounds produced up to 400 rad equivalents of DNA breaks. HOCl reaction products of aniline and the model bicyclic aryl compounds differed in their DNA-breaking characteristics. HOCl-reacted 1-[14C]NOH was stable and bound to DNA at up to 124 pmol/mg DNA. Sodium thiosulfate, glutathione, and taurine inhibited the transformation reactions; but only the former two blocked binding of HOCl-reacted 1-NOH to DNA. Ultraviolet spectra showed that HOCl reacted rapidly (less than 1 min) and equally well with 1-NOH at pH 7.2 or at an intraphagosomal pH of 5.0. Reaction concentrations of HOCl in this study were 2- to 11-fold lower than levels generated in vitro by stimulated neutrophils. These results show that certain aryl compounds can react readily with approximated physiological levels of HOCl (-OCl) to form relatively long-lived products that bind DNA and are genotoxic to human cells.

1-Naphthylamine↗
PubMed1992

Isolation of a malondialdehyde-deoxyguanosine adduct from rat liver DNA.

In previous studies, an adduct of malondialdehyde (MDA) with guanine was identified in rat and human urine. Subsequent detection of an adduct with deoxyguanosine (dG) in urine prompted an investigation of its possible occurrence in DNA. Rat liver DNA was hydrolyzed using nuclease P1 and alkaline P-ase and subjected to deoxyribonucleoside analysis using reverse phase high-pressure liquid chromatography (HPLC) with fluorescence detection. A compound was isolated that could not be separated from a synthetic pyrimidinopurine adduct of MDA and dG (dG-MDA). Partial hydrolysis released guanine (Gua), Gua-MDA, and dG in amounts that, in aggregate, were the molar equivalent of the starting material calculated by fluorescence analysis as dG-MDA. Complete acid hydrolysis of the isolate yielded an equimolar amount of MDA. Analysis of liver DNA isolated from growing rats yielded a value for dG-MDA content of 9.0 +/- 1.6 pmol/100 micrograms DNA (mean +/- SEM, N = 5). This value is approximately 7 times those reported for the 8-hydroxy deoxyguanosine content of rat liver nuclear DNA. This study demonstrates that DNA is modified in vivo by reactions of its guanylate moiety with MDA, and indicates that, at least in the case of rat liver DNA, the prevalence of such modifications is greater than those caused by reactions with hydroxyl radicals.

Animals↗