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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 1,333 records · Page 74Linked to original sources
PubMed1989

Membrane signal transduction in T cells in aging humans.

The interaction of the T cell receptor complex with the ligand is associated with early molecular events involved in the process of signal transduction. These events include, changes in membrane potentials, intracellular free calcium [(Ca++)i], and the activation and translocation of protein kinase C (PKC). The aim of this study was to elucidate the abnormalities in membrane signal transduction pathway as the basis of T cell-mediated immune deficiency associated with aging. Peripheral blood mononuclear cells from aging humans and sex-matched young subjects were stimulated with anti-CD3 monoclonal antibody, WT31 monoclonal antibody (defines epitopes for alpha/beta T cell receptor genes), and phytohemagglutinin (PHA), and examined for the changes in plasma membrane potentials, changes in (Ca++)i, and the activation of PKC. The membrane potentials were measured with DiOC5 dye using FACS. Intracellular free calcium was measured with quin-2 dye and spectrofluorimeter, and the membrane and cytosolic PKC were measured by an enzyme assay. The resting membrane potentials in aging T cells were decreased (plasma membrane depolarized) when compared to T cells from young subjects. In T cells from aging humans, there was a lack of a change in the membrane potentials or membrane potentials were increased (plasma membrane hyperpolarized) following activation with anti-CD3 and WT31 monoclonal antibodies, whereas in young T cells membrane potentials were decreased (depolarized). The basal [Ca++]i levels in aging T cells were less than that in young T cells, and a much smaller rise in [Ca++]i was observed following activation with PHA and anti-CD3 monoclonal antibody in aging T cells than in the young T cells. In aging cells there was less translocation of PKC from cytosol to the membrane following activation with anti-CD3 and WT31. This study demonstrates that the abnormal membrane signal transduction pathway plays a role in T cell dysfunctions associated with human aging.

Adult↗
PubMed1989

Escherichia coli derivatives lacking both alcohol dehydrogenase and phosphotransacetylase grow anaerobically by lactate fermentation.

Escherichia coli mutants lacking alcohol dehydrogenase (adh mutants) cannot synthesize the fermentation product ethanol and are unable to grow anaerobically on glucose and other hexoses. Similarly, phosphotransacetylase-negative mutants (pta mutants) neither excrete acetate nor grow anaerobically. However, when a strain carrying an adh deletion was selected for anaerobic growth on glucose, spontaneous pta mutants were isolated. Strains carrying both adh and pta mutations were observed by in vivo nuclear magnetic resonance and shown to produce lactic acid as the major fermentation product. Various combinations of adh pta double mutants regained the ability to grow anaerobically on hexoses, by what amounts to a homolactic fermentation. Unlike wild-type strains, such adh pta double mutants were unable to grow anaerobically on sorbitol or on glucuronic acid. The growth properties of strains carrying various mutations affecting the enzymes of fermentation are discussed in terms of redox balance.

Acetyltransferases↗
PubMed1989

Methotrexate pneumonitis. Bronchoalveolar lavage findings suggest an immunologic disorder.

Methotrexate (MTX) is used widely for the treatment of a variety of tumors as well as for non-neoplastic conditions. Its association with pneumonitis is well established, but the mechanism of lung injury is unknown. To clarify this issue, we performed bronchoalveolar lavage (BAL) in six patients with MTX pneumonitis and in three control groups. In those with drug-induced pneumonitis, there was a significant increase in the total number of lavage cells recovered as well as in the percentage and absolute number of lymphocytes compared with those in the other groups. Patients receiving the drug without evidence for pulmonary toxicity had lavage findings that were not different from those in the other control groups. The ratio of BAL phenotypic helper/suppressor T-cells was studied in three patients with MTX toxicity and was found to be increased compared with that in normal healthy control subjects. Our findings show that MTX pneumonitis is characterized by a lymphocytic alveolitis with a predominance of phenotypic helper T-cells and a relative deficiency in the percentage of suppressor T-cells. The presence of increased lavage lymphocytes suggests that an immunologically mediated injury rather than a direct toxic effect of this drug may be a significant pathophysiologic mechanism in this disorder.

Adult↗
PubMed1989

Impact of a two-stage intervention program on cefazolin usage at a major teaching hospital.

To reduce antimicrobial drug costs associated with the administration of cefazolin, a two-stage therapeutic intervention--employing persuasive (informational) and power (therapeutic interchange) strategies--was initiated at this 1,000-bed major Canadian teaching hospital. The target of the intervention was to extend the dosage interval of cefazolin to q8h. During a 12-week preimplementation period, 32% of orders specified 8-hour dosage intervals. This percentage increased to 58% after the 3-week, initial informational stage of the intervention. When therapeutic interchange was employed, the percentage of orders for extended intervals rose to an average of 97% over a 32-week postimplementation period. An estimated annual cost savings of $58,000 resulted from this intervention. Manpower requirements to implement and maintain this program were minimal and prescriber antagonism was not encountered.

British Columbia↗
PubMed1989

Impact of a practical two-stage intervention on aminoglycoside usage.

To control aminoglycoside usage and costs, a two-stage intervention was implemented at this 1,000-bed, major Canadian teaching hospital. An informational stage, reviewing the therapeutic equivalence of netilmicin, gentamicin, and tobramycin in various internal publications, was followed by an automatic therapeutic interchange program. The intervention involved removing netilmicin from the formulary and substituting gentamicin for tobramycin. Comparing the 8-week pre-implementation period with the 24-week, post-implementation period, new orders for netilmicin declined from 42% to less than 1% of the total new aminoglycoside courses initiated. During the same time frame, new orders for gentamicin increased from 50% to 90%, orders for tobramycin remained stable at approximately 5.5%, and orders for amikacin remained unchanged at 1%. A retrospective health record review revealed a low incidence of microbiologically inappropriate interchanges. Pharmacy manpower requirements were minimal and prescriber acceptance was high. A +27,000 cost savings per year was estimated.

Aminoglycosides↗
PubMed1989

Secondary ichthyosis: report of 2 cases.

Two adolescent girls suffering from severe secondary ichthyosis in association with gross protein-energy malnutrition are reported. In one patient, it was sheer advanced malnutrition which appeared to be the cause of ichthyosis. The other subject seemed to have developed reversible gross ichthyosis secondary to severe malnutrition and the accompanying pulmonary tuberculosis. Acquired ichthyosis of such a magnitude as a result of malnutrition as the chief primary disease has not yet been recorded in the English medical literature.

Adolescent↗
PubMed1989

Networks of sexual contacts: implications for the pattern of spread of HIV.

This paper examines the influence of sexual contact patterns (mixing matrices) on the pattern of the AIDS epidemic in a male homosexual community via numerical studies of a mathematical model of the transmission dynamics of HIV. A discussion is presented of the range of possible structures of networks of sexual contacts with extremes of assortative (within sexual activity groups) and disassortative (between sexual activity groups) mixing. The assortative mixing extreme is shown to generate the most rapid growth in the incidence of infection in the early stages of the epidemic while the disassortative extreme is shown to generate the epidemic of the largest magnitude over a long period. High within-group mixing (assortative) may generate multi-peak epidemics. The results are discussed in the context of both the interpretation of observed patterns of the spread of HIV and the acquisition of data on sexual contact patterns.

Disease Outbreaks↗
PubMed1989

Influence of atrial natriuretic factor on 5-(N-ethyl-N-isopropyl)amiloride-sensitive 22Na+ uptake in rabbit aorta.

Because atrial natriuretic factor (Atriopeptin II, ANF) exerts potent effects on Na+ transport in a number of tissues, we examined its influence on 22Na+-uptake in isolated rabbit aorta segments and the possible relation to ANF-induced vasorelaxation. ANF increased 22Na+-uptake by 44% with an EC50 of 12 nM whereas sodium nitroprusside was without effect. The increase was blocked by the selective inhibitor of Na+/H+ exchange 5-(N-ethyl-N-isopropyl)amiloride (EIPA) but was not sensitive to the guanylate cyclase inhibitor LY 83583, indicating ANF-induced activation of Na+/H+ exchange via a cyclic GMP (cGMP) independent pathway. The ability of ANF to relax phenylephrine-induced contractions of rabbit aorta was inhibited by EIPA at concentrations which produced inhibition of Na+/H+ exchange whereas sodium nitroprusside-induced relaxation was only marginally affected. EIPA caused a 90% decrease in the ability of ANF to increase cGMP, but did not interfere with the sodium nitroprusside-induced increase. LY 83583 blocked the ability of ANF to increase cGMP formation but failed to reduce ANF-induced vasorelaxation. These results suggest that ANF activation of EIPA-sensitive 22Na+-uptake occurs before cGMP formation perhaps at the level of the ANF receptor itself. The vasorelaxant effects of ANF involve a significant cGMP-independent component which is EIPA sensitive.

Amiloride↗
PubMed1989

Evaluation of nickel complexes of bioligands-effect on distribution profile.

Distribution of various nickel-63 bioligand complexes in tissues of rats and their binding to subcellular fractions have been studied. Nickel-binding with glutathione and histidine significantly decreased nickel-63 accumulation while nickel-serum binding increased nickel body burden and its accumulation is subcellular fractions. Nickel-renal cytosol binding exhibited distribution pattern similar to serum complex only in lung tissue.

Animals↗
PubMed1989

Clinical, haemodynamic and echocardiographic study in chronic cor pulmonale.

Thirty patients of chronic cor pulmonale were studied clinically and by chest skiagram, electrocardiography, echocardiography, pulmonary function tests, arterial blood gas analysis and, wherever possible by right heart catheterization. Pulmonary arterial pressures (PAP) correlated significantly only with cardiomegaly on skiagram and with arterial oxygen tension (PaO2). There was no significant correlation between mean PA pressures and prominent pulmonary conus on RVH by ECG, FEV1, PaCO2 or right ventricular outflow tract dimensions by echocardiography. Left ventricular function, as assessed by pulmonary capillary wedge pressure on cardiac catheterization, by LV ejection fraction and fractional shortening on echocardiography was normal in all cases except two (6.67%). There was significant increase in left ventricular posterior wall thickness in the patients studied.

Adult↗
PubMed1989

Methyl 5(6)-(alpha-hydroxyphenyl methyl) benzimidazole-2-carbamate and cysticercosis: chemotherapeutic and electron microscopic studies.

Methyl 5(6)-(alpha-hydroxyphenyl methyl) benzimidazole-2-carbamate, a major metabolite of mebendazole was evaluated against Cysticercus fasciolaria (larval form of Taenia taeniaeformis) in rats. The metabolite was assessed in various doses. A regimen of 50 mg/kg x 10 (ip), given one day apart, was found to be most effective and killed all the mature cysticerci. On developing cysts, the treatment was initiated in two schedules; 5 days prior to (d-5 to d-1) and 5 days after (d + 6 to d + 10) administration of T. taeniaeformis eggs to rats. The later protocol with 100 mg/kg x 5 dose (ip) resulted in 95% inhibition in the establishment of cysticerci. Activity of mebendazole against mature cysts was parallel to metabolite whereas against developing cysts, it was inferior. The time related topographical changes that occurred in mature C. fasciolaris after treatment with metabolite (50 mg/kg x 10, ip, one day apart) were observed by scanning electron microscopy. There was loss of contractivity, gradual disappearance of microtriches and progressive degeneration of tegument. Similar changes were noticed with mebendazole. The possession of better efficacy and higher safety range [Indian J Exp. Biol, 25 (1987) 871], suggests that the metabolite can be a potential anthelmintic for man and animals.

Animals↗
PubMed1989

Tropical myositis. A clinical immunological and histopathological study.

Thirty cases of tropical myositis, (22 suppurative, 8 non-suppurative) aged 11 to 65 years were seen in a period of one year. There were 22 males and 8 females. There was a total of 78 muscular lesions in 22 suppurative cases and 19 muscular lesions in 8 non-suppurative cases. The most common presentation was localised myalgia (100%), fever (96.7%) generalized myalgia (56.7%), arthralgia (40%), pain in abdomen (33.3%) and breathlessness (30%). Extramuscular complications were present in 50% cases. Twenty four muscle biopsies were taken. Sixteen showed changes of suppurative myositis i.e. non-specific acute inflammatory reaction, muscle necrosis with myocytolysis, vacuolation of cytoplasm and loss of striations. Cell mediated immunity was found to be suppressed in patients of non-suppurative myositis in comparison with the suppurative group. IgG, IgA and IgM were significantly raised in patients in comparison to controls (p less than 0.05). The intact humoral immunity indicates good response to acute phase reaction and increased levels of IgG, IgA and IgM (specially IgG) can be taken as good prognostic parameter.

Abscess↗
PubMed1989

Effects of methyl [5 [[4-(2-pyridinyl)-1-piperazinyl]carbonyl]-1H-benzimidazol-2-yl] carbamate on energy metabolism of Ancylostoma ceylanicum and Nippostrongylus brasiliensis.

Effects of methyl [5[[4-(2-pyridinyl)-1-piperazinyl] carbonyl] 1H-benzimidazol-2-yl] carbamate (CDRI Comp. 81-470) and mebendazole on the energy metabolism of A. ceylanicum and N. brasiliensis were compared. At 10 and 50 microM concentration both compounds inhibited glucose uptake and its conversion into metabolic endproducts. The shift towards the increased production of lactic acid appeared to be the result of inhibition of PEP carboxykinase and increase in LDH activity. The compounds also caused significant inhibition of ATP production in mitochondria.

Ancylostoma↗
PubMed1989

Antibody-dependent cellular cytotoxicity by polymorphonuclear leucocytes in patients with AIDS and AIDS-related complex.

Polymorphonuclear leucocytes (PMN) play an important role in host defense against bacterial and certain fungal infections. Furthermore, PMN are effectors in antibody-dependent cellular cytotoxicity (ADCC) against a variety of tumor and non-tumor target cells. In this study we examine the PMN-mediated ADCC in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC), using chicken red blood cells (CRBC) in the presence of anti-CRBC antibody as targets. Ten subjects each with AIDS, ARC and healthy controls were evaluated. Among AIDS patients one had Kaposi's sarcoma (KS) and 9 had opportunistic infection(s). A significantly decreased (p less than 0.005) ADCC was observed in both patients with AIDS and ARC. Although ADCC tended to be lower in ARC than in AIDS, however the difference between AIDS and ARC was not significant (p greater than 0.5). We suggest that the deficient PMN-mediated ADCC in human immunodeficiency virus (HIV) infection might play a role in increased predisposition to bacterial and certain opportunistic infections and perhaps in the spread of HIV infection.

AIDS-Related Complex↗