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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 1,189 records · Page 66Linked to original sources

Generalized peritonitis in India--the tropical spectrum.

Generalized peritonitis is a common surgical emergency in India, the 'Tropical Spectrum' of generalized peritonitis being different from the western spectrum. A total 155 cases of generalized peritonitis were surgically treated at the All India Institute of Medical Sciences between 1981 and 1987, all patients undergoing peritoneal toilet with drainage after the cause of their peritonitis had been treated. The most common cause of peritonitis was peptic ulcer perforation, with simple closure being associated with a 2 per cent mortality, while typhoid perforation was the second most common cause. The diagnosis was clinical, supported by the operative findings of a terminal ileal perforation while bacteriological, serological and histopathological confirmation was retrospective. Appendicular perforations were less common than in the west but the clinical picture was the same. Tubercular perforations were not uncommon with a previous history of subacute intestinal obstruction and evidence of tuberculosis on chest X-ray suggesting the diagnosis. Ruptured amebic liver abscess was the most common hepatobiliary cause of generalized peritonitis with drainage of the abscess producing good results. The average hospital stay was 15 days with an overall mortality of 8 per cent.

Adult↗

T cell activation via the T cell receptor: a comparison between WT31 (defining alpha/beta TcR)-induced and anti-CD3-induced activation of human T lymphocytes.

The T cell receptor (TcR) heterodimer of alpha/beta glycoprotein is noncovalently associated with CD3 glycoprotein forming TcR/CD3 complex. The TcR have been shown to recognize antigen, and CD3 antigen is responsible for signal transduction. In this study we compared the effects of WT31 (defining alpha/beta TcR) monoclonal antibody (MoAb) and anti-CD3 MoAb on various steps of human T cell activation. Both antibodies depolarized plasma membranes, increased cell volume, induced IL-2 production and the expression of IL-2 receptors (CD25 antigen) and induced DNA synthesis. Furthermore, the two antibodies showed no synergistic effect on any of these parameters. However, both MoAb showed synergism with phorbol ester (PMA). WT31-induced T cell activation was Ca(2+)-dependent because the addition of EGTA to the medium inhibited DNA synthesis and CD25 antigen expression. The blockers of protein kinase C (PKC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and staurosporin, in a dose-dependent manner inhibited WT31-induced DNA synthesis. Cholera toxin but not the pertussis toxin inhibited WT31-induced T cell activation, suggesting involvement of G protein in WT31-induced T cell activation. These data indicate that WT31 antibody activates human T cells by a pathway that is similar to that of anti-CD3-induced T cell activation.

Antibodies, Monoclonal↗

Possible role of hyaluronectin on cell adhesion in rat histiocytoma.

Distribution of hyaluronectin, a 68-kDa cell surface glycoprotein, has been demonstrated in normal peritoneal, alveolar macrophages as well as in macrophages of the AK-5 tumor cell line. AK-5, a transplantable histiocytic tumor cell line, is a mixture of four different populations and can be grown in both ascites and solid tumors. We are able to demonstrate a differential expression of hyaluronectin on the cell surface of these subpopulations of AK-5 when studied by immunocytochemical staining followed by cytofluorometric analysis. Cell fractions responsible for developing both ascites and solid tumors contain higher amounts of hyaluronectin than fractions which are capable of producing only ascites, suggesting its involvement in solid tumor formation. Furthermore, we established a secretory nature of hyaluronectin as it can be detected in the serum-free medium of AK-5 cells. Since it is localized on the cell surface and secreted into the medium, the cell adhesiveness of hyaluronectin has been examined. Hyaluronectin coating on the plates allowed more cells to attach, which could be specifically blocked by the antibody raised against hyaluronectin, indicating its possible role in cell attachment. The adhesive property of hyaluronectin and its role in tumor formation was further confirmed. The pretreatment of AK-5 cells with hyaluronectin antibody abolished their capacity to grow as solid tumors; however, the cells retained their capacity to grow as ascites tumor. We discuss our observations of hyaluronectin as a cell attachment protein and its specific role on tumor formation.

Animals↗

Polyamine metabolism in some helminth parasites.

Polyamine levels of some helminth parasites were analyzed by reverse phase HPLC of benzoyl derivatives. Setaria cervi, Acanthocheilonema viteae, Hymenolepis nana, H. diminuta, and Ascaridia galli contained higher levels of spermine than spermidine while in Ancylostoma ceylanicum and Nippostrongylus brasiliensis the spermidine levels were higher than spermine; putrescine was either absent or present in minor quantities. The enzymes of polyamine biosynthesis viz., ornithine decarboxylase, S-adenosyl methionine (SAM)-decarboxylase, and arginine decarboxylase were present in very low to negligible amounts in all the parasites examined. A. ceylanicum exhibited high activity of ornithine amino transferase (OAT) and catalyzed appreciable decarboxylation of ornithine. The ornithine decarboxylating activity of A. ceylanicum was localized in the particulate fraction containing mitochondria, not inhibited by alpha-difluoromethyl ornithine, the specific inhibitor of ornithine decarboxylase (ODC), but inhibited in the presence of glutamate, suggesting the involvement of mitochondrial OAT rather than a true ODC in ornithine decarboxylation in this parasite. Significant activity of polyamine oxidase was also detected in helminth parasites. The absence of polyamine biosynthesizing enzymes in helminth parasites suggests their dependence on hosts for uptake and interconversion of polyamines, providing a potential target for chemotherapy.

Ancylostoma↗

Circadian time dependence of erythropoietic and respiratory responses of Indian garden lizard, Calotes versicolor, to mammalian urinary erythropoietin and thyroxine.

The circadian stage-dependent effects of mammalian urinary erythropoietin (Ep) and thyroxine (T4) on tissue energy metabolism (in vivo and in vitro) and erythropoiesis were examined in the Indian garden lizard. Both T4 and Ep increased erythropoiesis and also affected hepatic and muscle energy metabolism. Although both treatments increased circulating RBC count, irrespective of the timing of the treatment, the maximum erythropoietic stimulation was achieved only in the late photophase (9 hr after light onset, HALO). Hepatic oxygen uptake was significantly elevated at 3 and 9 HALO following in vivo Ep administration and 3, 9, and 15 HALO following in vivo T4 injection. In contrast, in vitro addition of either Ep or T4 to hepatic homogenates of untreated lizards significantly elevated respiratory rate, irrespective of the time of tissue collection. The rate of muscle tissue respiration was statistically elevated when Ep was administered in vivo at 9 and 15 HALO. The oxygen uptake was stimulated by T4 only at 15 HALO. While in vitro addition of Ep to tissue homogenates significantly depressed the respiratory rate of muscle collected at 3 HALO, addition of T4 stimulated oxygen uptake by the muscle tissue collected at 9 and 15 HALO. It is concluded that the effectiveness of Ep or T4 largely depends upon the phase of the organism's circadian system(s).

Animals↗

NADH oxidase and fumarate reductase of Ancylostoma ceylanicum.

Ancylostoma ceylanicum, the hookworm parasite of cat, dog and man, was found to contain NADH and/or NADPH oxidase as well as fumarate reductase activities. Both the enzyme systems were predominantly located in the membranes of mitochondrial-rich preparations. The membranes also exhibited the presence of a reduced pyridine nucleotide transhydrogenase activity which transferred hydrogen from NADPH to NAD. Amongst respiratory inhibitors, rotenone (Site I inhibitor) markedly depressed both NADH oxidase and fumarate reductase while others, namely antimycin-A, KCN and azide, had a lesser effect.

Ancylostoma↗

Expression of intercellular adhesion molecule 1 (ICAM-1) in Alzheimer's disease.

In this study, 13 clinically and pathologically diagnosed cases of Alzheimer's disease were analyzed for the presence of intercellular adhesion molecule 1 (ICAM-1), ICAM-2, lymphocyte function associated antigen-1 (LFA-1), HLA-DR, LN-1, and LN-2. ICAM-1 was observed primarily on neuritic plaques and cerebrovascular endothelium. ICAM-1 was also shown to be present in brain tissue derived from 14 normal cases; however, the degree of immunoreactivity was quantitatively less compared to Alzheimer cases and was largely restricted to cerebrovascular endothelium. LFA-1 was shown to be present on microglial cells and leukocytes. Consistent with the findings of previous reports, HLA-DR was found to be expressed on microglial cells. In this study we failed to demonstrate dual immunolocalization for ICAM-1 and LFA-1, ICAM-1 and HLA-DR, or ICAM-1 and LN-2. As microglial cells express both HLA-DR and LFA-1, they may serve to mediate antigen presentation functions by interacting with lymphocyte ICAM-1. Alternately, the expression of these immune-associated glycoproteins on glial cells may be epiphenomenal occurring secondary to some aspect of the disease process. Finally, the presence of ICAM-1 within neuritic plaques raises the question as to whether adhesion may play some role in the process of neurite outgrowth and neurodegeneration.

Alzheimer Disease↗

Protein kinase C independent restoration of specific immune responsiveness in common variable immunodeficiency.

7,8-Disubstituted guanine ribonucleosides represent a class of B lymphocyte agonists that utilize a protein kinase C-independent signaling pathway. These compounds provide an alternate T helper signal for B cells and enhance antigen-specific humoral responses in the murine model and in an IL-2-dependent human model in vitro. They effectively restore high level immune responses in a variety of murine models of immunodeficiency both in vivo and in vitro. In this study we examined the potential of these compounds to improve antibody responses generated by cultured cells from patients with common variable immunodeficiency (CVI). The inability to mount normal humoral responses to antigen was confirmed in nine patients with diagnosed CVI (CVI: 37 +/- 16, normal 653 +/- 116 plaque-forming cells (PFC)/culture; P less than 0.001). In cultured lymphocytes from eight of the nine patients studied, a normal level or greater responses to nominal antigen could be elicited by antigen in the presence of the immunostimulatory nucleoside 7-methyl-8-oxoguanosine (7m8oGuo). The average response to antigen increased from 37 +/- 16 without nucleoside to 1733 +/- 488 PFC/culture in its presence (P less than 0.002). Restoration of specific immune responses was an antigen-dependent and nucleoside dose-dependent event. Signaling by 7m8oGuo rendered the response to antigen protein kinase C independent in cultures of cells from normal donors as well as from CVI patients. These data substantiate (i) that a non-C-kinase signaling pathway for antigen-dependent differentiation exists, (ii) that this pathway can function normally in B cells from patients with CVI when triggered appropriately, and (iii) that 7,8-disubstituted guanine ribonucleosides can convert a C-kinase-dependent signaling event to a C-kinase-independent signaling event. Substituted guanine ribonucleosides may have potential as immunotherapeutic agents for patients with CVI.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Tetraethylammonium, a K+ channel blocker, inhibits interferon-gamma-induced major histocompatibility class II antigen (Ia) expression and DNA synthesis in rat astrocytes.

Astrocytes play an important role in antigen presentation to T lymphocytes by their ability to express major histocompatibility class II (Ia) antigen upon exposure to a number of agents, including interferon-gamma (IFN-gamma). Astrocytes have been shown to express a variety of voltage-sensitive ion channels including voltage-sensitive K+ channels. The function(s) of these channels in astrocyte functions is not clearly understood. In this investigation, we examined: (1) the comparative effects of mouse, rat, and human recombinant IFN-gamma (rIFN-gamma) on the induction of Ia antigen and DNA synthesis in rat astrocytes; (2) the effect of tetraethylammonium (TEA), a K+ channel blocker, on rat IFN-gamma-induced Ia expression and DNA synthesis in rat astrocytes. Our data show that all INF-gamma induce DNA synthesis in rat astrocytes but only rat and mouse and not the human IFN-gamma will induce Ia expression. TEA in a dose-dependent manner inhibited both Ia expression and DNA synthesis in rat astrocytes. The concentration kinetics of TEA with regard to maximum inhibition of Ia and DNA synthesis were different. Furthermore, these inhibitory effects were not a result of toxic or nonspecific effect of TEA on astrocytes as demonstrated by viability data and lack of any effect of tetramethylammonium, an analogue of TEA, that does not block K+ ion channels. These data suggest a role of K+ channels in Ia expression and DNA synthesis, therefore in immunological functions of astrocytes.

Animals↗

Mobilization of cadmium by liposome-encapsulated meso-2,3-dimercaptosuccinic acid in pre-exposed mice.

meso-2,3-Dimercaptosuccinic acid (DMSA) treatment in free of liposome-encapsulated form was given to mice pre-exposed to cadmium as CdCl2 (2 intraperitoneal injections; 0.5 mg Cd/kg along with 5 microCi 109CdCl2 in 4 ml volume within 24 h). Both treatments removed cadmium from liver, spleen, testis and blood with liposomal DMSA exhibiting higher efficacy in mobilizing cadmium not only from whole organs but also from liver proteins. It also resulted in higher excretion of cadmium via urine as compared with free DMSA or saline treatment. Whereas this treatment eliminated significantly higher amounts of cadmium via the fecal route throughout the period examined, free DMSA responded only 48 h after treatment and was less effective. The results suggest mobilization of cadmium from intracellular sites of deposition. However, DMSA in the dose administered (24 mumol/kg i.v.) in either form was ineffective in decorporating cadmium from the kidney, the critical organ in cadmium intoxication.

Animals↗

Effects of embelin, a male antifertility agent, on absorptive and digestive functions of rat intestine.

Oral administration of embelin (75 mg/kg per day, daily for 15 and 30 days) to male rats caused significant elevation in the uptake of D-glucose, L-alanine, L-leucine and calcium in small intestinal segments. Embelin also produced significant increases in intestinal brush border membrane-associated enzymes (sucrase, lactase, maltase, alkaline phosphatase and leucine aminopeptidase) in both intestinal homogenates and partially purified brush border membrane preparations. Significant increases were also noted for microsomal glucose-6-phosphatase and cytosolic lactate dehydrogenase. Increase in brush border membrane-associated total lipids, phospholipids, cholesterol, triacylglycerol, unesterified fatty acids and ganglioside sialic acid were seen but not in the cholesterol/phospholipid molar ratio. All these changes returned to control or near control levels following withdrawal of the drug.

Administration, Oral↗

Substituted guanine ribonucleosides as B cell activators.

Monosubstituted (at C8) and disubstituted (at C8 and N7) guanine ribonucleosides activate human and murine B lymphocytes. A newly developed disubstituted analog, 7-allyl 8-oxoguanosine (7ally18oGuo), in a dose-dependent manner induced anti-tetanus-specific IgG antibody response in peripheral blood mononuclear cells in humans. In addition, 7ally18oGuo activated monocytes from healthy subjects and patients with common variable immunodeficiency to produce interleukin 1. Furthermore, 7ally18oGuo induced changes in plasma membrane potentials and intracellular pH in human peripheral blood mononuclear cells. The role of monosubstituted and disubstituted compounds in restoring immunodeficient states in mice and humans, both in vivo and in vitro, is reviewed.

B-Lymphocytes↗

Preferential binding of oxidized LDL to rat glomeruli in vivo and cultured mesangial cells in vitro.

Hyperlipidemia may contribute to the pathogenesis of glomerular sclerosis. We therefore compared binding and uptake of native LDL and oxidized LDL (Ox-LDL) to cultured mesangial cells (MC) and the resulting effects on prostaglandin generation and cell proliferation. Ox-LDL, prepared from native LDL by incubation with copper, was bound to MC in a concentration dependent manner with a four- to fivefold increase in binding over LDL. In competition binding experiments Ox-LDL competed to 90% with LDL for binding sites, but LDL only displaced Ox-LDL to 15%. Furthermore polyinosinic acid, which blocks binding of Ox-LDL to macrophages, inhibited binding of Ox-LDL but not that of LDL to MC. Mesangial cells also preferentially took up Ox-LDL over LDL, and Ox-LDL resulted in higher [14C] oleate incorporation into cholesteryl esters than LDL, findings consistent with different handling of Ox-LDL and LDL by MC. LDL slightly stimulated mesangial cell proliferation at low concentration (10 to 50 micrograms/ml of LDL) returning to control levels at 100 and 250 micrograms/ml. In contrast Ox-LDL inhibited cell proliferation in a concentration-dependent manner, starting at concentrations as low as 10 to 25 micrograms/ml of Ox-LDL. Direct observations of mesangial cells by phase contrast microscopy confirmed the cytotoxic effects of Ox-LDL. Addition of Ox-LDL to mesangial cells resulted in a concentration-dependent increase in PGE2 synthesis within one hour, while at this time point LDL had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of cerebral perfusion reserve using 5% CO2 and SPECT neuroperfusion imaging.

Anatomic features of carotid artery stenosis, as defined angiographically, do not necessarily correlate with the hemodynamic significance of the narrowing. The concept of regional cerebral vasodilatory (or perfusion) reserve has been advocated as a means of defining the hemodynamic compromise associated with carotid lesions. We evaluated the feasibility of using SPECT imaging with 5% CO2 using I-123 IMP (N-isopropyl iodoamphetamine) or Tc-99m HMPAO (hexamethylpropylene amineoxime) to measure cerebral perfusion reserve. Imaging was performed on six asymptomatic subjects and one patient with a history of transient ischemic attacks but no evidence of carotid artery disease. A perfusion reserve index (PRI) was defined to represent the percent increase in blood flow during 5% CO2 breathing in regions supplied by the middle cerebral artery normalized for injected dose and changes in blood pressure. Significant increases in cerebral perfusion were seen in six of the seven subjects studied while breathing the 5% CO2 (P less than 0.01). The mean of the PRI values for the seven subjects was 32%, with a range of -5% to 58%. We conclude that SPECT imaging with IMP or HMPAO can be used to quantitatively measure the cerebral perfusion response to 5% CO2.

Administration, Inhalation↗

The role of a critical care unit in an epidemic.

The role of a critical care unit in life-threatening situations is well established. The management of 52 children with acute gastroenteritis and 22 children with acute paralytic poliomyelitis as part of recent epidemics is described. The solutions to the problems in the critical care management of these 74 victims (out of a total of 6197 patients admitted during the epidemics) are discussed.

Acute Disease↗

A comprehensive immunological analysis in chronic fatigue syndrome.

A detailed analysis of cell-mediated and antibody-mediated immunity was performed in 20 CDC-defined patients with chronic fatigue syndrome (CFS) and 20 age- and sex-matched healthy controls. CD3+, CD4+, CD8+, and CD20+ lymphocytes were comparable in two groups. Natural killer cells as defined by CD16, CD56 and CD57 antigens were significantly reduced in CFS. A significant increase in the proportions of CD4+ ICAM 1+ T cells was observed in CFS. Monocytes from CFS displayed increased density (as determined by mean fluorescence channel numbers) of intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function associated antigen 1 (LFA-1), but showed decreased enhancing response to recombinant interferon-gamma in vitro. The lymphocyte DNA synthesis in response to phytohaemoglobulin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was normal but the response to soluble antigens was significantly reduced. Serum IgM, IgG, IgA, and IgG subclasses were normal. In vivo specific antibody response to pneumococcus vaccine was depressed in CFS. Forty percent of patients showed titres of anti-human herpes virus 6 (anti-HHV-6) antibody higher than that in the controls (greater than or equal to 1/80). These data suggest immunological dysfunction in patients with chronic fatigue syndrome. The significance of these observations is discussed.

Adult↗

Is pyloroplasty necessary following intrathoracic transposition of stomach? Results of a prospective clinical study.

Twenty four patients underwent oesophagectomy for oesophageal cancer. The oesophagogastric anastomosis was performed in the neck in all patients. Following oesophagectomy and gastric mobilization patients were randomly selected into pyloroplasty and no pyloroplasty groups. Pre and postoperative gastric emptying of these patients evaluated by radioisotope technique were then compared. The results suggest significantly delayed postoperative gastric emptying in both the groups though it was less pronounced in the pyloroplasty group. All patients were then carefully followed until death (period varying between 6 months and 4 years) for ill effects of delayed gastric emptying which were present in some patients of both the groups. It was thus concluded that emptying of thoracic stomach is delayed and pyloroplasty fails to improve it completely. Postoperatively patients behave much the same way with or without pyloroplasty.

Anastomosis, Surgical↗

Sepsis after Ivalon sponge rectopexy: an unusual case.

A case with an unusual presentation of sepsis after Ivalon sponge rectopexy is reported. A strong index of suspicion is important for correct diagnosis. Early removal of infected sponge allows quick resolution of the sepsis without recurrent prolapse.

Abscess↗