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Biomedical subjects

S Cherian

Publications and source records attributed to S Cherian.

At least 37 records · Page 2Linked to original sources

Effect of leucopelargonin derivative from Ficus bengalensis Linn. on diabetic dogs.

Dimethoxy ether of Leucopelargonidin-3-0-alpha-L rhamnoside isolated from the bark of the Indian Banyan tree Ficus bengalensis Linn. was tested for antidiabetic effect. At a medium effective dose (100 mg/kg) on oral administration, the compound showed significant hypoglycemic and serum insulin raising action in normal as also moderately diabetic dogs (induced by alloxan) during a period of two hours. The mechanism of action of the glycoside compound seems to be similar to that of drugs which stimulate insulin secretion. On acute and chronic administration in single doses of 0.2-1.8 g/kg to different groups of mice and daily administration of 100, 250 and 500 mg/kg to rats for a period of one month respectively did not show any toxic effect and the compound was not lethal even at the high dose of 1.8 g/kg in experimental animals.

Alloxan↗

Evidence that TGF-beta can inhibit human T-lymphocyte proliferation through paracrine and autocrine mechanisms.

Transforming growth factor-beta (TGF-beta) has been documented as having an inhibitory effect on the proliferation and growth of human T-lymphocytes. We examined the relative contribution of both exogenous and endogenous TGF-beta to this inhibitory action. Purified human peripheral blood T-cells were cultured with Con A (0.2 microgram/ml), washed with methyl mannopyranoside, and then cultured in rIL-2 (5 U/ml) with or without TGF-beta (80 pM). Proliferation, as measured by uptake of tritiated thymidine at 72 hr, was inhibited by added active TGF-beta. Addition of neutralizing anti-TGF-beta antibodies at the initiation of culture abrogated the antiproliferative effects of TGF-beta. A mink lung cell bioassay was used to measure endogenous TGF-beta production by the T-cells following transient acidification of the supernatants to activate latent TGF-beta. T-lymphocytes cultured with rIL-2 alone produced low levels of TGF-beta, first detectable at 72 hr. The addition of (active) TGF-beta to these cultures resulted in earlier and higher levels of endogenously produced latent TGF-beta protein. This was reflected at the mRNA level as well. The exogenously added active TGF-beta appeared to be depleted during the culture period, presumably by the activated T-cells, which exhibited elevated levels of types I, II, and III TGF-beta receptors. The increase in TGF-beta protein levels was due to endogenous TGF-beta synthesis and secretion as supported by a capture assay using 35S-labeled culture supernatants. These findings indicate that both paracrine and autocrine mechanisms are involved in the inhibitory effects of TGF-beta on the proliferation of normal human T-lymphocytes and suggest that other TGF-beta-producing cells can augment production of TGF-beta by activated T-lymphocytes.

Drug Administration Schedule↗

Antidiabetic effects of a glycoside of leucopelargonidin isolated from Ficus bengalensis Linn.

Glycoside of leucopelargonidin isolated from the bark of F. bengalensis demonstrated significant hypoglycemic, hypolipidemic and serum insulin raising effects in moderately diabetic rats with close similarities to the effects of a minimal dose of glibenclamide. The main difference observed in their effects was that the former significantly enhanced the fecal excretion of sterols and bile acids while the later has no such action even though both controlled hypercholesteremia.

Animals↗

Antidiabetic effect of a glycoside of pelargonidin isolated from the bark of Ficus bengalensis Linn.

The antidiabetic effect of a dimethoxy derivative of perlargonidin 3-O-alpha-L rhamnoside (250 mg/kg, single dose study and 100 mg/kg/day long term study) isolated from the bark of Ficus bengalensis Linn. has been compared with that of glibenclamide (2 mg/kg and 0.5 mg/kg/day respectively) in moderately diabetic rats. The single dose glycoside treatment decreased fasting blood glucose by 19% and improved glucose tolerance by 29%. The corresponding effects of glibenclamide were 25% and 66% respectively over the control values. On one-month treatment the fasting blood glucose levels went down almost to half of the pretreatment levels in both the groups and their glucose tolerance improved by 41% in glibenclamide group and by 15% in glycoside treated group. Urine sugar decreased to traces in both the groups and they appeared healthy. In vitro studies showed that insulin secretion by beta-cells was more in presence of the pelargonidin derivative than in presence of a leucocyanidin derivative, reported to be a good anti-diabetic agent.

Animals↗

Comparative studies on the properties of glycogen phosphorylases from the foot muscles of two benthic bivalves, Sunetta scripta and Villorita cyprenoides, having different habitats.

Glycogen phosphorylase (1,4-alpha-D-glucan:orthophosphate-alpha-D-glucosyl transferase, EC 2.4.1.1) was partially purified from two bivalves found in different habitats, viz. Villorita cyprenoides, an estuarine bivalve, and Sunetta scripta, a marine bivalve, and their properties compared with other animal phosphorylases. While the kinetic mechanism was same as that of phosphorylases from other animal sources, it differed in the control mechanism from other phosphorylases. The observed differences support the earlier finding that the control mechanism adopted by different animals is dependent on the evolutionary status and energy needs.

Animals↗

Effects of cigarette smoke on the immune response. II. Chronic exposure to cigarette smoke inhibits surface immunoglobulin-mediated responses in B cells.

We have previously reported that chronic exposure of rats to cigarette smoke inhibits the antibody-forming cell (AFC) response to both T-dependent and T-independent antigens and may reflect B cell dysfunction. In this communication we extend these studies to show that T cell functions are normal in chronically smoke-exposed rats (SM) as judged by their responses to mitogens and "nominal" or alloantigens. While B cells from SM respond significantly to the B cell mitogen lipopolysaccharide (LPS), they fail to proliferate in response to anti-IgM (anti-mu) or to produce significant AFC response to sheep red blood cells. On the basis of the number of rosettes formed with trinitrophenylated (TNP) horse red blood cells; the frequency of TNP-binding cells (TNP-ABC) in the spleens of SM is comparable to sham control rats. However, the proliferation of TNP-ABC to TNP-Brucella abortus is significantly decreased in SM. These differences in SM B cell responses, i.e., between LPS and anti-mu/antigen, may to be related to the ability of LPS to bypass a portion of the membrane signal transduction cascade. These results suggest that cigarette smoke affects an early step(s) in the antigen-dependent B cell signal transduction pathway.

Animals↗

Bacterial contamination of contrast media stored after opening.

A barium suspension, iohexol, iopamidol and ioxaglate which were diluted with tapwater and 0.9% NaCl and dextrose saline (4% and 0.18%) were made into aliquots of 10 ml and stored at 4 degrees C, room temperature and 37 degrees C for 8 weeks. Regular handling and bacterial cultures were performed. These studies confirmed that environmental organisms do contaminate these solutions and that they also support viable organisms, but do not become significantly colonized at room temperature or 4 degrees C. The solutions should be stored at room temperature or at 4 degrees C. The diluted barium solution was the contrast medium least contaminated and if it is not contra-indicated for other reasons should be used in preference to low osmolality water soluble contrast media on the basis of its cost, radiological contrast and low microbial contamination rate.

Bacteria↗

Cigarette smoke causes inhibition of the immune response to intratracheally administered antigens.

Chronic inhalation of cigarette smoke in rats preferentially inhibited the plaque-forming cell (PFC) response of lung-associated lymph nodes (LALN) to sheep red blood cells (SRBC), compared to anatomically distant lymph nodes. Inhibition of the antibody response in LALN of smoke-exposed animals was first detected at 21 weeks of smoke inhalation and was well established by the 27th week of smoke exposure. After prolonged exposure (greater than 34 weeks) to cigarette smoke, similar smoke-induced changes in PFC response took place in other lymphoid tissues as well. Cigarette smoke affected the response of LALN cells to a T cell-dependent antigen (SRBC). Exposure to cigarette smoke, however, did not alter the relative percentages of W3/13-positive (T cells) or Ig-positive (B cells) cells, nor did it alter the relative percentages of T cell subsets as scored by their surface phenotypes, i.e., T helper (W3/25+) or T suppressor/cytotoxic (OX-8+) cells. The percentage of phagocytic cells and the accessory cell functions of macrophages remained comparable between sham and smoke-exposed animals. Exposure to cigarette smoke did not significantly alter the response of LALN cells to T cell mitogens (concanavalin A and phytohemagglutinin). However, response to a T cell-independent antigen trinitrophenyl Brucella abortus was also significantly reduced. These results show that cigarette exposure in the rat results in a decreased antibody response and this exposure to cigarette smoke may primarily affect the B cell function.

Animals↗

Domperidone.

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Child↗

Differential requirement for accessory cells in polyclonal T-cell activation.

Highly purified rat Ia-negative (OX-6-) and Ia-positive (OX-6+) T cells were employed to examine the requirement for accessory cells (AC) and/or soluble factors in the activation of resting T cells with Con A, PHA, sodium periodate, or antigen. A variety of cells were employed as AC, including Ia-positive and Ia-negative macrophages (M phi), gamma-irradiated (2000 rad) or non-irradiated OX-6+ T cells, and several Ia-negative adenovirus-transformed rat embryo fibroblast cell lines. Our results suggested that for the expression of IL-2 receptors (IL-2R) and proliferation of OX-6- T cells in response to Con A, PHA, or antigen, there was an obligatory requirement for the presence of AC which could not be overcome by the addition of IL-1 and/or IL-2. Activation of OX-6- T cells with antigen required the presence of Ia+ AC, while activation with mitogens could be initiated with Ia- AC. M phi were efficient in AC function in all responses tested, while the AC function of OX-6+ T cells (TAPC) proved discriminatory under different conditions. The optimal response to PHA required much higher concentrations of TAPC as AC than for the Con A response. TAPC failed to stimulate sodium periodate-treated T cells under any conditions tested. Furthermore, when TAPC were employed as AC, their antigen-presenting ability was radiosensitive, while their AC function for Con A and PHA was radioresistant. These results suggest that molecules involved in T cell-AC interactions may differ, depending on the source of AC and/or type of the proliferative stimulus provided to T cells. This data has been discussed in the context of T-cell activation.

Animals↗

Immune responsiveness of monkeys exposed chronically to cigarette smoke.

Eleven adult male stumptailed monkeys (Macaca arctoides) were chronically exposed to either a low dose (human equivalent of 1 pack/day) or a high dose (human equivalent of 3 packs/day) of high-tar, high-nicotine University of Kentucky reference cigarette smoke for 4-8 years. Several parameters of their immunological response were compared to six nonsmoked control animals. The results from these experiments suggest that cigarette smoking does not significantly affect the response of spleen cells to the mitogens phytohemagglutinin or lipopolysaccharide. However, spleen cells from animals subjected to the heavy dose of cigarette smoke demonstrated a significant reduction in their natural killer cell-mediated lytic activity and a decreased response to concanavalin A. These results suggest that cigarette smoking may have a differential effect on lymphocyte subpopulations, and that the effects on the immune response are related to the dose of cigarette smoke.

Animals↗

Immunoregulation in the rat: characteristics of a suppressor T cell that inhibits antigen-dependent cell proliferation.

We have examined the characteristics of a rat suppressor T cell (Ts) that inhibited the antigen-dependent proliferative response of antigen-primed T cells. The kinetics of in vitro induction of Ts from lymph node T cells obtained from antigen-primed rats indicated that Ts were induced in the presence of the priming antigen within 48 hr of culturing. The Ts produced during the first 48 hr of in vitro cultures were radiosensitive (2000 rad) but became partially radioresistant within the next 48 hr of culturing. In the presence but not the absence of priming antigen, Ts inhibited the antigen-dependent proliferative response to the priming antigen as well as to heterologous antigens. Suppression appeared to be mediated via a nondialyzable suppressor factor (TsF). The induction of Ts in cultures required the presence of OX-6-/OX-8- T cells, antigen-presenting cells, and the antigen. Although a majority of cells recovered from the induced cultures were OX-8+, there was no evidence that OX-8+ antigen expression per se was related to Ts activity. Addition of highly purified IL 2 augmented the Ts-mediated suppression. The immunoregulatory implications of these findings are discussed.

Animals↗

Antigen presentation in the rat. II. An Ia+ radiosensitive T cell can present antigen to primed Ia- T cells.

We demonstrated previously the presence of an Ia+ (OX-6+) antigen-presenting cell within the rat T cell fraction that is capable of presenting antigen to antigen-primed OX-6-T cells. This antigen-presenting cell (T-APC) reacted with the monoclonal antibodies W3/25 and W3/13, which is known to react mainly with rat T cells. Further characterization of the T-APC indicated that the cell also reacted with the monoclonal antibody OX-19, which is highly specific for rat T cells. Moreover, the antigen-presenting function of the T-APC was sensitive to treatment with mitomycin C or gamma-irradiation (2000 rad). Under similar conditions, antigen presentation by partially purified dendritic cells or macrophages was totally resistant to these treatments. The antigen-presenting activity of gamma-irradiated T-APC was not reconstituted by the addition of the lymphokines IL 1, IL 2, or Con A supernatants. Although unirradiated T-APC were able to stimulate an MLR response, this function was also sensitive to gamma-irradiation, whereas the MLR-stimulating ability of macrophages and dendritic cells was resistant to gamma-irradiation. These data indicate that Ia+ T cells from the rat are capable of presenting antigen to antigen-primed T lymphocytes and that, in contrast to antigen presentation by macrophages and dendritic cells, the function of T-APC is gamma-radiation sensitive.

Animals↗

Antigen presentation in the rat: role of a nonadherent, nonphagocytic, W3/13, OX-6 positive T cell in the presentation of antigen to primed T lymphocytes.

The nature of accessory cells in rat lymph nodes which can present antigen to primed T cells was investigated. Removal of adherent, phagocytic cells from antigen-primed lymph node cells by passage over glass-bead and nylon wool columns followed by treatment with carbonyl iron did not abrogate the antigen-specific proliferative response to keyhole limpet hemocyanin (KLH) or to the synthetic polypeptide L-glutamic acid-L-alanine-L-tyrosine (GAT). This T cell-enriched population was free of contaminating macrophages as determined by latex bead ingestion and morphological criteria during a 4-day culture period. Treatment of the T cell preparation with rabbit anti-rat IgG and complement or rosetting with IgG-coated sheep erythrocytes to remove any remaining B cells or macrophages did not significantly affect the proliferative response to antigen. Analysis of the T cell preparation by panning techniques with monoclonal antibodies to T cell surface markers suggested that both the responding T cell and the antigen-presenting cell were positive for the rat T cell marker, W3/13. The KLH-primed LN T cell-enriched fraction contained two distinct cell populations that were separable on the basis of their reactivity to OX-6 antibody. Two populations, an OX-6+ and an OX-6-, interacted synergistically in a KLH-dependent in vitro proliferative response. The cells within the T cell-enriched fraction that were positive for the OX-6 marker functioned primarily as the APCs, while the OX-6- cell fraction contained cells that proliferated to antigen when OX-6+ cells from either the T cell fraction or the adherent fraction were present. The implications of these findings are discussed.

Animals↗

T-lymphocyte heterogeneity in the rat: separation of distinct rat T-lymphocyte populations which respond in syngeneic and allogeneic mixed lymphocyte reactions.

These experiments were designed to determine if separate subpopulations of T cells were involved in the syngeneic and allogeneic mixed lymphocyte reaction. Rat lymph node T cells were separated into W3/25+ and W3/25- subpopulations by panning with the monoclonal antibody W3/25 and tested for their ability to proliferate in both syngeneic (SMLR) and allogeneic (MLR) mixed lymphocyte responses, as well as to develop cytotoxicity against allogeneic, syngeneic, and trinitrophenol (TNP)-modified syngeneic targets. The W3/25+ T cells reacted strongly in the SMLR and the MLR whereas the W3/25- fraction proliferated only in response to allogeneic stimulation and with a kinetic pattern distinct from W3/25+. Furthermore, addition of W3/25 monoclonal antibody directly to the cultures was shown only to inhibit the proliferation of the W3/25+ T-cell fraction. The W3/25- subpopulation contained cytotoxic T cells (CTLs) against both allogeneic determinants and TNP-modified self. However the requirements for the activation of allospecific CTLs were distinct from those for CTLs for TNP-self in that W3/25- allospecific CTLs required no detectable help from W3/25+ T cells but generation of the CTL response against TNP-self required the presence of W3/25+ helper T cells (Th). These data suggest that in the rat, there exist subsets of T cells recognized by their cell surface phenotype that distinguish between self and nonself determinants and the requirements for activation are different for each of these populations.

Animals↗