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Biomedical subjects

G Sharma

Publications and source records attributed to G Sharma.

At least 37 records · Page 2Linked to original sources
PubMed1999

CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha.

CC-chemokine receptor (CCR) 6 is the only known receptor for macrophage inflammatory protein (MIP)-3alpha, a CC chemokine chemotactic for lymphocytes and dendritic cells. Using anti-serum that we raised against the N-terminal residues of CCR6, we have characterized the surface expression of CCR6 on peripheral blood leukocytes and we have correlated CCR6 expression with responses to MIP-3alpha. We found that CCR6 was expressed only on memory T cells, including most alpha4beta7 memory cells and cutaneous lymphocyte-associated Ag-expressing cells, and on B cells. Accordingly, chemotaxis of T cells to MIP-3alpha was limited to memory cells. Moreover, calcium signals on T cells in response to MIP-3a were confined to CCR6-expressing cells, consistent with CCR6 being the only MIP-3alpha receptor on peripheral blood T cells. Unlike many CC chemokines, MIP-3alpha produced a calcium signal on freshly isolated T cells, and CCR6 expression was not increased by up to 5 days of treatment with IL-2 or by cross-linking CD3. Despite their surface expression of CCR6, freshly isolated B cells did not respond to MIP-3alpha. In addition to staining peripheral blood leukocytes, our anti-serum detected CCR6 on CD34+ bone marrow cell-derived dendritic cells. Our data are the first to analyze surface expression of CCR6, demonstrating receptor expression on differentiated, resting memory T cells, indicating differences in receptor signaling on T cells and B cells and suggesting that CCR6 and MIP-3alpha may play a role in the physiology of resting memory T cells and in the interactions of memory T cells, B cells, and dendritic cells.

Cell Line↗
PubMed1999

Hepatic fibrogenesis using chronic arsenic ingestion: studies in a murine model.

Chronic oral arsenic (As) ingestion has been alleged to cause hepatic fibrosis, non-cirrhotic portal fibrosis and cirrhosis of the liver. The present study was aimed to investigate if hepatic fibrogenesis and non-cirrhotic portal fibrosis (NCPF) is caused by arsenic. A significant increase in the hepatic protein and collagen was seen compared with controls; hepatic 4-hydroxyproline levels, indicative of fibrogenesis, were increased 4-14 folds with different dosages of arsenic compared to the controls. Hepatocellular necrosis and inflammation were negligible to mild in all the groups. None of the animals developed significant splenomegaly or features of non-cirrhotic portal hypertension. The results suggest that (i) prolonged oral arsenic ingestion in mice leads to significant hepatic fibrogenesis and collagen synthesis with minimal hepato-cellular injury; (ii) arsenic ingestion alone is unlikely to cause non-cirrhotic portal fibrosis or cirrhosis of liver. This murine model of arsenic feeding could be used for the evaluation of new antifibrotic agents for the liver.

Animals↗
PubMed1999

Safety of Ghasa.

Explore the source record for details and available documents.

Child, Preschool↗
PubMed1998

Successful long-term in vitro cultivation of Theileria annulata schizonts in media supplemented with homologous and heterologous sera.

The efficacy of medium RPMI-1640 supplemented with either foetal bovine, normal bovine, goat or sheep sera was compared for prolonged in vitro propagation of Theileria annulata (Hisar) schizonts. Medium RPMI-1640 supplemented with 20% foetal bovine serum (standard growth medium) resulted in optimum growth of T. annulata (Hisar) schizonts in vitro. Comparable viability and non-viability counts were observed in growth media supplemented with normal bovine or goat sera. However, viability counts in medium supplemented with sheep serum were significantly lower than that of the standard medium. Mitotic indices of cultures of T. annulata (Hisar) schizonts were directly related to the extent of cell growth and were lower in various growth media supplemented with normal bovine, goat or sheep sera than in that of the standard medium. The results suggested that normal bovine and goat sera could be successfully used in place of foetal bovine serum in the growth medium for long-term in vitro propagation of T. annulata schizonts. The study will help in reducing the cost of large-scale in vitro propagation of T. annulata aimed at mass production of the cell culture vaccine.

Animals↗
PubMed1997

STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1.

The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4(+) cells can be explained, at least partly, by the selective use of G protein-coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor-like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line-tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection.

Amino Acid Sequence↗
PubMed1997

Examining PTSD as a Complication of Infertility.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may develop following exposure to threatened or actual injury or death. While commonly associated with war or natural disaster, symptoms of PTSD have been described in patients who are undergoing or who have completed infertility treatment or high-risk pregnancies. Three case studies of patients who developed PTSD following such pregnancies are discussed, demonstrating the variety of symptoms and presentations of these patients. The clinician must be vigilant in monitoring infertility patients with PTSD. These women, as the result of infertility, may be at increased risk of developing PTSD, one of the recognized postpartum psychiatric disorders. It is important to distinguish PTSD from postpartum depression, because treatment guidelines vary.

Journal Article↗
PubMed1996

Interactions between two divalent ion binding sites in N-methyl-D-aspartate receptor channels.

N-methyl-D-aspartate receptor channels exhibit a high permeability for calcium ions. In this report, we confirm that calcium ions permeate effectively through the wild-type channels, and find that their presence within the pore blocks the flux of sodium and other ions. Further proof for this ionic block comes from the analysis of the epsilon 1(N614Q) mutation where the high permeability of calcium is unchanged but the block by calcium ions is increased twofold. In both the wild-type and mutant channels, calcium ion block is independent of membrane voltage; therefore, the calcium binding site is outside the voltage gradient through the pore and must be close to the extracellular mouth of the ion conductance pathway. This calcium site is distinct from the magnesium binding site, which lies 80% into the pore's electrostatic field and thus exhibits a marked voltage dependence of binding. The epsilon 1(N614Q) mutation reduces the affinity of magnesium ion for its binding site but increases the affinity of calcium ion for its binding site. Since a single mutation perturbs two distinct binding sites in opposite ways, we postulate that binding of divalent ions at the two sites interact.

Binding Sites↗
PubMed1996

A mutation that alters magnesium block of N-methyl-D-aspartate receptor channels.

N-Methyl-D-aspartate (NMDA) receptors are blocked at hyperpolarizing potentials by extracellular Mg ions. Here we present a detailed kinetic analysis of the Mg block in recombinant wild-type and mutant NMDA receptors. We find that the Mg binding site is the same in the wild-type and native hippocampal NMDA receptor channels. In the mutant channels, however, Mg ions bind with a 10-fold lower affinity. On the basis of these results, we propose that the energy well at the Mg binding site in the mutants is shallow and the binding is unstable because of an increase in the rate of dissociation. We postulate that the dipole formed by the amide group of asparagine 614 of the epsilon 1 subunit contributes to the structure of the binding site but predict that additional ligands will be involved in coordinating Mg ions.

Amino Acid Sequence↗
PubMed1996

Meaningful features of voice range profiles from patients with organic vocal fold pathology: a preliminary study.

This preliminary study identifies features that have the potential to be meaningful descriptors of voice range profiles (VRPs) for 15 patients with organic vocal fold pathologies before and after laryngeal surgery. This study also explores the utility of the VRP as an outcome measure of change in vocal function after surgery. Potentially meaningful features for these patients are the semitone range, intensity level of the lower contour, frequency locus of the lower frequency values, smoothness of the contours, and the presence of intermittencies in the VRP contours. These features are not suggested for differential diagnosis, but for aiding the understanding of each individual patient's phonatory status. Initial use of these features suggests that the VRP may be a useful outcome measure for these patients.

Adult↗
PubMed1995

The construction and characterization of colanic acid deficient mutants in an extraintestinal isolate of Escherichia coli (O4/K54/H5).

Extraintestinal strains of Escherichia coli possess a variety of virulence factors that enable them to cause disease. These strains express a group 2 capsular polysaccharide which is important in the pathogenic process. Extraintestinal strains evaluated to date are also capable of producing the group 1 capsular polysaccharide colanic acid. The blood isolate CP9 (O4/K54/H5) constitutively produces the group 2, K54 capsule but can be induced to produce colanic acid. In this report we assess whether colanic acid contributes to the pathogenesis of this extraintestinal pathogen. CP9 and its derivatives that are deficient in their ability to produce colanic acid (TR94), the K54 group 2 capsule +/- colanic acid (CP9.137, TR1374) and the O4 specific antigen +/- colanic acid (CP921,CP925) were used to test whether the group 1 capsule colanic acid conferred protection against the bactericidal effects of serum and recombinant bactericidal/permeability-increasing protein (rBPI-23) in vitro. Additionally, CP9, CP9.137 and TR94 were evaluated in the rat granuloma pouch, an in vivo model for localized infection, and by intraperitoneal inoculation into mice, a systemic infection model. In summary, the inability of CP9 to produce colanic acid in the presence or absence of its K54 and O4 antigens had no effect on its ability to survive these host defenses in vitro and did not affect its virulence in these two in vivo models of infection.

Animals↗
PubMed1995

Loss of the O4 antigen moiety from the lipopolysaccharide of an extraintestinal isolate of Escherichia coli has only minor effects on serum sensitivity and virulence in vivo.

The O-specific antigen in extraintestinal isolates of Escherichia coli is believed to be an important virulence factor. To assess its role in the pathogenic process, proven isogenic derivatives with either a complete (CP921) or nearly complete (CP920) deficiency of the O4 antigen were obtained by TnphoA'1-mediated transposon mutagenesis of an O4/K54/H5 blood isolate (CP9). By utilizing a previously reported isogenic K54 capsule-deficient derivative (CP9.137), additional isogenic derivatives deficient in both the K54 capsular antigen and either all (CP923) or nearly all (CP922) of the O4 antigen were also constructed. These strains and their wild-type parent were evaluated in vitro for serum sensitivity and in vivo by intraperitoneal challenge of outbred mice. The complete or nearly complete loss of the O4 antigen (CP920 and CP921) resulted in only a minor increase in serum sensitivity. In contrast, CP9.137 had a significant increase in serum sensitivity, and CP922 and CP923 were extremely serum sensitive. When tested in vivo, the complete or nearly complete loss of the O4 antigen resulted in a small but significant increase (P < or = 0.05), not the expected decrease, in virulence compared with its wild-type parent. In contrast, CP9.137 and CP922 were significantly less virulent (P < or = 0.05). These studies do not exclude a role for the O4 antigen moiety of lipopolysaccharide in the pathogenesis of extraintestinal E. coli infection; however, they demonstrate that the O4 antigen plays only a minor role in serum resistance in vitro and that its loss does not diminish and perhaps enhances the virulence of CP9 in vivo after intraperitoneal challenge.

Animals↗
PubMed1994

Differential assembly of coexpressed glutamate receptor subunits in neurons of rat cerebral cortex.

In the rat, subunits of the glutamate receptor family fall into three pharmacologically distinct groups: alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid preferring receptors (Glu R1-4), kainate preferring receptors (Glu R5-7, KA 1, KA 2), and N-methyl-D-aspartate preferring receptors (NMDA R1, NMDA R2A-2D). In the present study, we demonstrate immunocytochemically that the majority of neurons in rat cerebral cortex coexpress members of all three groups of glutamate receptor subunits, Glu R2/3, Glu R5/6/7, and NMDA R1. Using immunoaffinity purified or immunoprecipitated alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate and N-methyl-D-aspartate receptors, we show that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors containing Glu R1-4, kainate receptors containing Glu R6, Glu R7, and KA 2 and N-methyl-D-aspartate receptors containing NMDA R1 each form distinct protein complexes that do not share subunits. Our data indicate that a mechanism exists which allows for the specific assembly of selected glutamate receptor subunits into functionally and structurally distinct heteromeric receptors.

Animals↗
PubMed1993

[Permanent cardiac pacing in children. Personal experience].

Pacemaker implantation was performed in 26 children aged from 5 months to 15 years (mean 4.6). The indications for pacemaker implantation were: sick sinus syndrome in 4 patients, III degrees idiopathic A-V block in 2 both with congenital heart disease and III degrees post-op. A-V block in 20 patients. 34 pacemakers produced by seven different companies were implanted. Epicardial electrode was used in all but one patient in whom endocardial electrode was introduced. Demand for impulse voltage was 2.4-5.2 V (mean 4.4 V), impulse duration was from 0.25 ms to 1.65 ms (mean 0.62 ms). Three out of 26 pts. (11.5%) died (1-intraoperative bleeding, 1-ventricular rhythm disturbances, 1-sudden death). In seven children first exchange of the pacemaker (one for mechanic damage and 6 for exhausted batteries) was performed mean 4.3 years after previous implantation. In two children second battery exchange was necessary mean 7.5 years after previous (both exhausted batteries). In five children a damaged epicardial electrodes were exchanged (21%).

Adolescent↗
PubMed1992

Tunicamycin resistance in Saccharomyces cerevisiae: genetic studies.

Tunicamycin is a nucleoside antibiotic complex produced by Streptomyces lysosuperficus which inhibits glycosylation. Several mutants have been isolated in this laboratory that are resistant to tunicamycin, of which the majority are recessive and a few are dominant. The mutations are possibly due to some loss of transport function or alteration in the membrane. These recessive mutations have been mapped to chromosome 1 by the 2 mu mapping method. Studies are underway to map the dominant mutations as well and to group these mutations into its complementation groups and to characterize them biochemically. Both mating types of these mutant strains have been generated in our laboratory.

Chromosome Mapping↗
PubMed1992

Effect of ethanol on the distribution of cadmium between the cadmium metallothionein- and non-metallothionein-bound cadmium pools in cadmium-exposed rats.

In an attempt to assess the effect of ethanol on cadmium accumulation, metallothionein (MT) synthesis, Cd-binding capacity and lipid peroxidation, rats were administered either Cd, ethanol or their combination for a period of 4 weeks. A significant increase in Cd accumulation was observed in all the organs of rats under study co-exposed to Cd and ethanol as compared to only Cd-treated rats. Increased MT levels in response to Cd were associated with a marked alteration in the distribution of Cd amongst the two pools of intracellular Cd i.e. Cd bound to MT (Cd-MT) and Cd not bound to MT (non-MT-Cd). Higher levels of non-MT-Cd were observed in liver, kidney and heart of Cd+ethanol-exposed rats as compared to only Cd-exposed rats. Lesser binding of 109Cd to the protein peak was observed in Cd+ethanol-exposed rats than the Cd-treated rats when hepatic supernatants from all the groups were chromatographed on Sephadex G-75 columns, suggesting that ethanol has a redistributing effect on Cd amongst the two pools. A marked increase in lipid peroxidation was observed which was linear to the increase in non-MT-Cd levels. A positive correlation between non-MT-Cd levels and lipid peroxidation was observed in liver, kidney and heart suggesting that non-MT-Cd levels are more crucial and toxicologically more important than total Cd levels.

Animals↗
PubMed1992

Cloning of a putative glutamate receptor: a low affinity kainate-binding subunit.

Kainate, a glutamate receptor agonist, is a potent neuroexcitatory agent that produces epileptiform activity and selective neuronal degeneration. Binding studies using neuronal membrane homogenates or brain sections have identified sites having either high or low affinity for [3H]kainate. Here we report the cloning of a gene, GluR7, with approximately 75% sequence identity with the previously cloned GluR5 and GluR6 subunit genes. Transcripts of the GluR7 gene are evident in brain areas that bind [3H]kainate and are susceptible to kainate-induced neurotoxicity. We have performed ligand binding studies with membranes of transfected HeLa cells expressing GluR6 or GluR7 subunits. Our data show that the GluR6 and GluR7 subunits have a rank order of agonist affinity (domoate greater than kainate much greater than L-glutamate, quisqualate much greater than AMPA, NMDA) and a dissociation constant for kainate (95 and 77 nM, respectively) characteristic of the low affinity kainate-binding sites described in the brain.

Amino Acid Sequence↗
PubMed1992

Background noise in healthy volunteers--a consideration in adverse drug reaction studies.

In adverse drug reaction studies proper control over 'Back ground noise' is to be maintained to avoid erroneous conclusions to be drawn for adverse drug effects. Healthy volunteers, not taking any medication, were surveyed by a questionnaire to obtain data on the occurrence of any symptoms, often ascribed to side effects of drugs. Only 62 subjects out of a total of 236 (26.27%) stated experiencing none of these symptoms during the previous 3 days. The remaining subjects reported some symptoms, with an median number of symptoms experienced per person being 2; the most common being fatigue; headache, inability to concentrate and excessive sleepiness.

Adolescent↗