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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 865 records · Page 48Linked to original sources
PubMed1995

Withdrawal-emergent dyskinesia in patients with schizophrenia during antipsychotic discontinuation.

We examined whether patients exhibiting withdrawal-emergent dyskinesia (WE-D) represent a group vulnerable to subsequent development of tardive dyskinesia (TD). WE-D was defined as moderate abnormal movements during antipsychotic withdrawal in persons without persistent TD. We assessed patients with schizophrenia-spectrum illness participating in withdrawal from antipsychotic medication. Patients with WE-D were compared to those without dyskinesia and to those with persistent TD. Clinical measures included duration of illness and antipsychotic exposure, negative symptoms, and neurologic soft signs. We hypothesized that WE-D patients would not differ from persistent-TD patients across the above variables, but would differ from non-TD patients. Patients without TD significantly differed from persistent TD in duration of illness, medication exposure and neurologic soft signs. WE-D did not differ from TD across these measures. No-TD patients also showed less duration of medication exposure and neurologic soft signs than those with WE-D.

Adolescent↗
PubMed1995

Dynamic interactions in malaria: host heterogeneity meets parasite polymorphism.

The spectrum of disease severity in Plasmodium falciparum malaria can be attributed to heterogeneity in parasite virulence or to heterogeneity in host factors. However, the two are not necessarily separate explanations for the same phenomena: they may actually complement each other. The conjoint effects of host and parasite heterogeneity can serve to explain certain intriguing epidemiological observations, such as, why there is a reduction in incidence of severe malaria in certain host genotypes without a concomitant reduction in mild disease. By assuming that severe disease is caused by a rare independently transmitted parasite strain, and that the probability of disease is nonlinearly related to the number of effective infections by a certain strain, the disproportionate reduction in the rate of the rarer disease within resistant host genotypes may be explained. Conversely, heterogeneity in host resistance may, under certain circumstances, facilitate the maintenance of diversity in parasite virulence. In this paper we discuss the coevolutionary consequences of heterogeneity in host resistance and diversity in parasite virulence by using a simple mathematical model that attempts to integrate the population genetics of the system with its ecological dynamics. This allows a unified perspective on malaria transmission that synthesises current evidence regarding the effects of host and parasite heterogeneities on malarial disease.

Animals↗
PubMed1995

Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15.

The cytokines interleukin 2 (IL-2) and IL-15 have similar biological effects on T cells and bind common hematopoietin receptor subunits. Pathways that involve Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) have been shown to be important for hematopoietin receptor signaling. In this study we identify the STAT proteins activated by IL-2 and IL-15 in human T cells. IL-2 and IL-15 rapidly induced the tyrosine phosphorylation of STAT3 and STAT5, and DNA-binding complexes containing STAT3 and STAT5 were rapidly activated by these cytokines in T cells. IL-4 induced tyrosine phosphorylation and activation of STAT3 but not STAT5. JAK1 and JAK3 were tyrosine-phosphorylated in response to IL-2 and IL-15. Hence, the JAK and STAT molecules that are activated in response to IL-2 and IL-15 are similar but differ from those induced by IL-4. These observations identify the STAT proteins activated by IL-2 and IL-15 and therefore define signaling pathways by which these T-cell growth factors may regulate gene transcription.

Base Sequence↗
PubMed1995

Premorbid adjustment as a predictor of phenomenological and neurobiological indices in schizophrenia.

Previous studies have demonstrated relationships between poor premorbid adjustment and a variety of phenomenological and neurobiological indices in schizophrenic patients. Using the Modified Premorbid Adjustment Scale we re-examined these relationships in a large sample (n = 131) of schizophrenic patients. Subjects were evaluated with the Comprehensive Assessment of Symptoms and History (CASH) and magnetic resonance imaging. Multiple correlation indicated that poor premorbid adjustment was significantly associated with prominence of negative symptoms, early age of onset, educational problems, chronicity, and neurological soft signs, but not with any MRI measures. These results confirm poor premorbid adjustment as an important predictor of a malignant form of schizophrenia as evidenced by an earlier age of onset, poorer educational performance, prominent negative symptoms, presence of soft signs, and chronicity of course.

Brain↗
PubMed1995

Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR.

Signaling by the T-cell antigen receptor (TCR) involves both phospholipase C (PLC)-gamma 1 and p21ras activation. While failing to induce Shc/Grb2 association, ligation of the TCR/CD3 receptor in Jurkat T-cells induced hSos1-Grb2 complexes. In addition to hSos1, Grb2 participates in the formation of a tyrosine phosphoprotein complex that includes 145-, 95-, 70-, 54-, and 36-38-kDa proteins. p145 was identified as PLC-gamma 1 and p70 as the protein tyrosine kinase, ZAP-70. Although of the same molecular weight, p95 was not recognized by an anti-serum to p95 Vav. The SH2 domains of Grb2 and PLC-gamma 1 were required for the formation of this protein complex. In anti-CD3-treated cells, Grb2 redistributed from the cytosol to a particulate cell compartment along with p36/p38, ZAP-70, and PLC-gamma 1. Part of the Grb2 complex associated with the particulate compartment could be extracted with Nonidet P-40, while the rest was Nonidet P-40 insoluble. In both the detergent-soluble and -insoluble fractions, Grb2 coimmunoprecipitated with the zeta-chain of the TCR. Taken together, these results indicate that anti-CD3 induces Grb2-hSos1-PLC-gamma 1-p36/p38-ZAP70 complexes, which localize in the vicinity of TCR-zeta.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy of humans, affects over 400 million people. The geographical correlation of its distribution with the historical endemicity of malaria suggests that this disorder has risen in frequency through natural selection by malaria. However, attempts to confirm that G6PD deficiency is protective in case-control studies of malaria have yielded conflicting results. Hence, for this X-linked disorder, it is unclear whether both male hemizygotes and female heterozygotes are protected or, as frequently suggested, only females. Furthermore, how much protection may be afforded is unknown. Here we report that, in two large case-control studies of over 2,000 African children, the common African form of G6PD deficiency (G6PD A-) is associated with a 46-58% reduction in risk of severe malaria for both female heterozygotes and male hemizygotes. A mathematical model incorporating the measured selective advantage against malaria suggests that a counterbalancing selective disadvantage, associated with this enzyme deficiency, has retarded its rise in frequency in malaria-endemic regions. Although G6PD deficiency is now regarded as a generally benign disorder, in earlier environmental conditions it could have been significantly disadvantageous.

Africa↗
PubMed1995

Lack of interferon gamma receptor beta chain and the prevention of interferon gamma signaling in TH1 cells.

The ability of interferon gamma (IFN-gamma) to inhibit the proliferation of type 2 T helper cells (TH2), but not that of type 1 (TH1) cells, suggests that helper cell subsets might differ in their activation of the IFN-gamma signaling pathway. The IFN-gamma-inducible signal transducing factor (STF-IFN gamma) was activated in murine TH2 but not in TH1 cell clones, because in the latter the second chain of the IFN-gamma receptor (accessory factor 1 or IFN-gamma R beta) was absent. Thus, TH1 cells use receptor modification to prevent the activation of STF-IFN gamma and achieve an IFN-gamma-resistant state.

Animals↗
PubMed1995

Integration of transplanted hepatocytes into host liver plates demonstrated with dipeptidyl peptidase IV-deficient rats.

To analyze mechanisms of liver repopulation, we transplanted normal hepatocytes into syngeneic rats deficient in dipeptidyl peptidase IV activity. When isolated hepatocytes were injected into splenic pulp, cells promptly migrated into hepatic sinusoids. To examine whether transplanted hepatocytes entered liver plates and integrated with host hepatocytes, we analyzed sharing of hepatocyte-specific gap junctions and bile canaliculi. Colocalization studies showed gap junctions uniting adjacent transplanted and host hepatocytes in liver plates. Visualization of bile canalicular domains in transplanted and host hepatocytes with dipeptidyl peptidase IV and ATPase activities, respectively, demonstrated hybrid bile canaliculi, which excreted a fluorescent conjugated bile acid analogue. These results indicate that transplanted hepatocytes swiftly overcome mechanical barriers in hepatic sinusoids to enter liver plates and join host cells. Integration into liver parenchyma should physiologically regulate the function or disposition of transplanted hepatocytes and benefit applications such as gene therapy.

Adenosine Triphosphatases↗
PubMed1995

Gamma chain-associated cytokine receptors signal through distinct transducing factors.

The IL-2, IL-4, and IL-7 signaling pathways have been shown to utilize shared components. The receptors for these cytokines are composed of ligand-specific binding chains that associate with a shared signaling subunit, the common gamma (gamma c) chain. In addition, IL-2, IL-4, and IL-7 induce activation of a common set of nonreceptor tyrosine kinases, Jak-1 and Jak-3. We have further investigated the signaling events induced by these cytokines and find that the gamma c-associated receptors activate distinct signal transducing factors (STFs). In addition, we show that a 94-kDa STAT-related protein (p94) is activated in response to IL-2 and IL-7, but not IL-4. These data indicate that IL-2, IL-4, and IL-7 activate distinct signaling molecules which might be differentially recruited to the receptor complex by the ligand-specific units of the IL-2, IL-4, and IL-7 receptors.

Amino Acid Sequence↗
PubMed1995

Cellular protein kinase C isoform zeta regulates human parainfluenza virus type 3 replication.

Phosphorylation of the P proteins of nonsegmented negative-strand RNA viruses is critical for their function as transactivators of the viral RNA polymerases. Using unphosphorylated P protein of human parainfluenza virus type 3 (HPIV3) expressed in Escherichia coli, we have shown that the cellular protein kinase that phosphorylates P in vitro is biochemically and immunologically indistinguishable from cellular protein kinase C isoform zeta (PKC-zeta). Further, PKC-zeta is specifically packaged within the progeny HPIV3 virions and remains tightly associated with the ribonucleoprotein complex. The P protein seems also to be phosphorylated intracellularly by PKC-zeta, as shown by the similar protease digestion pattern of the in vitro and in vivo phosphorylated P proteins. The growth of HPIV3 in CV-1 cells is completely abrogated when a PKC-zeta-specific inhibitor pseudosubstrate peptide was delivered into cells. These data indicate that PKC-zeta plays an important role in HPIV3 gene expression by phosphorylating P protein, thus providing an opportunity to develop antiviral agents against an important human pathogen.

Animals↗
PubMed1995

Isolation of a previously unidentified polysaccharide (MAR-10) from Hyssop officinalis that exhibits strong activity against human immunodeficiency virus type 1.

A polysaccharide (MAR-10) was isolated from the aqueous extract of the plant Hyssop officinalis and examined for its activity against HIV-1 (SF strain) in HUT78 T cell line and primary cultures of peripheral blood mononuclear cells. MAR-10, in a concentration-dependent manner, inhibited HIV-1 replication as demonstrated by the inhibition of HIV-1 p24 antigen and syncytia formation. Furthermore, MAR-10 had no significant direct toxicity or effect on lymphocyte functions or CD4+ and CD8+ T cell counts. In addition, MAR-10 has broad spectrum anti-glycosidase activity. Our study demonstrates that MAR-10 contains strong anti-HIV-1 activity that may be useful in the treatment of patients with HIV-1 infection.

Antiviral Agents↗
PubMed1995

The membrane immunoglobulin receptor utilizes a Shc/Grb2/hSOS complex for activation of the mitogen-activated protein kinase cascade in a B-cell line.

Ligation of membrane immunoglobulin M (mIgM) receptor in the Ramos B-cell line induced tyrosine phosphorylation of several intracellular substrates, including the adaptor protein. Shc. Phosphorylated Shc could be seen to associate with Grb2 in a complex which included hSOS. Inasmuch as hSOS is involved in p21ras activation, we also demonstrated that mIgM ligation activated a Ras-dependent kinase cascade in which sequential activation of Raf-1 and MEK-1 culminates in the activation of p42 mitogen-activated protein (MAP) kinase (ERK-2). The tumour promoter and protein kinase C agonist, phorbol 12-myristate 13-acetate (PMA), also activated Raf-1, MEK-1, and MAP kinase in Ramos cells, but did not induce tyrosine phosphorylation of Shc or Shc/Grb2 association. Okadaic acid, another tumour promoter and serine/threonine phosphatase inhibitor, activated p42 MAP kinase without activating Raf-1 or MEK-1, suggesting the existence of a serine/threonine phosphatase which directly regulates MAP kinase activity.

Adaptor Proteins, Signal Transducing↗