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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 883 records · Page 49Linked to original sources
PubMed1995

Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine.

Protein kinases activated by dual phosphorylation on Tyr and Thr (MAP kinases) can be grouped into two major classes: ERK and JNK. The ERK group regulates multiple targets in response to growth factors via a Ras-dependent mechanism. In contrast, JNK activates the transcription factor c-Jun in response to pro-inflammatory cytokines and exposure of cells to several forms of environmental stress. Recently, a novel mammalian protein kinase (p38) that shares sequence similarity with mitogen-activated protein (MAP) kinases was identified. Here, we demonstrate that p38, like JNK, is activated by treatment of cells with pro-inflammatory cytokines and environmental stress. The mechanism of p38 activation is mediated by dual phosphorylation on Thr-180 and Tyr-182. Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. Together, these data establish that p38 is a member of the mammalian MAP kinase group.

Animals↗
PubMed1995

Rapid decreases in indigenous covalent DNA modifications (I-compounds) of male Fischer-344 rat liver DNA by diquat treatment.

I-compounds are indigenously appearing covalent DNA modifications that can be detected by 32P-postlabeling assay in tissues of normal animals without known exposure to any carcinogens or toxins. Although these compounds have not been structurally identified, indirect evidence from earlier work suggested the possibility of involvement of molecular fragments derived from lipid peroxides. Diquat is a herbicide that stimulates lipid peroxidation and massive intrahepatic oxidant stress through redox cycling-mediated generation of reactive oxygen species. In the present study, we examined the effects of diquat on hepatic I-compounds of male Fischer-344 rats. Two groups of rats, approximately 14 weeks and 8 weeks old, were given a hepatotoxic dose (0.1 mmol/kg) of diquat or equal volumes of saline, i.p. Two and 6 h later plasma alanine aminotransferase (ALT) activities were measured and hepatic DNA I-compound levels were examined by nuclease P1-enhanced 32P-postlabeling. Elevated ALT activities were observed in some animals in both groups, at both time points, but considerable inter-animal variation was seen. A total of 15-16 I-compound fractions were measured in control and in diquat-treated animals, but no extra spots indicative of treatment-induced adducts were detected. Despite the qualitative similarities, the quantities of individual I-compounds were markedly decreased at 2 h in diquat-treated animals of both age groups. In 14 week old rats the hepatic I-compound contents were decreased at 2 h by 22-59%, which was statistically significant (ANOVA, P < 0.05) for all of the 9 polar I-compound fractions and none of the non-polar fractions. Eleven I-spots from this group showed significant negative linear correlations (P < 0.05) with ALT values. In 8 week old rats treated with diquat a 22-43% depletion in I-compound contents was statistically significant for 4 of the 7 nonpolar and 2 of the 8 polar adduct fractions, but there was no significant correlation of I-compound contents with ALT values at the 2 h time point. By 6 h most of the I-spot levels had returned to normal or above normal values in both groups of animals. While most I-spots from 14 week old rats did not correlate with ALT levels at 6 h, two I-spots displayed positive correlations in the 8 week group. Overall, the susceptibility to diquat-associated DNA alterations appeared to differ with age.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine Transaminase↗
PubMed1995

Transcription factor ATF2 regulation by the JNK signal transduction pathway.

Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation causes activation of the c-Jun NH2-terminal protein kinase (JNK). Activating transcription factor-2 (ATF2) was found to be a target of the JNK signal transduction pathway. ATF2 was phosphorylated by JNK on two closely spaced threonine residues within the NH2-terminal activation domain. The replacement of these phosphorylation sites with alanine inhibited the transcriptional activity of ATF2. These mutations also inhibited ATF2-stimulated gene expression mediated by the retinoblastoma (Rb) tumor suppressor and the adenovirus early region 1A (E1A) oncoprotein. Furthermore, expression of dominant-negative JNK inhibited ATF2 transcriptional activity. Together, these data demonstrate a role for the JNK signal transduction pathway in transcriptional responses mediated by ATF2.

Activating Transcription Factor 2↗
PubMed1995

Epidemiologic study of diet and coronary risk factors in relation to central obesity and insulin levels in rural and urban populations of north India.

In a population survey of 162 rural and 152 urban subjects aged 26-65 years at Moradabad, the findings are compared with existing data on Indian immigrants to Britain and United States. In comparison with rural subjects, urban subjects had a higher prevalence of coronary artery disease (8.6 vs. 3.0%) and diabetes (7.9 vs 2.5%), higher blood pressures, total and low density lipoprotein cholesterol, triglycerides and postprandial 2-h blood glucose and plasma insulin similar to observations made in UK in immigrants compared to Europeans. Fasting plasma insulin and high density lipoprotein cholesterol levels in urban subjects were comparable with rural subjects. Mean body weights were significantly higher in urban women, but not in men, than in rural subjects. However the body mass index (22.9 +/- 4.2 vs. 21.6 +/- 2.4 kg/m2) and waist-hip girth ratio (0.89 +/- 0.10 vs. 0.86 +/- 0.07) were significantly higher in urban men compared to rural men without such differences in women. Underlying these differences in risk factors, urban subjects had three times better socioeconomic status than rural subjects and were eating higher total and saturated fat, cholesterol and refined carbohydrates and lower total and complex carbohydrates compared to rural men and women. Energy expenditure during routine and spare time physical activity was significantly higher in rural compared to urban subjects. Those patients who had risk factors, showed lesser physical activity and had greater adverse factors in the diet compared to subjects without risk factors. Body mass index and waist-hip girth ratio in patients with risk factors were significantly higher than in subjects without risk factors. The findings suggest that decreased consumption of total and saturated fat and increased physical activity may be useful for prevention of coronary artery disease among urbans as well as in immigrants.

Adult↗
PubMed1995

Evidence for LFA-1/ICAM-1 dependent stimulation of protein tyrosine phosphorylation in human B lymphoid cell lines during homotypic adhesion.

JK32.1 and SKW6.4 are Epstein-Barr virus (EBV)-positive human B cell lines that undergo spontaneous, lymphocyte function-associated antigen 1 (LFA-1) dependent homotypic adhesion in culture. This process is associated with induction of tyrosine phosphoproteins of molecular mass 90, 106, and 120 kDa and could be reproduced when these cells were centrifugationally aggregated. Antibodies to the beta 2 (CD18) chain of LFA-1 interfered with induction of p120, p106, and p90 during cellular aggregation. Response induction was abrogated when cells were incubated with protein tyrosine kinase (PTK) inhibitors (erbstatin, genistein, and geldanomycin) or cytochalasin B prior to aggregation. An in vitro kinase assay did not reveal activation of focal adhesion kinase. Although the role of LFA-1-dependent tyrosine phosphorylation in B cells is uncertain, patients with the leukocyte adhesion defect (LAD) exhibit humoral abnormalities. Moreover, aggregation did not induce specific tyrosine phosphoproteins in an EBV-transformed B cell line from a LAD patient. These results suggest that an LFA-1-dependent PTK pathway may play an important role in human B cell function.

Antibodies, Monoclonal↗
PubMed1995

Can varying flow velocity across an arterial anastomosis prevent thromboembolic injury?

In this study, simulated "poor" repairs applied to transverse incisions in the iliac arteries of 40 rats were the basis for comparing the effect of variations in blood flow on thromboembolism. Using vital microscopy and digital image processing, we performed 2 experiments. In the first experiment (n = 20), the reduction of post-repair blood flow by approximately 50% resulted in an 83% reduction in the total number of emboli appearing in the microcirculation of the cremaster muscle distal to the repair. In the second experiment (n = 20), the same reduction in blood flow typically resulted in larger repair-site thrombi which required significantly more time to grow to their maximum size. We conclude that reducing pedicle artery blood flow to approximately half in our rat model during reperfusion can protect the downstream microcirculation from embolic injury without increasing the incidence of thrombotic occlusion.

Anastomosis, Surgical↗
PubMed1995

Preliminary report: detrusor hyperreflexia in schizophrenia.

The object of this study was to demonstrate detrusor hyperreflexia (DH) in schizophrenic patients. Twelve consecutive schizophrenic patients were evaluated by DSM-IIIR diagnostic criteria and other standard psychiatric measures, urological history and examination, and urodynamic study. All were referred for clinical indication, voiding dysfunction, or incontinence. Two patients were excluded for confounding variables, mental retardation and benign prostatic hypertrophy. Of the ten evaluable patients, four had DH. Detrusor hyperreflexia does occur in a subset of schizophrenic patients, even in the absence of other recognized disease to explain the occurrence. This relationship, previously unreported, warrants further investigation.

Adult↗
PubMed1995

Changes in the subcellular localization of replication initiation proteins and cell cycle proteins during G1- to S-phase transition in mammalian cells.

DNA replication in eukaryotic cells is restricted to the S-phase of the cell cycle. In a cell-free replication model system, using SV40 origin-containing DNA, extracts from G1 cells are inefficient in supporting DNA replication. We have undertaken a detailed analysis of the subcellular localization of replication proteins and cell cycle regulators to determine when these proteins are present in the nucleus and therefore available for DNA replication. Cyclin A and cdk2 have been implicated in regulating DNA replication, and may be responsible for activating components of the DNA replication initiation complex on entry into S-phase. G1 cell extracts used for in vitro replication contain the replication proteins RPA (the eukaryotic single-stranded DNA binding protein) and DNA polymerase alpha as well as cdk2, but lack cyclin A. On localizing these components in G1 cells we find that both RPA and DNA polymerase alpha are present as nuclear proteins, while cdk2 is primarily cytoplasmic and there is no detectable cyclin A. An apparent change in the distribution of these proteins occurs as the cell enters S-phase. Cyclin A becomes abundant and both cyclin A and cdk2 become localized to the nucleus in S-phase. In contrast, the RPA-34 and RPA-70 subunits of RPA, which are already nuclear, undergo a transition from the uniform nuclear distribution observed during G1, and now display a distinct punctate nuclear pattern. The initiation of DNA replication therefore most likely occurs by modification and activation of these replication initiation proteins rather than by their recruitment to the nuclear compartment.

Base Sequence↗
PubMed1995

Anti-CD3-induced changes in protein kinase C isozymes expression in human CD4+ and CD8+ T lymphocytes.

In order to determine whether there is a differential expression and activation of PKC isozymes between CD4+ and CD8+ T cells, peripheral blood mononuclear cells were stimulated with anti-CD3 monoclonal antibody (moAb) for various time intervals and the expression of calcium-dependent PKC isozymes (alpha, beta, gamma) and calcium-independent PKC isozymes (delta, epsilon, zeta) was analyzed with dual color flow cytometry, using anti-PKC isozyme antibodies and anti-CD4 or anti-CD8 antibodies. The basal fluorescence intensity of all PKC isozymes was comparable between CD4+ T cells and CD8+ T cells. Following activation with anti-CD3 moAb a marked increase in the fluorescence intensity of all PKC isozymes in both CD4+ and CD8+ T cells, albeit to a different extent and with different kinetics was observed. Among all PKC isozymes studied, the least striking changes were observed in PKC zeta isozyme and the most striking changes were observed in PKC-epsilon isozyme. Laser-based confocal microscopic studies confirmed that the increase in fluorescence intensity of PKC isozymes following anti-CD3 moAb stimulation, as measured by flow cytometry was accompanied by the translocation of PKC isozymes from cytosol to the plasma membrane. This study demonstrates a differential effect of anti-CD3 moAb on the expression of PKC isozymes between CD4+ and CD8+ T cells and suggests that flow cytometry can be used to study the translocation of PKC isozymes from cytosol to the plasma membrane.

Antibodies, Monoclonal↗
PubMed1995

Central pontine myelinolysis following 'slow' correction of hyponatremia.

Two patients with central pontine myelinolysis are described for the peculiar mode of development. Both patients were in chronic renal failure and admitted in a stuporous state due to hyponatremia. Both developed central pontine myelinolysis during the hospital stay following slow and judicious correction of hyponatremia. The role of chronicity of hyponatremia prior to its correction, in the genesis of central pontine myelinolysis, particularly in the patients who have chronic debilitating illness, septicemia or malnutrition, is highlighted.

Adult↗
PubMed1995

Volume of the pineal gland in schizophrenia; an MRI study.

Pineal gland abnormality has been proposed as a possible biological defect in schizophrenia. This study was designed to investigate volumetric differences of the pineal gland using Magnetic Resonance Imaging (MRI). Patients with a DSM-III-R diagnosis of schizophrenia or schizophreniform disorder (n = 45) and normal controls (n = 86) were scanned using a 1.5 Tesla scanner. The volume of the pineal was obtained by blind manual tracing of the gland on T1 weighted images, using locally developed software, BRAINS. The inter-rater reliability (n = 25) yielded an intraclass r of 0.92. Comparison of the volumes by t-test showed no significant difference between patients and normal controls (p = 0.77). This study, backed by a large sample size, suggests that there are no volumetric differences between schizophrenic patients and controls in regard to the pineal gland.

Adult↗
PubMed1995

Diagnostic utility of the estimation of mycobacterial Antigen A60 specific immunoglobulins IgM, IgA and IgG in the sera of cases of adult human tuberculosis.

SETTING: An ELISA assay based on mycobacterial Antigen A60 for the estimation of Mycobacterium-specific immunoglobulins in the serum has been used successfully for the rapid diagnosis of tuberculosis in studies done in the Western countries. There are hardly any similar large scale studies in India. OBJECTIVE: To evaluate the utility of this ELISA test for rapid diagnosis of different clinical forms of tuberculosis in an adult Indian population. DESIGN: ELISA test based on mycobacterial antigen A60 (Anda Biologicals, France) was used to estimate specific IgM, IgA and IgG antibodies in the sera obtained from 337 cases of tuberculosis and 131 controls in the population of Delhi (India). RESULTS: Of the 131 controls, only 9.9% were positive for IgM, 7.6% for IgG, 6.1% for IgA and 9.9% when an IgA and IgG combination was considered. Of 122 cases of active pulmonary tuberculosis, 41% were positive for IgM, 86.8% for IgA, 88.5% for IgG and a very high positivity (98.3%) was seen when IgA and IgG estimations were combined. A relatively low seropositivity was observed in 25 cases of pleural tuberculosis. The corresponding figures in 130 cases of extrapulmonary tuberculosis were 22.3%, 68.4%, 73.8% and 86.15%. When 60 cases of pulmonary tuberculosis who had been successfully treated with antituberculosis drugs were analyzed the rates of seropositivity fell to 11.6%, 46.6%, 58.3% and 66.6% respectively. CONCLUSION: Our findings point to a very good sensitivity (91.6%) and specificity (90.0%) of the test when combined IgA and IgG antibody titres are considered, to detect cases of adult tuberculosis. The role of IgM estimation can be restricted to the detection of cases of reactivation of tuberculosis.

Adult↗
PubMed1995

Evidence for a terminal differentiation process in the rat liver.

In rapidly renewing epithelia, such as skin and gut, as well as hemopoietic cells and stromal fibroblasts, the process of progenitor cell maturation, terminal differentiation and senescence from cells of a fetal phenotype is strikingly similar. To examine hepatocellular maturation, we studied embryonic, suckling and young adult rat liver cells with multiparametric fluorescence activated cell sorting (FACS), after exclusion of hemopoietic, endothelial, Kupffer, and nonviable cells. With maturation, cell granularity and autofluorescence exponentially increased from fetal liver to suckling and adult liver as the proportion of S phase cells progressively declined from 33.8% +/- 1.3% to 4.9% +/- 2.8% and 1.1% +/- 0.6% (P < 0.05), respectively. In liver from fetal and suckling rats, all hepatocytes were mononuclear and contained diploid DNA whereas 21.2% +/- 5.9% hepatocytes in adult liver were binucleated. Analysis of nuclear DNA content in adult hepatocytes demonstrated that 53.3% +/- 3.9% of the nuclei were diploid, 43.6% +/- 3.5% tetraploid and 0.5 +/- 0.6% octaploid. However, in the adult liver, small, mononuclear cells were also present with granularity and autofluorescence comparable to fetal hepatoblasts, as well as glucose-6-phosphatase activity, diploid DNA in 89.0% +/- 2.1% of the nuclei, and with increased granularity in culture. Since general features of terminal cellularity differentiation and senescence include cessation of mitotic activity, polyploidy and accumulation of autofluorescent secondary lysosomes, our data suggest that liver cells too undergo a process of terminal differentiation.

Animals↗
PubMed1995

Celiac sprue and macroamylasemia: potential clinical and pathophysiological implications. Case study.

In a patient with celiac sprue, abdominal complaints were ascribed to acute pancreatitis in the setting of hyperamylasemia and choledocholithiasis. The problem turned out to be macroamylasemia associated with elevated serum immunoglobulin A. The patient remained stable for 4 years with no specific intervention except gluten restriction. An association between celiac sprue or other malabsorptive states and macroamylasemia requires more study.

Amylases↗