Search PubMed⌕ Search

Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 19 recordsLinked to original sources
PubMed1992

Signal transduction within the nucleus by mitogen-activated protein kinase.

The nucleus is an important target of signal transduction by growth factor receptors that stimulate mitogen-activated protein (MAP) kinases. We tested the hypothesis that MAP kinases have a signaling role within the nucleus by examining the effect of the expression of a human MAP kinase isoform (p41mapk) in tissue culture cells. The expressed p41mapk was found to be localized in both the cytoplasmic and nuclear compartments of the cells. Significantly, the expression of p41mapk caused an increase in the phosphorylation of a nuclear substrate: Ser62 of c-Myc. Phosphorylation at Ser62 stimulated the activity of the NH2-terminal transactivation domain of c-Myc. Thus, p41mapk causes the phosphorylation and regulation of a physiologically significant nuclear target of signal transduction. These data establish that at least one MAP kinase isoform has a nuclear role during signal transduction.

Amino Acid Sequence↗
PubMed1992

Effect of fat-modified and fruit- and vegetable-enriched diets on blood lipids in the Indian Diet Heart Study.

This study was designed to test the efficacy of the administration of fruits and vegetables for 12 weeks as an adjunct to a prudent diet in decreasing blood lipids in 310 (intervention; group A) and 311 (control; group B) patients with risk factors of coronary artery disease (CAD) in a parallel, single-blind fashion. At entry to the study, sex, mean age, body weight, body mass index, systolic and diastolic blood pressures, and blood lipoproteins were comparable between both groups. Tasty fruits and vegetables were given to patients to eat before major meals for better nutrient adherence and adequacy. Dietary intakes were determined by questionnaires and by weighing of fruit and vegetable intake. Fruits and vegetables decreased total cholesterol level by 6.5% and low-density lipoprotein cholesterol level by 7.3% in group A, whereas the levels were unchanged in group B. The high-density lipoprotein cholesterol levels that decreased during the diet stabilization period in both groups, increased by 5.6% in group A after 12 weeks. Serum triglycerides also decreased (7%) more in group A than B. Fasting blood glucose decreased by 6.9% in group A and by 2.6% in group B. The combined effect of a fat-modified diet plus fruits and vegetables was greater than these changes. Because tasty fruits were taken by the patients before meals (when they are hungry) and are easily available at reasonable cost in our marketing and buying capacity, the compliance was excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Abnormal chloride conductance in multidrug resistant HL60/AR cells.

Chloride channel currents were measured in drug sensitive parental HL60 and multidrug resistant (MDR) subline HL60/AR cells, using a whole cell patch-clamp technique. In addition, the in vitro effects of 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), a Cl- channel blocker, on intracellular accumulation and sensitivity to daunorubicin and intracellular pH (pH(i)) in HL60 cells were examined. Baseline DIDS blockable Cl- currents were consistently lower in HL60/AR cells (0.9 pA/pF) as compared to HL60 cells (7.0 pA/pF). Similarly cAMP-activated Cl- currents were minimal in HL60/AR cells (0.2 pA/pF) as compared to HL60 cells (8 pA/pF). In vitro treatment of drug sensitive HL60 cells with DIDS resulted in concentration-dependent decreased accumulation and increased resistance to daunorubicin and decreased pH(i). These data show that altered Cl- permeability is associated with MDR and suggest that Cl- channels may play a role in MDR.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Detection of a human intracisternal retroviral particle associated with CD4+ T-cell deficiency.

A number of non-human-immunodeficiency-virus (HIV) type 1 disorders are associated with CD4+ T-cell deficiency and dysfunction. However, the etiopathogenesis of CD4+ T-cell immunodeficiency in these disease states remains unclear. Human intracisternal retroviral (HICRV) particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from a patient with severe CD4+ T-cell deficiency without risk factors for HIV infection. Ultrastructurally, the HICRV is distinct from HIV-1, HIV-2, human T-lymphotropic virus (HTLV) type I, and HTLV-II. Supernatants of activated mononuclear cells showed significant reverse transcriptase activity that was predominantly Mn2+ dependent. The patient's mononuclear cells were negative for HIV-1, HIV-2, HTLV-I, and HTLV-II proviruses as demonstrated by the lack of amplification by PCR. Also, the patient's serum was negative for antibodies to HIV-1, HTLV-I, and HTLV-II and for HIV-1 p24 antigen; however, serum was positive for antibodies against the HICRV as demonstrated by Western blot. Similar HICRV particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from the patient's daughter, who showed CD4+ T-cell dysfunction. The HICRV may be associated with CD4+ T-cell immunodeficiency and dysfunction in patients without risk for HIV-1, HIV-2, HTLV-I, and HTLV-II.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Protein kinase C isoforms in multidrug resistant P388/ADR cells: a possible role in daunorubicin transport.

To identify the role of protein kinase C (PKC) isoforms in multidrug resistance in tumor cells, we examined the PKC isoform pattern in the multidrug resistant P388/ADR cell line and studied the effect of down regulation of PKC isoforms on intracellular daunorubicin accumulation and P-glycoprotein expression. Using monoclonal antibodies to PKC alpha, beta and gamma and flow cytometry technique we showed that P388/ADR cells overexpressed PKC alpha and beta as compared to drug sensitive P388 cells. Prolonged treatment of P388/ADR cells with phorbol myristate acetate (PMA), a procedure that is known to down regulate PKC, resulted in the down regulation of total PKC activity and the PKC beta isoform (at the protein level) that was accompanied by the correction of daunorubicin accumulation in P388/ADR cells. The level of expression of P-glycoprotein in PMA treated cells was similar to that of untreated cells. These results suggest that PKC beta regulates the drug efflux function of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Effect of anthelmintics on the antioxidant system of Nippostrongylus brasiliensis.

To understand the mode of anthelmintic action of thiabendazole and methyl-[5-[[4-(2-pyridinyl)-l-piperazinyl]carbonyl]-1H-benzimidazole- 2-yl] carbamate (C.D.R.I. compound 81/470) against Nippostrongylus brasiliensis, their effect on the metabolism of reactive oxygen species in the parasite as well as in rat intestine was examined. Both drugs produced a significant depression in the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) of the parasite. Release of antioxidant enzymes by the drug-treated worms was also found to be appreciably lowered. Both thiabendazole and compound 81/470 induced a depression in the levels of all five constituents of the antioxidant system of rat intestine but significant alterations were detected only in the GSH content of infected and the SOD activity of normal intestine. The production of O2- by treated intestine was, on the other hand, markedly enhanced. Increased formation of O2- by the host intestine accompanied with the reduced level of SOD and GSH in N. brasiliensis appear to have a deleterious effect on the parasite. Consequently, the drug-treated worms are unable to retain themselves in situ and are ultimately expelled. The greater effect produced on these parameters by thiabendazole compared to compound 81/470 is consistent with the relative efficacy of these anthelmintics.

Animals↗
PubMed1992

Audit of open cholecystectomy in a district general hospital.

This retrospective study audited all non-malignant biliary surgery carried out in a district general hospital between January 1985 and December 1990. Surgery was performed on 722 patients: 555 (77 per cent) were women and 167 (23 per cent) were men. The mean(s.d.) age of the patients was 49(16) years. Elective admissions accounted for 70 per cent of cases and 30 per cent were emergency admissions. Ultrasonography confirmed the diagnosis in 93 per cent of cases. An elective operation was performed in 542 patients and 180 patients underwent an urgent or emergency operation. Simple cholecystectomy was performed on 616 patients (85 per cent); 92 (13 per cent) also underwent common bile duct exploration and 14 (2 per cent) had an additional unrelated procedure. The mean(s.d.) hospital stay was 12.3(6.3) (range 4-34) days. There was one perioperative death. The general overall morbidity rate was 25 per cent and the procedure-related morbidity rate was 7 per cent. For simple cholecystectomy (n = 630) there were no deaths; the general morbidity rate was 15 per cent and the procedure-related rate was 3 per cent.

Adolescent↗
PubMed1992

Mitogenic effects of hepatic stimulator substance on cultured nonparenchymal liver epithelial cells.

We determined whether hepatic stimulator substance shares its mitogenic specificity for hepatocytes with nonparenchymal epithelial cells in the hepatocyte lineage. Cell lines designated HTC (derived from a rat hepatoma known to respond to hepatic stimulator substance) and FNRL, K-16 and K-22 (derived from rat liver nonparenchymal epithelial cells) were used. After exposure to hepatic stimulator substance, [3H]-thymidine incorporation into DNA was significantly increased (p less than 0.001) in HTC, FNRL and K-16 cells, but not in K-22 cells. Fluorescence-activated cell sorting demonstrated that the mitogenic response to hepatic stimulator substance was associated with a greater proportion of cells entering the S phase. Epidermal growth factor, alone or in combination with hepatic stimulator substance, had no significant mitogenic effect on FNRL cells, but exposure of these cells to transforming growth factor-beta 1 inhibited [3H]-thymidine incorporation into DNA and reduced the proportion of cells in the S and G2/M phases. Simultaneous exposure of FNRL cells to hepatic stimulator substance and transforming growth factor-beta 1 abrogated the inhibitory effect of transforming growth factor-beta 1. Comparison of butyrate-synchronized HTC cells with hepatic stimulator substance-treated HTC cells showed that S-phase progression in these conditions was different, with no intervening cell cycle arrest after treatment with hepatic stimulator substance. Mitogenic stimulation of FNRL and K-16 cells with the liver-specific growth factor hepatic stimulator substance suggests that these cells are of hepatocyte lineage. These results strengthen the evidence for a possible link between hepatocytes and nonparenchymal liver epithelial cells during liver biogenesis and differentiation.

Animals↗
PubMed1992

Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial.

A prospective randomized double-blind study was conducted to evaluate the efficacy of sodium benzoate in the treatment of acute portal-systemic encephalopathy. Seventy-four consecutive patients with cirrhosis or surgical portasystemic anastomosis and hepatic encephalopathy of less than 7 days duration were randomized to receive lactulose (dose adjusted for 2 or 3 semiformed stools/day) or sodium benzoate (5 gm twice daily). Assessment of response included mental status, asterixis, arterial ammonia level, electroencephalogram and number-connection test. Each was given a score between 0 and 4+. A portal-systemic encephalopathy index was calculated with these scores. Visual, auditory and somatosensory evoked potentials and a battery of psychometric tests for intelligence and memory were also performed to assess improvement. Thirty-eight patients received sodium benzoate; 36 took lactulose. Thirty patients (80%) receiving sodium benzoate and 29 (81%) receiving lactulose recovered; the remaining patients died. Improvement in portal-systemic encephalopathy parameters occurred in both treatment groups and was similar (p greater than 0.1). Electroencephalogram and evoked potentials were not as helpful as mental status in assessing of recovery. Psychometric test scores remained abnormal after recovery of mental status (21 to 42 days) and were probably too sensitive for monitoring of these patients. The incidence of side effects was similar in the two treatment groups. The cost of lactulose for one course of therapy was 30 times that of sodium benzoate. We conclude that sodium benzoate is a safe and effective alternative to lactulose in the treatment of acute portasystemic encephalopathy.

Acute Disease↗
PubMed1992

Analysis of hepatocellular proliferation: study of archival liver tissue is facilitated by an endogenous marker of DNA replication.

Assessment of liver regeneration with endogenous genes that are expressed during DNA replication is physiological, specific and direct. To determine whether H3 histone messenger RNA expression (which is tightly coupled with DNA synthesis) could be used for this purpose, we initially examined liver regeneration in a mouse model. After partial hepatectomy, RNA transblot studies showed induction of H3 histone messenger RNA expression in regenerating mouse livers. In situ molecular hybridization demonstrated that the overall pattern of H3 histone messenger RNA expression correlated with [3H]thymidine labeling of hepatocytes. After partial hepatectomy, H3 histone messenger RNA expression in hepatocytes peaked at 48 hr (greater than 60 times greater than at 24 hr; p less than 0.001) and then rapidly declined. Although hepatocyte labeling with [3H]thymidine showed similar kinetics of liver regeneration, use of this parameter resulted in overestimation of the proliferative compartment when it was compared with H3 histone messenger RNA expression. Next we determined whether H3 histone messenger RNA expression could be used to study hepatocellular proliferation in archival human material. H3 histone messenger RNA-expressing hepatocytes were identified on in situ hybridization in patients with acute or chronic active hepatitis and active cirrhosis, but not inactive cirrhosis. These studies demonstrate that H3 histone messenger RNA is expressed in a phasic manner during liver regeneration. Use of H3 histone messenger RNA expression to evaluate hepatocellular proliferation should facilitate clinical studies and greatly advance our understanding of the pathophysiology of liver regeneration.

Adolescent↗
PubMed1992

Macronodular adrenal hyperplasia causing Cushing's syndrome: report of two cases and an overview.

Of the various entities producing adrenal hyperfunction, nodular adrenal hyperplasia is rarely described, however, recent reports have established it as a distinct cause of Cushing's syndrome. Although the etiology of this disease remains uncertain, two distinct forms are recognised, namely: macronodular hyperplasia and micronodular dysplasia. Establishing the diagnosis preoperatively is difficult but essential to ensure the correct treatment is performed. Two cases of macronodular hyperplasia are reported herein followed by a review of the available literature on this subject.

Adrenal Glands↗
PubMed1992

Psychosis in Asian immigrants from the Indian sub-continent: preliminary findings from a follow-up study including a survey of general practitioners.

The paper presents preliminary findings from a follow-up study of 86 first-generation immigrants to the United Kingdom from the Indian sub-continent, and a matched indigenous English-born control group. All subjects had originally been seen at the Bethlem Royal and Maudsley Hospitals and had been diagnosed as suffering from a functional psychosis. Attempts to locate the patients 5-20 years later revealed that a significantly higher proportion of the immigrant group could not be traced to a general practitioner within the United Kingdom, or otherwise accounted for. Possible explanations for this finding are advanced; the fact itself has important implications for those concerned with the provision of care and services for mentally ill immigrants in this country.

Bangladesh↗