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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 955 records · Page 53Linked to original sources
PubMed1994

Mycobacterium tuberculosis induces expression of P-glycoprotein in promonocytic U1 cells chronically infected with HIV type 1.

A productive infection with HIV-1 is associated with an increased expression of a 170 kd plasma membrane P-glycoprotein (P-gp), that functions as a metabolically active drug efflux pump, in human T and macrophage cell lines. In this investigation we show that phagocytosis of M. tuberculosis by U1 cells, that are chronically infected with HIV-1 but produce minimal or no virus, resulted in an expression of P-gp that was associated with increased production of HIV-1 p24 antigen. In addition, U1 cells that had phagocytosed M. tuberculosis accumulated significantly less intracellular isoniazid (INH) as compared to U1 cells. Furthermore, verapamil, that binds to P-gp, increased the intracellular accumulation of INH and the sensitivity of M. tuberculosis to INH. These data suggest induction of P-gp expression may be one of the host mechanisms for the development of multidrug resistant M. tuberculosis in HIV 1 infection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Role of protein kinase C isozymes in activation of human immunodeficiency virus type 1 in chronically infected promonocytic cells: evidence against a role of PKC beta 1.

Protein kinase C (PKC) plays an important role in activation of human immunodeficiency virus type 1 (HIV-1). Because of a molecular and biochemical heterogeneity of PKC, we have studied the effects of PKC isozymes in HIV-1 activation in a latently infected promonocytic cell line, U1, using various PKC isozyme agonists. 12-Deoxyphorbol 13-phenylacetate (dPP), an agonist of both Ca(++)-dependent and Ca(++)-independent isozymes, and thymeleatoxin (TT), an agonist of Ca(++)-dependent PKC isozymes, induced HIV-1 production at 10 nM with increase in a concentration dependent manner, whereas 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), an PKC beta I isozyme agonist, did not induce viral production at 100 nM. We verified that dPPA induced translocation of PKC beta isozyme with the isozyme-specific monoclonal antibody using flow cytometry. This study demonstrates that activation of PKC isozymes leads to an induction of latent HIV-1 in U1 cells whereas PKC beta I isozyme may not be important.

Cell Survival↗
PubMed1994

Antigenic diversity and the transmission dynamics of Plasmodium falciparum.

The average age of humans at their first infection with Plasmodium falciparum is typically less than 1 year in most endemic areas. This has been interpreted as evidence of the high transmissibility of the parasite, with the implication that control of malaria will require high levels of coverage with a potential vaccine. This interpretation is challenged by mathematical models that demonstrate that the long period required to develop immunity to malaria permits a high risk (or low average age) of infection even when parasite transmissibility is low. Patterns of seroconversion to five antigenically distinct isolates of P. falciparum in a highly malarious area of Papua New Guinea indicate that each is only mildly transmissible and that malaria, as a construct of several such independently transmitted strains, has a basic reproductive rate (or transmissibility) that is an order of magnitude lower than other estimates.

Aging↗
PubMed1994

Control of MAP kinase activation by the mitogen-induced threonine/tyrosine phosphatase PAC1.

Intracellular signalling following mitogenic stimulation of quiescent cells involves the initiation of a phosphorylation cascade that leads to the rapid and reversible activation of the mitogen-activated protein (MAP) kinases ERK1 and ERK2. MAP kinase activation is mediated by dual phosphorylation within the motif Thr-Glu-Tyr by MAP kinase kinase (MEK). Following activation, the MAP kinases translocate into the nucleus where they phosphorylate several transduction targets, including transcription factors. We have previously identified PAC1 as an immediate-early mitogen-inducible tyrosine phosphatase in nuclei of T cells. Here we present several lines of evidence indicating that PAC1 is a physiologically relevant MAP kinase phosphatase. Recombinant PAC1 in vitro is a dual-specific Thr/Tyr phosphatase with stringent substrate specificity for MAP kinase. Constitutive expression of PAC1 in vivo leads to inhibition of MAP kinase activity normally stimulated by epidermal growth factor, phorbol myristyl acetate, or T-cell receptor crosslinking. The inactivation of MAP kinase by PAC1 results in inhibition of MAP kinase-regulated reporter gene expression.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1994

Effect of Calphostin C (PKC inhibitor) on daunorubicin resistance in P388/ADR and HL60/AR cells: reversal of drug resistance possibly via P-glycoprotein.

Calphostin C is a potent and specific inhibitor of protein kinase C (PKC). In this investigation we examined the effect of Calphostin C (without prior exposure to light) on daunorubicin (DNR) accumulation and sensitivity to DNR in multidrug-resistant (MDR) murine leukemia P388/ADR and human myeloid leukemia HL60/AR cells. P388/ADR cells overexpress P-glycoprotein, whereas HL60/AR cells lack any expression of P-glycoprotein (both at mRNA and protein levels). Calphostin C, in a concentration-dependent manner, increased the accumulation of DNR in P388/ADR cells and partially reversed (threefold) the DNR resistance in P388/ADR cells but had no effect on either of the parameters in HL60/AR cells. Calphostin C-induced increased accumulation of DNR in P388/ADR cells was due to increased uptake and decreased efflux of DNR. Furthermore, Calphostin C increased the uptake and decreased the efflux of rhodamine 123 (a substrate for P-gp) in P388/ADR cells but had no such effect in P388 cells. In addition, Calphostin C without exposure to light did not inhibit PKC activity in any of the cell lines studied. Taken together, these data suggest that Calphostin C may reverse drug resistance via P-glycoprotein independently of its effect on PKC activity. Therefore, any data regarding the effect of Calphostin C on the reversal of MDR should be interpreted in the light of these findings.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Exposure to lead in stained glass work. An environmental evaluation.

An environmental evaluation was conducted to determine lead exposure in a group of crafts people who produce stained glass and Tiffany glass. The environmental evaluation consisted of air sampling for potential lead emissions from solder and of work area dusts. In addition, the completion of a questionnaire, observation of work practices and noting of other details relevant to hazardous exposures were carried out. Lead concentrations in air were found to be well below the ACGIH TLV-TWA of 150 micrograms/m3. High lead concentrations were found in the work area dust samples. Exposure to high concentrations of lead could occur by ingestion as a result of neglect of basic hygiene precautions.

Adolescent↗
PubMed1994

Laparoscopy and colon cancer. Is the port site at risk? A preliminary report.

PURPOSE: To quantify the magnitude of the risk for port/extraction site recurrence of laparoscopically resected colon cancer in a defined study population. METHODS: The data from a prospective laparoscopic bowel surgery registry was used to identify cases of colon cancer that were resected laparoscopically, with a minimum follow-up of 1 year. A questionnaire was sent to the surgeons who performed the procedures. RESULTS: A total of 252 cases were identified from the registry. Questionnaires were returned in 208 of those cases, a response rate of 82.5%. Three cases of port or extraction site recurrence were noted, two of them associated with diffuse peritoneal carcinomatosis. All the patients had a Dukes' stage C tumor at the time of initial surgery. CONCLUSIONS: The incidence of port/extraction site recurrence following laparoscopic colon cancer surgery is low. All the recurrences were in patients with Dukes' stage C tumors, and there was diffuse peritoneal carcinomatosis in two of the three cases, suggesting that port/extraction site recurrence may be attributable to the advanced nature of the disease rather than the laparoscopic technique. Longer follow-up and more cases are required to confirm these findings.

Colonic Neoplasms↗
PubMed1994

111Indium labeling of hepatocytes for analysis of short-term biodistribution of transplanted cells.

Hepatocyte transplantation is useful for ex vivo gene therapy and liver repopulation. Methods for hepatic reconstitution have recently been developed but optimization of hepatocyte transplantation systems is necessary. To develop systems for noninvasive assessment of the biodistribution of transplanted cells, we labeled hepatocytes with 111indium-oxine. Our initial studies showed that hepatocytes incorporated 111indium-oxine with an efficiency of approximately 20%. After labeling, cell viability was unchanged and 111indium was present in hepatocytes after overnight culture, as well as after intrasplenic transplantation. Transplanted cells were successfully localized by means of scintigraphic imaging. The scintigraphic patterns of cell distribution were different when hepatocytes were transplanted by means of either spleen or internal jugular vein, which deposit cells into separate vascular beds. Quantitative analysis of the biodistribution of 111indium-labeled hepatocytes indicated that within 2 hr of intrasplenic transplantation, cells were predominantly localized in liver and spleen, and occasionally in lungs. To determine whether the rate of intrasplenic cell injection influenced translocation of hepatocytes, we transplanted cells in normal rats. Despite intrasplenic cell injection at a variety of rates, organ-specific distribution of 111indium-labeled hepatocytes remained unchanged. Labeling with 111indium did not affect long-term survival of transplanted hepatocytes. These results indicate that 111indium-labeling of hepatocytes should greatly assist noninvasive analysis in the short-term of the biodistribution of transplanted hepatocytes.

Animals↗
PubMed1994

A new RFLP marker, SP282, at the btk locus for genetic analysis in X-linked agammaglobulinaemia families.

X-linked agammaglobulinaemia is an inherited recessive disease in which the primary defect lies in the failure of pre-B cells to develop into mature circulating B cells, due to a defective B-cell cytoplasmic tyrosine kinase (btk). For this study we introduced a new RFLP marker, SP282, which is tightly linked to the XLA locus. In conjunction with the marker DXS178, SP282 was used to identify a carrier female and predict her male offspring to be normal. Subsequently the fetus was shown to have a normal number of circulating B cells, and at 2.5 years of age, the non-affected phenotype of the child was confirmed.

Agammaglobulinemia↗
PubMed1994

Biliary excretion of lysosomal enzymes, iron, and oxidized protein in Fischer-344 and Sprague-Dawley rats and the effects of diquat and acetaminophen.

Administration of hepatotoxic doses of diquat to male Fischer-344 rats increases biliary excretion of nonheme iron, whereas comparably hepatotoxic doses of acetaminophen decrease biliary export of iron. The effects of acetaminophen and diquat on the activities in bile of representative lysosomal enzymes, beta-N-acetylglucosaminidase (beta-NAG) and beta-glucuronidase (beta-GLUC) were examined as a means of assessing the possible role of lysosomal exocytosis in the effects of these hepatotoxins on biliary excretion of iron. In pentobarbital-anesthetized male Fischer-344 rats, diquat at 0.1 mmol/kg increased the biliary export of biliary beta-NAG and beta-GLUC, in conjunction with similar increases in iron. Sprague-Dawley rats, which are resistant to diquat-induced hepatic necrosis despite showing marked oxidant stress responses, showed no increases in biliary efflux of iron, beta-NAG, or beta-GLUC in response to diquat. Conversely, acetaminophen at doses of 400 or 1500 mg/kg markedly decreased biliary concentrations and efflux rates of beta-NAG and beta-GLUC in Fischer-344 rats in parallel with decreases in biliary iron, suggesting that the hepatotoxin-induced effects on biliary iron excretion may be mediated through effects on lysosomal exocytosis. Both acetaminophen and diquat increased total protein content of bile in both strains of rats; however, the proteins excreted after administration of diquat to Fischer-344 rats showed marked increases in contents of protein carbonyls, as assayed with 2,4-dinitrophenylhydrazine, whereas biliary proteins in acetaminophen-treated animals were not more oxidized than in controls. Sprague-Dawley rats given diquat showed no increase in the biliary excretion of protein carbonyls, despite the increased excretion of glutathione disulfide observed in these animals. The significant increases in biliary excretion of protein carbonyls by the diquat-treated Fischer-344 rats suggest oxidation of cellular proteins catalyzed by chemically reactive iron chelates and the excretion of at least some of the oxidized proteins to the bile, possibly through lysosomal exocytosis. The effects of acetaminophen on biliary protein excretion do not appear to involve oxidation.

Acetaminophen↗
PubMed1994

MR imaging and angiography in tuberculous meningitis.

MRI was performed on 26 patients with tuberculous meningitis, with particular reference to document the cranial nerve abnormalities. MR angiography (MRA) was performed in 20 of the patients. Meningeal enhancement in the basal cisterns or over the convexity of brain was seen in all patients; two show ependymal enhancement. Tuberculomas, single (3), multiple (12) or miliary (2) were detected in 17 patients. Of the 9 patients with cranial nerve palsies, 7 showed contrast enhancement with or without thickening of the involved nerve. Abnormality signal intensity of the involved nerve was seen on proton density and T2-weighted images in one of these patients. MRA revealed focal arterial narrowing in 10 patients, the vessels commonly affected being the terminal segment of the internal carotid artery and the proximal segments of the middle and anterior cerebral arteries. One patient also had a small aneurysm of the proximal middle cerebral artery. Infarcts, haemorrhagic (8) or bland (6), were detected in 14 patients; most were the basal ganglia and internal capsules, large middle or anterior cerebral arterial territory infarcts being seen in only two cases.

Adolescent↗
PubMed1994

MRI in intraspinal tuberculosis.

We studied 20 patients with intraspinal tuberculosis (TB), to characterise the MRI features of tuberculous meningitis and myelitis. MRI leptomeningitis and intramedullary involvement in 11 patients, intramedullary lesions alone in 5, leptomeningitis alone in 2, and isolated extradural disease in 2. TB leptomeningitis was characterised by loculation of the cerebrospinal fluid (CSF), nerve root thickening and clumping (seen only in the lumbar region) or complete obliteration of the subarachnoid space on unenhanced images. Gd-DTPA-enhanced images proved useful in 6 cases, revealing linear enhancement of the surface of the spinal cord and nerve roots or plaque-like enhancement of the dura-arachnoid mater complex. Intramedullary lesions included tuberculomas (8), cord oedema (5) and cavitation (3). In seven cases of intramedullary tuberculoma multiple lesions with skip areas were seen, without significant cord swelling. One patient had an isolated lesion in the conus medullaris. The lesions were iso- or hypointense on T1-weighted images, iso-, hypo- or hyperintense on T2-weighted images and showed rim or nodular enhancement with contrast medium.

Adolescent↗
PubMed1994

12-Deoxyphorbol-13-O-phenylacetate 20 acetate [an agonist of protein kinase C beta 1 (PKC beta 1)] induces DNA synthesis, interleukin-2 (IL-2) production, IL-2 receptor alpha-chain (CD25) and beta-chain (CD122) expression, and translocation of PKC beta isozyme in human peripheral blood lymphocytes: evidence for a role of PKC beta 1 in human T cell activation.

To determine a role of protein kinase C (PKC) isozymes in lymphocyte activation, human peripheral blood mononuclear cells were activated with 12-deoxyphorbol-13-O-phenylacetate (dPP; an agonist of both calcium-dependent and calcium-independent PKC isozymes), thymeleatoxin (TX; an activator of calcium-dependent PKC alpha, beta, and gamma), and 12-deoxyphorbol-13-O-phenylacetate 20 acetate (dPPA; an activator of PKC beta 1 isozyme) and examined for DNA synthesis, lymphocyte proliferation, interleukin-2 (IL-2) production, expression of IL-2 receptor alpha and beta chains on CD3+, CD4+, and CD8+ T lymphocytes and CD20+ B lymphocytes, and translocation of PKC beta isozyme from cytosol to membrane fraction. The results show that dPPA activates lymphocytes by inducing the above changes in a manner analogous to that of dPP, TX, and phorbol myristate acetate. These data suggest that PKC beta 1 is involved in the activation of human peripheral blood T and B lymphocytes.

DNA↗
PubMed1994

Stability of a recombinant shuttle plasmid in Bacillus subtilis and Escherichia coli.

The recombinant shuttle plasmid pCPPS-31, which confers carboxymethylcellulase (CMCase) production and neomycin resistance (Ner), was segregationally but not structurally unstable in both B. subtilis (50-60%) and Escherichia coli (80-90%) when grown in serial batch cultures for 72 h diluting 1:1,000 with fresh medium every 24 h. The plasmid showed 80-100% segregational and complete structural stability in B. subtilis during batch, fed-batch, and continuous culture fermentations in minimal M9 medium. In E. coli the instability was > or = 50% in 36 h of batch or continuous culture and approached 100% in 72 h of continuous fermentation. The plasmid was more stable (> or = 60%) during fed-batch fermentation. Stability in B. subtilis and instability in E. coli may be attributed to (i) the significant growth-rate advantage of plasmid-free (P-) cells over plasmid-harboring (P+) cells in the case of E. coli, an advantage that was absent in B. subtilis, and (ii) the existence of plasmid in oligomeric forms in E. coli and in mainly monomeric forms in B. subtilis.

Bacillus subtilis↗