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Biomedical subjects

A Ray

Publications and source records attributed to A Ray.

At least 109 records · Page 6Linked to original sources
PubMed1996

Influence of subchronic exposure to lindane on humoral immunity in mice.

Lindane suppressed both primary and secondary antibody responses to sheep red blood cell (SRBC) in albino mice, the effects being more pronounced on the secondary than the primary response. However, a longer duration of pesticide exposure induced similar degrees of immunosuppression on both responses. The sequential study of plaque forming cells (PFC) kinetics revealed that suppression of plaque formation not only occurred at peak days but also on pre and post peak days, and there was no delay in peak antibody formation. Moreover, reduction in the primary PFC was not associated with decrease in the antibody response to SRBC. The results indicate that lindane suppresses both primary and secondary humoral immune responses in a time and dose dependent manner, and suggest a threshold susceptibility to exposure.

Animals↗
PubMed1996

Critical evaluation of references in drug advertisements: an Indian experience.

Drug advertisements have important effect in prescribing habits of physicians. WHO states that all the claims in drug advertisements should be supported by suitable documentary evidences (references). The present study evaluated citations (mentioned/not mentioned), sources (journals, books, conferences/symposia, personal testimonial, unpublished data in file) and adequacy (complete/incomplete) of the references in 585 drug advertisements supplied by medical detail persons to different clinical departments of our hospital. The references were cited only in 37.9% of the drug advertisements. In total, 1032 references (76% of journals, 15% of books, 2% of conferences/symposia, 4% of personal testimonials, 1% of unpublished data and 2% of data in file) were cited. Only 10% references of journals, 7% of books and 12% of conferences/symposia were found complete (according to standard bibliographic norms). The current situation can be improved if the government, industry and the prescribers formulate some guidelines for the mentioning of adequate references in drug advertisements.

Advertising↗
PubMed1995

Role of a distal enhancer containing a functional NF-kappa B-binding site in lipopolysaccharide-induced expression of a novel alpha 1-antitrypsin gene.

alpha 1-Antitrypsin (alpha 1-AT) is one of the major proteinase inhibitors in serum. Its primary physiological function is to inhibit neutrophil elastase activity in lung, but it also inhibits other serine proteases including trypsin, chymotrypsin, thrombin, and cathepsin. We have previously reported a novel alpha 1-AT, S-2 isoform, from rabbit that is induced up to 100-fold in the liver during acute inflammatory condition (Ray, B. K., Gao, X., and Ray, A. (1994) J. Biol. Chem. 269, 22080-22086). Here, we present evidence that the expression of this alpha 1-AT S-2 gene is also induced in lipopolysaccharide (LPS)-treated peripheral blood monocytes. From the cloned genomic DNA, we have identified a distal LPS-responsive enhancer located between -2438 and -1990 base pairs upstream of the transcription start site. In vitro DNA-binding studies demonstrated an interaction of an LPS-inducible NF-kappa B-like nuclear factor with a kappa B-element present in this enhancer region. Antibodies against p65 and p50 subunits of NF-kappa B supershifted the DNA-protein complex. A mutation of the NF-kappa B-binding element virtually abolished the LPS-responsive induction of the chimeric promoter in monocytic cells. Furthermore, overexpression of NF-kappa B induced the wild-type promoter activity. Taken together, these results demonstrated that during LPS-mediated inflammation, NF-kappa B/Rel family of transcription factors play a crucial role in the transcriptional induction of the inflammation responsive alpha 1-AT gene.

Animals↗
PubMed1995

Glucocorticoids.

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Animals↗
PubMed1995

Regulation of dihydropyridine and ryanodine receptor gene expression in skeletal muscle. Role of nerve, protein kinase C, and cAMP pathways.

The dihydropyridine (DHP) and ryanodine (RY) receptors play a critical role in depolarization-induced calcium release in skeletal muscle, yet the factors which govern their expression remain unknown. We investigated the roles of electrical activity and trophic factors in the regulation of the genes encoding the alpha 1, alpha 2, and beta subunits of the DHP receptor as well as the RY receptor in rat skeletal muscle in vivo. Muscle paralysis, induced by denervation, had no effect on the DHP receptor mRNA levels while the RY receptor mRNA was decreased. In contrast, chronic superfusion of tetrodotoxin onto the sciatic nerve resulted in a marked increase in mRNA levels and transcriptional activity of both DHP and RY receptor genes. Since nerve can induce changes in second messenger pathways which modulate muscle gene expression, we attempted to identify factors which regulate DHP and RY receptor expression using cultured myotubes. Elevated cAMP levels specifically inhibited the expression of RY receptor mRNA while 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C, increased the transcripts encoding the RY receptor and the alpha 1 subunit of the DHP receptor. Changes in the level of mRNAs were paralleled by altered receptor numbers. Neither cAMP nor protein kinase C altered transcriptional activity of the DHP and RY receptor genes. These results demonstrate that neural factor(s) regulate DHP and RY receptor mRNA levels in vivo via transcriptional mechanisms while protein kinase C and cAMP can modulate DHP and RY receptor transcript levels by a transcription-independent process.

Alkaloids↗
PubMed1995

Energy metabolism response to calcium activation in isolated rat hearts during development and regression of T3-induced hypertrophy.

The effect of calcium activation on energy production was investigated in isolated perfused hearts from rats treated with triiodothyronine (T3) during 15 days (0.2 mg/kg/day) and in hearts of rats allowed to recover after T3-treatment during 15 days. Changes in phosphorylated compound concentrations were followed in the isolated hearts perfused with a glucose-pyruvate medium by 31P-NMR spectroscopy, when the external calcium concentration was increased from 0.5-1, 1.5 and 2 mM. As expected, T3-treatment resulted in the hypertrophy of the heart (50% increase in HW/BW) that was nearly reversible 15 days after discontinuation of the treatment. When compared to controls, creatine, phosphocreatine (PCr) and glycogen contents were lower (58, 24 and 17% decrease respectively) in the hypertrophied hearts and higher (10, 14 and 18% respectively) after regression of hypertrophy. Intracellular pH, ATP, inorganic phosphate concentrations and the phosphorylation potential were not altered under T3-treatment and after regression of hypertrophy, while calculated free ADP concentration was lower in hypertrophied hearts (control: 40 +/- 2 microM, T3-treatment: 21 +/- 1 microM, regression: 37 +/- 1 microM). Increasing the calcium concentration induced a similar increase in left ventricular developed pressure in the three groups of hearts, with inorganic phosphate concentration increasing with cardiac work. The PCr concentration slightly decreased while the ATP concentration did not change. In spite of different initial PCr concentrations, the evolutions of PCr and Pi concentrations for each stepwise increase in external calcium were similar in the three groups. It is concluded that, in spite of the well-known decrease in efficiency induced by the drug, the mechanisms of PCr (ATP) production remain able to respond to an acute moderate increase in energy demand provoked by a physiological stimulus. This adaptation also persists after the treatment when the energy metabolism balance is apparently improved.

Adenosine Diphosphate↗
PubMed1995

Activation of the interleukin-5 promoter by cAMP in murine EL-4 cells requires the GATA-3 and CLE0 elements.

Interleukin-5 (IL-5) plays a central role in the growth and differentiation of eosinophils and contributes to several disease states including asthma. Accumulating evidence suggests a role for cAMP as an immunomodulator; agents that increase intracellular cAMP levels have been shown to inhibit production of cytokines predominantly produced by T helper (Th) 1 cells such as IL-2 and interferon gamma (IFN-gamma). In contrast, the production of IL-5, predominantly produced by Th2 cells, is actually enhanced by these agents. In this report, we have performed transient transfection experiments with IL-5 promoter-reporter gene constructs, DNase I footprinting assays, and electrophoretic mobility shift assays to investigate the key regulatory regions necessary for activation of the IL-5 promoter by dibutyryl cAMP and phorbol esters in the mouse thymoma line EL-4. Taken together, our data demonstrate the critical importance of two sequences within the IL-5 5'-flanking region for activation by these agents in EL-4 cells: one, a highly conserved 15-base pair element present in genes expressed by Th2 cells, called the conserved lymphokine element 0 (CLE0; located between -53 and -39 in the IL-5 promoter), and the other, two overlapping binding sites for the transcription factor GATA-3 (but not GATA-4) between -70 and -59. Taken together, our data suggest that activation via the unique sequence combination GATA/CLE0 results in selective expression of the IL-5 gene in response to elevated levels of intracellular cAMP.

Animals↗
PubMed1995

Effects of intrahypothalamic morphine and its interactions with oxytocin and vasopressin during food intake in rats.

The effects of intra-hypothalamic microinjections of morphine (MOR) into the ventromedial (VMH) and lateral (LH) nucleus and its interactions with oxytocin (OXY) and vasopressin (AVP) were evaluated during food intake FI) in rats. Acute MOR clearly enhanced FI during the dark phase (6-24 h) of the diurnal cycle, while no appreciable changes in the light phase (0-6 h) FI was seen after intra-VMH or LH injections. Long term MOR administration into both VMH and LH attenuated the enhancements in FI seen after acute MOR during the dark phase, while FI was enhanced during the light phase. Pretreatment with OXY or AVP clearly antagonized such tolerance or reverse tolerance/sensitization development to the orexic effect of MOR. These results are discussed in the light of complex peptidergic interactions in the hypothalamus during ingestive behavior.

Analysis of Variance↗
PubMed1995

Cloning of a differentially expressed I kappa B-related protein.

We have cloned a cDNA corresponding to a novel gene from a human epithelial cell line by subtractive hybridization and polymerase chain reaction techniques. This gene is expressed at the message level and at the protein level in a lung alveolar type II-like epithelial cell line but not in lung fibroblasts. In adult human tissues, the mRNA for this gene was detected only in the heart and the skeletal muscle, but not in the brain, placenta, whole lung, liver, or kidney. We have named this gene I kappa BR (for I kappa B-related) since its 52-kDa protein product has significant homology to the I kappa B family of proteins which function as inhibitory cytoplasmic retention proteins for the vertebrate rel/NF-kappa B transcription factors. Although the important role of NF-kappa B in gene activation in cells of the immune system is now well established, a similar role in other cell types or in vertebrate development is less clear. The deduced amino acid sequence of I kappa BR has the most significant homology to the Drosophila protein Cactus which inhibits the function of the NF-kappa B-like protein Dorsal. In electrophoretic mobility shift experiments, I kappa BR inhibited the ability of the p50:p65 NF-kappa B heterodimer to bind DNA. The DNA binding ability of the p50 homodimer but not the p65 homodimer was drastically inhibited by I kappa BR. In transfection experiments, overexpression of I kappa BR significantly inhibited NF-kappa B-dependent transcription from the Ig kappa enhancer. This new member of the I kappa B family of proteins, I kappa BR, may play an important role in regulation of NF-kappa B function in epithelial cells.

Amino Acid Sequence↗
PubMed1995

Concerted participation of NF-kappa B and C/EBP heteromer in lipopolysaccharide induction of serum amyloid A gene expression in liver.

The promoter region of the rabbit serum amyloid A (SAA) gene contains two adjacent C/EBP and one NF-kappa B binding element. Involvement of these elements in SAA gene induction, following lipopolysaccharide (LPS) stimulation of the liver, has been studied by investigating LPS-activated transcription factors and their interaction with the promoter elements of the SAA gene. Appearance of complexes in the electrophoretic mobility shift assay has indicated that DNA-binding proteins that interact with the NF-kappa B element of the SAA promoter are induced in the LPS-treated rabbit liver. Presence of RelA (p65 subunit of NF-kappa B) in these complexes was demonstrated by the ability of RelA-specific antisera to supershift the DNA-protein complexes. LPS also induced several members of the C/EBP family of transcription factors, which interacted with the C/EBP motifs of the SAA promoter. Activated C/EBP and RelA form a RelA-C/EBP heteromeric complex that associates with varying affinity to NF-kappa B and C/EBP elements of the SAA gene. Transfection assays using both transcription factor genes have demonstrated that the heteromeric complex of NF-kappa B and C/EBP is a much more potent transactivator of SAA expression than each transcription factor alone. The heteromeric complex efficiently promotes transcription from both NF-kappa B and C/EBP sites.

Animals↗
PubMed1995

The mcm2-1 mutation of yeast causes DNA damage with a RAD9 requirement for repair.

The minichromosome maintenance mutation, mcm2-1, has been found to synthesize damaged DNA at 35 degrees C. Growth at this temperature rendered the mutant strain more sensitive to killing by ultraviolet irradiation. DNA damage could also be detected by pulsed-field gel electrophoresis, where a higher fraction of the DNA loaded was retained in the inserts at the wells. During the exponential phase of growth at this temperature about 50% of the cells had large buds, with the nucleus at or near the neck of the bud in most cases. The incorporation of the rad9 deletion in the mcm2-1-carrying strain caused a reduction in the percentage of large-budded cells and a moderate loss of cell viability. The results are consistent with mcm2-1 causing DNA damage leading to the arrest of cells in the S/G2 phase of the cell cycle, which was partially dependent on the RAD9 gene product.

Cell Cycle↗
PubMed1995

Lipopolysaccharide-mediated induction of the bovine interleukin-6 gene in monocytes requires both NF-kappa B and C/EBP binding sites.

The interleukin-6 (IL-6) gene expression in bovine monocytes is highly induced following bacterial lipopolysaccharide (LPS) stimulation. To identify the promoter element(s) involved in the inducible transcription of IL-6, a 5'-flanking region containing 230 bp of the bovine IL-6 gene was linked to a reporter gene coding for bacterial chloramphenicol acetyltransferase (CAT) and analyzed for its ability to confer LPS-responsiveness to the reporter CAT gene in monocytic cells. Using mutant reporter genes, we demonstrate that although mutation in the NF-kappa B element produces the major loss of induction, both NF-kappa B and C/EBP elements are necessary for maximal transcriptional activation of the bovine IL-6 gene. Gel electrophoretic mobility-shift assays have detected induced DNA-binding activities in the LPS-stimulated monocytes. Further characterization has revealed the activation and interaction of C/EBP-alpha, C/EBP-beta (NF-IL6), NFKB1 (p50), and RelA (p65) to their specific binding elements present in the bovine IL-6 gene. These results suggest a model in which induction of C/EBP-alpha in differentiating monocytes contributes and synergizes with induced C/EBP-beta and NF-kappa B, which are activated following LPS stimulation, to mediate a high rate of IL-6 transcription under inflammatory conditions.

Animals↗