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Biomedical subjects

A Ray

Publications and source records attributed to A Ray.

At least 181 records · Page 10Linked to original sources
PubMed1991

The basolateral amygdala, dopamine and gastric stress ulcer formation in rats.

Bilateral microinjections of dopamine (DA, 0.3, 3.0 or 30.0 micrograms) or the DA-agonist, bromocriptine (3.0 micrograms) into the basolateral amygdala (BLA) dose-dependently attenuated cold restraint stress (3 h at 4 degrees C)-induced gastric ulcer formation in rats. On the other hand, intra-BLA injections of the neurotoxin, 6-hydroxydopamine (10 micrograms) of the DA-antagonist, haloperidol (0.1 or 1.0 micrograms) aggravated such stress ulcer formation. All these effects were seen only when the injection sites were localized in the posterior (and not the anterior) BLA. Further, pretreatment of rats with haloperidol (0.1 micrograms) clearly antagonized the gastric cytoprotective effects of DA or bromocriptine (both at 3.0 micrograms), when both chemicals were injected in the posterior BLA. The results indicate that DA-ergic mechanisms in the posterior BLA are important for the regulation of gastric mucosal integrity during cold restraint stress.

Amygdala↗
PubMed1991

Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product.

The aberrant overexpression of interleukin 6 (IL-6) is implicated as an autocrine mechanism in the enhanced proliferation of the neoplastic cell elements in various B- and T-cell malignancies and in some carcinomas and sarcomas; many of these neoplasms have been shown to be associated with a mutated p53 gene. The possibility that wild-type (wt) p53, a nuclear tumor-suppressor protein, but not its transforming mutants might serve to repress IL-6 gene expression was investigated in HeLa cells. We transiently cotransfected these cells with constitutive cytomegalovirus (CMV) enhancer/promoter expression plasmids overproducing wt or mutant human or murine p53 and with appropriate chloramphenicol acetyltransferase (CAT) reporter plasmids containing the promoter elements of human IL-6, c-fos, or beta-actin genes or of porcine major histocompatibility complex (MHC) class I gene in pN-38 to evaluate the effect of the various p53 species on these promoters. Murine and human wt p53 derived from pCMVNc9 and pC53-SN3, respectively, strongly repressed the IL-6 (promoter position -225 to +13), c-fos (-711 to +42), beta-actin (-3400 to +912), and MHC (-528 to -38) promoters in serum-induced HeLa cells; additionally, IL-6 promoter/CAT transcription unit constructs induced by IL-1, phorbol ester, or pseudorabies virus were also repressed by wt human and murine p53. The murine transforming mutant p53 (pCMVc5) was less active in repressing the IL-6, c-fos, beta-actin, and MHC promoter constructs. The human p53 mutant derived from pC53-SCX3 was also less active than the wt protein in repressing the IL-6, c-fos, beta-actin, and MHC promoters, except that serum-induced IL-6/CAT expression was equally repressed by both human wt and mutant p53. In similar transient transfection experiments in HeLa cells, overexpression of the wt human retinoblastoma susceptibility gene product, RB, was found to repress the serum-induced IL-6 (-225 to +13), c-fos (-711 to +42), and beta-actin (-3400 to +912) promoters but not the PRV-induced IL-6 (-110 to +13) or the serum-induced MHC (-528 to -38) promoters. These observations identify transcriptional repression as a property of p53 and suggest that p53 and RB may be involved as transcriptional repressors in modulating IL-6 gene expression during cellular differentiation and oncogenesis.

Chloramphenicol O-Acetyltransferase↗
PubMed1991

Repressor to activator switch by mutations in the first Zn finger of the glucocorticoid receptor: is direct DNA binding necessary?

Transfection of HeLa cells with cDNA vectors expressing the wild-type human glucocorticoid receptor (GR) enabled dexamethasone to strongly repress cytokine- and second messenger-induced expression of cotransfected chimeric reporter genes containing transcription regulatory DNA elements from the human interleukin 6 (IL-6) promoter. Deletion of the DNA-binding domain or of the second Zn finger or a point mutation in the Zn catenation site in the second finger blocked the ability of GR to mediate repression of the IL-6 promoter. Unexpectedly, deletion of the first Zn finger, a point mutation in the Zn-catenation site in the first finger, or one in the steroid-specificity domain at the base of the first finger converted GR into a dexamethasone-responsive activator that enhanced basal and interleukin 1-induced IL-6 promoter function. These first-finger mutants of GR also mediated dexamethasone-responsive enhancement of expression of the herpesvirus thymidine kinase-chloramphenicol acetyltransferase (TK-105-CAT and TK-80-CAT) reporter genes but not of the murine mammary tumor virus long terminal repeat-CAT or the c-fos-CAT (pFC700) reporter genes. Wild-type GR was able to specifically bind to DNA fragments containing glucocorticoid response element sequences in both the murine mammary tumor virus and IL-6 promoters, albeit weakly to the latter, in a sequential DNA-binding immunoprecipitation assay. The first-finger mutants of GR, however, were inactive in this assay. Thus, mutations in the first Zn finger unmask unusual promoter-specific activation properties of GR that may not require direct high-affinity binding of the mutant GR to target DNA.

Amino Acid Sequence↗
PubMed1991

Molecular cloning and nucleotide sequence of complementary DNA encoding rabbit alpha 1-acid glycoprotein.

Alpha 1-acid glycoprotein (AGP) complementary DNA clone has been isolated from an acute phase rabbit liver library. Complete and full-length nucleotide sequence of this cDNA has been determined. The cDNA contains 35 nucleotides 5' untranslated region followed by 606 nucleotides of coding region and a 112 nucleotides 3' untranslated region. Comparison of this sequence with that of human, rat and mouse reveals a high degree of homology with human alpha 1-AGP. Northern blot analysis of messenger RNA for alpha 1-AGP in normal and acute livers demonstrates remarkable induction of transcription of this gene in rabbit in response to acute inflammation by the administration of turpentine. Such a response of AGP gene expression makes it a major member of the acute phase responsive genes in rabbit liver.

Amino Acid Sequence↗
PubMed1991

TRH-enkephalin interactions in the amygdaloid complex during gastric stress ulcer formation in rats.

The formation of gastric stress ulcers was studied as a function of interactions between thyrotropin releasing hormone (TRH) and endogenous opioids in the central amygdalar nucleus (CEA) in rats. Bilateral microinjections of TRH (1 or 10 micrograms) into the CEA produced dose-related aggravations in cold restraint stress (CRS, 3 h at 4 degrees C)-induced gastric ulcer formation. Similar stress ulcer facilitating effects were also seen with intra-CEA injections of the opioid antagonists, naloxone (1 or 10 micrograms). On the other hand, the enkephalin analog, D-Ala2-metenkephalinamide (DAMEA, 1, 10 or 20 micrograms) produced dose-dependent attenuations in gastric stress pathology, the effects being most marked with the latter two doses. Pretreatment of rats with intra-CEA naloxone (1 microgram) (a) antagonized the gastric cytoprotective effects of DAMEA (20 micrograms) and (b) further aggravated the ulcerogenic response of TRH (1 microgram), without influencing significantly the TRH (10 micrograms) effect. Further, when DAMEA (20 micrograms) was administered intra-CEA just after TRH (10 micrograms), the stress ulcer facilitating effects of the latter was neutralized. The results indicate that TRH-enkephalin interactions are possible at the level of the CEA during CRS-induced gastric ulcer formation.

Amygdala↗
PubMed1991

Complementary DNA cloning and nucleotide sequence of rabbit serum amyloid A protein.

A complementary DNA clone encoding serum amyloid A protein has been isolated from an acute rabbit liver cDNA library. Complete nucleotide sequence analysis reveals that the cloned gene contains a 24 bases 5' untranslated region, 369 bases coding region and a 106 bases 3' untranslated region. Primer extension analysis indicates that the full-length 5' untranslated region contains 80 nucleotides. Northern blot analysis of mRNA from normal and acute rabbit livers demonstrates that this gene is expressed constitutively at a low level and undergoes induction of transcription in response to acute inflammation by the administration of turpentine.

Amino Acid Sequence↗
PubMed1991

Variability in LPS composition, antigenicity and reactogenicity of phase variants of Bordetella pertussis.

Comparison of lipopolysaccharides (LPS) from phase variants of different strains of Bordetella phase variants of different strains of Bordetella pertussis has shown a difference in their composition, antigenicity and reactogenicity. Phase I variants of B. pertussis, with the exception of strain 134, contain a preponderance of LPS I whereas the major component of LPS of phase IV variants is LPS II. Sera raised to LPSs of phase I strains, other than 134, cross-react with each other but not with phase IV LPSs; and similarly all sera raised to phase IV LPSs cross-react with each other and with LPS from 134 phase I. The LPSs of all phase I variants, including that of 134, are approximately ten-fold or more reactive in the limulus amoebocyte lysate assay (LAL) than phase IV LPSs. In the human mononuclear cell pyrogen assay phase IV LPSs also stimulated a lower response than phase I LPSs. The B. pertussis phase I LPSs are 10-times more reactive than Escherichia coli standard endotoxin in the LAL assay but 100-times less reactive than E. coli LPS in the monocyte test for pyrogen. The SDS-PAGE profiles of B. pertussis LPSs are quite different from those of B. parapertussis and B. bronchiseptica strains. B. pertussis LPSs produced a typical lipo-oligosaccharide (LOS) pattern. B. bronchiseptica LPS produced a similar pattern but was antigenically distinct from B. pertussis LPSs I and II. B. parapertussis in contrast produced a ladder pattern typical of smooth type LPS.

Animals↗
PubMed1991

Expression and function of interleukin-6 in epithelial cells.

Epithelial cells both produce and are affected by interleukin-6 (IL-6). Experiments with an adenocarcinoma-derived cell line (HeLa) reveal that activation of the transfected human IL-6 promoter occurs largely through two partially overlapping second messenger (cAMP, phorbol ester)- and cytokine (IL-1, TNF, serum)-responsive enhancer elements (MRE 1, -173 to -151 and MRE II, -158 to -145). MRE I contains the typical GACGTCA cAMP and phorbol ester-responsive (CRE-TRE) motif, whereas MRE II defines a new CRE/TRE motif that contains an imperfect dyad repeat. The mechanism of dexamethasone-mediated repression of IL-6 gene expression in epithelial cells involves occlusion of the entire MRE enhancer region and of the core-promoter elements (TATA-box and RNA start site) by ligand-activated glucocorticoid receptor. Enhanced levels of IL-6 expression are observed in many solid tumors and in the hyperproliferative (and glucocorticoid-suppressible) lesions of psoriasis. In cell culture, IL-6 enhances, inhibits, or has no effect on the proliferation of epithelial cells depending upon the cell-type examined. IL-6 enhances proliferation of keratinocytes but inhibits that of breast carcinoma cell lines ZR-75-1 and T-47D. In these breast carcinoma cells, IL-6 elicits a major change in cell phenotype which is characterized by a fibroblastoid morphology, enhanced motility, increased cell-cell separation, and decreased adherens type junctions (desmosomes and focal adhesions). The new data identify IL-6 as a regulator of epithelial cell growth and of cell-cell association.

Animals↗
PubMed1991

Suppressive effect of quinalphos on the activity of accessory sex glands and plasma concentrations of gonadotrophins and testosterone in rats.

Biochemical estimation of prostatic acid phosphatase and fructose content in accessory sex glands, along with radioimmunoassay of plasma gonadotrophins (FSH and LH) and testosterone were performed in Wistar rats following treatment with quinalphos, an organophosphorus insecticide, for 13 and 26 days. Prostatic acid phosphatase activity and fructose content of the accessory sex glands, and plasma levels of testosterone and FSH were significantly lower in all rats treated with quinalphos. However, the degree of inhibition was more extensive in the 26 day-treatment group who, in addition also exhibited a significant reduction in relative weights of the testes and accessory sex organs, and plasma levels of LH. All these adverse effects of quinalphos were prevented when exogenous HCG was administered in concomitant with the insecticide for 26 days. These results suggest that quinalphos may exert a suppressive effect on the functional activity of accessory sex glands by decreasing testicular testosterone production following inhibition of pituitary gonadotrophins release.

Animals↗
PubMed1991

The amygdala. Emotions and gut functions.

Studies are reviewed that indicate that the amygdala, and its temporal lobe pathways connecting it with entorhinal cortex and hippocampus, modulates the effects of stressful conditions on the development of gastric pathology. The amygdala integrates aversive stimulus conditions with the defensive behaviors and visceral reactions seen under such circumstances. The transmitter mechanisms for these effects include dopamine, gamma-aminobutyric acid, thyrotropin-releasing hormone, neurotensin, enkephalins, and endorphins. Recording data also show that distinct neural "signatures" in this temporal lobe region correlate with the vulnerability to stressful experiences. The efficacy of synaptic transmission, as represented by potentiation or suppression of recorded neuronal responses, is an indication of coping adjustments, ie, habituation or behavioral helplessness. Glutamate receptors in this brain region, activated by N-methyl-D-aspartate, are implicated in these behavioral strategies. It is proposed that the neurophysiology of these limbic system structures produces individual differences in stress ulcer severity.

Amygdala↗
PubMed1991

Role of diurnal variation and receptor specificity in the opioidergic regulation of food intake in free-fed and food-deprived rats.

The effects of opioid agonists, morphine (MOR) and ketocyclazocine (KCZ), and antagonists, naltrexone (NALTX) and Mr2266, were investigated on food intake under various conditions, i.e., during light and dark phases of diurnal cycle and free-fed and fasting states in rats. NALTX showed a greater anorexic effect during dark phase, whereas Mr2266 produced such effect during light phase. This suggests that mu-receptors play a major role during dark phase while kappa-receptors are more important in light phase. The comparison of effects of different opioidergic drugs in fasted and free-fed rats showed that NALTX and Mr2266 reduced the elevated basal food intake in 18-h fasted rats to free-fed control levels. Therefore, it appears that enhanced endogenous mu- and kappa-directed neural mechanisms are one of the factors responsible for enhancing food intake in fasted rats. Differential role of MOR and KCZ on food intake in free-fed and fasted rats is also indicated in our study. Both agonists produced a biphasic response in fasted rats, i.e., hyperphagia (0-1 h) followed by hypophagia (1-6 h). However, a generalized hyperphagic effect is observed in free-fed rats (except during 3-6 h by MOR). The initial hyperphagic effect is more prominent in fasted rats which may be due to additive effects of endopioid mechanisms. Specificity of the response at various intervals is confirmed by blockade with NALTX and Mr2266. NALTX appears more potent than Mr2266 in antagonising the effects of MOR but markedly less potent than Mr2266 in inhibiting the effects of KCZ. This suggests that both MOR and KCZ have a mu as well as kappa component in food intake response.

Animals↗
PubMed1991

Role of histaminergic mechanisms in the regulation of some stress responses in rats.

The involvement of histaminergic mechanisms in the regulation of some stress responses was studied in rats. The brain neuronal histamine (HA) depletor, alpha-fluoromethyl histidine (alpha-FMH), at doses (50 or 100 mg/kg) which markedly lower brain HA, significantly attenuated the gastric ulcer formation and the elevation in plasma corticosterone in response to cold restraint stress (CRS). alpha-FMH also appreciably reduced gastric mucosal HA content. The H1-antagonist, pheniramine (25 mg/kg), attenuated both the gastric mucosal and endocrine response to CRS, while the effects of the H2-antagonist, cimetidine (200 mg/kg), were on the plasma corticosterone levels. These results are discussed in light of complex HA-ergic mechanisms in the maintenance of physiological homeostasis during stress.

Animals↗
PubMed1991

Effects of acute and chronic morphine on food intake in rats: modulation by oxytocin and vasopressin.

The effects of acute and chronic morphine administration and the interaction with oxytocin and vasopressin on food intake response were investigated at various intervals during a 24-h schedule in rats. Acute morphine (5 mg/kg, IP) produced a generalized hyperphagic effect in both light (0-6 h) and dark (6-24 h) phases, the most marked effects being at 0-1 h, 1-3 h and 6-24 h. Chronic morphine (7 days) in an escalating dose schedule (5-35 mg/kg/day) produced (a) an enhancement of the hyperphagic effect in the light phase and (b) an attenuation of the food intake response during the dark phase. Neither oxytocin nor vasopressin had any significant influence on food intake, per se, after either acute or chronic administrations. However, both OXY and AVP reduced the hyperphagic response to acute morphine throughout the 24-h observation period. Further, on chronic administration, both neurohypophyseal peptides blocked the enhancements of morphine-induced hyperphagia (reverse tolerance) during light phase, whereas only vasopressin was effective in attenuating the reduction of hyperphagia (tolerance) during dark phase. These results are discussed in light of complex opiate-oxytocin/vasopressin interactions in the regulation of food intake.

Animals↗