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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
PubMed1995

Influence of dietary protein on DDT-induced immune responsiveness in rats.

The influence of protein deficiency was evaluated on immune responsiveness after subchronic DDT exposure in albino rats. Rats were given 20%, 12% and 3% protein diets and exposed to DDT (20, 50 or 100 ppm) for 4 weeks. DDT (50 and 100 ppm) induced humoral and cellular immune suppression only in rats fed on 3% protein diet. There was (a) an increase in the albumin/globulin ratio, (b) suppression in IgM and IgG levels, and (c) attenuation in the tetanus toxoid-induced antibody responses. Further, in rats immunized with tetanus toxoid, the leucocyte and macrophage migration inhibition were also attenuated. Moreover, these animals maintained on 3% protein diet showed depression in humoral and cellular immune responses to antigen in a dose-dependent pattern after exposure to DDT at dose levels which were not immunosuppressive for rats on 12% or 20% protein diet. These results suggest that dietary protein content may predispose to the immunotoxic effects of DDT exposure, and also be a crucial determinant in DDT detoxification.

Animals↗
PubMed1995

Antinociceptive action of Azadirachta indica (neem) in mice: possible mechanisms involved.

Azadirachta indica (AI, Neem) was tested for analgesic potency in experimental pain models in mice. In the glacial acetic acid (GAA) induced writhing test, AI (10, 30 and 100 mg/kg) dose-dependently reduced both the incidence and the number of writhes. Similarly, AI, at the dose levels tested, also enhanced tail withdrawal latencies in the tail-flick test for nociception. In the interaction studies, pretreatment with the opioid antagonist, naloxone (1 mg/kg) and the central noradrenaline depleter, DSP-4 (50 mg/kg) attenuated AI analgesia by differential degrees in both experimental models, whereas, the serotonin synthesis inhibitor, PCPA (300 mg/kg) potentiated the same. These results suggest that both central and peripheral mechanisms and complex neural pathways, opioid and non-opioid, may be involved in AI induced analgesia.

Analgesics↗
PubMed1994

Sp1-mediated transactivation of the rabbit alpha 1 acid glycoprotein-encoding gene involves a cis-acting element in the 5'-proximal promoter region.

Analysis of the regulatory promoter region of the rabbit alpha 1-acid glycoprotein (alpha 1-AGP)-encoding gene revealed the presence of a G + C-rich region that is a potential binding site for the transcription factor Sp1. DNase I footprinting and competition with Sp1-specific wild-type oligodeoxyribonucleotides showed that Sp1 interacts with a tandem array of GGGCGG motifs within the alpha 1-AGP promoter. Transfection assays using both liver and nonliver cells have demonstrated that these Sp1-binding elements are transcriptionally active and overproduction of Sp1 can significantly induce the expression of this gene. Previously, we have identified two adjacent C/EBP-binding elements just upstream from these Sp1-binding regions. We now demonstrate by both in vivo and in vitro analyses that C/EBP and Sp1 bind to the alpha 1-AGP promoter and transactivate the expression of this gene in an independent manner.

Animals↗
PubMed1994

Expression and structural analysis of a novel highly inducible gene encoding alpha 1-antitrypsin in rabbit.

alpha 1-Antitrypsin is a major plasma proteinase inhibitor whose primary function is to control the proteolytic activity of neutrophil elastase that hydrolyzes structural proteins. This protein, in rabbit is expressed as three isoforms designated as F, S-1, and S-2. An inducible form of this protein has been cloned from an acute-phase cDNA library of rabbit liver. Structural study has revealed that the cloned cDNA is the S-2 isoform previously identified by partial peptide sequence analysis. The amino acid sequence of the reactive center of the S-2 form is not conserved and thus can be categorized as of unorthodox type. mRNA analysis has indicated that the transcription of the S-2 isoform which is normally present at a very low concentration increases more than 100-fold under inflammatory conditions while the expression of the F and S-1 isoforms changes about 1.5-fold under similar conditions. The S-2 isoform is biologically active and capable of inhibiting both elastase and chymotrypsin. The high level of induction of this active isoform of alpha 1-antitrypsin under inflammatory conditions and its apparent resistance to oxidation-mediated inactivation, common to the orthodox forms of alpha 1-antitrypsin, make the S-2 isoform suitable for gene therapy in diseases associated with alpha 1-antitrypsin deficiency.

Acute-Phase Reaction↗
PubMed1994

Temporal differences in the induction of dihydropyridine receptor subunits and ryanodine receptors during skeletal muscle development.

The expression of the dihydropyridine (DHP) and ryanodine receptors in skeletal muscle was investigated during development of rat myotubes in culture as well as during embryonic and postnatal development in the rat. Through the use of specific gene probes, antibodies and radioligand binding ([3H]PN 200-110 (DHP) and [3H]ryanodine), we identified a significant difference between the time course of appearance of the DHP receptor and the ryanodine receptor during muscle development. Although the number of DHP receptors dramatically increased at early stages of development (up to day 7 in tissue culture and day 20 postnatal), increase in the ryanodine receptor density occurred comparatively later at day 10 in culture and day 30 postnatal. This process was associated with parallel changes in the expression of the mRNA encoding the alpha 1, alpha 2, and beta subunits of the DHP receptor and the skeletal muscle ryanodine receptor. The genes encoding the DHP receptor subunits were activated in a temporally distinct transcript appeared and plateaued first, at the onset of myoblast fusion and day 16 embryonic. This was followed closely by an increase in expression of the mRNAs for alpha 1 and alpha 2 subunits which coincided with the sharp rise in the DHP receptor density. Ryanodine receptor gene expression was induced well after the DHP receptor gene expression had plateaued. The temporal appearance of the polypeptides comprising the DHP receptor subunits and the ryanodine receptor paralleled the induction of the genes encoding these receptors. These results imply that gene expression is a major mechanism that contributes to the regulation of DHP and ryanodine receptor numbers during muscle development. The temporal differences in the induction of the genes encoding the DHP receptor subunits and the ryanodine receptor suggests that these genes are under the control of distinct endogenous factors. These differences in expression of the DHP receptor and the ryanodine receptor may contribute to the different mechanisms of excitation-contraction coupling in immature versus adult skeletal muscle.

Animals↗
PubMed1994

Arabidopsis floral homeotic gene BELL (BEL1) controls ovule development through negative regulation of AGAMOUS gene (AG).

Ovules are the developmental precursors of seeds. In angiosperms the ovules are enclosed within the central floral organs, the carpels. We have identified a homeotic mutation in Arabidopsis, "bell" (bel1), which causes transformation of ovule integuments into carpels. In situ hybridization analysis shows that this mutation leads to increased expression of the carpel-determining homeotic gene AGAMOUS (AG) in the mutant ovules. Introduction of a constitutively expressed AG transgene into wild-type plants causes the ovules to resemble those of bel1 mutants. We propose that the BEL1 gene product directs normal integument development, in part by suppressing AG expression in this structure. Our results allow expansion of the current model of floral organ identity to include regulation of ovule integument identity.

Arabidopsis↗
PubMed1994

Expression of the gene encoding alpha 1-acid glycoprotein in rabbit liver under acute-phase conditions involves induction and activation of beta and delta CCAAT-enhancer-binding proteins.

Transcription of the gene encoding alpha 1-acid glycoprotein is highly induced during acute inflammation which has been previously shown to be mediated by some inducible members of the CCAAT-enhancer-binding (C/EBP) transcription-factor family. In this study, we demonstrate that the involved inducible C/EBP isoforms are C/EBP-beta and C/EBP-delta, and together they control the high-level induction of the alpha 1-acid glycoprotein gene in response to inflammatory signals. We observed that dephosphorylation severely inhibits the DNA-binding ability of C/EBP-delta and its transactivating potential increases in the presence of cellular phosphatase inhibitors, such as okadaic acid and sodium orthovanadate. These results suggest that C/EBP-delta is regulated by phosphorylation. Transient transfections using expression vectors of C/EBP-alpha, C/EBP-beta and C/EBP-delta have shown that while individually all three isoforms can transactivate the alpha 1-acid glycoprotein-chloramphenicol-acetyltransferase gene transcription, co-expression of C/EBP-alpha and C/EBP-beta isoforms results in lower levels of reporter gene expression than the levels predicted from their additive transactivation level. In vitro DNA-binding studies have shown that C/EBP-alpha and C/EBP-beta isoforms both interact and form complexes with the alpha 1-acid glycoprotein gene C/EBP-binding element under normal noninduced conditions during which alpha 1-acid glycoprotein is expressed at a very low level. Higher than additive levels of reporter gene expression are observed when combinations of C/EBP-delta and C/EBP-beta or C/EBP-delta and C/EBP-alpha are used. Together, these data demonstrate that C/EBP-beta and C/EBP-delta are the major proteins responsible for the acute-phase induction of alpha 1-acid-glycoprotein gene expression and they require phosphorylation for transactivation potential.

Acute-Phase Reaction↗
PubMed1994

Effect of carbachol in the absence and presence of phenylephrine on Rb+ efflux and tension in rabbit left atria.

The muscarinic agonist carbachol produced a concentration-dependent increase in 86Rb+ efflux and decrease in tension in isolated, electrically stimulated rabbit left atria. However, the lowest concentration of carbachol tested produced only a very small increase in 86Rb+ efflux, while it caused a relatively greater decrease in tension. 4-Aminopyridine and pertussis toxin attenuated the carbachol-stimulated 86Rb+ efflux and negative inotropic effect. However, 4-aminopyridine had a greater inhibitory effect on carbachol-stimulated 86Rb+ efflux than on carbachol-induced decreases in tension. Pre-treatment of rabbits with pertussis toxin completely abolished the increase in 86Rb+ efflux and decrease in tension produced by carbachol in the presence of the alpha-adrenoceptor agonist phenylephrine. 4-Aminopyridine attenuated the negative inotropic response to carbachol in the presence of phenylephrine, but had less effect on the carbachol-induced increase in 86Rb+ efflux under these conditions. These results suggest that carbachol-induced increases in K+ efflux may contribute at least in part to the negative inotropic responses to carbachol in the presence and absence of phenylephrine. However, this may not be sufficient to explain the direct negative inotropic response of left atria to carbachol.

4-Aminopyridine↗
PubMed1994

Down-modulation of interleukin-6 gene expression by 17 beta-estradiol in the absence of high affinity DNA binding by the estrogen receptor.

The mechanism of repression of the interleukin-6 (IL-6) promoter by 17 beta-estradiol (E2) was investigated in cells transfected with wild-type (wt) or mutant estrogen receptor (ER) expression vectors. In transient transfection experiments, IL-1-induced activation of the IL-6 promoter was efficiently inhibited by wt ER. However, estrogen receptors carrying mutations within or over-lapping with the DNA binding domain did not repress IL-6 promoter activity. A mutant receptor lacking the N-terminal transactivator function-1 but retaining the C-terminal transactivator function-2 also repressed activation of the IL-6 promoter. Our recent experiments indicate the requirement for both the nuclear factor (NF)-IL6 and the NF-kappa B sites in the IL-6 promoter for activation by IL-1. We now show that activation of the IL-6 promoter, elicited by a combination of NF-IL6 and the p65 subunit of NF-kappa B, can be inhibited by the wt receptor but not by a receptor containing a mutation in its DNA binding domain. Although a deletion within the DNA binding domain of ER abolished the repressor function of the receptor, a chimeric receptor ER-GR CAS1, in which the DNA binding domain of ER was swapped with the complementary region from the glucocorticoid receptor, retained the inhibitory effects on the IL-6 promoter. This was in contrast to the absolute dependence of ER on its own DNA binding domain for activation of typical estrogen response element-containing promoters, as reported previously by other investigators. Furthermore, the repression of the IL-6 promoter by a combination of ER and E2, unlike activation of estrogen response elements by the same combination, did not appear to be mediated via high affinity binding of the receptor to the promoter. In functional experiments, the transactivator function of ER was totally inhibited by overexpression of p65 and to a lesser extent by that of NF-IL6. These results indicate that ER may repress gene expression in the absence of high affinity DNA binding.

Base Sequence↗
PubMed1994

Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor.

Glucocorticoids, which are widely used as antiinflammatory agents, downregulate the expression of the interleukin 6 gene and of additional cytokine genes involved in inflammatory responses. Conversely, the transcription factor NF-kappa B, a member of the Rel family of transcription factors, has been implicated in the induction of multiple genes involved in the early processes of immune and inflammatory responses. This prompted us to investigate whether one of the mechanisms by which glucocorticoids exert their antiinflammatory activities is through inhibition of gene activation mediated by NF-kappa B. We report that, in intact cells, activation of the interleukin 6 promoter by a combination of the factor NF-IL6 and the p65 subunit of NF-kappa B is inhibited by dexamethasone (ligand)-activated glucocorticoid receptor. Conversely, activation of the mouse mammary tumor virus promoter by a combination of dexamethasone and glucocorticoid receptor is inhibited by overexpression of p65. Furthermore, we provide evidence for physical association between glucocorticoid receptor and p65 in protein crosslinking and coimmunoprecipitation experiments, using either in vitro translated proteins or those present in cell extracts. These studies suggest that direct interactions between NF-kappa B and glucocorticoid receptor may partly account for the antiinflammatory properties of glucocorticoids in vivo.

Base Sequence↗
PubMed1994

A differential dopamine receptor involvement during stress ulcer formation in rats.

The involvement of dopaminergic (DA) receptors and their possible interactions were evaluated during stress ulcer formation in rats. The DA1 antagonist SCH 23390 (0.025, 0.05, or 0.1 mg/kg) produced only marginal aggravations in gastric stress pathology when compared to vehicle controls. The DA2 antagonist sulpiride (10 or 50 mg/kg) had dose-related effects. The lower dose aggravated whereas the higher dose attenuated stress ulcerogenesis. The DA2 agonist bromocriptine (2.5 or 5.0 mg/kg), however, attenuated gastric stress ulcers. Pretreatment of rats with the DA depletor alpha-methyl-para-tyrosine or the DA1-antagonist SCH23390 clearly neutralized the stress ulcer-attenuating effects of bromocriptine. These results reaffirm a gastric cytoprotective role for DA and further suggest that DA1-DA2 receptor interactions are crucial during DAergic regulation of gastric mucosal integrity during stress.

Animals↗
PubMed1994

Role of dopaminergic mechanisms in the regulation of stress responses in experimental animals.

The effects of some dopaminergic agents were evaluated on stress responses in normal and immunized experimental animals. Restraint stress (RS) consistently induced gastric mucosal lesions and elevated plasma corticosterone in rats. Pretreatment with alpha-methyltyrosine (alpha-MT), haloperidol, or sulpiride aggravated both responses, whereas bromocriptine attenuated them. In rats immunized with sheep red blood cells (SRBCs), RS prevented the booster-induced rise in anti-SRBC antibody titre. This response was further suppressed by alpha-MT, haloperidol, or sulpiride pretreatment, whereas bromocriptine potentiated the humoral immune response. In mice immunized with SRBCs, antigen challenge-induced increase in footpad thickness was inhibited by RS. Similar inhibitions in this response were also seen after alpha-MT or haloperidol treatment. The results are discussed in light of complex dopaminergic mechanisms in the regulation of visceral, endocrinological, and immune responses during stress.

Animals↗
PubMed1994

Study on the activities of testes and accessory sex glands after losulazine treatment in rats.

Losulazine hydrochloride, an antihypertensive agent, was administered intraperitoneally to adult male Wistar rats in doses of 1, 2 and 5 mg/kg/day for 1 seminiferous epithelium cycle to determine its effects on testicular steroidogenesis, spermatogenesis and accessory sex gland function. Administration of low doses of losulazine (1 and 2 mg/kg) resulted in a significant elevation of the steriodogenic key enzymes activity along with significant depletion of cholesterol content in testicular tissue. In addition, a significant rise in acid phosphatase activity in testes and prostate, and fructose content in accessory sex glands was also observed after low doses of losulazine. However, treatment with a higher dose of losulazine (5 mg/kg) significantly reduced the activities of testicular steroidogenic enzymes and acid phosphatase, and the content of fructose in accessory sex glands. Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle and epididymal sperm count in all losulazine-treated rats revealed a persistant prominent detrimental change in spermatogenesis. The results of our present experiment demonstrate an adverse action of losulazine treatment on functional activities of testes and accessory sex glands in adult rats.

17-Hydroxysteroid Dehydrogenases↗
PubMed1994

sin 1, a mutation affecting female fertility in Arabidopsis, interacts with mod 1, its recessive modifier.

In Arabidopsis thaliana, a mutation in the SIN 1 gene causes aberrant ovule development and female-specific sterility. The effect of the sin 1 mutation is polymorphic and pleiotropic in different genetic backgrounds. The polymorphism concerns morphology of the mutant ovules. The pleiotropism involves internodal distance and inflorescence initiation time. The particular ovule phenotype and the length of internodes are dependent on an interaction of sin 1 with a second recessive gene, which we term mod 1. The recessive mod 1 allele in a homozygous sin 1 mutant plant reduces internode length and ovule integument size. The mutation sin 1, but not mod 1, has a demonstrable effect on ovule morphology when acting independently. In our crosses mod 1 was inseparably linked to the well known mutation erecta that is known to cause a reduction in internode and pedicle lengths.

Arabidopsis↗
PubMed1994

Serum amyloid A gene expression under acute-phase conditions involves participation of inducible C/EBP-beta and C/EBP-delta and their activation by phosphorylation.

Serum amyloid A (SAA) is a plasma protein whose synthesis is markedly increased in the liver during the inflammatory process. Previous analysis of SAA promoter function implicated the involvement of the CCAAT/enhancer-binding protein (C/EBP) in controlling this process. In this study, using antibodies against three C/EBP isoforms in DNA-binding and Western blot (immunoblot) assays, we found that in response to inflammatory signals, both C/EBP-delta and C/EBP-beta are induced and that their interactions with the SAA promoter element are necessary for the increased SAA gene expression. Cotransfections of liver cells with an SAA promoter-linked reporter chloramphenicol acetyltransferase gene and murine sarcoma virus-expressed C/EBP-delta or C/EBP-beta confirm such phenomena. The increased transactivating ability in the presence of the cellular phosphatase inhibitors okadaic acid and sodium orthovanadate, coupled with the observation that dephosphorylation severely inhibits the DNA-binding ability in vitro, implicates a role of phosphorylation in the regulation of the activities of the C/EBP-delta isoform. Consistent with these findings, we have detected higher levels of DNA-binding activity of C/EBP-delta prepared from cells treated with phosphatase inhibitors. We also present evidence that C/EBP-delta is a phosphoprotein. These results suggest that C/EBP-delta is regulated by phosphorylation and, in conjunction with C/EBP-beta, is one of the major proteins responsible for the increased transcription of the SAA gene in response to inflammatory stimuli.

Animals↗
PubMed1993

The amygdaloid complex, corticotropin releasing factor and stress-induced gastric ulcerogenesis in rats.

The amygdaloid complex and corticotropin releasing factor (CRF) are both important in stress reactions and we thus evaluated the effects of intra-amygdalar CRF on stress ulceration in rats. Bilateral micro-applications of CRF (0.05, 0.5 or 5.0 micrograms) into the central amygdala (CEA) attenuated cold restraint-induced gastric mucosal lesions in a dose-related manner. Similar gastric cytoprotective effects were seen with intra-CEA noradrenaline (NA; 3.0 micrograms), whereas the NA neurotoxin, DSP-4 (25 micrograms), or the beta-adrenoceptor antagonist, propranolol (1 microgram), aggravated stress ulcer pathology. Intra-CEA pretreatment with DSP-4 or propranolol clearly reversed the ulceroprotective effects of CRF during stress. These results indicate that the CEA is a neural substrate for CRF effects, and CRF-NA interactions in this limbic area are crucial for the regulation of stress ulcerogenesis.

Amygdala↗