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Biomedical subjects

A Ray

Publications and source records attributed to A Ray.

At least 91 records · Page 5Linked to original sources
PubMed1998

Immunohistochemical expression of c-erbB-2 oncoprotein and EGF-R in pre- and postmenopausal breast cancer.

Tissues from 40 cases each of premenopausal and postmenopausal breast cancer were studied immunohistochemically for epidermal growth factor receptor (EGF-R) and c-erbB-2 oncoprotein. In the premenopausal group, immunopositivity for c-erbB-2 was 15% and for EGF-R 22.5%, whereas in the postmenopausal group, 45% of cases were positive for c-erbB-2 and 42.5% for EGF-R. The difference in immunoexpression of c-erbB-2 between the two groups was significant. A significant correlation was observed between the concomitant expression of c-erbB-2 as well as EGF-R and lymph node involvement. Furthermore, an association was found between c-erbB-2 positivity and histological grading of the tumour. It is interesting that the pattern of the investigated parameters indicates the difference in the pathological events of pre- and postmenopausal breast cancer.

Adult↗
PubMed1998

Isolation and functional characterization of cDNA of serum amyloid A-activating factor that binds to the serum amyloid A promoter.

Serum amyloid A (SAA), a plasma protein inducible in response to many inflammatory conditions, is associated with the pathogenesis of several diseases including reactive amyloidosis, rheumatoid arthritis, and atherosclerosis. We have previously reported an element of the SAA promoter, designated SAA-activating sequence (SAS), that is involved in the inflammation-induced SAA expression, and a nuclear factor, SAS-binding factor (SAF), that interacts with the SAS element has been identified previously (A. Ray and B. K. Ray, Mol. Cell. Biol. 16:1584-1594, 1996). To evaluate how SAF is involved in SAA promoter activation, we have investigated structural features and functional characteristics of this transcription factor. Our studies indicate that SAF belongs to a family of transcription factors characterized by the presence of multiple zinc finger motifs of the Cys2-His2 type at the carboxyl end. Of the three cloned SAF cDNAs (SAF-1, SAF-5, and SAF-8), SAF-1 isoform showed a high degree of homology to MAZ/ZF87/Pur-1 protein while SAF-5 and SAF-8 isoforms are unique and are related to SAF-1/MAZ/ZF87/Pur-1 at the zinc finger domains but different elsewhere. Although structurally distinct, all members are capable of activating SAS element-mediated expression and display virtually identical sequence specificities. However, varying levels of expression of members of this gene family were observed in different tissues. Functional activity of SAF is regulated by a posttranslational event as SAF DNA-binding and transactivation abilities are increased by a protein phosphatase inhibitor, okadaic acid, and inhibited by a protein kinase inhibitor, H7. Consistent with this observation, increased DNA binding of the cloned SAF and its hyperphosphorylation, in response to okadaic acid treatment of the transfected cells, were observed. Taken together, our results suggest that, in addition to tissue-specific expression, SAFs, a family of zinc finger transcription factors, undergo a modification by a posttranslational event that confers their SAA promoter-binding activity and transactivation potential.

Amino Acid Sequence↗
PubMed1998

The C terminus of the major yeast telomere binding protein Rap1p enhances telomere formation.

The telomeres of most organisms consist of short repeated sequences that can be elongated by telomerase, a reverse transcriptase complex that contains its own RNA template for the synthesis of telomere repeats. In Saccharomyces cerevisiae, the RAP1 gene encodes the major telomere binding protein Rap1p. Here we use a quantitative telomere formation assay to demonstrate that Rap1p C termini can enhance telomere formation more than 30-fold when they are located at internal sites. This stimulation is distinct from protection from degradation. Enhancement of formation required the gene for telomerase RNA but not Sir1p, Sir2p, Sir3p, Sir4p, Tel1p, or the Rif1p binding site in the Raplp C terminus. Our data suggest that Rap1p C termini enhance telomere formation by attracting or increasing the activity of telomerase near telomeres. Earlier work suggests that Rap1p molecules at the chromosome terminus inhibit the elongation of long telomeres by blocking the access of telomerase. Our results suggest a model where a balance between internal Rap1p increasing telomerase activity and Rap1p at the termini of long telomeres controlling telomerase access maintains telomeres at a constant length.

Binding Sites↗
PubMed1998

Organochlorine pesticide-induced oxidative stress and immune suppression in rats.

Effects of subchronic DDT and lindane exposure were evaluated on lipid peroxidation, antioxidant mechanisms and humoral immune response in rats. Oral administration of DDT, (100 and 200 ppm) and lindane (40 and 80 ppm) dose dependently increased thiobarbituric acid reactive substance (TBARS) levels in serum after 8 wk of treatment. Superoxide dismutase (SOD) activity in red blood cells (RBC) was also dose dependently increased by these compounds. In addition, such DDT or lindane exposure markedly suppressed the humoral immune response as assessed by anti-sheep RBC antibody titres. Simultaneous treatment with ascorbic acid (100 mg/kg) markedly attenuated the effects of DDT and lindane on (a) lipid peroxidation, (b) SOD activity and (c) humoral immune suppression. These results indicate the possible involvement of free radicals in organochlorine-induced immunotoxicity.

Animals↗
PubMed1998

A comparative evaluation of immunotoxicity of malathion after subchronic exposure in experimental animals.

The effects of sub-chronic doses of malathion exposure on humoral and cell-mediated immune (CMI) responses were studied in male albino mice, rats and rabbits using sheep red blood cells (SRBC), tetanus toxoid and ovalbumin as antigens. The humoral immune response was assessed by estimating serum immunoglobulin (IgM and IgG) concentrations, antibody titre against antigens and splenic-plaque forming cells (PFC). The CMI response was studied by using the leucocyte migration inhibition (LMI) and macrophage migration inhibition (MMI) tests. In general there were (a) attenuation in antigen induced antibody response, (b) suppression of PFC, and (c) marked inhibition of LMI and MMI factors. Sub-chronic malathion exposure induced differential degrees of humoral and CMI suppression in these experimental animals. However, both cellular and humoral immune responses were decreased in a dose-time dependent pattern and a consistent trend was observed. The threshold level of the malathion for inducing immune suppression depends on the animal species, type of antigen used, and the method of immunological assay. In view of the widespread use of malathion a comparative assessment of immune responses using different experimental animals and antigens is an important aspect of its safety evaluation.

Animals↗
PubMed1997

The effects of mutation of the anr gene on the aerobic respiratory chain of Pseudomonas aeruginosa.

The anr gene of Pseudomonas aeruginosa encodes a transcriptional regulator of anaerobic gene expression, homologous to the Fnr protein of Escherichia coli. We report here that Anr has a role in regulating the activity of the aerobic respiratory chain of P. aeruginosa. Strains with internal deletions in their anr gene had lowered levels of membrane bound cytochromes whilst the activity of the cytochrome c oxidase, cytochrome co (likely to be a cytochrome cbb3-type oxidase), and the cyanide-insensitive respiratory pathway was markedly higher than in the wild-type strains. These data, and the finding that provision of multiple copies of the anr gene led to severe repression of these respiratory activities, suggest that Anr is a repressor of aerobic respiratory pathways and possibly the terminal oxidases themselves. In contrast, Anr activated cytochrome c peroxidase, a respiratory chain linked enzyme induced under low oxygen conditions.

Aerobiosis↗
PubMed1997

Induction of serum amyloid A (SAA) gene by SAA-activating sequence-binding factor (SAF) in monocyte/macrophage cells. Evidence for a functional synergy between SAF and Sp1.

Serum amyloid A (SAA) is a plasma protein that is associated with many inflammatory diseases including amyloidosis, arthritis, and atherosclerosis. SAA level is significantly increased during inflammatory condition, and such abnormal expression of this protein is linked to the pathogenesis of the above-mentioned diseases. A promoter element, designated as SAA-activating sequence (SAS), located between -280 and -226 has been implicated in the induction mechanism and a nuclear factor, SAS-binding factor (SAF), has been shown to bind to this region. In this report, using a cloned SAF gene in transient transfection assay, we provide evidence that SAF potentiates SAA gene expression through SAS element. Furthermore, we show that during lipopolysaccharide-mediated induction of SAF, heteromeric complex with transcription factor Sp1 is formed. Transfection assays using both transcription factor genes have demonstrated that SAF-Sp1 heteromer is a highly potent transactivator of SAA expression.

Amyloid↗
PubMed1997

Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene.

Interleukin-5 (IL-5), which is produced by CD4(+) T helper 2 (Th2) cells, but not by Th1 cells, plays a key role in the development of eosinophilia in asthma. Despite increasing evidence that the outcome of many diseases is determined by the ratio of the two subsets of CD4(+) T helper cells, Th1 and Th2, the molecular basis for Th1- and Th2-specific gene expression remains to be elucidated. We previously established a critical role for the transcription factor GATA-3 in IL-5 promoter activation in EL-4 cells, which express both Th1- and Th2-type cytokines. Our studies reported here demonstrate that GATA-3 is critical for expression of the IL-5 gene in bona fide Th2 cells. Whereas mutations in the GATA-3 site abolished antigen- or cAMP-stimulated IL-5 promoter activation in Th2 cells, ectopic expression of GATA-3 in Th1 cells or in a non-lymphoid, non-IL-5-producing cell line activated the IL-5 promoter. During the differentiation of naive CD4(+) T cells isolated from T cell receptor transgenic mice, GATA-3 gene expression was up-regulated in developing Th2 cells, but was down-regulated in Th1 cells, and antigen- or cAMP-activated Th2 cells (but not Th1 cells) expressed the GATA-3 protein. Thus, GATA-3 may play an important role in the balance between Th1 and Th2 subsets in immune responses. Inhibition of GATA-3 activity has therapeutic potential in the treatment of asthma and other hypereosinophilic diseases.

Animals↗
PubMed1997

Selective up-regulation of cytokine-induced RANTES gene expression in lung epithelial cells by overexpression of IkappaBR.

We previously reported the cloning of a cDNA for IkappaBR (for IkappaB-related) from human lung alveolar epithelial cells. IkappaBR is related to the IkappaB proteins that function as regulators of the NF-kappaB family of transcription factors. Here, we investigated the consequence of IkappaBR overexpression on the expression of NF-kappaB-regulated chemokine genes in lung alveolar epithelial cells. Chemokines play an important role in many inflammatory diseases such as asthma and AIDS. Overexpression of IkappaBR in the lung cells resulted in a rapid 50-100-fold greater production of the RANTES (regulated upon activation, normal T expressed and presumably secreted) protein upon cytokine-induction compared with control cells. IkappaBR overexpression, however, did not enhance interleukin-8 or MIP-1alpha gene expression, despite the fact that the expression of all three chemokine genes are regulated by NF-kappaB. The up-regulation of RANTES gene expression resulting from overexpression of IkappaBR correlated with increased amounts of a unique RANTES-kappaB binding activity and decreased binding of p50 homodimers. Previous studies have shown that p50 homodimers function as repressors of certain kappaB sites. Our studies suggest that IkappaBR can aid activation of select NF-kappaB-regulated genes by sequestering p50 homodimers.

Base Sequence↗
PubMed1997

Repression of interleukin-6 gene expression by 17 beta-estradiol: inhibition of the DNA-binding activity of the transcription factors NF-IL6 and NF-kappa B by the estrogen receptor.

The cytokine interleukin-6 (IL-6), a key mediator of immune and acute phase responses of the liver, has also been implicated in uterine functions. Estrogens are potent repressors of IL-6 production by uterine stromal cells. In the endometrial adenocarcinoma cell line Ishikawa, phorbol ester-induced activation of the IL-6 promoter was inhibited to basal levels by 17 beta-estradiol (E2) in a wild-type receptor-dependent fashion. Although tamoxifen has been shown to have estrogenic effects on the endometrium, it did not inhibit induction of the IL-6 promoter. We previously showed that inhibition of IL-6 gene expression by E2 does not involve high-affinity binding of the estrogen receptor (ER) to IL-6 DNA. We now report that the ER can directly interact with the transcription factors NF-IL6 and NF-kappa B and can inhibit their ability to bind DNA which might be the molecular basis for repression of IL-6 gene expression by estrogens.

Adenocarcinoma↗
PubMed1997

Involvement of an SAF-like transcription factor in the activation of serum amyloid A gene in monocyte/macrophage cells by lipopolysaccharide.

Serum amyloid A (SAA) has been linked to atherosclerosis because of its ability to remodel high-density lipoprotein by the depletion of apolipoprotein A1, its ability to bind cholesterol, and its presence in the atherosclerotic plaques of coronary and carotid arteries. In the present study, we investigated the induction mechanism of SAA gene in THP-1 monocyte/macrophage cells which play a critical role in the development of atherosclerotic fatty streak and plaque formation. We and others have shown that SAA gene is induced in monocyte/macrophage cells by lipopolysaccharide (LPS). By promoter function analysis, we show that the SAA promoter sequence between -280 and -226 can confer LPS responsiveness. Gel electrophoretic mobility shift assay detected an induced DNA-binding activity in these cells in response to LPS. Characterization of the DNA-binding protein by UV cross-linking, Southwestern blot, and antibody ablation/supershift assays revealed that it is similar to a recently reported nuclear factor designated SAF. These results demonstrated that LPS-mediated SAA gene induction in monocyte/macrophage cells is primarily due to the induction of SAF activity.

Amyloid↗
PubMed1997

Influence of stress on DDT-induced humoral immune responsiveness in mice.

The effects of different durations/intensities of stress on DDT-induced modulation of humoral immune response were evaluated in mice. DDT (20, 50, or 100 ppm x 4 weeks) per se did not influence the primary antibody response to sheep red blood cells (SRBC). However, when DDT-pretreated mice were exposed to single and multiple sessions of restraint stress (RS), the anti-SRBC antibody titers were lower than the control values, the most prominent effects being seen after 50 and 100 ppm DDT exposure in combination with a single intense stressor (24 hr RS) or repeated stress (1 hr RS x 5). In the splenic plaque forming cells (PFC) assay, similar potentiations of DDT-induced immune suppression were seen at 50 and 100 ppm exposure levels in combination with 24 hr RS or 1 hr RS (x5) procedures. In addition, the 20 ppm DDT exposure effect was also potentiated in combination with the multiple RS model. Further, other forms of stress viz. 3 hr cold restraint stress (CRS) or 6 hr RS, which per se did not influence the antibody titer or PFC response, suppressed humoral immune responses, when combined with 100 ppm DDT exposure. These results are discussed in light of the possible interactions between physical/emotional and environmental/xenobiotic stressors in the regulation of humoral immune response.

Animals↗
PubMed1997

Effects of in-vivo generation of oxygen free radicals on immune responsiveness in rabbits.

Oxygen free radicals (OFRs) generated during biological processes are reportedly involved in the pathogenesis of several disease states and various reports have indicated that oxidative stress may alter immune competence. Hence, effects of in-vivo generation of OFRs by using xanthine/xanthine oxidase (X/XO) system on immune responsiveness were evaluated in rabbits. Intravenous injections of xanthine (0.14 mg/kg) along with xanthine oxidase (2 U/Kg) following primary and secondary immunizations of animals with sheep red blood cells (SRBC) significantly attenuated the primary and secondary antibody responses respectively. In tests for cell-mediated immunity, tuberculin sensitivity and leucocyte migration inhibition were also decreased significantly in sensitized animals following X/XO treatment. The observed changes in both humoral and cell-mediated immune responses following such in-vivo generation of OFRs indicate a possible nexus between OFR generation and immune suppression.

Animals↗
PubMed1997

Anabolic androgenic steroids increase beta-endorphin levels in the ventral tegmental area in the male rat brain.

The levels of beta-endorphin and Met-enkephalin-Arg-Phe (MEAP) immunoreactivity in various brain regions (including amygdala, cortex, hippocampus, hypothalmus, nucleus accumbens, pituitary and ventral tegmental area) were studied in male rats subjected to daily intramuscular injections during 14 days of high doses (5 and 15 mg/kg) of the anabolic androgenic steroid (AAS), nandrolone decanoate. At the nandrolone dose of 15 mg/kg a significant (about 20-fold) increase in beta-endorphin levels in the ventral tegmental area (VTA) was observed. The steroid did not significantly affect the concentration of the peptide at any dose in other brain areas examined. The levels of MEAP remained unaltered in all studied regions. A slight increase in serum concentrations of both peptides was also found but this elevation was not statistically significant. The observed increase in beta-endorphin in VTA was suggested to be involved in a mechanism by which the steroid may influence the reward system in the brain. An opioid mediated stimulation of the reward system following injection of AAS supports a previous hypothesis that AAS may induce psychological dependence.

Anabolic Agents↗
PubMed1997

Serum amyloid A gene expression level in liver in response to different inflammatory agents is dependent upon the nature of activated transcription factors.

Serum amyloid A (SAA) is highly induced during many inflammatory episodes. The induction mechanism in response to turpentine and lipopolysaccharide (LPS), two major inducers of this gene, was investigated. Here we present evidence that although both agents triggered expression, SAA mRNA synthesized in the turpentine-injected rabbit liver is many-fold higher compared to that found in LPS-injected rabbit liver. We demonstrate that differential level of activation of C/EBP and NF-kappaB that interact with the proximal promoter of SAA gene is responsible for the differential expression. A very high level of C/EBP induction with little or no activation of NF-kappaB factors was noted when turpentine was used as the inducer. LPS, on the other hand, activated NF-kappaB and C/EBP, which were detected only at the early phase of induction process. These results indicate that different pathways might be activated for the regulation of hepatic expression of SAA by different inflammatory agents. One of the pathways, triggered by LPS, requires participation of both NF-kappaB and C/EBP. A second pathway, triggered by turpentine, involves only C/EBP family of transcription factors.

Animals↗
PubMed1997

Pollen tube guidance by the female gametophyte.

In flowering plants, pollen grains germinate on the pistil and send pollen tubes down the transmitting tract toward ovules. Previous genetic studies suggested that the ovule is responsible for long-range pollen tube guidance during the last phase of a pollen tube's journey to the female gametes. It was not possible, however, to unambiguously identify the signaling cells within an ovule: the haploid female gametophyte or the diploid sporophytic cells. In an effort to distinguish genetically between these two possibilities, we have used a reciprocal chromosomal translocation to generate flowers wherein approximately half the ovules do not contain a functional female gametophyte but all ovules contain genotypically normal sporophytic cells. In these flowers, pollen tubes are guided to the normal but not to the abnormal female gametophytes. These results strongly suggest that the female gametophyte is responsible for pollen tube guidance, but leave open the possibility that the gametophyte may accomplish this indirectly through its influence on some sporophytic cells.

Arabidopsis↗
PubMed1997

Effects of stress on gamma glutamyl transpeptidase (GGT) activity in lymphoid system of rats: modulation by drugs.

Effects of stress and its modulation by adaptogens were evaluated on gamma glutamyl transpeptidase (GGT) activity in different tissues of the lymphoid system in rats. Restrain stress (RSx5) suppressed the GGT activity in different tissues of lymphoid system viz. the lymphocyte, the spleen, the thymus and the macrophage, and the maximum effect was seen in the spleen. Chlordiazepoxide, a prototype anti-stress agent, which did not alter GGT activity per se, reversed the effect of RS on this enzyme activity in tissues of lymphoid system studied. Azardirachta indica (Al, Neem), an indigenous adaptogen stimulated the GGT activity per se and nearly normalised RS induced suppression of GGT in lymphoid system. The observed suppression of GGT activity in lymphoid system by stress and its modulation by natural and synthetic adaptogens indicates that GGT could be a consistent cellular/biochemical marker of stress responsiveness and stress-induced immunomodulation.

Animals↗