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Biomedical subjects

S Ray

Publications and source records attributed to S Ray.

At least 73 records · Page 4Linked to original sources

Merging the cognitive behavioral and psychopharmacological paradigms in comparative studies: controversies, issues, and some solutions.

In the past, many studies attempting to compare pharmacological and psychosocial treatments for mood and anxiety disorders have been conducted by partisans of either approach. More recently, rigorously conducted, unbiased comparative studies have begun to appear. Here we reviewed our own experience in designing and conducting a multicenter study comparing medication and cognitive behavioral therapy and their combination for the treatment of panic disorder.

Cognitive Behavioral Therapy↗

Electronic structure of Sr2FeMoO6

We have analyzed the unusual electronic structure of Sr2FeMoO6 combining ab initio and model Hamiltonian approaches. Our results indicate that there are strong enhancements of the intra-atomic exchange strength at the Mo site as well as the antiferromagnetic coupling strength between Fe and Mo sites. We discuss the possibility of a negative effective Coulomb correlation strength ( U(eff)) at the Mo site due to these renormalized interaction strengths.

Journal Article↗

Catalase activity of oxygenase domain of rat neuronal nitric oxide synthase. Evidence for product formation from L-arginine.

Nitric oxide synthases (NOSs) catalyze the formation of nitric oxide from L-arginine. We purified the heme containing, tetrahydrobiopterin-free, oxygenase domain of rat neuronal nitric oxide synthase (nNOSox) overexpressed in Escherichia coli. We found catalase activity in nNOSox. This is significant because H(2)O(2) may also be a product of nitric oxide synthases. We found H(2)O(2) assisted product formation from N-hydroxy-L-arginine and even from L-arginine both in the presence and in absence of tetrahydrobiopterin. We propose how heme moiety of the oxygenase domain alone is sufficient to carry out both steps of the NOS catalysis.

Animals↗

Review article: transcriptional events controlling the terminal differentiation of intestinal endocrine cells.

Secretin-producing enteroendocrine cells arise from a multipotential endocrine progenitor in the crypts of the small intestine. As these cells migrate up the crypt-villus axis, they produce secretin and stop dividing as they terminally differentiate and die. Transcription of the secretin gene is controlled by a complex enhancer binding to multiple transcription factors. The basic helix-loop-helix protein, BETA2, binds to an E box sequence and associates with the p300 coactivator to activate transcription of the secretin gene. Basic helix-loop-helix proteins appear to play a pivotal role in the control of cellular differentiation. BETA2 induces cell cycle arrest and apoptosis in addition to activating secretin gene expression. Thus BETA2 may function as a master regulatory gene to coordinate terminal differentiation of secretin cells.

Apoptosis↗

Expression of estrogen receptor coactivators in the rat uterus.

Nuclear receptor coactivators associate in a ligand-dependent manner with estrogen receptors (ER) and other nuclear receptors, and they enhance ligand-dependent transcriptional activation. This study examined basal coactivator expression in rat uterus to investigate if expression of these genes is regulated by estradiol-17 beta or tamoxifen. Ovariectomized mature and immature rats were injected with estradiol-17 beta, tamoxifen, or vehicle (i.e., sesame oil) alone. Uteri were collected and analyzed for changes in coactivator mRNA expression using Northern blot and in situ hybridization analyses. Constitutive uterine mRNA expression of switch protein for antagonist (SPA), SRC-1, GRIP1, RAC3, RIP140, and p300 mRNAs was observed in control uteri, and treatment with ER ligands did not alter coactivator mRNA levels. The data suggest that expression of these coactivator genes is not sensitive to estradiol or tamoxifen in the rat uterus. No cell type-specific pattern of expression was apparent in uterine sections from mature and immature rats; however, silver grains were more abundant in luminal and glandular epithelial cells compared with the stroma and myometrium, indicating that coactivator mRNA levels vary among the uterine compartments. Thus, to our knowledge, we show for the first time that there is constitutive expression of several uterine nuclear receptor coactivators in a physiological setting that remains insensitive to estrogenic regulation. Furthermore, we speculate that higher constitutive levels of coactivator expression in glandular and luminal epithelial cells may be associated with increased hormonal responsiveness by these uterine compartments.

Adaptor Proteins, Signal Transducing↗

The industry manipulation attitudes of smokers and nonsmokers.

A cross-sectional random sample was obtained of Florida youth between the ages of 12-17. Data were collected through a telephone survey after obtaining parent and child consent. Industry manipulation attitudes of three groups (self-identified nonsmokers who did not use cigarettes in the past 30 days, self-identified nonsmokers who used cigarettes in the past 30 days, and self-identified smokers who used cigarettes in the past 30 days) were compared. Constraints resulting from the method of data collection resulted in a conservative estimate of the strength of the association between industry manipulation attitudes and smoking behavior.

Adolescent↗

Prognostic implications of ventricular fibrillation in acute myocardial infarction: new strategies required for further mortality reduction.

OBJECTIVE: To determine the changing risk of ventricular fibrillation, the prognostic implications, and the potential long term prognostic benefit of earlier hospital admission, after acute myocardial infarction. DESIGN: Prospective observational study. SETTING: A district general hospital in east London. PATIENTS: 1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction. MAIN OUTCOME MEASURES: Time of onset of pain and ventricular fibrillation, and long term survival of patients admitted with acute myocardial infarction. RESULTS: The rate of ventricular fibrillation in these hospital inpatients was high in the first hour from onset of pain (118 events/1000 persons/h; 95% confidence interval (CI) 50.7 to 231) and fell rapidly to an almost constant low level by six hours; 27.4% of patients with early ventricular fibrillation died in hospital, compared with 11.6% of those without (p < 0.0001), but mortality in patients who survived to hospital discharge was not altered by early ventricular fibrillation (five year survival: 75.0% (95% CI 60.0% to 84.8%) with ventricular fibrillation v 73.3% (95% CI 69.6% to 76.6%) without ventricular fibrillation). CONCLUSIONS: Patients successfully resuscitated from early ventricular fibrillation have the same prognosis as those without ventricular fibrillation after acute myocardial infarction. Faster access to facilities for resuscitation must be achieved if major improvements in the persistently high case fatality of patients after acute myocardial infarction are to be made.

Aged↗

A stable latent reservoir for HIV-1 in resting CD4(+) T lymphocytes in infected children.

HIV-1 persists in a latent state in resting CD4(+) T lymphocytes of infected adults despite prolonged highly active antiretroviral therapy (HAART). To determine whether a latent reservoir for HIV-1 exists in infected children, we performed a quantitative viral culture assay on highly purified resting CD4(+) T cells from 21 children with perinatally acquired infection. Replication-competent HIV-1 was recovered from all 18 children from whom sufficient cells were obtained. The frequency of latently infected resting CD4(+) T cells directly correlated with plasma virus levels, suggesting that in children with ongoing viral replication, most latently infected cells are in the labile preintegration state of latency. However, in each of 7 children who had suppression of viral replication to undetectable levels for 1-3 years on HAART, latent replication-competent HIV-1 persisted with little decay, owing to a stable reservoir of infected cells in the postintegration stage of latency. Drug-resistance mutations generated by previous nonsuppressive regimens persisted in this compartment despite more than 1 year of fully suppressive HAART, rendering untenable the idea of recycling drugs that were part of failed regimens. Thus the latent reservoir for HIV-1 in resting CD4(+) T cells will be a major obstacle to HIV-1 eradication in children.

Adolescent↗

Effect of retinoic acid on integrin receptors of B16F10 melanoma cells.

The intriguing problem of metastasis requires the spreading of metastatic cells through the basement membrane barrier. The interaction of the basement membrane with the metastatic cell is a cell surface activity involving the function of integrin receptors. Integrins are a group of alpha,beta heterodimeric proteins responsible for transducing intracellular signals on binding to the extracellular matrix proteins present in the basement membrane. To understand the role of integrin receptors in tumor metastasis, the cell surface receptor functions were modulated by All Trans Retinoic Acid (ATRA) treatment in B16F10 tumor cells. Our experimental results clearly indicate that All Trans Retinoic Acid (ATRA) inhibit metastatic potential of highly metastatic B16F10 melanoma cells by 1) downregulating the cell surface integrin receptors against ECM proteins specially laminin and vitronectin and 2) by inhibiting the 72 kd collagenase activity.

Antineoplastic Agents↗

Current understanding of pathogenesis of coronary artery disease and its future implications.

Coronary artery disease (CAD) is the most important cause of morbidity and mortality in a population. Percutaneous coronary intervention and coronary artery by-pass grafting have greatly changed the treatment of CAD, still many questions remain unanswered. Atherosclerosis is a normal consequence of ageing but some patients may experience it at an earlier age. As regarding pathogenesis of atherosclerosis, it is described often as a focal process which is diffuse in nature primarily involving the vessel intima. Salient features of 'lesion prone areas' in atherosclerosis include increased endothelial permeability to an intimal accumulation of plasma proteins, including albumin, fibronogen and LDL. The clinical expression of atherosclerotic disease activities is determined by pathologic events leading to coronary thrombosis. A vulnerable plaque has the characteristics of: Extracellular lipid pool occupies a large proportion of overall plaque volume, the fibrous cap which separates the lipid core from luminal blood is thinner within, and high macrophage density. Typically these plaques cause < 50% cross-sectional stenosis of the artery. The contribution of CAD is clearly of both genetic and environmental in origin. An increase in shedding of cell adhesion molecules may be a characteristic of atherosclerotic lesion. There is also suggestion that plasminogen activation inhibitor type I (PAI-1) has an important role in atherogenesis. Angiogenic growth factors and their endothelial receptors function as major regulators of blood vessel formation. Thereapeutic angiogenesis can be achieved by exogenously adding VEGF and/or other angiogenic growth factors.

Angiogenesis Inducing Agents↗

Breeding habitats and larval indices of Aedes aegypti and Ae. albopictus in the residential areas of Calcutta City.

Aedes aegypti and Ae. albopictus larvae were found breeding in almost all indoor and outdoor, temporary and/or permanent collections of water, either alone or in association with each other in residential areas of the city, the former throughout the year (June'97-May'98) and the latter during monsoons and post-monsoons only. Ae. aegypti showed preference for breeding in chowbachhas, indoors and Ae. albopictus for collections of water in flower pots and discarded containers and outdoors. The larval indices of both the species were highest during monsoons and post-monsoons.

Aedes↗

On the Nature of the Compact Star in 4U 1728-34.

The discovery of kilohertz quasi-periodic oscillations (kHz QPOs) in low-mass X-ray binaries (LMXBs) with the Rossi X-Ray Timing Explorer has stimulated extensive studies of these sources. Recently, Osherovich & Titarchuk suggested a new model for kHz QPOs and the related correlations between kHz QPOs and low-frequency features in LMXBs. Here we use their results to study the mass-radius relation for the atoll source 4U 1728-34. We find that, if this model is correct, 4U 1728-34 is possibly a strange star rather than a neutron star.

Journal Article↗

Crystal structure of the ectodomain of human transferrin receptor.

The transferrin receptor (TfR) undergoes multiple rounds of clathrin-mediated endocytosis and reemergence at the cell surface, importing iron-loaded transferrin (Tf) and recycling apotransferrin after discharge of iron in the endosome. The crystal structure of the dimeric ectodomain of the human TfR, determined here to 3.2 angstroms resolution, reveals a three-domain subunit. One domain closely resembles carboxy- and aminopeptidases, and features of membrane glutamate carboxypeptidase can be deduced from the TfR structure. A model is proposed for Tf binding to the receptor.

Amino Acid Sequence↗

Mechanistic studies to evaluate the enhanced antiproliferation of human keratinocytes by 1alpha,25-dihydroxyvitamin D(3)-3-bromoacetate, a covalent modifier of vitamin D receptor, compared to 1alpha,25-dihydroxyvitamin D(3).

1alpha,25-Dihydroxyvitamin D(3)-3-bromoacetate (1, 25(OH)(2)D(3)-3-BE), an affinity labeling analog of 1alpha, 25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), displayed stronger antiproliferative activities than 1,25(OH)(2)D(3) at 10(-10)-10(-6) M dose levels in cultured human keratinocytes (CHK). Additionally, preincubation of the cells with 10(-6) M 1,25(OH)(2)D(3), followed by treatment with various doses of 1,25(OH)(2)D(3)-3-BE, resulted in a significantly stronger antiproliferative activity by the mixture than individual reagents at every dose level. To search for a mechanism of this observation, we determined that [(14)C]1, 25(OH)(2)D(3)-3-BE covalently labeled human recombinant 1alpha, 25-dihydroxyvitamin D(3) receptor (reVDR) swiftly (<1 min) with a 1:1 stoichiometry and induced conformational changes (in VDR) that are different from 1,25(OH)(2)D(3), by limited tryptic digestion. Furthermore, a protein band, corresponding to reVDR, was specifically labeled by [(14)C]1,25(OH)(2)D(3)-3-BE in CHK extract, indicating that VDR is the main target of [(14)C]1, 25(OH)(2)D(3)-3-BE. The above-mentioned observations suggest that a rapid covalent labeling of VDR in CHK might alter the interaction between the holo-VDR and 1,25(OH)(2)D(3)-controlled genes. Furthermore, we observed that 1,25(OH)(2)D(3)-3-BE significantly decreased the binding of VDR to human osteocalcin vitamin D responsive element (hOCVDRE), as well as the dissociation rate of VDR from hOCVDRE, compared with 1,25(OH)(2)D(3) in COS-1 cells, transiently transfected with a VDR construct. Additionally, 1, 25(OH)(2)D(3)-3-BE was found to be more potent in inducing 1alpha, 25-dihydroxyvitamin D(3)-24-hydroxylase (24-OHase) promoter activity and mRNA expression in keratinocytes. The accumulation of 24-OHase message was also prolonged by the analog. Collectively these results indicated that rapid covalent labeling of VDR in keratinocytes (by 1, 25(OH)(2)D(3)-3-BE) might result in the conversion of apo-VDR to a holo-form, with a conformation that is different from that of the 1, 25(OH)(2)D(3)-VDR complex. This resulted in an enhanced stability of the 1,25(OH)(2)D(3)-3-BE/VDR-VDRE complex and contributed to the amplified antiproliferative effect of 1,25(OH)(2)D(3)-3-BE in keratinocytes.

3T3 Cells↗

Anticlastogenic effects of centchroman and its enantiomers in Swiss albino mice. I. Acute study and their comparison with tamoxifen.

Centchroman (CC), a non steroidal oral contraceptive and a candidate drug for breast cancer, has been reported to exhibit partial to complete remission of lesions in 40.5% of breast cancer patients. Recently, we have reported the antimutagenic effects of CC in multiple mutational assays. The potent antioestrogenic activity, negligible side effects, anti-breast cancer activity and antimutagenic effects of CC prompted us to evaluate the anticlastogenic effects of CC and two of its enantiomers. i.e. D-centchroman (DC) and L-centchroman (LC) in the acute in vivo studies in female Swiss albino mice as measured by chromosome aberrations (CA) and sister chromatid exchange (SCE) assays against two known positive mutagen compounds, i.e. dimethylbenz[a]anthracene (DMBA) and cyclophosphamide (CP). The results of anti-mutagenicity assays of CC and its enantiomers have been compared to the known breast cancer drug tamoxifen (TM). CC and LC reduced both DMBA and CP induced CA when compared with the group treated with only DMBA and CP. DC did not reduce the DMBA-induced CA when compared with the DMBA-treated group alone. It reduces only the CP induced CA. TM also reduces both DMBA and CP induced CA when compared with group received only DMBA or CP. SCE were carried out only for LC. A weak but significant decrease in SCE was observed in both LC plus DMBA- and LC plus CP-treated groups when compared with respective positive controls alone. Thus the overall results indicate that both CC and LC are more effective in reducing the genotoxic effects of DMBA and CP than DC.

9,10-Dimethyl-1,2-benzanthracene↗