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Biomedical subjects

S Ray

Publications and source records attributed to S Ray.

At least 145 records · Page 8Linked to original sources

Attenuation or absence of circadian and seasonal rhythms of acute myocardial infarction.

OBJECTIVES: To examine the circadian, seasonal, and weekly rhythms of acute myocardial infarction, and to identify subgroups in whom the rhythms are attenuated or absent to provide further information about the mechanisms of the rhythms and the processes responsible for triggering plaque events. DESIGN AND SETTING: Prospective, observational study in a general hospital. PATIENTS AND METHODS: 1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction were studied. Admission rates were calculated according to the hour of the day (circadian rhythm), day of the week (weekly rhythm), and month of year (seasonal rhythm). The data were analysed for variations within the whole group and within subgroups. RESULTS: A weekly rhythm of acute myocardial infarction could not be demonstrated but there was a trend towards higher admission rates at the beginning of the week. However, the time of onset of symptoms showed significant circadian variation for the group as a whole, peaking in the morning (P = 0.006), against an otherwise fairly constant background rate. Subgroup analysis showed complete absence of the circadian rhythm in patients who were diabetic, South Asian, or taking beta blockers or aspirin on admission. Significant seasonal variation in admission rates was also demonstrated for the group as a whole with a winter peak and a summer trough (P = 0.009). Again, no seasonal rhythm could be demonstrated in patients who were diabetic, South Asian, or taking beta blockers or aspirin on admission. CONCLUSIONS: The absence of circadian and seasonal rhythms of acute myocardial infarction in almost identical subgroups suggests that common mechanisms are involved in driving these rhythms. The autonomic nervous system is a likely candidate because the rhythms were absent in patients taking beta blockers as well as in patients in whom derangement of autonomic function commonly occurs.

Adrenergic beta-Antagonists↗

klingon, a novel member of the Drosophila immunoglobulin superfamily, is required for the development of the R7 photoreceptor neuron.

klingon is a member of the Immunoglobulin superfamily and is expressed in a restricted pattern of neurons during embryonic neurogenesis and in the R7 photoreceptor precursor throughout its development. Starting from the H214 enhancer trap line, we identified a transcription unit, klingon, that encodes a putative protein of 528 amino acids and contains three C2-type Immunoglobulin-like domains followed by one fibronectin type III repeat. When Klingon is expressed in S2 tissue culture cells, it is associated with the cell membrane by a glycosyl-phosphatidylinositol linkage and can mediate homophilic adhesion. Genetic analysis has revealed that klingon is an essential gene that participates in the development of the R7 neuron. Ectopic expression of klingon in all neurons in a sevenless background can alter the position of the R8 rhabdomere.

Amino Acid Sequence↗

Effect of herbal preparation on immune response of immunosuppressed mice.

The present study was undertaken to study the effect of a herbal formulation (Septilin) as immunomodulator, on immune response in mice. The study of this formulation in respect to humoral and cell mediated immune response has suggested that, oral administration of Septilin (500 mg/kg) alone or in combination with an immuno-suppressive drug (prednisolone 4 mg/kg), enhances both primary and secondary immune response, in mice immunized with sleep red blood cells (SRBC).

Adjuvants, Immunologic↗

Correlation of constitutive activation of raf-1 with morphological transformation and abrogation of tyrosine phosphorylation of distinct sets of proteins in human squamous carcinoma cells.

We and others have reported an association between raf-1 protein serine/threonine kinase activity and transformation of mammalian cells. Because constitutive tyrosine phosphorylation of specific polypeptides is, in general, indicative of the transformed state of cells, we investigated the effect of activation of raf-1 on phosphotyrosine-containing proteins in a human head and neck squamous cell carcinoma-derived cell line, PCI-06A. raf-1 expression and activity were modulated in PCI-06A cells by means of stable DNA transfection of either the entire coding domain of the human c-raf-1 cDNA (in the sense or antisense orientation) or a fragment of c-raf-1 cDNA coding for the kinase domain of raf-1. Our data showed that constitutive activation of raf-1 correlated with morphological transformation, whereas the inhibition of raf-1 expression and activity had no detectable effect on cell morphology as compared with the untransfected cells. Immunoprecipitation of whole-cell lysates with anti-phosphotyrosine antibody followed by anti-phosphotyrosine immunoblotting revealed four phosphotyrosine-containing proteins of approximately 129, 120, 110, and 63 kDa (I-IV, respectively) in the antisense c-raf-1 cDNA-transfected cells showing relatively diminished raf-1 activity but not in the transfectants expressing activated raf. We concluded that tyrosine phosphorylation of I-IV proteins is abrogated in PCI-06A squamous carcinoma cells transformed with constitutively active raf-1 protein kinase.

Carcinoma, Squamous Cell↗

HIV seroconversion among factory workers in Harare: who is getting newly infected?

OBJECTIVE: Zimbabwe, like other countries in sub-Saharan Africa, is experiencing a rapidly growing HIV/AIDS epidemic. It is crucial to determine risk events and socio-demographic characteristics associated with incident infections in order to tailor prevention messages accordingly. A cohort was established among factory workers with the objectives of estimating HIV incidence, seroprevalence, correlates of infection and subsequently evaluating the impact of prevention interventions. SETTING: 40 factories in Harare, Zimbabwe. DESIGN AND METHODS: HIV seroindicence [total new infections over person time (years) follow up] was estimated in a longitudinal cohort of male factory workers before and during a randomised peer education intervention. Correlates of seroconversion were identified using Cox regression analysis. RESULTS: Of 2,992 subjects enrolled there were 129 seroconversions during 1993 to 1996 follow up, yielding a 2.96 per 100 person year (PY) seroconversion incidence (95% CI = 2.47 to 3.52). Reporting a genital ulcer during follow up (Hazard ratio [HR] = 4.9, p = 0.001) having multiple sexual partners (HR = 1.9, p = 0.04), having a urethral discharge (HR = 2.1, p = 0.001), being single (HR = 2.3, p = 0.001), widowed or married but not residing with wife were independent factors significantly associated with risk of HIV seroconversion. CONCLUSIONS: Incidence of HIV identified in this economically productive sector is unacceptably high, and, disturbingly, is increasing in some age groups. Although the impact of the present intervention remains to be evaluated, the high incidence of HIV infection, points to the need for a more aggressive prevention effort in the general population.

Adult↗

Interaction of aldehydes with glyoxalase I and the status of several aldehyde metabolizing enzymes of Ehrlich ascites carcinoma cells.

The possible effect of several physiologically important aldehydes has been tested on partially purified glyoxalase I of Ehrlich ascites carcinoma (EAC) cells. The results indicate that D, and L-lactaldehyde are strong non-competitive inhibitors of glyoxalase I and the effect with the D-isomer is more pronounced, whereas both D,L-glyceraldehyde and acetaldehyde are moderately inhibitory and the nature of inhibition is strictly competitive. Moreover, D,L-glyceraldehyde strongly inhibits the utilization of methylglyoxal by intact EAC cells. A search for the presence of several aldehyde metabolizing enzymes in EAC cells indicates that non-specific aldehyde reductase, methylglyoxal reductase, aldehyde dehydrogenase and alcohol dehydrogenase are apparently absent in this rapidly growing, highly de-differentiated malignant cell.

Acetaldehyde↗

Maternal effects of the short integument mutation on embryo development in Arabidopsis.

Maternal gene products deposited in an animal egg determine the polarity of embryonic axes and regulate embryonic cell-cell communication important for morphogenesis. Here we report the first maternal-effect embryo-defective mutation discovered in a plant. Recessive mutations in the SHORT INTEGUMENT (SIN1) gene in Arabidopsis were previously shown to influence ovule development and flowering time. Here we show that a sin1 mutation has a pronounced maternal effect on zygotic embryo development. A homozygous sin1 mutant embryo is normal when nursed by a sin1/+ heterozygous maternal sporophyte. Strikingly, a sin1 or a sin1/+ embryo that is nursed by a sin1 homozygous maternal sporophyte develops morphogenetic defects in the apical-basal and radial axes. The defects resemble those seen in some zygotic-effect embryonic pattern formation mutants. These results imply that in maternal cells the SIN1 gene either codes for or controls the production of a diffusible morphogen necessary for proper zygotic embryogenesis.

Arabidopsis↗

Risk factors for HIV infection at enrollment in an urban male factory cohort in Harare, Zimbabwe.

Between March 1993 and March 1995, volunteers at 40 Harare factories were interviewed regarding sociodemographic characteristics and behavior; HIV serostatus was also determined. Among 2,691 men enrolled, HIV prevalence was 19.4%. Prevalence rose 2-fold with each year of age in young men (< 23 years). In a multivariate logistic model that included sociodemographic and behavioral variables, compared with those between 25 and 44 years, both younger men (OR = 0.51) and older men (OR = 0.49) were less likely to be HIV positive. In addition, marriage (OR = 2.01), history of sexually transmitted disease (STD) (genital ulcer, OR = 4.93, urethral discharge OR = 1.75), multiple partners (OR = 1.58), cash payment for sex (OR = 2.55) and condom use (OR = 1.35) were all independent risk factors for HIV infection. Home ownership conferred lower risk. Self-reported condom use was seen as a marker of correct personal risk assessment men who used condoms reported more risk behavior and had a higher prevalence of HIV, either because condom use was not consistent or because infection occurred prior to adoption of condoms. This study confirms established risk factors in a general population sample not selected for high risk of HIV infection. It suggests rapid acquisition of infection among young men and the importance of marriage (and separation of spouses) as correlates of HIV infection.

Adolescent↗

The effect of donor age on the processing of UV-damaged DNA by cultured human cells: reduced DNA repair capacity and increased DNA mutability.

Aging in humans carries an increased risk of skin cancer, a disorder linked to somatic mutations in sun damaged skin. DNA repair plays a major role in protection against sun damage. We found an age-related decline in post-UV DNA repair capacity (measured by the ability to repair a UV-treated plasmid (pCMVcat)) of-0.6% per year (p = 0.0001) in cultured primary skin fibroblasts from normal donors from the first to the tenth decade of life. There was a corresponding age-related increase in post-UV mutability (measured as mutations introduced into a transfected, UV-treated plasmid (pSP189)) of +0.6% per year (p = 0.001) in lymphoblastoid cell lines from normal donors of the same age range. This study indicates that aging in humans is associated with decreasing ability to process new UV-induced DNA damage and this age-related reduction in DNA repair capacity and increase in DNA mutability is reflected in cultured skin and blood cells.

Adolescent↗

Activation of Raf by ionizing radiation.

The critical pathways through which ionizing radiation induces malignant transformation and cell death are not well defined. Raf-1, a cytoplasmic serine-threonine protein kinase, mediates the transmission of mitogenic signals initiated at the cell membrane to the nucleus, resulting in the activation of transcription factors that regulate cell growth and proliferation. Moreover, Raf-1 overexpression and activation increases the survival response of mammalian cells to the toxic effects of ionizing radiation by an as-yet unknown mechanism (refs 3, 4 and V. Soldatenkov et al.; manuscript submitted). Somewhat analogous to mitogen-induced signalling, radiation stimulates protein-tyrosine kinase(s) and transcription factors. No direct biochemical link has been established, however, between radiation-stimulated protein tyrosine phosphorylation and downstream signals. Here we report a series of radiation-responsive events in which protein-tyrosine phosphorylation is followed by membrane recruitment, then tyrosine phosphorylation and activation of Raf-1 in vivo. Our results show that radiation-stimulated protein-tyrosine kinase(s) modify Raf-1, and implicate Raf-1 in the ionizing-radiation signal-transduction pathway.

Biological Transport↗

Quantification of salivary gland function in thyroid cancer patients treated with radioiodine.

PURPOSE: Damage to salivary gland function following external irradiation has been documented. However, the extent of damage following radioiodine (131I) therapy for thyroid cancer has not been adequately studied. We evaluated salivary dysfunction in Ca-thyroid patients treated with therapeutic doses of 131I. METHODS AND MATERIALS: A simple acquisition and analysis protocol using 99mTcO4- (pertechnatate) and a gamma camera computer system was planned. The uptake of 99mTcO4- by the salivary glands at 10 min and percent of excretion of 99mTcO4- from the glands in response to a sialogogue (lemon juice) was studied in 33 patients treated with 1.369-38.702 GBq of 131I (Mean = 10.16 GBq, standard deviation = 7.659 GBq) in addition to 14 athyreotic controls. RESULTS: Significant damage to the salivary gland in terms of abnormal percent uptake or excretion was noted in 72.73% of the patients. Forty-eight percent of the patients treated with 131I showed asymmetrical involvement of the salivary complexes as opposed to none of the controls. Reduction in uptake of 99mTc4- or response to sialogogue was dose dependent, being more marked with higher radioiodine doses. Parotid glands were more affected than submandibular glands following 131I therapy. CONCLUSIONS: 131I therapy produces a significant effect on salivary gland function that is dose related and becomes evident over a period of several months after treatment.

Humans↗

Reduction of methylglyoxal in Escherichia coli K12 by an aldehyde reductase and alcohol dehydrogenase.

Two enzymes, one NADPH-dependent and another NADH-dependent which catalyze the reduction of methylglyoxal to acetol have been isolated and substantially purified from crude extracts of Escherichia coli K12 cells. Substrate specificity and formation of acetol as the reaction product by both the enzymes, reversibility of NADH-dependent enzyme with alcohols as substrates and inhibitor study with NADPH-dependent enzyme indicate that NADPH-dependent and NADH-dependent enzymes are identical with an aldehyde reductase (EC 1.1.1.2) and alcohol dehydrogenase (EC 1.1.1.1) respectively. The K(m) for methylglyoxal have been determined to be 0.77 mM for NADPH-dependent and 3.8 mM for NADH-dependent enzyme. Stoichiometrically equimolar amount of acetol is formed from methylglyoxal by both NADPH- and NADH-dependent enzymes. In phosphate buffer, both the enzymes are active in the pH range of 5.8-6.6 with no sharp pH optimum. Molecular weight of both the enzymes were found to be 100,000 +/- 3,000 by gel filtration on a Sephacryl S-200 column. Both NADPH- and NADH-dependent enzymes are sensitive to sulfhydryl group reagents.

Alcohol Dehydrogenase↗

Affinity labeling of the 1 alpha,25-dihydroxyvitamin D3 receptor.

Genomic actions of the calciotropic hormone 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) involves a multistep process that is triggered by the highly specific binding of 1,25(OH)2D3 to 1 alpha, 25-dihydroxyvitamin D3 receptor, VDR. In order to study this key step in the cascade, we synthesized 1 alpha,25-dihydroxy[26(27)-3H]vitamin D3-3-deoxy-3 beta-bromoacetate (1,25(OH)2[3H]D3-BE) and 1 alpha,25-dihydroxyvitaminD3-3 beta-[1-14C]bromoacetate(1,25(OH)2D3-[14C]BE) binding-site directed analogs of 1,25(OH)2D3, and affinity-labeled baculovirus-expressed recombinant human VDR (with 1,25(OH)2[3H]D3-BE), and naturally occurring VDRs in cytosols from calf thymus homogenate and rat osteosarcoma (ROS 17/2.8) cells (with 1,25(OH)2D3-[14C]BE). In each case, specificity of labeling was demonstrated by the drastic reduction in labeling when the incubation was carried out in the presence of an excess of nonradioactive 1 alpha,25(OH)2D3. These results strongly suggested that 1,25(OH)2[3H]D3-BE and 1,25(OH)2D3-[14C]BE covalently modified the 1,25(OH)2D3-binding sites in baculovirus-expressed recombinant human VDR and naturally occurring calf thymus VDR and rat osteosarcoma VDR, respectively.

Affinity Labels↗

Effect of time lag on non-living resource in a simple food chain.

This paper deals with a system of one non-living resource detritus, detritivores and their predators where time delay has been considered in the detritus formation. Local stability criteria are derived in the absence of delays. Conditions are derived under which there can be no change of stability whatever the value of time lag and finally we obtain criteria under which the system admits a finite number of stability switchings as the time lag increases.

Ecology↗

Amarogentin, a naturally occurring secoiridoid glycoside and a newly recognized inhibitor of topoisomerase I from Leishmania donovani.

A MeOH extract of Swertia chirata found to inhibit the catalytic activity of topoisomerase I of Leishmania donovani was subjected to fractionation to yield three secoiridoid glycosides: amarogentin (1), amaroswerin (2), and sweroside (3). Amarogentin is a potent inhibitor of type I DNA topoisomerase from Leishmania and exerts its effect by interaction with the enzyme, preventing binary complex formation.

Animals↗