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Biomedical subjects

S Abraham

Publications and source records attributed to S Abraham.

At least 109 records · Page 6Linked to original sources

Changes in Australian women's perception of the menopause and menopausal symptoms before and after the climacteric.

The symptoms and perceptions of menopause of 60 Australian women were studied, by questionnaire, when they were premenopausal and 10 years later when they were postmenopausal. Menopausal symptoms expected and experienced by the women were compared, fewer women experiencing hot flushes, headache, depression and nervousness and more experiencing insomnia, increase in appetite, abdominal fullness, numbness and muscular problems. The symptoms women thought were due to hormonal changes at menopause were compared. In 1993 more women cited osteoporosis, insomnia, loss of libido, obesity and loss of muscle tone as due to hormone change while fewer cited depression. The premenstrual symptoms and their severity experienced by a woman when she was premenopausal significantly predicts the type and severity of the menopausal symptoms experienced by the woman. The expected menopausal symptoms and their severity cited by a woman also significantly predicts the type of severity of the menopausal symptoms experienced. More premenstrual symptoms predict the menopausal symptoms than those menopausal symptoms the women expected. The expectation menopause will be 'a relief' or 'a nuisance' significantly predicted the overall menopause experience described by the women. Their negative attitudes about doctors' understanding and information available about menopause remained unchanged but they forget menstrual cycle problems over the 10 years. The results suggest a possible physiological basis for premenstrual and menopausal symptoms. Assistance for women with their premenstrual and menstrual cycle symptoms may improve their quality of life at menopause.

Adult↗

Serum ferritin, hematocrit and mean corpuscular volume in hemodialysis.

Prior to beginning to administration erythropoietin (EPO) in 1989, we examined the relationships of hematocrit (HCT), mean corpuscular volume (MCV), and serum ferritin (FER) in one group of hemodialysis patients (group A, n = 117) and replicated the findings in a second group (group B, n = 73). The groups had similar mean (+/- SD) HCT (A: 25.7 +/- 5.3%; B: 25.2 +/- 5.1%), MCV (A: 83.3 +/- 6.5 fl; B: 83.5 +/- 7.5 fl) and FER (A: 607 +/- 1446 micrograms/l; B: 374 +/- 601 micrograms/l). For group A, iron stores [log (FER)] correlated inversely with HCT (r = -0.44, p < 10(-4)) and directly with MCV (r = 0.32, p < 10(-3)). After dividing group A into octiles by the FER level, the lowest octile (mean FER 17.8 +/- 6.2 micrograms/l) had the highest mean HCT (29.5 +/- 6.4%) and lowest mean MCV (80.8 +/- 7.1 fl), while the highest octile (mean FER 3,312 +/- 3,005 micrograms/l) had the lowest mean HCT (21.9 +/- 2.8%) and the second-highest mean MCV (86.4 +/- 4.9 fl). The trends were similar in group B. We conclude that increased erythropoiesis appeared to cause or, at least, unmask iron deficiency in HD patients even prior to the advent of EPO therapy. Variations in the level of erythropoiesis among these patients (presumably due to variation in EPO levels, chronic inflammation) strongly influenced the determinants of iron stores (i.e., marrow utilization of iron, transfusion need); iron stores, in turn, influenced MCV.

Adult↗

Attitudes to body weight, weight gain and eating behavior in pregnancy.

The eating behavior and attitudes to body weight of 100 healthy women were studied 3 days after the birth of their first child. During pregnancy women 'watch their weight' and use a range of methods of weight control which include cigarette smoking and inducing vomiting. During pregnancy 41 women reported weight control problems and 20 women considered their weight and eating problems to be greater than at any previous time. Picking was the most common unwanted behavior. Binge eating was experienced by 44 women, nine of whom reported it to be a 'severe' problem. Although women were ambivalent about being weighed at each antenatal visit, 81 recommended weighing once each month. The women held differing opinions on the effects of breastfeeding on body weight and on the need for nutritional supplements during pregnancy. Women reporting 'disordered eating' were more likely to have antenatal complications and give birth to low birthweight babies. The results suggest good obstetric care should include a history of the woman's eating behavior and body weight.

Adolescent↗

Psychological and sexual changes after the cessation of breast-feeding.

OBJECTIVE: To characterize the effect of breast-feeding cessation on the mood and sexuality of women after the birth of their first child. METHODS: Women in good physical and psychological health, who had been breast-feeding for 6-23 months and had responded to a request for subjects in a parents' magazine, collected data daily for 2 months before and 2 months after weaning. They were asked to rate 14 measures of psychological, physical, and sexual variables at the same time each day on 3- or 5-point scales. RESULTS: Nineteen women completed the study. Five of these subjects became pregnant before weaning and ceased breast-feeding when pregnancy was confirmed; their last menstrual period was 6 weeks before weaning. The non-pregnant women weaned their babies just before or during menstruation. After weaning, the nonpregnant women reported a significant decrease in fatigue, improvement in mood, and an increase in sexual activity, sexual feelings, and frequency of coitus. Significant changes in fatigue and mood occurred during the second week after weaning; in fatigue, sexual activity, and sexual intercourse during the third week; and in the frequency of sexual intercourse in the fourth week. THe results were not caused by the subjects' expectations about breast-feeding and sexuality or perineal comfort. The women who conceived did not show these changes; a gradual increase in fatigue and decline in sexuality was observed. CONCLUSION: In women who are not pregnant, the cessation of breast-feeding is associated with an improvement in mood, fatigue, and sexuality.

Adult↗

Pyruvate stimulates hormonal induction of lipogenic enzymes in primary cultured rat hepatocytes.

Hormonal inductions of lipogenic enzyme activities (fatty acid synthetase, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and ATP-citrate lyase) were studied in primary cultured rat hepatocytes. Insulin, triiodothyronine and dexamethasone markedly stimulated the inductions of the enzymes (particularly G6PD and ME) in the presence of pyruvate. Lactate also induced their activities. The activities of these enzymes in the presence of appropriate hormone combinations and a substrate amount of pyruvate were as high as, or higher than those in the liver of rats on high-carbohydrate, low-fat diet. The aldolase and glucokinase activities induced by these hormones were not enhanced by the addition of pyruvate. The induction by pyruvate was inhibited by actinomycin D or cycloheximide. The ATP content of rat hepatocytes was maintained without increase during culture with pyruvate for 6 days. These results indicate that the additions of pyruvate, or its metabolites to cultures of isolated hepatocytes have specific effects on the inductions of certain hepatic enzymes, possibly acting at the level of transcription. Their effects are similar to those of feeding a high-carbohydrate, low-fat diet to intact animals.

ATP Citrate (pro-S)-Lyase↗

Acute toxicity of tedisamil, a new potassium channel blocking drug.

The acute intravenous toxicity of tedisamil, a new potassium channel blocker, was assessed by infusing it at various rates (1.5 to 10 mg/kg/min.) to ventilated or spontaneously breathing rats subjected to blockade of their peripheral somatic and autonomic nervous systems. The lethal doses for ventilated rats (including pithed animals) were 2-3 times higher than those for spontaneously breathing animals. In spontaneously breathing rats death appeared to be due to respiratory depression which was possibly of central origin since the lethality of tedisamil was not markedly altered by vagotomy, bilateral carotid artery ligation, nor by autonomic nervous system blockade. On the other hand, in all of the artificially ventilated groups, death occurred at higher doses and was related to direct cardiac actions, possibly involving blockade of cardiac potassium and sodium channels. The cardiovascular responses to infusions of tedisamil included tachyarrhythmias, bradycardia, blood pressure changes, increased QRS width and Q-T interval duration. Arrhythmias occurred at sublethal doses and were eliminated by autonomic blockade and pithing. However, the bradycardia, ECG and blood pressure changes induced by tedisamil infusions were unaltered by the various treatments. Thus tedisamil may induce arrhythmias by actions on the autonomic system.

Animals↗

Human immunodeficiency virus gp120 binding C'C" ridge of CD4 domain 1 is also involved in interaction with class II major histocompatibility complex molecules.

Using site-directed mutagenesis informed by high-resolution CD4 structural data, we have investigated the role of residues of the C'C'' ridge region of human CD4 on class II major histocompatibility complex (MHC) binding. This C'C'' ridge is homologous to the CDR2 loop of an immunoglobulin variable domain and is known to contain the binding site for human immunodeficiency virus (HIV) coat glycoprotein gp120. Here we report that this region is also involved in interaction with class II MHC. Exposed positively charged residues Lys-35, Lys-46, and Arg-59 and the exposed hydrophobic residue Phe-43 contribute significantly to class II MHC binding. Moreover, mutations in the buried residues Trp-62 and Ser-49, which support the top and bottom of the C'C'' ridge, respectively, disrupt class II MHC interaction. The HIV binding region appears to involve a restricted area of the larger class II MHC binding site on CD4. Strategies of drug design aimed at interrupting CD4-HIV interaction will need to consider the extensive overlap between class II MHC and HIV gp120 binding surfaces in this region of CD4.

Animals↗

The human immunodeficiency virus gp120 binding site on CD4: delineation by quantitative equilibrium and kinetic binding studies of mutants in conjunction with a high-resolution CD4 atomic structure.

The first immunoglobulin V-like domain of CD4 contains the binding site for human immunodeficiency virus gp120. Guided by the atomic structure of a two-domain CD4 fragment, we have examined gp120 interaction with informative CD4 mutants, both by equilibrium and kinetic analysis. The binding site on CD4 appears to be a surface region of about 900 A2 on the C" edge of the domain. It contains an exposed hydrophobic residue, Phe43, on the C" strand and four positively charged residues, Lys29, Lys35, Lys46, and Arg59, on the C, C', C", and D strands, respectively. Replacement of Phe43 with Ala or Ile reduces affinity for gp120 by more than 500-fold; Tyr, Trp, and Leu substitutions have smaller effects. The four positively charged side chains each make significant contributions (7-50-fold). This CD4 site may dock into a conserved hydrophobic pocket bordered by several negatively charged residues in gp120. Class II major histocompatibility complex binding includes the same region on CD4; this overlap needs to be considered in the design of inhibitors of the CD4-gp120 interaction.

Antibodies, Monoclonal↗

Immunocytochemical demonstration of neural cell adhesion molecule (NCAM) along the migration route of luteinizing hormone-releasing hormone (LHRH) neurons in mice.

Contact between the developing forebrain and the ingrowing central processes of the olfactory, vomeronasal and terminal nerves is preceded by a migration of neural cell adhesion molecule (NCAM)-immunoreactive cells from the epithelium of the olfactory pit and the formation of an NCAM-immunoreactive cellular aggregate in the mesenchyme between the olfactory pit and the forebrain. The axons of the olfactory, vomeronasal, and terminal nerves, also NCAM-immunoreactive, grow into the cellular aggregate, which as development proceeds, becomes continuous with the rostral tip of the forebrain. The lateral and more rostral part of the cellular aggregate receives the ingrowing axons of the olfactory nerves and becomes the olfactory nerve layer of the olfactory bulb. The medial, more caudal part receives the central processes of the vomeronasal and terminal nerves. The vomeronasal nerve ends in the accessory olfactory bulb. The central processes of the terminal nerve end in the medial forebrain. Luteinizing hormone-releasing hormone (LHRH)-immunoreactive neurons, like the vomeronasal and terminal nerves, originate from the medial part of the olfactory pit. These LHRH cells migrate into the brain along and within a scaffolding formed by the NCAM-immunoreactive axons of the vomeronasal and terminal nerves, and they are never seen independent of this NCAM scaffold as they cross the nasal lamina propria. The results suggest that: (1) NCAM is likely to be necessary for scaffold formation, and (2) the scaffold may be essential for the subsequent migration of LHRH neurons into the brain. Because they aggregate, migrating LHRH-immunoreactive neurons, on which we did not detect NCAM immunoreactivity, may interact via other cell adhesion molecules (CAM). Inasmuch as the interaction between the LHRH-immunoreactive neurons and the NCAM-immunoreactive scaffold is heterotypic, the possibility of a heterophilic (NCAM to other CAM) interaction is not ruled out. These findings focus our attention on the functional role of NCAM in this migratory system.

Animals↗

p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein.

Products of the ras gene family, termed p21ras, are GTP-binding proteins that have been implicated in signal transduction via receptors encoding tyrosine kinase domains. Recent findings have defined a superfamily of hemopoietin receptors that includes receptors for a number of interleukins and colony-stimulating factors. The intracellular portions of these receptors show only restricted homologies, have no tyrosine kinase domain, and provide no clues to the mode of signal transduction. However, in most cases the factors stimulate tyrosine phosphorylation. We demonstrate here that ligand-induced activation of the interleukin (IL)-2, IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor receptors resulted in activation of p21ras in various hemopoietic cell lines. The only cytokine tested that binds to a hemopoietin receptor and that did not activate p21ras was IL-4. Activation of p21ras was also observed in response to Steel factor, which stimulates the endogenous tyrosine kinase activity of the c-kit receptor, as well as with phorbol esters, which activate protein kinase C. Experiments with protein kinase inhibitors implicated tyrosine kinase activity, but not protein kinase C activity, as the upstream signal in p21ras activation via these growth factor receptors. Attempts to demonstrate tyrosine phosphorylation of the p21ras GTPase-activating protein (GAP) were negative, suggesting that phosphorylation of GAP may not be the major mechanism for regulation of p21ras activity by tyrosine kinases.

Animals↗

Phosphorylation of multiple CD3 zeta tyrosine residues leads to formation of pp21 in vitro and in vivo. Structural changes upon T cell receptor stimulation.

T lymphocyte activation resulting from antigen recognition involves a protein tyrosine kinase pathway which triggers phosphorylation of several cellular substrates including the CD3 zeta subunit of the T cell receptor (TCR) to form pp21. The homologous TCR-associated protein, CD3 eta, is an alternatively spliced product of the same gene locus as CD3 zeta. CD3 eta lacks one of six cytoplasmic tyrosine residues (Tyr-132) found in CD3 zeta and is itself not phosphorylated. Site-directed mutagenesis in conjunction with in vitro and in vivo phosphorylation studies herein demonstrates that Tyr-132 is required for the formation of pp21. Moreover, the differential phosphorylation of CD3 zeta versus CD3 eta is not due to a selective association of the known TCR-associated protein tyrosine kinase, p59fyn; p59fyn but not p56lck or p62yes is associated with each of the three TCR isoforms containing CD3 zeta 2, or CD3 eta 2, or CD3 zeta-eta. This association occurs through components of the TCR complex distinct from CD3 zeta or CD3 eta. In addition, we show that pp21 formation is not only dependent on Tyr-132 but results from concomitant phosphorylation of other CD3 zeta residues including Tyr-121. Mutation of Tyr-90, -121, or -132 does not alter primary signal transduction as shown by the ability of individual CD3 zeta Tyr----Phe mutants to produce interleukin-2 upon TCR stimulation. Thus, the substantial structural changes in CD3 zeta upon TCR stimulation as reflected by alteration in its mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis may affect subsequent events such as receptor desensitization, receptor movement, and/or protein associations.

Amino Acid Sequence↗

T cell receptor complexes containing Fc epsilon RI gamma homodimers in lieu of CD3 zeta and CD3 eta components: a novel isoform expressed on large granular lymphocytes.

CD3 zeta and CD3 eta form disulfide-linked homo- or heterodimers important in targeting partially assembled Ti alpha-beta/CD3 gamma delta epsilon T cell receptor (TCR) complexes to the cell surface and transducing stimulatory signals after antigen recognition. Here we identify a new TCR isoform expressed on splenic CD2+, CD3/Ti alpha-beta+, CD4-, CD8-, CD16+, NK1.1+ mouse large granular lymphocytes (LGL), which are devoid of CD3 zeta and CD3 eta proteins. The TCRs of this subset contain homodimers of the gamma subunit of the high affinity receptor for IgE (Fc epsilon RI gamma) in lieu of CD3 zeta and/or CD3 eta proteins. The LGL display natural killer-like activity and are cytotoxic for B cell hybridomas producing anti-CD3 epsilon and anti-CD16 monoclonal antibodies, demonstrating the signaling capacity of both TCR and CD16 in this cell type. These findings provide evidence for an additional level of complexity of TCR signal transduction isoforms in naturally occurring T cell subsets.

Animals↗

Ischemic but not reperfusion arrhythmias depend upon serum potassium concentration.

The effects of variations in serum concentrations of potassium on the occurrence and severity of ischemia- and reperfusion-induced arrhythmias have been studied in conscious rats. Serum potassium concentrations were modified by maintaining rats on diets which varied in potassium concentration, by treatment with hydrochlorothiazide, amiloride, spironolactone or infusions of potassium chloride. An inverse linear relationship was demonstrated between ischemia-induced arrhythmias and log(e) serum potassium concentration such that a 50% reduction in arrhythmias occur with a 3.8-fold increase in serum potassium concentration. On the other hand, the incidence of reperfusion-induced arrhythmias after 7 min of regional ischemia prior to reperfusion in previously untreated rats were not influenced by elevation of serum potassium concentrations prior to and after reperfusion. Effects on ischemia-induced arrhythmias could not be explained by changes in blood pressure or heart rate. It is speculated that modification of potassium concentration in non-ischemic or border zone ventricular tissue may directly modify arrhythmogenesis due to ischemia but not that due to reperfusion.

Animals↗

The 9-kDa hydrophobic protein encoded at the 3' end of the porcine transmissible gastroenteritis coronavirus genome is membrane-associated.

The open reading frame potentially encoding a 78 amino acid, 9101 Da hydrophobic protein (HP) and, mapping at the 3' end of the porcine transmissible gastroenteritis coronavirus (TGEV) genome, was shown to be expressed during virus replication. The cloned HP gene was placed in a plasmid under control of the T7 RNA polymerase promoter and in vitro translation of transcripts generated in vitro yielded a 9.1-kDa protein that was immunoprecipitable with porcine hyperimmune anti-TGEV serum. Antiserum raised in rabbits against a 31 amino acid synthetic polypeptide that represented the central hydrophilic region of HP specifically immunoprecipitated HP from TGEV-infected cells. HP was further shown to become associated with microsomal membranes during synthesis in vitro and was found to be closely associated with the endoplasmic reticulum and cell surface membranes in infected cells. The intracellular location of HP suggests that it may play a role in the membrane association of replication complexes or in virion assembly.

Amino Acid Sequence↗

Gene expression: nutrient control of pre- and posttranscriptional events.

Regulation of gene expression by specific nutrients has become a major frontier for the next generation of nutrition scientists. The techniques of molecular biology allow us to define nutrient needs, as well as the outcomes of nutrient excesses, in terms of events that govern gene transcription, mRNA processing, mRNA stability, and mRNA translation. Evidence is presented showing that dietary constituents specifically modulate the nuclear events governing gene transcription and transcript processing. For example, fatty acid synthase gene transcription is inhibited by specific polyunsaturated fatty acids; S14 and pyruvate kinase genes contain a specific carbohydrate response element; and editing of apo B-100 to apo B-48 is enhanced by dietary carbohydrate. Nutrients such as iron and glucose are shown to control mRNA stability and translational rates of certain transcripts by regulating the interaction of cytosolic proteins with specific nucleotide sequences. The data of this review clearly demonstrate that nutrients play an active and specific role in governing the expression of select genes.

Animals↗

The teaching of behavioural sciences.

Medical science over the last few decades has undergone vast changes. Technologically it has advanced at a rapid pace. There has been a realization as well that the behaviour of individuals and communities also influences the occurrence of disease. Medical schools around the globe have realized the need for incorporating behavioural sciences as an integral part of the basic sciences taught to medical students. This paper presents the experience of Christian Medical College, Vellore in teaching behavioural sciences. Students are taught sociology, psychology and medical anthropology through a community-based, problem-oriented teaching programme. The students have first-hand experience of living in a community and learn by observation and interaction. Pre- and post-assessment has shown a significant improvement of their knowledge and attitude. Feedback from students also indicates that they find this programme relevant and interesting.

Behavioral Sciences↗