PubMed Health⌕ Search

Biomedical subjects

C Abraham

Publications and source records attributed to C Abraham.

At least 37 records · Page 2Linked to original sources
PubMed1998

Decreased PKC-alpha expression increases cellular proliferation, decreases differentiation, and enhances the transformed phenotype of CaCo-2 cells.

Previous studies have shown that PKC-alpha protein expression is decreased in sporadic human colon cancers, as well as in colonic tumors of rats induced by chemical carcinogens. To elucidate the potential role of PKC-alpha on several phenotypic characteristics of colon cancer cells, we have transfected cDNAs for PKC-alpha in sense or antisense orientations into CaCo-2 cells, a human colonic adenocarcinoma cell line. Transfected clones were isolated that demonstrated approximately 3-fold increases (sense transfectants) and approximately 95% decreases (antisense transfectants) in PKC-alpha expression with no significant alterations in other PKC isoforms. Transfection of CaCo-2 cells with PKC-alpha in the antisense orientation resulted in enhanced proliferation and decreased differentiation, as well as in a more aggressive transformed phenotype compared with empty vector-transfected control cells. In contrast, cells transfected with PKC-alpha cDNA in the sense orientation demonstrated decreased proliferation, enhanced differentiation, and an attenuated tumor phenotype compared with these control cells. These data show that alterations in the expression of PKC-alpha induce changes in the proliferation, differentiation, and tumorigenicity of CaCo-2 cells. Furthermore, these findings indicate that loss of PKC-alpha expression in sporadic human and chemically induced colonic cancers may confer a relative growth advantage during colonic malignant transformation.

Animals↗
PubMed1998

Protein kinase C alpha modulates growth and differentiation in Caco-2 cells.

BACKGROUND & AIMS: Caco-2 cells have been used extensively to elucidate events involved in intestinal cell proliferation and differentiation. Because individual isoforms of protein kinase C (PKC) and p21waf1, a cyclin-dependent kinase inhibitor, may regulate these processes, their role(s) on the growth and differentiation of Caco-2 cells were assessed. METHODS: Protein abundance and subcellular distribution of several PKC isoforms, as well as the expression of p21waf1, were examined in preconfluent and postconfluent cells. RESULTS: In cells at confluence (approximately 7 days postplating) and during their postconfluent phase (up to 20 days postplating), both total protein expression of PKC-alpha and its particulate distribution increased compared with their 3-day postplated counterparts. These findings were in agreement with those obtained by immunocytochemistry of PKC-alpha. In contrast, neither the total expression nor the subcellular distribution of PKC-betaI, -betaII, -delta, or -zeta changed significantly during these time periods. In addition, the expression of p21waf1, which can be induced by PKC-alpha, increased in postconfluent cells. CONCLUSIONS: PKC-alpha, but not other isoforms of PKC, may modulate the proliferation and differentiation of Caco-2 cells. This regulation appears to be mediated, at least in part, via a mechanism involving p21waf1.

Caco-2 Cells↗
PubMed1998

Towards a psycho-social theoretical framework for sexual health promotion.

Numerous interventions have been designed to promote safer sexual behaviour amongst young people. However, relatively few have proved effective, which is, at least partially, due to the lack of development of theoretically based programmes. An understanding of the origins and control of sexual behaviour can be derived from basic social science research. Unless this is applied to the design of behaviour-change programmes they are unlikely to target the most important determinants of young people's sexual behaviour and are, therefore, unlikely to be effective. This paper outlines some of the key theoretical insights which have been drawn upon in the development of a new sex education programme currently being tested in Scottish schools. The theoretical basis is intentionally eclectic, combining social psychological cognitive models with sociological interpretations, since we are not concerned to advance any particular theory but to find which are most useful in promoting sexual health. First, the social influences on sexual behaviour are considered, and then the way in which these translate into individual perceptions and beliefs. Finally, the paper attempts to develop a theoretical understanding of sexual interaction and the social contexts of sexual behaviour.

Adolescent↗
PubMed1998

Can social cognitive models contribute to the effectiveness of HIV-preventive behavioural interventions? A brief review of the literature and a reply to Joffe (1996; 1997) and Fife-Schaw (1997)

A recent debate in the British Journal of Medical Psychology has considered the role of social cognitive models, such as the theory of reasoned action and the theory of planned behaviour, in understanding HIV-preventive behaviour. In this paper we clarify some of the assumptions involved in applications of social cognitive models. We briefly review available evidence on the capacity of such models to predict HIV-preventive sexual behaviour and outline a number of criteria for judging their predictive success. The importance of behavioural prediction for the development of effective HIV-preventive behavioural interventions is discussed and recent evaluations of interventions based on these models are reviewed. We conclude that the models are effective in predicting HIV-preventive behaviours and provide empirically supported theoretical guidance on psychological changes likely to result in HIV-preventive behaviour change. In addition we argue that, to date, evaluations of theoretically specified interventions are encouraging. Further development and rigorous testing of HIV/AIDS interventions based on social cognitive models is recommended.

Cognition↗
PubMed1998

Scientific thinking in ophthalmology.

Science, medicine and ophthalmology have all evolved and progressed through varied but powerful influences over the centuries. While the tremendous technological advances in ophthalmology in the past 20 years are readily appreciated, many clinicians fail to grasp the impact of the several clinical trials that have contributed to better patient care. This article briefly traces the history of science, medicine and ophthalmology, and explains how scientific thinking could be applied to the clinical and academic aspects of ophthalmology.

Clinical Trials as Topic↗
PubMed1997

1,25 dihydroxyvitamin D3 stimulates phospholipase C-gamma in rat colonocytes: role of c-Src in PLC-gamma activation.

Our laboratory has previously demonstrated that 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) rapidly stimulated polyphosphoinositide (PI) hydrolysis, raised intracellular Ca2+, and activated two Ca2+-dependent protein kinase C (PKC) isoforms, PKC-alpha and -betaII in the rat large intestine. We also showed that the direct addition of 1,25(OH)2D3 to isolated colonic membranes failed to stimulate PI hydrolysis, but required secosteroid treatment of intact colonocytes, suggesting the involvement of a soluble factor. Furthermore, this PI hydrolysis was restricted to the basal lateral plasma membrane of these cells. In the present studies, therefore, we examined whether polyphosphoinositide-phospholipase C-gamma (PI-PLC-gamma), a predominantly cytosolic isoform of PI-PLC, was involved in the hydrolysis of colonic membrane PI by 1,25(OH)2D3. This isoform has been shown to be activated and membrane-associated by tyrosine phosphorylation. We found that 1,25(OH)2D3 caused a significant increase in the biochemical activity, particulate association, and the tyrosine phosphorylation of PLC-gamma, specifically in the basal lateral membranes. This secosteroid also induced a twofold increase in the activity of Src, a proximate activator of PLC-gamma in other cells, with peaks at 1 and 9 min in association with Src tyrosine dephosphorylation. 1,25(OH)2D3 also increased the physical association of activated c-Src with PLC-gamma. In addition, Src isolated from colonocytes treated with 1,25(OH)2D3, demonstrated an increased ability to phosphorylate exogenous PLC-gamma in vitro. Inhibition of 1,25(OH)2D3-induced Src activation by PP1, a specific Src family protein tyrosine kinase inhibitor, blocked the ability of this secosteroid to stimulate the translocation and tyrosine phosphorylation of PLC-gamma in the basolateral membrane (BLM). Src activation was lost in D deficiency, and was reversibly restored with the in vivo repletion of 1,25(OH)2D3. These studies demonstrate for the first time that 1,25(OH)2D3 stimulates PLC-gamma as well as c-Src in rat colonocytes, and indicate that PLC-gamma is a direct substrate of secosteroid-activated c-Src in these cells.

Animals↗
PubMed1996

Interaction of S 21007 with 5-HT3 receptors. In vitro and in vivo characterization.

The interaction of S 21007 [5-(4-benzyl piperazin-1-yl)4H pyrrolo [1,2-a]thieno[3,2-e]pyrazine] with serotonin 5-HT3 receptors was investigated using biochemical, electrophysiological and functional assays. Binding studies using membranes from N1E-115 neuroblastoma cells showed that S 21007 is a selective high affinity (IC50 = 2.8 nM) 5-HT3 receptor ligand. As expected of an agonist, S 21007 stimulated the uptake of [14C]guanidinium (EC50 approximately 10 nM) in NG 108-15 cells exposed to substance P, and this effect could be prevented by the potent 5-HT3 receptor antagonist ondansetron. In addition, like 5-HT and other 5-HT3 receptor agonists (phenylbiguanide and 3-chloro-phenylbiguanide), S 21007 (EC50 = 27 microM) produced a rapid inward current in N1E-115 cells. The 5-HT3 receptor agonist action of S 21007 was also demonstrated in urethane-anaesthetized rats as this drug (120 micrograms/kg i.v.) triggered the Bezold-Jarisch reflex (rapid fall in heart rate), and this action could be prevented by pretreatment with the potent 5-HT3 receptor antagonist zacopride. Finally, in line with its 5-HT3 receptor agonist properties, S 21007 also triggered emesis in the ferret. Evidence for 5-HT3 receptor antagonist-like properties of S 21007 was also obtained in some of these experiments since previous exposure to this compound prevented both the 5-HT-induced current in N1E-115 cells and the Bezold-Jarisch reflex elicited by an i.v. bolus of 5-HT (30 micrograms/kg) in urethane-anaesthetized rats. These data suggest that S 21007 is a selective 5-HT3 receptor agonist which can exhibit antagonist-like properties either by triggering a long lasting receptor desensitization or by a partial agonist activity at 5-HT3 receptors in some tissues.

Animals↗
PubMed1996

Systemic inflammatory response syndrome after cardiac operations.

BACKGROUND: A systemic inflammatory response after open heart operation may be responsible for hyperdynamic circulatory instability and organ dysfunction. To what extent mediator release is involved needs to be clarified. METHODS: Ten patients with postoperative hyperdynamic circulatory dysregulation (group I) requiring application of alpha-constrictors and 10 patients with routine cardiac procedures and stable postoperative hemodynamic indices (group II) were analyzed for mediator release and metabolic and hemodynamic changes until the third postoperative day. RESULTS: Group I patients showed a significantly increased cardiac index and decreased systemic vascular resistance after bypass (cardiac index, group I: 5.2 +/- 1.2 L.min-1.m-2, group II: 2.5 +/- 1.6 L.min-1.m-2; systemic vascular resistance, group I: 495 +/- 204 dyne.s. cm-5, group II: 1,356 +/- 466 dyne.s.cm-5) and at 3 hours (cardiac index, group I: 4.4 +/- 0.8 L.min-1.m-2, group II: 2.9 +/- 0.6 L.min-1.m-2; systemic vascular resistance, group I: 567 +/- 211 dyne.s.cm-5, group II: 1,053 +/- 273 dyne.s.cm-5). Significantly higher serum levels of interleukin-6 were assessed in group I (postbypass, group I: 6,812 +/- 9,293 pg/mL, group II: 295 +/- 303 pg/mL; 3 hours, group I: 3,474 +/- 5,594 pg/mL, group II: 286 +/- 296 pg/mL). Concentrations of elastase, tumor necrosis factor, soluble tumor necrosis factor receptor, and interleukin-8 were elevated in group I (not significant). Early postoperative levels of soluble E-selectin and soluble intercellular adhesion molecule were also higher in group I (not significant). Continuously increased levels of endotoxin could be detected in only 3 of 10 patients in group I. Severe lactic acidosis (> or = 5 mmol/L) occurred in group I only. CONCLUSIONS: Postoperative hyperdynamic instability after open heart operations appears to be associated with a certain pattern of mediator release. In particular, interleukin-6 appears to be involved in circulatory dysregulation and metabolic derangement.

Acidosis, Lactic↗
PubMed1996

Violence and gynecologic health in women <50 years old.

OBJECTIVE: Our purpose was to examine, in women aged 18 to 49, the relationship of violent experiences (child abuse, violent crime, spouse abuse) to gynecologic problems. STUDY DESIGN: Data from 1599 participants in a randomized, sociodemographically representative telephone survey of U.S. women were used. Gynecologic problems wer measured by self-report of receiving a physician's diagnosis of severe menstrual problems, a sexually transmitted disease, or a urinary tract infection. Statistical analyses used were the chi2 test and multiple logistic regression. RESULTS: A total of 31.5% of participants reported a diagnosis of gynecologic problems in the past 5 years. Those with problems were more likely to report childhood abuse, violent crime victimization, and spouse abuse. In logistic regression models controlling for sociodemographic factors and access to medical care, violence events remained significantly associated with gynecologic problems. CONCLUSIONS: A history of gynecologic problems may indicate that a patient has been harmed by violence. However, all women are at risk of being harmed by violence, and a violence history should be obtained as part of the intake protocol for all patients. Physicians need to be prepared to provide information about local community services, including counseling, domestic violence centers, shelters, and advocacy groups.

Adolescent↗
PubMed1996

Why I want to be a psychiatric nurse: constructing an identity through contrasts with general nursing.

The justification of psychiatric specialization among undergraduate nursing students is examined. The data highlight how students are able to produce a positive view of their initial entry into nursing and then later create a positive and distinctive specialist occupational identity through negative comparisons with general nursing. Their experience in both psychiatric and general settings is drawn upon to add credibility to their claims. Contrasts based on the work schedules, patient focus, professional autonomy, opportunity for professional development, and required skills are considered.

Career Choice↗
PubMed1995

Radioimmunoassay of the APC gene product using antibodies against its middle and carboxyl regions.

A radioimmunoassay (RIA) has been developed for the adenomatous polyposis coli protein (APC). High-avidity rabbit polyclonal antibodies were produced against synthetic peptides corresponding to amino acids 1865-1881 (APC-1) and to amino acids 1336-1350 (APC-2) in APC's 2844 amino acid sequence. Both antibodies were utilized in RIA to evaluate full-length APC that is present in the insoluble particulate fraction of cell lysates. High salt extraction, often employed for coiled-coil type protein preparations, was found to be useful for extraction of APC from lysates of normal colonic epithelium. Proteolytic digestion of high salt extracts increased antibody reactivity toward both epitopes, suggesting that APC-1 and APC-2 antigenic sites are partially concealed due to APC's involvement in multiprotein complexes. Thus, RIA using our antibodies will provide a valuable tool for APC protein purification and in studies for elucidating APC's biologic function.

Adenomatous Polyposis Coli Protein↗
PubMed1995

The WHO objectives for palliative care: to what extent are we achieving them?

This paper examines recent research in palliative care in the light of the guiding principles set out by the World Health Organization. It outlines the gaps in the literature and suggests priorities for future research. Areas of unmet need are documented and it is argued that research comparing outcomes across care settings and relating particular care practices to outcome measures would help to set care targets. Further definition of the expected outcomes of psychological and spiritual care, as well as care for carers, is recommended. Available measures are reviewed and suggestions made for the development of additional measures. Finally, some key methodological problems are discussed, including making cross-setting comparisons, identifying appropriate outcome measures, prioritizing patients' own identification of outcomes, using different methodologies as death approaches, and combining different perspectives offered by patients, lay carers and professional carers. The role of qualitative data as an indicator of rating scale validity is discussed in this context.

Health Priorities↗
PubMed1994

Modelling and modifying young heterosexuals' HIV-preventive behaviour; a review of theories, findings and educational implications.

Studies applying social cognitive frameworks such as the health belief model and the theory of reasoned action to HIV-prevention are reviewed. These models suggest that appropriate beliefs, attitudes, social norms, intentions and perceived self-efficacy are sufficient psychological conditions for safer sexual behaviour. Limitations inherent in these accounts are identified and additional factors which need to be incorporated in psychological models and health education programmes are highlighted. These include, the motivational complexity of sexual behaviour, the emotional and arousal states in which it is enacted, the difficulties of planning what is regarded as spontaneous interaction and contextual factors which can undermine HIV-preventive intentions. Health education interventions aimed at individual, group and community levels are examined in light of this theoretical review and action-focused, empowering interventions grounded in youth culture are recommended.

Adolescent↗
PubMed1994

Measurement of condom use in 72 studies of HIV-preventive behaviour: a critical review.

Ninety-four distinct measures of condom use were identified in a review of 72 psychosocial studies of HIV-prevention. A coding scheme was developed which characterised each measure in terms of: (1) type of measure (e.g. frequency of use, use at last intercourse), (2) response alternatives (e.g. Likert scale), (3) recall period (e.g. lifetime, last month), (4) partner specification (e.g. 'new' partner), and (5) activity specification (e.g. vaginal or anal intercourse). Results show a great deal of inconsistency in measurements of condom use across studies. Single-item frequency or consistency measures were most common. Several difficulties with measures employed to date were identified. These included indeterminate reliability and validity of measures, lack of attention to the epidemiological significance of different types of use and terminological and self-presentational problems with items assessing use. Implications of extant measurement approaches for the accumulated knowledge base on predictors of 'safer' sex and suggestions for future research in this area are outlined.

Condoms↗
PubMed1994

In vivo comparison of free coronary grafts using the inferior epigastric (IEA), the gastroepiploic (GEA) and the internal thoracic artery (ITA).

The validity of alternative arterial conduits for myocardial revascularization in comparison to internal thoracic artery (ITA) has not been sufficiently defined. Evaluation of the functional in vivo vascular properties of the different conduits may be appropriate to give a perspective on long-term graft qualities. The intraoperative function of single free grafts to the left anterior descending artery (LAD) was compared in inferior epigastric (IEA, n = 13), internal thoracic (ITA, n = 12) and gastroepiploic artery (GEA, n = 12) conduits. Graft flows were measured at four points of time, 1) in situ free flow after distal dissection (IEA: 42.2 ml/min, ITA: 68.8 ml/min, GEA: 61.1 ml/min), 2) free flow following proximal grafting to the aorta (IEA: 48.1 ml/min, ITA: 63.7 ml/min, GEA: 84.2 ml/min), 3) selective graft flow after distal attachment to the LAD (IEA: 52.6 ml/min, ITA: 77.5 ml/min, GEA: 102.8 ml/min), and 4) selective LAD graft flow following paraverine (Pap) stimulation (IEA: 98.4 ml/min, ITA: 128.0 ml/min, GEA: 142.9 ml/min). Endothelium-dependent and -independent relaxation was evaluated by examination of the intraluminal graft pressures at mechanically controlled constant flow rates. Following stimulation with substance P (SP), the change of intraluminal pressure (dp) was similar in IEA (dp: -20.0 mmHg) and GEA grafts (dp: -21.1 mmHg). Only ITA conduits were less reactive to SP (-9.7 mmHg). The response to acetylcholine (ACh) could only be assessed in ITA (dp: -16.0 mmHg) and IEA (dp: -10.7 mmHg) grafts. Gastroepiploic arteries did not react on ACh stimulation (dp: +0.4 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1994

Biguanide derivatives: agonist pharmacology at 5-hydroxytryptamine type 3 receptors in vitro.

The effects of 24 biguanide and four guanidine derivatives on 5-hydroxytryptamine (5-HT)3 receptors in N1E-115 neuroblastoma cells were examined using radioligand binding and whole-cell voltage-clamp techniques. Displacement of the selective 5-HT3 receptor antagonist [3H]BRL 43694 by phenylbiguanide (PBG) derivatives revealed Ki values ranging from 3.4 x 10(-4) to 4.4 x 10(-10) M. The rank order of potency of agonists was 2,3,5-trichloro-PBG > 2,3-dichloro-PBG = 2,5-dichloro-PBG = 3,5-dichloro-PBG > 3,4-dichloro-PBG = 3-chloro-PBG > 2-chloro-PBG = 4-chloro-PBG = 2-methyl-PBG = 2,4-difluoro-PBG > PBG = 2-trifluoro-5-chloro-PBG > 4-fluoro-PBG = 3-trifluoromethyl-PBG > 4-nitro-PBG = 1,5-bis-4-chloro-PBG = 3,5-ditrifluoromethyl-PBG > 4-ethoxy-PBG >> 4-sulfonic acid-PBG. All of the benzylbiguanides and indanylbiguanide were inactive on [3H]BRL 43694 binding or displaced it only weakly. The four guanidine derivatives were quite inactive. In the PBG series, all antagonist competition curves were steep (pseudo-Hill coefficients ranging from 1.05 to 1.58), monophasic, and best fit with a one-site model. Among PBG derivatives, the chlorinated compounds exhibited a good degree of selectivity for 5-HT3 receptors versus other 5-HT receptor subtypes and other neurotransmitter binding sites. Electrophysiological studies showed that the PBG derivatives tested produced rapid inward currents, at a holding potential of -65 mV, that showed rapid desensitization. The current induced by the 2,3,5-trichloro-PBG derivative was inhibited by the specific 5-HT3 receptor antagonist ICS 205-930 but was unaffected by the 5-HT2 receptor antagonist ketanserin. Analysis of concentration-response curves for the PBG derivatives gave EC50 values ranging from 2.2 x 10(-5) to 2.7 x 10(-8) M and Hill slopes ranging from 1.02 to 2.10. The rank order of potency was similar to that obtained from the binding data, and a good correlation was found between Ki and EC50 values. It is concluded that the triple-chloro substitution yielded a compound that is 30-fold more potent than 3-chloro-PBG and approximately 10-fold more potent than dichloro-PBG derivatives, making 2,3,5-trichloro-PBG the most potent 5-HT3 agonist described thus far.

Biguanides↗