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T Thomas

Publications and source records attributed to T Thomas.

356 records · Page 20Linked to original sources
PubMedDate not supplied

Central nervous system control of cardiovascular function: neural mechanisms and novel modulators.

1. Studies are described that indicate that hypothalamic stimulation, at sites eliciting the defence reaction, results in an increase in adenosine levels in both the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) of the rat. 2. Adenosine receptor antagonists applied to these sites attenuate the pressor response elicited by hypothalamic stimulation. Adenosine appears to be produced extracellularly from ATP, which is released from axon terminals in both the NTS and RVLM. 3. The implications of these observations for the pharmacology of hypothalamic actions on reflex inputs that modify cardiorespiratory function are discussed.

Animals↗
PubMedDate not supplied

Chronic illness and plan satisfaction under managed care.

This DataWatch uses data from the 1993 Employee Health Care Value Survey (EHCVS) to compare the experiences of respondents with and without chronic illnesses under managed care. After controlling for potential confounders, we found that chronic illness was associated with increased odds of dissatisfaction in both independent practice association plans and prepaid group practices, but not under fee-for-service coverage. Chronic illness appeared to exacerbate difficulties and to attenuate the benefits experienced by healthy persons under managed care. We conclude that persons with chronic illnesses may be at particular risk under managed care; their experiences may warrant particular attention when health plan performance is being monitored.

Adult↗
PubMedDate not supplied

Differential effects of estradiol and its analogs on cyclin D1 and CDK4 expression in estrogen receptor positive MCF-7 and estrogen receptor-transfected MCF-10AEwt5 cells.

Estradiol stimulates the growth of a majority of human breast tumors containing the estrogen receptors (ERs), proteins that mediates estrogen function. Opposing effects of estradiol have been found in cells expressing endogenous ER and those containing a transfected ER. To understand the role of estradiol structure in diverse estrogenic responses related to cell cycle regulation, we evaluated the effects of estradiol and its analogs on cell cycle progression, and the expression of cyclin D1 and the cyclin dependent kinase 4 (CDK4) in ER-positive MCF-7 and ER-transfected MCF-10AEwt5 cells. Four analogs of estradiol, with a re-positioned or a deleted hydroxyl group, were used. Our results show that estradiol and all of the analogs facilitated cell cycle progression of MCF-7 cells. In contrast, only estradiol inhibited the cell cycle progression of MCF-10AEwt5 cells significantly. Western blot analysis revealed that cyclin D1 protein increased to the maximal level by 6 h after the initiation of cell cycle from G1 phase of MCF-7 cells. The least effective analog in inducing cyclin D1 was 3-hydroxyestratriene. However, this analog was most effective at inducing CDK4, contributing to its efficacy in facilitating MCF-7 cell cycle. In contrast to MCF-7 cells, the level of cyclin D1 protein was not influenced significantly by estradiol or its analogs in MCF-10AEwt5 cells. Sucrose gradient sedimentation analysis of ER from MCF-7 cells showed that the major peak of [3H]-estradiol bound to ER could be displaced by a 10-fold excess of unlabelled estradiol or any of the analogs. In contrast, several analogs were less effective than unlabelled estradiol in competitive displacement of [3H]-estradiol bound to ER from MCF-10AEwt5 cells. These data indicate that the induction of cyclin D1 is an important part of the growth stimulatory effects of estrogens in MCF-7 cells, but it may not be involved in growth inhibition of MCF-10AEwt5 cells. Our results also show that estrogenic compounds interact with ER from MCF-10AEwt5 cells with altered ligand binding affinity, possibly due to the absence or dysfunction of certain transcription factors or ER-associated proteins that co-regulate ER function.

Breast Neoplasms↗
PubMedDate not supplied

Effects of genistein and structurally related phytoestrogens on cell cycle kinetics and apoptosis in MDA-MB-468 human breast cancer cells.

We have studied the effects of phytoestrogens (genistein, quercetin, daidzein, biochanin A and kaempferol) on proliferation, cell cycle kinetics, and apoptosis of MDA-MB-468 breast cancer cells. Genistein and quercetin inhibited cell growth with IC50 values of 8.8 and 18.1 muM, respectively, while the other phytoestrogens were less effective. Flow cytometric analysis showed G2/M cell cycle arrest with 25 muM and higher concentrations of genistein. At 100 muM, genistein, quercetin and kaempferol caused accumulation of 70, 60 and 35% of cells, respectively, in G2/M phase by 24 h. In contrast, biochanin A and daidzein were ineffective. APO-BRDU analysis revealed apoptosis with 10 muM genistein (19.5%), reaching 86% at 100 muM. Apoptosis by genistein was confirmed by Hoechst 33342 staining and fluorescence microscopy. With 100 muM quercetin, 47% of the cells were apoptotic, while the other bioflavonoids had little effect. Genistein treatment resulted in a biphasic response on cyclin B1: 70% increase in cyclin B1 level at 25 muM, and 50 and 70% decrease at 50 and 100 muM, respectively. In contrast, the action of quercetin involved an increase in cyclin B1 level. Genistein had no effect on cdc2 level up to 50 muM concentration; however, there was a decrease in the phosphorylated form of the protein at 100 muM. Quercetin had no effect on cdc2 levels. Our results suggest that the action of genistein and quercetin involves G2/M arrest and apoptosis in MDA-MB-468 cells. Biochanin A and daidzein, although structurally related to genistein, did not share this mechanism. Thus, structurally related phytoestrogens have discrete target sites and mechanisms in their growth inhibitory action on breast cancer cells.

Apoptosis↗
PubMedDate not supplied

Practice variability in the management of infrarenal arterial stenoses in seven Belgian hospitals.

This multicentre retrospective study describes the variation of therapeutic options, treatment outcomes and costs for treating infrarenal arterial stenoses as observed in daily practice in 1997-99 in seven Belgian hospitals. Data were obtained from clinical record review and from the sickness fund claims database, and included preoperative functional state, presence of acute ischaemia, diabetes and polyvascular disease, state of the lower-leg run-off arteries, anatomical site and type of lesion, type of treatment, result at 30 days and up to 4 years. A total of 442 episodes were studied, but most analyses dealt with a subgroup of 240 lesions in the common iliac up to the superficial femoral artery. The proportion of surgical treatments (as compared to an endovascular or mixed approach) varied from 15% to 81% between the hospitals. In univariate survival analysis, relapse or failure rates at 4 years ranged from 5% for the common iliac artery to 35% for the superficial femoral artery. Polyvascular disease, a poor run-off, multiple stenoses and chronic occlusion were significant risk factors; age and diabetes were not. In the multivariate (stratified Cox regression) analysis, only a location in the superficial femoral artery and a poor preoperative clinical stage were significant risk factors, but type of therapeutic approach was not. The total average cost of treatment was 5300 Euro, of which 15% was contributed by the patient. Surgery was associated with longer stays (median at 12 days) than endovascular treatments (median 2 d), and was 1.9 times more expensive. In conclusion, the results of the present study suggest that a multidisciplinary approach, orienting the patient to the most appropriate therapeutic pathway could increase both the quality and the cost-effectiveness of the care. In many clinical situations, the endovascular approach appears to offer similar long-term results as surgery, but at a substantially lower cost, both for the patient and for society, especially when performed in a (semi-)ambulatory radiology setting.

Aged↗