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41.
Antibodies to tumor necrosis factor alpha prevent increases in cell replication in liver due to the potent peroxisome proliferator, WY- 14,643 总被引:7,自引:6,他引:7
Bojes HK; Germolec DR; Simeonova P; Bruccoleri A; Schoonhoven R; Luster MI; Thurman RG 《Carcinogenesis》1997,18(4):669-674
Several structurally dissimilar hypolipidemic drugs, plasticizers and
halogenated hydrocarbons induce peroxisomes in hepatocytes, and cause
hepatocellular adenoma and carcinoma in rats and mice. The mechanism by
which these agents act is unknown, although recent studies have suggested a
link between increased cell proliferation and hepatic cancer caused by
peroxisome proliferators. Here, we demonstrate that neutralizing antibodies
to tumor necrosis factor alpha (TNF alpha) block increases in protein
kinase C and cell proliferation due to [4-
chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14,643), a
hypolipidemic drug and potent peroxisome proliferator that causes tumors.
WY-14,643 moderately elevated the level of TNF alpha mRNA in the liver. TNF
alpha was detected immunohistochemically exclusively in Kupffer cells.
These results demonstrate that WY-14,643 acts as an indirect mitogen on
hepatocytes via TNF alpha. We propose that the Kupffer cell, a major source
of TNF alpha in the liver, is involved in the mechanism of the mitogenic
effect of WY-14,643.
相似文献
42.
DR Heller 《Archives of disease in childhood》1994,70(4):339-41; discussion 41-2
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Grönefeld GC Israel CW Padmanabhan V Koehler J Cuijpers A Hohnloser SH;WorldWide Gem DR Study Group 《Pacing and clinical electrophysiology : PACE》2002,25(12):1708-1714
Reviews of stored electrograms from ICDs revealed a 5-30% incidence of short-long-short intervals preceding the onset of recurrent ventricular tachyarrhythmias. Rate stabilization by dedicated antibradycardia pacing algorithms has, therefore, been suggested to prevent onset of pause dependent tachyarrhythmias. However, the clinical efficacy of this approach has not been studied systematically. In a prospective multicenter crossover study, patients were randomized to activation or deactivation of an implemented ventricular rate stabilization algorithm (VRS) after first implant of a dual chamber ICD. After 3 months, all patients were crossed over to the alternate programming. The rate of appropriate spontaneous VA episodes was compared between VRS On and VRS Off. Stored electrograms were reviewed for evaluation of the mode of onset of tachyarrhythmias. Overall efficacy analysis was based on 309 patients enrolled in the study. Forty percent (124/309) of the patients experienced 4,973 VA episodes. Based on an intention-to-treat analysis, VRS Off and On arrhythmia incidence was 10.2 and 6.6 normalized to 3 months, respectively (risk reduction 35%; P = 0.18) On an on-treatment basis, a reduction from 9.0 episodes to 8.1 episodes (10% risk reduction, P = 0.24) was seen. In an extended Cox model adjusting for confounding variables, the relative risk for recurrent episodes was 0.92 during VRS On compared to Off (95% CI: 0.58-1.48; P = 0.74). During VRS Off, pause dependent onset was documented in only 36 (8%) of 427 visually analyzed episodes. There was no significant reduction in the incidence of recurrent ventricular tachyarrhythmias with VRS On compared to the Off programming in this prospective study. 相似文献
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Jill R Stewart Rebecca J Gast Roger S Fujioka Helena M Solo-Gabriele J Scott Meschke Linda A Amaral-Zettler Erika del Castillo Martin F Polz Tracy K Collier Mark S Strom Christopher D Sinigalliano Peter DR Moeller A Fredrick Holland 《Environmental health : a global access science source》2008,7(Z2):S3
Innovative research relating oceans and human health is advancing our understanding of disease-causing organisms in coastal ecosystems. Novel techniques are elucidating the loading, transport and fate of pathogens in coastal ecosystems, and identifying sources of contamination. This research is facilitating improved risk assessments for seafood consumers and those who use the oceans for recreation. A number of challenges still remain and define future directions of research and public policy. Sample processing and molecular detection techniques need to be advanced to allow rapid and specific identification of microbes of public health concern from complex environmental samples. Water quality standards need to be updated to more accurately reflect health risks and to provide managers with improved tools for decision-making. Greater discrimination of virulent versus harmless microbes is needed to identify environmental reservoirs of pathogens and factors leading to human infections. Investigations must include examination of microbial community dynamics that may be important from a human health perspective. Further research is needed to evaluate the ecology of non-enteric water-transmitted diseases. Sentinels should also be established and monitored, providing early warning of dangers to ecosystem health. Taken together, this effort will provide more reliable information about public health risks associated with beaches and seafood consumption, and how human activities can affect their exposure to disease-causing organisms from the oceans. 相似文献
49.
Thickett DR Poole AR Millar AB 《Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders》2001,18(1):27-33
Diffuse interstitial lung disease (DLD) is characterised by varying degrees of inflammation and fibrosis that result in derangement of the gas-exchanging units of the lung. A hallmark of these diseases is the abnormal deposition of collagen, which is a prime determinant of clinical course. This review considers the current information concerning collagen turnover in diffuse fibrotic lung disease. Considerable experimental evidence implicates both increased collagen production and reduced degradation in these diseases. Reduced degradation may result from both reduced production of collagenases and increased inhibition by tissue inhibitors. The known effects upon collagen turnover of novel therapeutic agents for pulmonary fibrosis (pirfenidone and interferon gamma) are discussed. 相似文献
50.
Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992 总被引:1,自引:1,他引:0 下载免费PDF全文
DB Langille MR Joffres KM MacPherson P Andreou SA Kirkland DR MacLean 《Canadian Medical Association journal》1999,161(8):S3-S9
BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification. 相似文献