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51.
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
52.
Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care 总被引:1,自引:0,他引:1
Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression anlysis or occurred in the best available control group with comparable scores ( p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants. 相似文献
53.
54.
Family response to cystic fibrosis 总被引:2,自引:0,他引:2
55.
To establish relative protection against methacholine and histamine, 40 micrograms of ipratropium bromide, an anticholinergic compound, 1.3 mg of metaproterenol or placebo aerosols were administered by metered-dose inhaler prior to inhalation challenge with methacholine or histamine in nine asthmatic subjects. Double-blind, randomized challenges were performed. Subjects required a mean methacholine dose of 1.72 +/- 0.73 and 2.46 +/- 0.72 (Ln inhalation units), and mean histamine dose of 2.16 +/- 0.65 and 2.68 +/- 0.49, to cause a drop of 20% and 35% respectively in the FEV1 following the placebo. In the methacholine challenges, both ipratropium bromide and metaproterenol had significant protection as compared to placebo (P less than 0.001). There was no statistical difference in the degree of protection against methacholine between ipratropium bromide and metaproterenol. In histamine challenges, metaproterenol had significant protection as compared to the placebo, while ipratropium bromide did not protect against histamine. 相似文献
56.
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58.
Many features of celiac disease resemble those of intestinal sucrase-isomaltase deficiency, a recognized inborn error of metabolism. Both diseases usually present in the first few years of life, have a high familial incidence, and involve intolerance to a specific foodstuff which tends to diminish in later childhood. It is proposed that celiac disease is an inborn error of metabolism involving deficiency of an intestinal peptidase. This allows a number of aspects of celiac disease to be explained and certain predictions to be made about the disorder. 相似文献
59.
H J Cornell R R Townley 《Clinica chimica acta; international journal of clinical chemistry》1973,49(2):181-188
Several fractions of a peptic-tryptic-pancreatic digest of wheat gliadin were evaluated for their effect on rat liver lysosomes as part of a study of the aetiology and pathogenesis of coeliac disease.On incubation with lysosome suspensions, Fraction 9 caused a greater degree of disruption of the lysosomes than did any other primary fraction of the digest. Peptides remaining after incubation of Fraction 9 with homogenates of duodenal mucosa from patients with coeliac disease in remission still had an appreciable effect on lysosomal membranes, in contrast to residues obtained from digestion with homogenates from control individuals.The results lend further support to the hypothesis of an intestinal peptidase deficiency in coeliac disease and point to peptides present in Sub-fraction 2 of Fraction 9 as being the most active to lysosomes.Since it has been shown that Fraction 9 and Sub-fraction 2 are incompletely digested by remission coeliac mucosa, the disruption of lysosomal bodies may possibly be a factor in the pathogenesis of coeliac disease. 相似文献