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61.
Xu M; Schut HA; Bjeldanes LF; Williams DE; Bailey GS; Dashwood RH 《Carcinogenesis》1997,18(11):2149-2153
Indole-3-carbinol (I3C) inhibits the formation of colonic aberrant crypt
foci and DNA adducts in rats given heterocyclic amine colon carcinogens,
such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Mechanism studies
indicate that I3C induces cytochromes P4501A1 and 1A2 (CYP1A1 and CYP1A2),
isozymes that respectively metabolize IQ via ring hydroxylation or activate
the carcinogen by N-hydroxylation. The present study examined the
dose-response for induction of CYP1A1 versus CYP1A2 by I3C, and compared
the profiles of induction with the dose- response for inhibition of IQ-DNA
adducts in the colon of the F344 rat. Dietary equivalent doses of I3C in
the range 100-1000 p.p.m. increased in a dose-related manner both
ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase
(MROD) activities in the liver and colonic mucosa, and Western blots showed
a corresponding induction of CYP1A1 and CYP1A2 proteins. However, dietary
equivalent doses of I3C in the range 10-25 p.p.m. (i) reduced hepatic EROD
and MROD activities and CYP1A protein levels compared with controls, (ii)
increased the ratio of CYP1A2 versus CYP1A1, and (iii) activated IQ to a
more potent mutagen when liver microsomes from rats given I3C were used for
metabolic activation in the Salmonella assay. Rats given a single oral dose
of I3C shortly before administering IQ (5 mg/kg body wt, p.o.) exhibited
dose-related inhibition of colonic IQ-DNA adducts in the range 25-100
p.p.m. I3C, reaching 95% inhibition at doses > or = 100 p.p.m. I3C, but
IQ-DNA adducts were elevated slightly at the lowest I3C dose as compared
with the controls. The possible significance of the low versus high dose
effects of I3C are discussed in the context of human dietary exposures to
I3C and the reported chemopreventive mechanisms of I3C in vivo.
相似文献
62.
Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure 总被引:2,自引:0,他引:2
Pomponio RJ; Narasimhan V; Reynolds TR; Buck GA; Povirk LF; Wolf B 《Human molecular genetics》1996,5(10):1657-1661
Biotinidase is responsible for recycling the vitamin biotin from biocytin
that is formed after the proteolytic degradation of the biotin- dependent
carboxylases. We have identified a deletion/insertion mutation within exon
D of the human biotinidase gene in a child with biotinidase deficiency. The
mutation causes a frame shift and premature termination which are predicted
to result in a truncated protein. We propose that the mutation occurred
during DNA replication by either of two mechanisms. Both mechanisms involve
formation of a quasipalindromic hairpin loop in the template and
dissociation of DNA polymerase alpha. This mutation supports the formation
of palindromic structures as a possible cause of deletions in eukaryotes,
and supports the proposal, derived from in vitro studies, that polymerase
alpha may preferentially arrest or dissociate at specific template
sequences.
相似文献
63.
64.
二苯乙烯类化合物对蛋白激酶C的抑制作用 总被引:14,自引:0,他引:14
报道15种二苯乙烯类化合物对蛋白激酶C(PKC)活性的影响。其中从中药金雀根中分得的3种二苯乙烯类低聚体α-viniferin,kobophenol A 和 miyabenolC,它们抑制PKC的IC50分别为62.5,52.0和27.5μmol·L-1。另外6种含酚羟基的二苯乙烯化合物对PKC也显示不同程度的抑制作用,但当酚羟基全甲基化或全乙酰化后其抑制作用大大降低甚至消失。酶动力学研究证明miyabenolC对PKC的抑制作用属于非竞争性抑制。 相似文献
65.
Eplov LF Jørgensen T Birket-Smith M Segel S Johansen C Mortensen EL 《Epidemiology (Cambridge, Mass.)》2005,16(2):226-232
BACKGROUND: Studies have demonstrated that mental vulnerability (ie, a tendency to experience psychosomatic symptoms or inadequate interpersonal interactions) is associated with various diseases. The objective of our study is to evaluate whether mental vulnerability is a risk factor for early mortality. METHODS: We conducted a prospective cohort study of 3 random samples of the population in Copenhagen County, Denmark selected in 1976, 1982-1984, and 1991 (n = 6435). Baseline data collection included measures of mental vulnerability, social factors, comorbidity, biologic risk markers (eg, blood pressure, lipid levels), and lifestyle factors. We determined vital status of the study sample through linkage to the Civil Registration System until 2001 and to the Cause of Death Registry until 1998. The mean follow-up time was 15.9 years for analysis of total mortality and 13.6 years for analysis of mortality as the result of natural causes. The association between mental vulnerability and survival was examined using Kaplan-Meir plots and Cox proportional-hazard models adjusting for possible confounding factors. RESULTS: With respect to mental vulnerability, 79% of the sample was classified as not vulnerable, 13% as moderately vulnerable, and 8% as highly vulnerable. Compared with the nonvulnerable group, highly vulnerable persons showed increased total mortality (hazard ratio = 1.6; 95% confidence interval = 1.3-1.9) and increased mortality from natural causes (1.6; 1.2-2.0). The inclusion of the mental vulnerability score as a continuous variable gave similar results. CONCLUSIONS: Mental vulnerability may be an independent risk factor for premature mortality. The biologic mechanisms that may underlie this association need further exploration. 相似文献
66.
67.
ABSTRACT: Although most of what is known about the biology and function of arachidonic acid metabolites comes from the study of mammalian biology, these compounds can also be produced by lower eukaryotes, including yeasts and other fungi. It is also in this group of organisms that the least is known about the metabolic pathways leading to the production of these compounds as well as the functions of these compounds in the biology of fungi and yeasts. This review will deal with the discovery of oxylipins from polyunsaturated fatty acids, and more specifically the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic acid, prostaglandin F2alpha and prostaglandin E2, in yeasts starting in the early 1990s. This review will also focus on what is known about the metabolic pathways and/or proteins involved in the production of these compounds in pathogenic yeasts. The possible roles of these compounds in the biology, including the pathology, of these organisms will be discussed. 相似文献
68.
Analysis with antiidiotype antibody of a patient with chronic lymphocytic leukemia and a large cell lymphoma (Richter's syndrome) 总被引:1,自引:0,他引:1
Bertoli LF; Kubagawa H; Borzillo GV; Mayumi M; Prchal JT; Kearney JF; Durant JR; Cooper MD 《Blood》1987,70(1):45-50
A murine monoclonal antibody made against an idiotypic determinant (Id) of surface IgM/IgD lambda molecules on chronic lymphocytic leukemia (CLL) cells of a 71-year-old woman was used for clonal analysis by two- color immunofluorescence. The anti-Id antibody identified IgM+/IgD+/lambda+ B cells as the predominant cell type of her CLL clone. In addition, substantial proportions of the IgG and IgA B cells and most of the IgM plasma cells in her bone marrow and blood were Id+. Six years after diagnosis, the patient died of respiratory failure due to infiltration of lungs by malignant cells. Autopsy revealed a dramatic change in the tumor cell morphology. The lungs, hilar nodes, and liver were infiltrated by a diffuse large cell lymphoma admixed with the leukemic cells. By immunohistologic staining these anaplastic lymphoma cells were IgM+/IgD-/lambda+ B cells expressing the same Id noted earlier on the CLL cells. The immunoglobulin gene rearrangement pattern on Southern blot analysis was also the same in leukemic blood cells and in the tissues involved by the lymphoma. Thus, the combination of antiidiotype and immunoglobulin gene analyses in this patient with Richter's syndrome revealed that a CLL clone, seemingly "frozen" in differentiation, was actually undergoing isotype switching, differentiation into plasma cells, and evolution into a rapidly growing and fetal lymphoma. 相似文献
69.
Small lesions in the heart identified at electron beam CT: calcification or noise? 总被引:11,自引:0,他引:11
Bielak LF; Kaufmann RB; Moll PP; McCollough CH; Schwartz RS; Sheedy PF nd 《Radiology》1994,192(3):631
70.