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981.
Alterations in Notch signaling in neoplastic lesions of the human cervix. 总被引:31,自引:0,他引:31 下载免费PDF全文
P Zagouras S Stifani C M Blaumueller M L Carcangiu S Artavanis-Tsakonas 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(14):6414-6418
The development of cancer is a cellular process that reflects and is partly driven by alterations in cell determination. Mutations in various molecules responsible for cell determination have been identified as being oncogenic, but little is known about the involvement of normal cell fate-determining mechanisms in the oncogenic process. The Notch pathway defines an evolutionarily conserved, general cell interaction mechanism that controls fundamental aspects of cell determination during vertebrate and invertebrate development. We have explored the involvement of the human Notch pathway in human cervical tissues, which define a cellular environment where cell fate changes take place and where neoplastic conditions have been well characterized. Our evidence suggests that Notch expression is associated with cell populations that are undergoing cell fate changes and that Notch activity can be used to monitor cell fate abnormalities in cervical as well as other epithelial neoplasias. 相似文献
982.
BACKGROUND: Selenium dependent glutathione peroxidase (GPx) reduces hydrogen peroxide (H2O2) and organic hydrogen peroxides in both normal and pathological states. Chronic dietary deficiency of selenium results in a gradual decrease in GPx and altered response to environmental stress. However, glutathione-S-transferase (GST) isozymes may increase and compensate for chronic GPx deficiency. The pattern of antioxidant enzyme activity and immunolocalisation of various enzymes in rat lung has not been described in short term (< 3 weeks) acute selenium deficiency. METHODS: The time course of GPx depletion from rat lung (measured every five days in subgroups of rats) during acute dietary selenium deficiency was evaluated. After 20 days of depletion, enzyme activity of lung GPx, catalase, superoxide dismutase (SOD), glutathione reductase (GR), glucose-6-phosphodiesterase (G-6-PD), and GST were determined. Immunohistochemical localisation of GPx and SOD was also performed. The response to lethal hyperoxia (> 95%) in control and selenium deficient rats was then established. RESULTS: At 20 days, lung GPx activity in the rats fed a selenium deficient diet was one third less than in control animals who received a normal diet, while changes in blood enzymes between control and deficient animals were similar. Other lung enzyme activities remained normal with the exception of cyanide inhibited SOD activity measured in selenium deficient rat lungs which declined to approximately 50% of normal. Immunohistochemical localisation of GPx showed a generalised loss of the enzyme throughout the lung parenchyma with some possible sparing of activity in epithelial cells of the bronchioles. When exposed to lethal hyperoxia, selenium deficient animals were more susceptible than control rats. CONCLUSIONS: This is the earliest time at which dietary selenium deficiency has been shown to produce moderate loss of GPx activity. This change in activity was associated with increased susceptibility to pulmonary oxidant stress. However, the role of decreased SOD activity (presumed to represent copper, zinc SOD), although unexpected, may have been a major contributor to increased damage from hyperoxia. These results emphasise the complex potential interaction of elemental deficiency with the natural antioxidant response to lethal hyperoxia. 相似文献
983.
984.
The mutational specificity of the syn dihydrodiol epoxide of 5-methylchrysene in the supF gene of the pSP189 vector was examined. Transversion mutations at GC pairs predominated with G → T and G → C changes accounting for 42 and 21% of total base change mutations. The types of mutations found reflect the previously determined chemical preference of this reactive species for reaction with deoxyguanosine residues in DNA. 相似文献
985.
Xinyu D. Li Esperanza Arias Ramamohana R. Jonnala Shyamala Mruthinti Jerry J. Buccafusco 《Journal of molecular neuroscience : MN》1996,27(3):325-336
The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms.
One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors.
Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere
with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent
increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked
by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine
also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into
a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to
32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression
in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically
relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic
neurons susceptible to the neurotoxicity associated with Alzheimer’s disease. 相似文献
986.
Pamela E. B. Rodgers-Johnson Frederick W. Hickling Aggrey Irons Bruce K. Johnson Maureen Irons-Morgan Gary A. Stone Clarence J. Gibbs 《Journal of molecular neuroscience : MN》1996,28(1-3):237-243
Reports of an 18-fold higher incidence of schizophrenia among second-generation Afro-Caribbeans, and especially Jamaican migrants
in the United Kingdom were soon called “an epidemic of schizophrenia,” with the inference that a novel virus, likely to be
perinatally transmitted, was a possible etiological agent. This intriguing observation led us to explore a possible link with
human T-cell lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in the Caribbean Islands, is perinatally
transmitted, known to be neuropathogenic, and the cause of a chronic myelopathy (tropical spastic paraparesis/ HTLV-I associated
myelopathy). We therefore examined inpatients at the Bellevue Mental Hospital, Kingston, Jamaica and did standard serological
tests for retroviruses HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and DSM III-R criteria
for schizophrenia. Our results produced important negative data, since the seropositivity rates for HTLV-I, the most likely
pathogen, were no greater than the seropositivity range for HTLV-I carriers in this island population, indicating that HTLV-I
and the other retroviruses tested do not play a primary etiological role in Jamaican schizophrenics. 相似文献
987.
988.
化学染发剂和冷烫精的毒性及对人体健康影响的调查研究 总被引:7,自引:1,他引:6
本文通过化学染发剂和冷烫精对大白鼠骨髓多染红细胞,毛囊细胞的微核实验及人群健康影响调查,结果表明化学染发剂,冷烫清具有较强致突变作用,两者同时使用致突变明显增强,并提出研制高效无毒染发剂和加强防护的重要性。 相似文献
989.
D C Des Jarlais J Wenston S R Friedman J L Sotheran R Maslansky M Marmor S Yancovitz S Beatrice 《American journal of public health》1992,82(11):1531-1533
The Centers for Disease Control (CDC) has proposed revising the AIDS surveillance definition to include any HIV-seropositive person with a CD4 cell count of less than 200 cells per microliter. Based on a study of persons receiving treatment for HIV infection, this new definition would lead to an estimated 50% increase in the number of persons recognized as living with AIDS. Among 440 HIV-seropositive research subjects recruited from drug treatment programs and through street outreach in New York City, 59 met this definition, yet only 25% of those had been reported to the New York City AIDS registry. The new definition, if combined with HIV and T-cell testing at drug treatment and street outreach programs, could thus yield very large increases in the number of injecting drug users meeting the new surveillance definition of AIDS. 相似文献
990.