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Retinoids, which are important regulators of cell growth, differentiation, and apoptosis, have been used in treatment or chemoprevention of multiple cancers including prostate cancer. To elucidate the mechanism of action of retinoids in the context of the prostate, we used the Cre-loxP system to disrupt the retinoid X receptor alpha (RXRalpha) gene specifically in the prostatic epithelium of the mouse. Evidence for tissue-specific gene inactivation was obtained at DNA, RNA, and protein levels. Phenotypic changes in the prostate in the homozygous animals of different age groups ranging from 1 to 15 months were investigated. Developmentally, prostatic ductal branching appeared to be increased from the loss of RXRalpha function. There was also a significant change in the profile of secretory proteins in the RXRalpha mutant prostate relative to littermate controls with intact RXRalpha allele. Histopathologically, homozygous RXRalpha-deficient prostates showed multifocal hyperplasia as early as 4 months of age. Lesions, which could be described as low-grade prostatic intraepithelial neoplasias, were detected after 5 months. Subsequently, beginning at approximately 10 months, high-grade prostatic intraepithelial neoplasias developed in some animals. The incidences of low-grade prostatic intraepithelial neoplasias and high-grade prostatic intraepithelial neoplasias among the animals 10-15 months of age were 62 and 17%, respectively. The heterozygous mutant mice also developed similar prostatic phenotypes but in a delayed manner, implying a role of haploinsufficiency. Together, these results indicated for the first time that a major component of retinoid action in the prostate is mediated by a retinoid receptor, RXRalpha, the inactivation of which in the prostatic epithelium leads to the development of preneoplastic lesions.  相似文献   
995.
Isolation and characterization of novel oligosaccharides related to Ziracin   总被引:1,自引:0,他引:1  
Five novel oligosaccharide antibiotics, Sch 58769 (1), Sch 58771 (2), Sch 58773 (3), Sch 58775 (4), and Sch 58777 (5), were isolated from the fermentation broth of Micromonospora carbonacea var africana. Their structures were determined by spectroscopic methods, including MS and (1)H and (13)C NMR experiments. A comparison of the obtained data with that for Ziracin (Sch 27899) revealed that these oligosaccharides belong to the same everninomicin family of compounds. Ziracin demonstrates potent activity against Gram-positive bacteria both in vitro and in vivo including multiply resistant strains of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci faecalis.  相似文献   
996.
The role of mitochondrial DNA deletions (dmtDNA) in involutional bone loss seen in elderly men and women has never been examined. The present investigation was carried out to determine the extent of dmtDNA in cortical bone of elderly patients undergoing knee and hip arthroplasties. The majority of earlier studies have employed the polymerase chain reaction (PCR) to detect and quantify dmtDNA in different body tissues. In the present study, Southern blotting was used to screen bone biopsies from 30 patients undergoing orthopaedic surgery (mean age+/-SD 67.5+/-9.6 years; range 49-87 years). The blotting of PvuII-digested genomic DNA, carried out using mtDNA probes covering the entire span of mtDNA, revealed high levels of deletions in six subjects (mean age+/-SD 63.0+/-10.1 years; range 49-78 years) and moderate to low levels of mutations in another 14 subjects (mean age+/-SD 64.9+/-8.9 years; range 53-87 years). The importance of this rather high prevalence of dmtDNA in the bone of the elderly is discussed in terms of possible involvement of increased production of oxygen-derived free radicals and oxidative stress, and its possible role in the accelerated bone loss leading to osteoporosis.  相似文献   
997.
During the past few decades, epidemics of dengue fever are causing concern in several South-East Asian countries including India. The rural areas of Hissar district of Haryana state, situated about 170 km North-West of Delhi, experienced an outbreak of febrile illness during July-August 1996. A total of 13 villages in eight affected primary health centres reported fever cases. The clinical, epidemiological and entomological findings indicated that the present episode was due to dengue fever. The aetiological agent of the current outbreak, the DEN-2 virus, was isolated from 12 acute-phase sera specimens. Though, in the recent past outbreaks have been reported from the rural areas of southern and western India, the present episode is the first outbreak being reported from the rural areas of northern India. The increasing frequency of dengue fever outbreaks in rural areas of various Indian states reflects the changing life style of the rural population as a result of urbanization process and calls for a suitable prevention and control policy based on strengthened surveillance, appropriate health education to the community coupled with proper training of health personnel.  相似文献   
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Between December 1999 and December 2000, teams from the National Institute of Cholera and Enteric Diseases, Calcutta, India, examined eight outbreaks of cholera, which occurred in different parts of the country distant from each other. In two of these outbreaks each, only V. cholerae O1 biotype ElTor or V. cholerae O139 could be isolated, while in the remaining four outbreaks, both O1 and O139 were isolated. The interesting feature is the escalating association of V. cholerae O139 with outbreaks of cholera; two of the most recent outbreaks, one in Calcutta and one in Orissa, were caused exclusively by O139. The O139 strains from the six different outbreaks were genotypically closely related. These trends indicate a shift in the outbreak propensity of V. cholerae O139.  相似文献   
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