PubMed · 5404552
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W Schulte. 1969-08-01. [Cerebral vessel sclerosis: involution-depression].. https://pubmed.ncbi.nlm.nih.gov/5404552/
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A comprehensive analysis of the bovine spongiform encephalopathy (BSE) epidemic in cattle in Great Britain assesses past, present and future patterns in the incidence of infection and disease, and allows a critical appraisal of different culling policies for eradication of the disease.
We have previously demonstrated that 1131 base pairs (bp) of the human gonadotropin-releasing hormone (hGnRH) gene promoter can target simian virus 40 T antigen expression to GnRH neurons in transgenic mice. In these animals, GnRH neurons were transformed before they migrated to their final location in the rostral hypothalamus, complicating an analysis of cell-specific expression. To localize regions of the hGnRH promoter that are important for cell-specific expression, we created transgenic mice with various 5'-flanking regions of the hGnRH gene fused to the luciferase reporter gene. When 3828 or 1131 bp of the hGnRH promoter 5'-flanking DNA were used (-3828/+5LUC and -1131/+5LUC, respectively), luciferase expression in adult transgenic mice was observed in the rostral hypothalamus and olfactory tissues, regions which have been shown to be loci of GnRH-expressing neurons. Luciferase expression was not observed in other brain or peripheral tissues. Double-labeled in situ hybridization further demonstrated that luciferase expression was invariably colocalized with GnRH expression. When transgenic animals were created with a construct consisting of 484 bp of the hGnRH 5'-flanking DNA fused to the luciferase gene (-484/+5LUC), luciferase expression was not observed in the hypothalamus or in olfactory tissues. This is the first report localizing DNA sequences responsible for cell-specific expression of the GnRH gene in vivo.
BACKGROUND: We and others have previously described a number of characteristics that are associated with delays in diagnosis and increased risk for inadequate treatment of older women and men with cancer. These characteristics include poor social support, limited access to transportation, and impaired cognition. However, there is little information on how these factors influence survival of older cancer patients. PURPOSE: The purpose of the study was to determine which patient characteristics predicted survival up to 10 years after the diagnosis of cancer. METHODS: In 1984, we initiated a population-based study of men and women who were 65 years of age or older, living in a six-county area of New Mexico, and newly diagnosed with cancer. For 646 individuals with cancer of the breast (n = 188), prostate (n = 247), or colon or rectum (n = 211), we assessed patient baseline characteristics, disease stage at diagnosis, and adequacy of treatment (definitive or nondefinitive) as determinants of survival for up to 10 years following diagnosis. Multivariate survival models were used to analyze the data; all P values were two-sided. RESULTS: In multivariate analyses, we first included all patient characteristics, except the stage at diagnosis and the adequacy of treatment. In this initial analysis, the following were among variables that were significantly associated with patient survival: age, education, cancer knowledge, ethnic group, and cognitive status. When stage at diagnosis and adequacy of treatment were added to the model, both advanced stage at diagnosis (hazard ratio = 1.7 [95% confidence interval ¿CI¿ = 1.3-2.1] for diagnosis at regional stage versus local stage; hazard ratio = 3.0 [95% CI = 2.0-4.7] for distant stage versus local stage) and inadequate treatment (hazard ratio = 1.6 [95% CI = 1.1-2.3]) were associated with poor survival. However, adding stage at diagnosis and adequacy of treatment to the analysis had little influence on the magnitude of the effect of patient characteristics on survival. In separate analyses of patient data by cancer site, receipt of nondefinitive therapy was associated with increased mortality among patients with colon/rectal cancer (hazard ratio = 7.8 [95% CI = 2.8-21.4]) and breast cancer (hazard ratio = 2.2 [95% CI = 1.1-4.3]) but not among patients with prostate cancer (hazard ratio = 1.0 [95% CI = 0.6-1.9]). CONCLUSIONS: Advanced stage at diagnosis and inadequate treatment of older cancer patients are associated with poor survival. Impaired cognition and inadequate education in elderly patients are also associated with poor survival. This decreased survival does not appear to be a consequence of known barriers to health care that are responsible for delays in diagnosis and for inadequate treatment. IMPLICATIONS: Efforts to facilitate early diagnosis and receipt of definitive treatment for cancer in older individuals may improve their survival.