ABSTRACT
Maternal undernutrition results in offspring nephron number reduction and hypertension that are hypothesized to begin as compensatory changes in fetal gene expression during gestation. To evaluate mechanisms of dysregulated nephrogenesis, pregnant Sprague Dawley rats were 50% food restricted from embryonic day (E) 10 to E20. At E20, fetal male kidneys were examined by microarray analysis. A total of 476 differentially expressed transcripts were detected including those regulating development and differentiation, mitosis and cell cycle, chromatin assembly, and steroid hormone regulation. Differentially regulated genes were detected in MAPK/ERK, Wnt, and Notch signaling pathways. Validation of the microarray results was performed for the Notch signaling pathway, an important pathway in nephron formation. Protein expression of Notch pathway factors by Western blotting showed significantly decreased Notch2 and downstream effector Hey1 protein expression, while Ctbp1 co-repressor was increased. These data together show that maternal undernutrition results in developmental disruption in fetal nephrogenesis gene expression signaling.
Subject(s)
Gene Expression Regulation, Developmental , Kidney Diseases/etiology , Kidney Diseases/genetics , Malnutrition/complications , Nephrons/embryology , Receptors, Notch/genetics , Animals , Basic Helix-Loop-Helix Transcription Factors/biosynthesis , Carrier Proteins/biosynthesis , Down-Regulation , Female , Male , Mitogen-Activated Protein Kinases/metabolism , Nephrons/metabolism , Pregnancy , Rats , Rats, Sprague-Dawley , Repressor Proteins/biosynthesis , Signal Transduction , Transcription Factors/biosynthesis , Wnt Proteins/metabolismABSTRACT
OBJECTIVE: To examine the impact of age, race, and medical funding on cervical cancer survival. MATERIALS AND METHODS: Study design was a retrospective chart review of cervical cancer patients. Charts were abstracted for demographic characteristics, Pap smear history, clinical presentation, treatment, and survival. Descriptive studies, Spearman correlation, and Cox's proportional hazards regression model were performed. RESULTS: One hundred-twenty-five cervical cancer patients were included. Mean age at diagnosis was 46.1 +/- 13.2 years, and median survival time from cervical cancer was 31 months; 11.2% of the study population was aged greater than 65 years; 63.4% were African American; and 44.6% had no medical funding. Diagnosis at age of at least 65 years was significantly correlated with suboptimal cervical cancer screening pattern (r = 0.36, p = .0003). Women aged at least 65 years old had a 3.39 time increased hazard of death compared to younger patients (p = .02; OR, 3.39; 95% CI, 1.20-9.56) after adjusting for advanced stage of disease and treatment modality. There was no significant association between medical funding or race on cervical cancer screening pattern, stage at diagnosis, or survival. CONCLUSION: Age at diagnosis (> or = 65 years), but not medical funding or race, was correlated with suboptimal cervical cancer screening pattern and poor survival.
