ABSTRACT
Chronic kidney disease (CKD) has recently been reported to be an independent risk factor for stroke. However, a detailed analysis was yet to be conducted according to stroke subtype. We attempted to determine the risk factors for stroke using data from the “specific health checkup” for metabolic syndrome conducted by the 9 hospitals affiliated with the Akita Prefectural Federation of Agricultural Cooperatives, and evaluate and determine the risk factors for stroke. There were 401 patients who had undergone metabolic syndrome checkups from 2007 and 2010 and suffered from stroke afterwards within 3 years after the screening. The controls were all 69,407 subjects who were screened during the same period. The predictors examined were sex, age, blood pressure, BMI, cholesterol values (HDL・LDL), history of diabetes mellitus, presence of atrial fibrillation, CKD, and drinking and smoking habits. Analysis was conducted using logistic regression. The risk factors for stroke as a whole were male sex, age, blood pressure, diabetes, atrial fibrillation, CKD, and smoking history. For cerebral infarction, the risk factors were male sex, age, blood pressure, diabetes, atrial fibrillation, CKD, and smoking habit. The risk factors for cerebral hemorrhage were age, blood pressure, and CKD. For subarachnoid hemorrhage, the risk factors were female sex, age, blood pressure, low HDLemia, and CKD. In conclusion, CKD is an independent risk factor for the 3 subtypes of stroke, and in particular plays an important role as a higher risk factor for cerebral hemorrhage. Smoking cessation and controls of blood pressure, diabetes and atrial fibrillation are the important measures for stroke prevention. In addition, the further intervention should also be targeted to those with the result of CKD revealed by specific health checkups.
ABSTRACT
Cellular senescence is an irreversible cell cycle arrest triggered by the activation of oncogenes or mitogenic signaling as well as the enforced expression of tumor suppressors such as p53, p16(INK4A) and promyelocytic leukemia protein (PML) in normal cells. E2F-binding protein 1 (E2FBP1), a transcription regulator for E2F, induces PML reduction and suppresses the formation of PML-nuclear bodies, whereas the down-regulation of E2FBP1 provokes the PML-dependent premature senescence in human normal fibroblasts. Here we report that the depletion of E2FBP1 induces the accumulation of PML through the Ras-dependent activation of MAP kinase signaling. The cellular levels of p16(INK4A) and p53 are elevated during premature senescence induced by depletion of E2FBP1, and the depletion of p16(INK4A), but not p53 rescued senescent cells from growth arrest. Therefore, the premature senescence induced by E2FBP1 depletion is achieved through the p16(INK4A)-Rb pathway. Similar to human normal fibroblasts, the growth inhibition induced by E2FBP1 depletion is also observed in human tumor cells with intact p16(INK4A) and Rb. These results suggest that E2FBP1 functions as a critical antagonist to the p16(INK4A)-Rb tumor suppressor machinery by regulating PML stability.
Subject(s)
Humans , Cell Line, Tumor , Cells, Cultured , Cellular Senescence , Genetics , Physiology , Cyclin-Dependent Kinase Inhibitor p16 , Genetics , Physiology , DNA-Binding Proteins , Genetics , Physiology , Down-Regulation , Fibroblasts , Gene Expression Regulation , Intranuclear Inclusion Bodies , Metabolism , MAP Kinase Signaling System , Nuclear Proteins , Genetics , Metabolism , Physiology , Promyelocytic Leukemia Protein , Protein Isoforms , Protein Stability , RNA Interference , Retinoblastoma Protein , Genetics , Physiology , Transcription Factors , Genetics , Metabolism , Physiology , Transfection , Tumor Suppressor Protein p53 , Physiology , Tumor Suppressor Proteins , Genetics , Metabolism , Physiology , Ubiquitination , ras Proteins , MetabolismABSTRACT
Non-tubercuous mycobacterial (NTM) infection in peritoneal dialysis (PD) patients has been rarely reported. We report a case of a 55-year-old female on continuous ambulatory peritoneal dialysis (CAPD). After a 2-year-history of recurrent exit-site infection of a PD catheter caused by Mycobacterium abscessus (M. abscessus), the patient was admitted to the hospital with signs of peritonitis. Since the same species, M. abscessus, was isolated from the CAPD effluent, multiple antibiotics were administered. However, the treatments could not relieve the symptoms of her infection. Consequently, the PD catheter was removed. Her condition gradually recovered over the course of subsequent, long-term, empirical antimicrobial therapies. NTMs, especially a rapidly growing NTM infection, have rarely been reported in PD patients and are commonly resistant to a variety of antimicrobial agents. Routine acid-fast staining is most likely helpful in promptly initiating treatment against NTM infection in PD patients. Moreover, an appropriate treatment regimen for a rapidly growing NTM infection should be established by accumulating data from cases as reported here.