Arylamine N-acetyltransferase type 1 (NAT1) is reported to be involved in the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs or carcinogens. Gene-specific hypomethylation frequently occurs in a range of cancers and hypomethylation of the genes often correlates well with increased transcription levels. This study was conducted in order to evaluate the methylation status and the transcriptional activity of NAT1 in breast cancer tissues (n=72), benign breast tissues (n=31) and morphologically normal breast tissues (n=30). Our findings showed that the methylation of the NAT1 gene was identified in 39 of the breast carcinomas (54.2%), 23 normal (76.7%) and 25 benign breast tissue samples (80.6%). The breast cancer tissues showed significantly lower methylation rates of the NAT1 promoters than the normal and benign tissues (P=0.012). Furthermore, cancer tissues showed lower methylation density rates than normal and benign breast tissues (P=0.012). The tissues that showed aberrant methylation of NAT1 showed significantly less mRNA expression compared with the unmethylated cases by a thousand fold (P<0.001). Twenty cancers from the methylated group showed positive staining for the estrogen receptor (ER) (51.3%), while 72.7% from the unmethylated group stained positive (P=0.063). Our results suggest that DNA hypomethylation in the NAT1 gene appears to be present in cancerous breast tissues thus indicating that this type of methylation may significantly influence the transcriptional activation of the gene. Therefore, hypomethylation of the NAT1 gene plays a significant role in breast carcinogenesis.
BackgroundDiabetic patients are predisposed to foot infections because of vascular insufficiency and peripheral neuropathy. Diabetic foot infection is a common cause of mortality and lower extremity amputations (LEAs) in patients with chronic kidney disease (CKD). We evaluated the risk factors for mortality and LEAs in patients with stage 3 CKD or higher with diabetic foot infections.MethodsWe retrospectively evaluated a cohort of 105 CKD patients with diabetic foot infections between July 1998 and December 2011. We reviewed their demographic characteristics and laboratory parameters to evaluate the risk factors for mortality and amputations at 24 weeks after diagnosis of a diabetic foot infection.ResultsThe mortality of the 105 enrolled CKD patients was 21% at 24 weeks after the diagnosis of a diabetic foot infection. Cox proportional regression analyses revealed that age 60 years or older [odds ratio (OR) 3.03, 95% confidence interval (CI) = 1.02-9.02, P = 0.047] and initial serum C-reactive protein (CRP) level ≥ 3 mg/dL (OR 3.97, 95% CI = 1.17-13.43, P = 0.027) were independent risk factors for mortality at 24 weeks. Twenty-four patients (23%) underwent LEAs. On Cox proportional regression analyses, peripheral vascular disease (OR=4.49, 95% CI=1.98–10.17, P=0.01) and cerebrovascular accident (OR 2.42, 95% CI=1.09–5.39, P=0.03) were independently associated with LEAs.ConclusionThis study showed that age and serum CRP level, were independent risk factors for mortality at 24 weeks in patients with stage 3–5 CKD with diabetic foot infections. Peripheral vascular disease and cerebrovascular accident were significantly associated with LEAs.
A systematically designed and synthesized ribitol phosphate (RboP) oligomer using a series of building blocks, which make up the wall teichoic acid (WTA) of S. aureus, is presented. Based on the use of a solution-phase phosphodiester synthesis, a library of ribitol phosphate tetramers, decorated with d-alanine and N-acetylglucosamine (GlcNAc), were generated. The synthesized RboP tetramers showed increased cytokine levels in mice in a subcutaneous air pouch model.
BackgroundContinuous veno-venous hemodiafiltration (CVVHDF) is a preferred treatment modality in hemodynamically unstable acute kidney injury (AKI) patients, because it has advantages over intermittent dialysis in terms of hemodynamic stability. However, this patient group still shows a significantly high mortality rate. To aid in the management of these high-risk patients, we evaluated the risk factors for mortality in CVVHDF-treated hypotensive AKI patients.MethodsWe studied 67 patients with AKI and hypotension who were treated with CVVHDF from February 2008 to August 2010. We reviewed patient characteristics and laboratory parameters to evaluate the risk factors for 90-day mortality.ResultsOf the 67 enrolled patients (male:female=42:25; mean age=69±14 years), 18 (27%) survived until 90 days after the initiation of CVVHDF. There was no significant difference in survival rates according to the etiology of AKI [hypovolemic shock 2/10 (20%), cardiogenic shock 4/20 (20%), septic shock 12/37 (32%)]. Univariate analysis did show significant differences between survivors and non-survivors in the frequency of ventilator use (44% vs. 76%, respectively; P=0.02), APACHE II score (29±7 vs. 34±7, respectively; P=0.01), SOFA score (11±4 vs. 13±4, respectively; P=0.03), blood pH (7.3±0.1 vs. 7.2±0.1, respectively; P=0.03), and rate of urine output <500 mL for 12 hours (50% vs. 80%, respectively; P=0.03). A multivariate Cox proportional hazards model showed that a urine output<500 mL for 12 hours was the only significant risk factor for 90-day mortality following CVVHDF treatment (odds ratio=2.1, confidence interval=1.01–4.4, P=0.048).ConclusionA urine output<500 mL for 12 hours before the initiation of CVVHDF is an independent risk factor for 90-day mortality in hypotensive AKI patients treated with CVVHDF.
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