Association between cigarette smoking and hypoxanthine guanine phosphoribosyltransferase activity

The aim of this study was to investigate the association between smoking behavior and hypoxanthine guanine phosphoribosyltransferase (HGPRT) activity. A cross-sectional study was performed of 82 men, including 38 non-smokers and 44 smokers. Inosine monophosphate (IMP), the product of HGPRT (used as the index of activity), was measured in peripheral blood mononuclear cells using high-performance liquid chromatography. The factors potentially associated with HGPRT activity included age, glutamyl oxaloacetic transaminase, glutamyl pyruvic transaminase, cholesterol, uric acid, triglycerides, creatinine, body mass index, gout, systolic blood pressure, diastolic blood pressure, alcohol consumption, and cigarette smoking. Mean HGPRT activity was 7.05 +/- 3.44 nmol/10(6) viable cells/hour for all participants, and was significantly lower for smokers than for non-smokers (6.24 +/- 3.40 vs 7.98 +/- 3.28 nmol/10(6) viable cells/hour; p = 0.02). In addition, as the number of smoked cigarettes increased, the HGPRT activity decreased (p < 0.05). The age at onset of cigarette smoking showed a positive correlation with HGPRT activity after adjusting for smoking duration, serum uric acid, and cigarettes smoked per year using a multiple regression model (p < 0.001). We concluded that the greater the number of cigarettes smoked, the lower the HGPRT activity, and that HGPRT activity was higher in smokers who had started smoking later.     

Insulin receptors on leukemia and lymphoma cells

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I- labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.     

A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16)

Mutations in the KCNJ13 gene that encodes the inwardly rectifying potassium channel Kir7.1 cause snowflake vitreoretinal degeneration (SVD) and leber congenital amaurosis (LCA). Kir7.1 controls the microenvironment between the photoreceptors and the retinal pigment epithelium (RPE) and also contributes to the function of other organs such as uterus and brain. Heterologous expressions of the mutant channel have suggested a dominant‐negative loss of Kir7.1 function in SVD, but parallel studies in LCA16 have been lacking. Herein, we report the identification of a novel nonsense mutation in the second exon of the KCNJ13 gene that leads to a premature stop codon in association with LCA16. We have determined that the mutation results in a severe truncation of the Kir7.1 C‐terminus, alters protein localization, and disrupts potassium currents. Coexpression of the mutant and wild‐type channel has no negative influence on the wild‐type channel function, consistent with the normal clinical phenotype of carrier individuals. By suppressing Kir7.1 function in mice, we were able to reproduce the severe LCA electroretinogram phenotype. Thus, we have extended the observation that Kir7.1 mutations are associated with vision disorders to include novel insights into the molecular mechanism of disease pathobiology in LCA16.     

A smoking cessation intervention among tuberculosis patients in rural China

Objective: To assess the integration of a smoking cessation intervention into routine tuberculosis (TB) services.Method: Consecutive TB patients registered from 1 March to 31 August 2010 were enrolled in an intervention for self-reported smoking to promote tobacco cessation during treatment for TB. Information on the harmful health effects of tobacco smoke and smoking and TB were provided to TB patients who self-reported as current smokers. Smoking status was reassessed at every follow-up visit during anti-tuberculosis treatment with reinforced health messages and advice to quit.Results: Of 800 TB patients enrolled, 572 (71.5%) were male and 244 (30.5%) were current smokers. Females were more likely to be non-smokers (100% vs. 35.8%, P < 0.001). Of the 244 current smokers, 144 (59.0%) started smoking at <20 years, 197 (80.7%) consumed ⩾20 cigarettes per day, 211 (86.5%) had perceived smoking dependence and 199 (81.6%) had made no attempt to quit before the diagnosis of TB. Of the 244 current smokers, 234 (95.9%) were willing to quit, and 156 (66.7%) reported abstinence at month 6. Challenges to implementing smoking cessation intervention were identified.Conclusion: The majority of current smokers among TB patients were willing to quit and remained abstinent at the end of anti-tuberculosis treatment. This intervention should be scaled up nationwide.     

Cancer Risk Assessment Tools in Primary Care: A Systematic Review of Randomized Controlled Trials

PURPOSE

We conducted this review to identify published randomized controlled trials (RCTs) of cancer risk assessment tools used in primary care and to determine their impact on clinical utility (clinicians), screening uptake (patients), and psychosocial outcomes (patients).

METHODS

We searched EMBASE, PubMed and the Cochrane databases for RCTs of cancer risk assessment tools in primary care up to May 2014. Only studies set in primary care, with patients eligible for screening, and English-language articles were included.

RESULTS

The review included 11 trials of 7 risk tools. The trials were heterogeneous with respect to type of tool that was used, type(s) of cancer assessed, and outcomes measured. Evidence suggested risk tools improved patient risk perception, knowledge, and screening intentions, but not necessarily screening behavior. Overall, uptake of a tool was greater if initiated by patients, if used by a dedicated clinician, and when combined with decision support. There was no increase in cancer worry. Health promotion messages within the tool had positive effects on behavior change. Trials were limited by low-recruitment uptake, and the heterogeneity of the findings necessitated a narrative review rather than a meta-analysis.

CONCLUSIONS

Risk tools may increase intentions to have cancer screening, but additional interventions at the clinician or health system levels may be needed to increase risk-appropriate cancer screening behavior.     

Serum soluble programmed death-1 levels predict the spontaneous HBeAg seroclearance in chronic hepatitis B

Journal of Gastroenterology - In chronic hepatitis B virus (HBV) infection, earlier seroclearance of hepatitis B e antigen (HBeAg) is associated with more favorable outcomes. Soluble programmed...     

A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model.

Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells and smooth muscle, and subepithelial fibrosis. We examined the role of leukotrienes in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 and 14, received intranasal OVA periodically Days 14-75. The OVA-treated mice developed an extensive eosinophil and mononuclear cell inflammatory response, goblet cell hyperplasia, and mucus occlusion of the airways. A striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated controls. The cysteinyl leukotriene(1) (CysLT(1)) receptor antagonist montelukast significantly reduced the airway eosinophil infiltration, mucus plugging, smooth muscle hyperplasia, and subepithelial fibrosis in the OVA-sensitized/challenged mice. The presence of Charcot-Leyden-like crystals in airway macrophages and the increased interleukin (IL)-4 and IL-13 mRNA expression in lung tissue and protein in BAL fluid seen in OVA-treated mice were also inhibited by CysLT(1) receptor blockade. These data suggest an important role for cysteinyl leukotrienes in the pathogenesis of chronic allergic airway inflammation with fibrosis.