Molecular cloning and nucleotide sequence of cDNA encoding the entire precursor of rat liver medium chain acyl coenzyme A dehydrogenase.

cDNA encoding the precursor of rat liver medium chain acyl-CoA dehydrogenase (EC 1.3.99.3) was cloned and sequenced. The longest cDNA insert isolated was 1866 bases in length. This cDNA encodes the entire protein of 421-amino acids including a 25-amino acid leader peptide and a 396-amino acid mature polypeptide. The identity of the medium chain acyl-CoA dehydrogenase clone was confirmed by matching the amino acid sequence predicted from the cDNA to the NH2-terminal and nine internal tryptic peptide sequences derived from pure rat liver medium chain acyl-CoA dehydrogenase. The calculated molecular masses of the precursor medium chain acyl-CoA dehydrogenase, the mature medium chain acyl-CoA dehydrogenase, and the leader peptide are 46,600, 43,700, and 2,900 daltons, respectively. The leader peptide contains five basic amino acids and only one acidic amino acid; thus, it is positively charged, overall. Cysteine residues are unevenly distributed in the mature portion of the protein; five of six are found within the NH2-terminal half of the polypeptide. Comparison of medium chain acyl-CoA dehydrogenase sequence to other flavoproteins and enzymes which act on coenzyme A ester substrates did not lead to unambiguous identification of a possible FAD-binding site nor a coenzyme A-binding domain. The sequencing of other homologous acyl-CoA dehydrogenases will be informative in this regard

Association between shift work and the risk of death from biliary tract cancer in Japanese men

Background: There is increasing evidence suggesting that shift work involving night work may increase cancer risk. Methods: We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46, 395 men recruited, 22, 224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. Results: During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. Conclusion: Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths

Sleep duration and risk of breast cancer : The JACC Study

PurposeThe evidence on beneficial or adverse effects of sleep duration on risk of breast cancer remains controversial and limited, especially in Asia.MethodsA prospective study of 34,350 women aged 40-79years in whom sleep duration, and menstrual and reproductive histories were determined by a self-administered questionnaire. The follow-up period was from 1988 to 2009, and hazard ratios (HRs) with 95% confidence intervals (CIs) of breast cancer incidence were calculated for shorter sleep duration in reference to sleep duration of 8h/day by Cox proportional hazard models.ResultsDuring 19.2-year median follow-up (236 cases), we found a significant inverse association between sleep duration and risk of breast cancer, especially among postmenopausal women and women with low parity (nulliparous and women with <3 children); the multivariable HRs (95% CIs) among postmenopausal women who reported 7h/day and 6h/day of sleep in reference to 8h/day were 1.49 (0.81-2.76) and 1.98 (1.08-3.70) (P for trend=0.028), respectively, and the corresponding values among women with low parity were 1.50 (0.96-2.35) and 1.76 (1.01-2.79) (P for trend=0.018).ConclusionsShort sleep duration was associated with increased risk of incident breast cancer, especially among postmenopausal women and women with low parity

Long-term use of carvedilol in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND:Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS:In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06). CONCLUSION:Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI. TRIAL REGISTRATION:CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635

Self-Reported Eczema in Relation with Mortality from Cardiovascular Disease in Japanese : the Japan Collaborative Cohort Study

Aim: Previous studies suggested a positive association between eczema and cardiovascular disease (CVD), probably through enhanced systemic inflammation. However, several studies reported null findings about eczema and CVD, so the evidence is still controversial. Methods: We asked 85,099 participants (35,489 men and 49,610 women), aged 40 to 79 years, without a history of CVD or cancer at baseline between 1988 and 1990, to complete a lifestyle questionnaire, including information eczema frequency (seldom, sometimes or often). Results: During the 6,389,818 person-years of follow-up, there were 1,174 deaths from coronary heart disease (CHD), 979 from heart failure, 366 from cardiac arrhythmia, 2,454 from total stroke, 1,357 from ischemic stroke, 1,013 from hemorrhagic stroke, and 201 from aortic aneurysm or dissection. The multivariable-adjusted model showed that individuals who "sometimes" or "often" had eczema had 0.82 (95%confidence interval (CI): 0.69-0.97) or 1.26 (95%CI: 1.01-1.56) times the risk of mortality from CHD, respectively, compared to those who "seldom" did. Individuals who "often" had 1.30 (95%CI: 1.05-1.61) times the risk of mortality from CHD, compared to those who "seldom or sometimes" did. There was no association of eczema with mortality from other CVD, or no interaction between eczema and sex or age, in relation to any CVD mortality risk. Conclusions: Self-reported frequent eczema was associated with increased risk of mortality from CHD, but not other major CVD, in a Japanese general population. Since steroid usage was not considered, future studies should include it as a potential confounding factor