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81.
Mar Pujades-Rodriguez Adam Timmis Dimitris Stogiannis Eleni Rapsomaniki Spiros Denaxas Anoop Shah Gene Feder Mika Kivimaki Harry Hemingway 《PloS one》2014,9(8)
Background
Recent experimental evidence suggests that socioeconomic characteristics of neighbourhoods influence cardiovascular health, but observational studies which examine deprivation across a wide range of cardiovascular diseases (CVDs) are lacking.Methods
Record-linkage cohort study of 1.93 million people to examine the association between small-area socioeconomic deprivation and 12 CVDs. Health records covered primary care, hospital admissions, a myocardial infarction registry and cause-specific mortality in England (CALIBER). Patients were aged ≥30 years and were initially free of CVD. Cox proportional hazard models stratified by general practice were used.Findings
During a median follow-up of 5.5 years 114,859 people had one of 12 initial CVD presentations. In women the hazards of all CVDs except abdominal aortic aneurysm increased linearly with higher small-area socioeconomic deprivation (adjusted HR for most vs. least deprived ranged from 1.05, 95%CI 0.83–1.32 for abdominal aortic aneurysm to 1.55, 95%CI 1.42–1.70 for heart failure; I2 = 81.9%, τ2 = 0.01). In men heterogeneity was higher (HR ranged from 0.89, 95%CI 0.75–1.06 for cardiac arrest to 1.85, 95%CI 1.67–2.04 for peripheral arterial disease; I2 = 96.0%, τ2 = 0.06) and no association was observed with stable angina, sudden cardiac death, subarachnoid haemorrhage, transient ischaemic attack and abdominal aortic aneurysm. Lifetime risk difference between least and most deprived quintiles was most marked for peripheral arterial disease in women (4.3% least deprived, 5.8% most deprived) and men (4.6% least deprived, 7.8% in most deprived); but it was small or negligible for sudden cardiac death, transient ischaemic attack, abdominal aortic aneurysm and ischaemic and intracerebral haemorrhage, in both women and men.Conclusions
Associations of small-area socioeconomic deprivation with 12 types of CVDs were heterogeneous, and in men absent for several diseases. Findings suggest that policies to reduce deprivation may impact more strongly on heart failure and peripheral arterial disease, and might be more effective in women. 相似文献82.
83.
Tsujimura S Kojima S Kano K Ikeda T Sato M Sanada H Omura H 《Bioscience, biotechnology, and biochemistry》2006,70(3):654-659
A novel FAD-dependent glucose dehydrogenase (FAD-GDH) was found and its enzymatic property for glucose sensing was characterized. FAD-GDH oxidized glucose in the presence of some artificial electron acceptors, except for O2, and exhibited thermostability, high substrate specificity and a large Michaelis constant for glucose. FAD-GDH was applied to an amperometric glucose sensor with Fe(CN)6(3-) as a soluble mediator. The use of a relatively high concentration of Fe(CN)6(3-) resulted in a good linearity between the current response and the glucose concentration, taking into account a large Michaelis constant for Fe(CN)6(3-). The glucose sensor was completely insensitive to O2 and responded linearly to glucose up to 30 mM. Compared to glucose, the response to other saccharides was negligible. The sensor can be stored at room temperature in a desiccator for at least one month without any change in the response or activity. 相似文献
84.
Masaki Setoguchi Shin Iimura Yuuichi Sugimoto Yoshiyuki Yoneda Jun Chiba Toshiyuki Watanabe Fumihito Muro Yutaka Iigo Gensuke Takayama Mika Yokoyama Tomoe Taira Misato Aonuma Tohru Takashi Atsushi Nakayama Nobuo Machinaga 《Bioorganic & medicinal chemistry》2013,21(1):42-61
We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7-fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5 mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F = 54%) in monkeys. 相似文献
85.
Saegusa M Murakami M Nakatani Y Yamakawa K Katagiri M Matsuda K Nakamura K Kudo I Kawaguchi H 《Journal of cellular physiology》2003,197(3):348-356
This study initially confirmed that, among prostaglandins (PGs) produced in bone, only PGE(2) has the potency to stimulate osteoclastogenesis and bone resorption in the mouse coculture system of osteoblasts and bone marrow cells. For the PGE(2) biosynthesis two isoforms of the terminal and specific enzymes, membrane-associated PGE(2) synthase (mPGES) and cytosolic PGES (cPGES) have recently been identified. In cultured mouse primary osteoblasts, both mPGES and cyclooxygenase-2 were induced by the bone resorptive cytokines interleukin-1, tumor necrosis factor-alpha, and fibroblast growth factor-2. Induction of mPGES was also seen in the mouse long bone and bone marrow in vivo by intraperitoneal injection of lipopolysaccharide. In contrast, cPGES was expressed constitutively both in vitro and in vivo without being affected by these stimuli. An antisense oligonucleotide blocking mPGES expression inhibited not only PGE(2) production, but also osteoclastogenesis and bone resorption stimulated by the cytokines, which was reversed by addition of exogenous PGE(2). We therefore conclude that mPGES, which is induced by and mediates the effects of bone resorptive stimuli, may make a target molecule for the treatment of bone resorptive disorders. 相似文献
86.
Mäkinen TM Raatikka VP Rytkönen M Jokelainen J Rintamäki H Ruuhela R Näyhä S Hassi J 《International journal of biometeorology》2006,51(1):27-36
The extent of outdoor exposure during winter and factors affecting it were examined in a cross-sectional population study in Finland. Men and women aged 25–74 years from the National FINRISK 2002 sub-study (n=6,591) were queried about their average weekly occupational, leisure-time and total cold exposure during the past winter. The effects of gender, age, area of residence, occupation, ambient temperature, self-rated health, physical activity and education on cold exposure were analysed. The self-reported median total cold exposure time was 7 h/week (8 h men, 6 h women),<1 h/week (2 h men, 0 h women) at work, 4 h/week (5 h men, 4 h women) during leisure time and 1 h/week (1 h men, 1.5 h women) while commuting to work. Factors associated with increased occupational cold exposure among men were: being employed in agriculture, forestry and industry/mining/construction or related occupations, being less educated and being aged 55–64 years. Factors associated with increased leisure-time cold exposure among men were: employment in industry/mining/construction or related occupations, being a pensioner or unemployed, reporting at least average health, being physically active and having college or vocational education. Among women, being a housewife, pensioner or unemployed and engaged in physical activity increased leisure-time cold exposure, and young women were more exposed than older ones. Self-rated health was positively associated with leisure time cold exposure in men and only to a minor extent in women. In conclusion, the subjects reported spending 4% of their total time under cold exposure, most of it (71%) during leisure time. Both occupational and leisure-time cold exposure is greater among men than women. 相似文献
87.
Viiri LE Raitakari OT Huhtala H Kähönen M Rontu R Juonala M Hutri-Kähönen N Marniemi J Viikari JS Karhunen PJ Lehtimäki T 《Journal of lipid research》2006,47(6):1298-1306
The common apolipoprotein E (apoE) gene (APOE) epsilon2/epsilon3/epsilon4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serum lipid levels within the most common APOE epsilon3/epsilon3 genotype group. We determined APOE -219G/T and +113G/C promoter genotypes and estimated APOE haplotypes in 525 participants of the Cardiovascular Risk in Young Finns Study. We studied the associations of the APOE promoter polymorphisms and their haplotypes with cross-sectional and longitudinal serum lipid and apolipoprotein concentrations as well as with flow-mediated dilatation (FMD), carotid artery compliance (CAC), and intima-media thickness (IMT) within the APOE epsilon3/epsilon3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids [low density lipoprotein-cholesterol (LDL-C), HDL-C, and triglycerides], apolipoproteins (apoA-I and apoB), or brachial artery FMD, CAC, or carotid IMT in either men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and, furthermore, carriers of the -219T/+113C/epsilon3 haplotype had significantly higher LDL-C and total cholesterol concentrations throughout the 21 year follow-up period compared with homozygous G allele carriers or noncarriers of the -219T/+113C/epsilon3 haplotype. Such associations were not found in females. In summary, the APOE promoter polymorphisms -219G/T and +113G/C as well as their haplotype are associated with longitudinal changes in LDL-C and total cholesterol concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC, or carotid IMT in males or females. 相似文献
88.
Tanja Babuke Mika Ruonala Melanie Meister Monia Amaddii Christina Genzler Alessandro Esposito Ritva Tikkanen 《Cellular signalling》2009,21(8):1287-1297
Reggie-1/flotillin-2 and reggie-2/flotillin-1 are membrane raft associated proteins which have been implicated in growth factor signaling, phagocytosis, regulation of actin cytoskeleton and membrane trafficking. Membrane and raft association of reggies is mediated by myristoylation, palmitoylation and oligomerization. We have shown that upon EGF stimulation of cells, reggie-1 is tyrosine phosphorylated by Src kinase and endocytosed into late endosomes. Here we have analyzed the mechanism of the EGF-stimulated endocytosis of reggies in more detail and show that the Src-mediated phosphorylation of reggie-1 is not the driving force for endocytosis. However, hetero-oligomerization with reggie-2 is necessary for the translocation of reggie-1, which does not take place in the absence of reggie-2. In addition, the Y163F mutant of reggie-1, which is not capable of undergoing endocytosis, oligomerizes poorly with reggie-2. EGF stimulation results in changes in the size but not in the stoichiometry of the reggie hetero-oligomers, and reggie-1 oligomer size is decreased by knockdown of reggie-2. Based on our findings, we propose a model according to which reggie hetero-oligomers are dynamic, and changes in the size of the hetero-oligomers result in endocytosis of the complex from the plasma membrane. 相似文献
89.
Takaaki Kobayashi Mizuki Watanabe Akira Yoshida Shizuo Yamada Mika Ito Hiroshi Abe Yoshihiro Ito Mituhiro Arisawa Satoshi Shuto 《Bioorganic & medicinal chemistry》2010,18(3):1076-1082
On the basis of the previous results on a histamine H4 receptor agonist 4-methylhistamine and a cyclopropane-based conformationally restricted analog CEIC (3) with potent H3/H4 receptor antagonistic effect, 4-methylhistamine analogs 4 and 5 of CEIC were designed and synthesized. Compound 4 showed strong affinity (Ki = 38.7 nM) for the H3 receptor, which was more potent than a well-known H3 antagonist thioperamide. Stable tautomer and conformation of 3 and 4, which can affect the pharmacological activity, were analyzed by ab initio calculations. 相似文献
90.
Miikka Tarkia Antti Saraste Christoffer Stark Tommi V?h?silta Timo Savunen Marjatta Strandberg Virva Saunavaara Tuula Tolvanen Jarmo Teuho Mika Ter?s Olli Mets?l? Petteri Rinne Ilkka Heinonen Nina Savisto Mikko Pietil? Pekka Saukko Anne Roivainen Juhani Knuuti 《PloS one》2015,10(6)