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Kario K.,Jichi Medical University | Yano Y.,Jichi Medical University | Matsuo T.,Hyogo Prefectural Awaji Hospital | Hoshide S.,Jichi Medical University | And 2 more authors.
European Heart Journal | Year: 2011

Aims Stroke events occur most frequently in the morning hours. Impaired haemostatic activity and morning blood pressure (BP) surge, defined as the morning BP increase from sleep, have individually been associated with stroke risk in general or hypertensive populations. However, their combined impact on the risk of a stroke remains unknown. Methods and results A total of 514 hypertensive patients aged >50 years (mean 72.3 years; 37men) underwent 24 h BP monitoring, measurement of haemostatic risk factors [plasma fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and prothrombin fragment 12(F12)], and brain MRI at baseline. The incidence of stroke was prospectively ascertained. During an average of 41 months (1751 person-years), there were 43 stroke events (ischaemic, 30; haemorrhagic, 5; undefined, 8). On multivariable analysis adjusted for confounding factors, the hazard ratio [HR (95 confidence interval (CI)] for stroke in the highest vs. lower quartiles of PAI-1 was 2.5 (1.34.6), that for F12 was 2.6 (1.45.0), and that for the morning BP surge was 1.2 (1.11.4; all P< 0.01). In particular, the ratio was substantially higher in cases with the highest quartile of both PAI-1 and F12 levels compared with those with the lower quartiles of both parameters (HR: 8.2; 95 CI: 3.718.2; P< 0.001). Among the patients with the highest quartile of the morning BP surge (n=128), the multivariable HR (95 CI) for the highest vs. lower quartiles of PAI-1 was 3.4 (1.39.1) and that for F12 was 3.3 (1.38.7) (both P< 0.05). Conclusion High levels of plasma PAI-1 and F12, as well as an excessive morning BP surge, are independently and additively associated with an increased risk of stroke in older hypertensive patients. © 2010 The Author.

Bito T.,Kobe University | Nishikawa R.,Kobe University | Hatakeyama M.,Kobe University | Kikusawa A.,Kobe University | And 10 more authors.
British Journal of Dermatology | Year: 2014

Background Current treatment with biologics has produced dramatic therapeutic effects in patients with psoriasis, although these agents occasionally decrease in efficacy. One of the main factors responsible for this attenuation is attributed to the development of antidrug antibodies (ADAs). Objectives To analyse the relationship between serum drug concentrations, the presence of ADAs and treatment efficacy of adalimumab and infliximab, and to determine the optimal use of these biologics. Methods This was a 1-year prospective study in the dermatology departments of Kobe University Hospital and collaborating hospitals. All patients starting a regimen of adalimumab and infliximab for psoriasis were included. We measured the serum concentration of the drugs and titres of antibodies to adalimumab and infliximab, as well as the Psoriasis Area and Severity Index scores at weeks 0, 4, 12, 24 and 48 during the first year of treatment. Results We observed a 50% positive rate of ADAs to adalimumab, and a 41% positive rate of ADAs to infliximab. The titres of ADAs showed a wide range from low to high titres. In the high-titre groups, the patients exhibited a decreased clinical response, and demonstrated a negative correlation between titre and clinical response. However, an equivalent therapeutic effect was observed between the low-titre group and the group with no antibodies detected for adalimumab. For infliximab, the patients with ADAs showed decreased clinical response. An apparent negative correlation between antibody production and reduced clinical response was observed. Conclusions Two biologics, adalimumab and infliximab, showed different therapeutic behaviour. The measurement of ADAs and drug concentrations has important implications for treatment with biologics. What's already known about this topic? High frequent production of antidrug antibodies (ADAs) has been observed in patients treated with biologics, and the production has caused impairment of treatment efficacy. What does this study add? The optimal use of the biologics should be determined by the measurement of ADAs and each drug concentration in each patient because the standard protocol may not uniformly fit all patients. © 2013 British Association of Dermatologists.

Hanafusa T.,Okayama University | Mohamed A.E.A.,Alexandria University | Kitaoka K.,Hyogo Prefectural Awaji Hospital | Ohue Y.,Okayama University | And 2 more authors.
Cancer Letters | Year: 2011

Serological analysis of a recombinant cDNA expression library (SEREX) derived from two lung adenocarcinoma cancer cell lines using autologous sera led to the isolation of 41 positive cDNA clones comprising 28 different antigens. They coded for a variety of nuclear and cytoplasmic proteins. Among the antigens, nucleoporin 107 (NUP107) was isolated most frequently (5 of 41 clones). The second most frequently isolated antigen was coded for by C21orf58 (4 of 41 clones). During serological analysis of selected antigens based on their reactivity to sera from normal individuals and lung cancer patients, none of the antigens showed a cancer-restricted recognition pattern. However, five genes including NUP107 showed higher expression when we examined the changes in gene expression in five different adenocarcinoma cell lines, including those used in SEREX, compared with their levels in normal lung tissues by cDNA microarray analysis. On the other hand, the expression levels of five genes including C21orf58 were down regulated in all adenocarcinoma cell lines. This SEREX study combining comprehensive gene expression assays has added to the growing list of lung cancer antigens, which may aid the development of diagnostic and immunotherapeutic reagents for patients with lung cancer. © 2010 Elsevier Ireland Ltd.

Tanaka S.-I.,Toyooka Hospital Hidaka Medical Center | Miki T.,Toyooka Hospital Hidaka Medical Center | Sha S.,Toyooka Hospital Hidaka Medical Center | Hirata K.-I.,Kobe University | And 2 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2011

Aim: Evidence of relationships between lipid peroxidation and the incidence of coronary heart disease is limited. We therefore investigated this association in a Japanese general population. Methods: We prospectively studied 1945 individuals who were apparently healthy at the baseline. Cox proportional-hazards models were used to investigate the relationship between serum levels of thiobarbituric acid-reactive substances (TBARS) as a marker of lipid peroxidation and the incidence of coronary heart disease, adjusted for established risk factors including age, sex, current smoking, body mass index, systolic blood pressure, glycohemoglobin A1c, serum total cholesterol, and serum high-density lipoprotein cholesterol levels. Results: During 20,226 person-years of follow-up (median follow-up, 10.9 years), 44 coronary events were documented. The risk of coronary heart disease increased in consecutive tertiles of the TBARS level. On age-and sex-adjusted analysis, the level of TBARS was significantly associated with the incidence of coronary heart disease. The hazard ratio in the highest tertile compared with the lowest tertile was 3.22 (95% confidence interval, 1.38 to 7.53; p = 0.007). On multivariate analysis adjusted for age, sex, and other established risk factors, this association remained significant (hazard ratio, 3.23; 95% confidence interval, 1.28 to 8.16; p = 0.01). Conclusions: Serum levels of TBARS are a strong and independent predictor of coronary heart disease. These findings support the hypothesis that lipid peroxidation is an important risk factor for coronary heart disease.

Itakura H.,Shinagawa East One Medical Clinic | Yokoyama M.,Hyogo Prefectural Awaji Hospital | Matsuzaki M.,Yamaguchi University | Saito Y.,Chiba University | And 11 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2011

Aim: The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants. Methods: In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/ stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model. Results: As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio = 0.83, p = 0.049, in all participants and hazard ratio = 0.71, p = 0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 μg/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 μg/mL) group. Conclusion: The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events.

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