Study profile on baseline survey of Daiko Study in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study)

The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) is a long-term cohort study to investigate the interactions among genotypes, lifestyles, and lifestyle-related diseases, especially cancer. This article reports the outline of the baseline survey of the Daiko Study, one site of the J-MICC Study. That survey was conducted between June 9, 2008 and May 31, 2010 at the Daiko Medical Center of Nagoya University in Nagoya, Japan. Subjects were registered residents of Nagoya City aged 35 to 69 years who had not participated in other J-MICC sites. Recruitment was mainly announced through leaflets distributed in mailboxes citywide, personal communications, and regional information, such as posters in public or commercial facilities. Participants provided blood plasma, serum, buffy coat, urine, and data on health check-ups. They also completed a self-reported questionnaire on lifestyle, disease history, family history, and for women, reproductive history. As of the end of September 2010, 4 out of 5172 registered participants had withdrawn from the study, leaving data from 5168 participants (1467 males and 3701 females) available for analysis. Mean age +/- standard deviation (SD) was 52.5 +/- 10.3 years. Current smokers accounted for 24.1% (n=354) of males and 6.9% (n=256) of females. Current drinkers included 74.9% (n=1099) of males and 45.9% (n=1699) of females. Lifestyle data and specimens were successfully collected to examine any associations among disease biomarkers, lifestyles, and genotypes.     

Surround modulation in cortical orientation map revealed by optical imaging and its dependency on receptive field eccentricity

Optical imaging was used to investigate the difference in surround modulation on orientation map related to receptive field eccentricity in cat visual cortex. Presentation of center–surround stimuli at the center of gaze resulted in no clear surround modulation; however, significant modulation was observed in its corresponding cortical area when the center–surround stimuli were presented at 10° eccentricity in more peripheral parts of the visual field. Modulation was observed both in the response magnitude and in the spatial pattern of the response. Surround orientation perpendicular to the orientation of a center patch grating showed the largest modulation in the response magnitude. The modulation became weaker as the orientation difference between the center and surround gratings became smaller. Regardless of the orientations for the central patch gratings, a similar response spatial pattern was observed in the cortical region where the underlying cells had their receptive fields covering the central patch, if the stimuli were with the same surround gratings. These properties support the notion of a relative specialization for visual information processing in peripheral representations of cortical areas.     

Regulation of osteoclast differentiation and function by receptor activator of NFkB ligand and osteoprotegerin

The differentiation and functions of osteoclasts (OCs) are regulated by osteoblast-derived factors. Receptor activator of NFkB ligand (RANKL) is one of the key regulatory molecules in OC formation. Osteoprotegerin (OPG) is a novel secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis and binds to RANKL. We examined the biological actions of macrophage-colony-stimulating factor (M-CSF), RANKL, and OPG on the differentiation of OCs isolated from cocultures of mouse osteoblastic cells and bone marrow cells. Preosteoclasts (pOCs) and OCs were characterized by their ultrastructure and the expression of OC markers such as tartrate-resistant acid phosphatase (TRAP) and vacuolar-type H(+)-ATPase. pOCs formed without any additives expressed TRAP, but showed little resorptive activity on cocultured dentine slices. TRAP-positive pOCs treated with M-CSF began to fuse with each other, but lacked a ruffled border (RB) and showed almost no resorptive activity. pOCs treated with RANKL became TRAP-positive multinucleated cells, which expressed intense vacuolar-type H(+)-ATPase along the RB membranes and exhibited prominent resorptive activity. Such effects of RANKL on pOCs were completely inhibited by the addition of OPG. OPG inhibited RB formation in mature OCs and reduced their resorptive activity, and also induced apoptosis of some OCs. These results suggest that 1) RANKL induces differentiation of functional OCs from pOCs, 2) M-CSF induces macrophage-like multinucleated cells, but not OCs, 3) OPG inhibits RB formation and resorptive activity in mature OCs, 4) OPG also induces apoptosis of OCs, and 5) RANKL and OPG are, therefore, important regulators of not only the terminal differentiation of OCs but also their resorptive function.     

Suitable albumin concentrations for enhanced drug oxidation activities mediated by human liver microsomal cytochrome P450 2C9 and other forms predicted with unbound fractions and partition/distribution coefficients of model substrates

1. Albumin has reportedly enhanced cytochrome P450 (P450)-mediated drug oxidation rates in human liver microsomes. Consequently, measurements of clearances and fractions metabolized could vary depending on the experimental albumin concentrations used.

2. In this study, the oxidation rates of diclofenac and warfarin by human liver microsomes were significantly enhanced in the presence of 0.10% (w/v) bovine serum albumin, whereas those of tolbutamide and phenytoin required 1.0% and 2.0% of albumin for significant enhancement. Values of the fractions metabolized by P450 2C9 for four substrates did not markedly change in the presence of albumin at the above-mentioned concentrations.

3. The oxidation rates of bupropion, omeprazole, chlorzoxazone and phenacetin in human liver microsomes were reportedly enhanced by 0.5%, 1%, 2% and 2% of albumin, respectively. Analysis of reported intrinsic clearance values and suitable albumin concentrations for the currently analyzed substrates and the reported substrates revealed an inverse correlation, with warfarin as an outlier.

4. Suitable albumin concentrations were multivariately correlated with physicochemical properties, that is, the plasma unbound fractions, octanol–water partition coefficient and acid dissociation constant (r?=?0.98, p<.0001, n?=?10). Therefore, multiple physicochemical properties may be determinants of suitable albumin concentrations for substrate oxidations in human liver microsomes.

     

Cross‐sectional multicenter observational study of psoriatic arthritis in Japanese patients: Relationship between skin and joint symptoms and results of treatment with tumor necrosis factor‐α inhibitors

Psoriatic arthritis (PsA) is an inflammatory arthritis with as yet unclear pathophysiology. This retrospective, multicenter, cross‐sectional study was conducted in 19 facilities in western Japan and aimed to identify patients’ characteristics and factors that affect the results of treatment with biologic agents. Of 2116 patients with psoriasis, 285 (13.5%) had PsA. Skin manifestations preceded joint manifestations in 69.8%, the onset was simultaneous in 17.2%, whereas PsA preceded skin manifestations in 2.5%. Peripheral arthritis was most common, occurring in 73.7%, compared with axial disease in 21.8%, enthesitis in 23.5% and dactylitis in 35.4%. Patients with severe skin manifestations were significantly younger at onset (P = 0.02) and more frequently had axial disease (P < 0.01). Biologic agents were used in 206 patients (72.3%), anti‐tumor necrosis factor (TNF)‐α antibodies being prescribed first to 157 of them. Anti‐TNF‐α antibodies were continued by 105 participants and discontinued by 47, the remaining five patients being lost to follow up. Patients who discontinued anti‐TNF‐α antibodies were significantly older than those who continued (55 vs 51 years, P = 0.04) and significantly older at onset of joint manifestations (50 vs 44 years, P = 0.01). Multivariate analysis revealed that patients over 50 years significantly more frequently terminated anti‐TNF‐α antibodies (P < 0.01). In conclusion, patients with PsA and severe skin manifestations have earlier onset and axial disease, which seriously impacts on quality of life. Anti‐TNF‐α antibodies were generally effective enough to continue but less so in patients aged over 50 years. Further detailed research is needed.     

Multifactor leadership styles and new exposure to workplace bullying: a six-month prospective study

This study investigated the prospective association between supervisor leadership styles and workplace bullying. Altogether 404 civil servants from a local government in Japan completed baseline and follow-up surveys. The leadership variables and exposure to bullying were measured by Multifactor Leadership Questionnaire and Negative Acts Questionnaire-Revised, respectively. The prevalence of workplace bullying was 14.8% at baseline and 15.1% at follow-up. Among respondents who did not experience bullying at baseline (n=216), those who worked under the supervisors as higher in passive laissez-faire leadership had a 4.3 times higher risk of new exposure to bullying. On the other hand, respondents whose supervisors with highly considerate of the individual had a 70% lower risk of new exposure to bullying. In the entire sample (n=317), passive laissez-faire leadership was significantly and positively associated, while charisma/inspiration, individual consideration, and contingent reward were negatively associated both after adjusting for demographic and occupational characteristics at baseline, life events during follow-up, and exposure to workplace bullying at baseline. Results indicated that passive laissez-faire and low individual consideration leadership style at baseline were strong predictors of new exposure to bullying and high individual consideration leadership of supervisors/managers could be a preventive factor against bullying.