High circulating adiponectin levels predict decreased muscle strength among older adults aged 70 years and over: A prospective cohort study.

BACKGROUND AND AIMS: Population-based researches indicate that circulating adiponectin is inversely associated with muscle strength. However, interpretation of the findings has been limited by the use of a cross-sectional design. This study aimed to examine the prospective relationship between baseline circulating adiponectin concentration and change in muscular function-related physical performance in older adults. METHODS AND RESULTS: A 1-year prospective cohort study of Japanese community-dwelling elderly was conducted between 2002 and 2003. Four hundred thirty-four older persons participated in the measurements of physical function, including leg extension power, functional reach, timed up-and-go test, and 10-m maximum walking speed, at baseline and follow-up. After adjustment for potential covariates, higher serum adiponectin concentration was found to be significantly associated with poorer physical performance at baseline (leg extension power [watt], P < 0.001; functional reach [cm], P < 0.001; log timed up-and-go test, P = 0.007; log 10-m maximum walking speed, P < 0.001). The results of the prospective analysis by analysis of covariance indicated that the elderly with higher serum adiponectin concentrations (tertiles) at baseline tended to have a decreased performance in leg extension power (means [95% confidence interval]: lowest, -105 [-125, -85.7]; middle, -117 [-135, -97.8]; highest, -140 [-160, -120], watt, P for trend = 0.021) and timed up-and-go test (lowest, -0.08 [-0.28, -0.12]; middle, -0.10 [-0.29, 0.10]; highest, 0.28 [0.07, 0.48], s, P for trend = 0.019), but not two other functioning. CONCLUSION: High circulating adiponectin concentration may be an indicator of decreased physical performance, especially muscle strength, in older adults.

Personality and suicide risk: the impact of economic crisis in Japan.

BACKGROUND: The interactive effect of personal factors and social factors upon suicide risk is unclear. We conducted prospective cohort study to investigate whether the impact of the economic crisis in 1997-1998 upon suicide risk differed according to Neuroticism and Psychoticism personality traits. METHODS: The Miyagi Cohort Study in Japan with a follow-up for 19 years from 1990 to 2008 has 29,432 subjects aged 40-64 years at baseline who completed a questionnaire about various health habits and the Japanese version of the Eysenck Personality Questionnaire - Revised Short Form in 1990. RESULTS: The suicide mortality rate increased from 4.6 per 100,000 person-years before 1998 to 27.8 after 1998. Although both Neuroticism and Psychoticism were significantly associated with an increased risk of mortality during the whole period from 1990 to 2008, the impact of the economic crisis upon suicide risk differed between the Neuroticism and Psychoticism personality traits. Compared with the lowest category, the hazard ratios (HRs) for the highest Neuroticism increased from 0.66 before 1998 to 2.45 after 1998. On the other hand, the HRs for the highest Psychoticism decreased from 7.85 before 1998 to 2.05 after 1998. CONCLUSIONS: The impact of the 1997-1998 economic crisis upon suicide risk differed according to personality. Suicide risk increased among these with higher Neuroticism after the economic crisis, but this was not the case for other personality subscales.

Coffee consumption and the risk of prostate cancer: the Ohsaki Cohort Study.

BACKGROUND: Epidemiological evidence regarding the effect of coffee on the incidence of prostate cancer is inconsistent. We aimed to investigate coffee consumption and the risk of prostate cancer risk in a general Japanese population. METHODS: We conducted a prospective cohort study in Ohsaki city, Japan, where 18 853 men aged 40-79 years participated in a baseline survey. Coffee consumption was assessed via a validated self-administered questionnaire. During 11 years of follow-up (from January 1 1995 to December 31, 2005), 318 incident cases of prostate cancer were detected. The Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). RESULTS: There was a significant inverse association between coffee consumption and the incidence risk of prostate cancer. Compared with those who did not drink coffee, the multivariate adjusted HRs were 0.81 (95% CI: 0.61-1.07), 0.73 (95% CI: 0.53-1.00), and 0.63 (095% CI: 0.39-1.00) for those who drank coffee occasionally, 1-2 cups per day, and > or =3 cups per day, respectively, with a P for trend of 0.02. CONCLUSION: This prospective finding from a Japanese population adds evidence that coffee intake is inversely associated with the incidence of prostate cancer.

Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium.

BACKGROUND: The evidence for a role of tobacco smoking, alcohol drinking, and body mass index (BMI) in the etiology of small intestine cancer is based mainly on case-control studies from Europe and United States. SUBJECTS AND METHODS: We harmonized the data across 12 cohort studies from mainland China, Japan, Korea, Singapore, and Taiwan, comprising over 500,000 subjects followed for an average of 10.6 years. We calculated hazard ratios (HRs) for BMI and (only among men) tobacco smoking and alcohol drinking. RESULTS: A total of 134 incident cases were observed (49 adenocarcinoma, 11 carcinoid, 46 other histologic types, and 28 of unknown histology). There was a statistically non-significant trend toward increased HR in subjects with high BMI [HR for BMI>27.5 kg/m2, compared with 22.6-25.0, 1.50; 95% confidence interval (CI) 0.76-2.96]. No association was suggested for tobacco smoking; men drinking>400 g of ethanol per week had an HR of 1.57 (95% CI 0.66-3.70), compared with abstainers. CONCLUSIONS: Our study supports the hypothesis that elevated BMI may be a risk factor for small intestine cancer. An etiologic role of alcohol drinking was suggested. Our results reinforce the existing evidence that the epidemiology of small intestine cancer resembles that of colorectal cancer.

Properties of L-type bovine spongiform encephalopathy in intraspecies passages.

The origin and transmission routes of atypical bovine spongiform encephalopathy (BSE) remain unclear. To assess whether the biological and biochemical characteristics of atypical L-type BSE detected in Japanese cattle (BSE/JP24) are conserved during serial passages within a single host, 3 calves were inoculated intracerebrally with a brain homogenate prepared from first-passaged BSE/JP24-affected cattle. Detailed immunohistochemical and neuropathologic analysis of the brains of second-passaged animals, which had developed the disease and survived for an average of 16 months after inoculation, revealed distribution of spongiform changes and disease-associated prion protein (PrP(Sc)) throughout the brain. Although immunolabeled PrP(Sc) obtained from brain tissue was characterized by the presence of PrP plaques and diffuse synaptic granular accumulations, no stellate-type deposits were detected. Western blot analysis suggested no obvious differences in PrP(Sc) molecular mass or glycoform pattern in the brains of first- and second-passaged cattle. These findings suggest failures to identify differences in mean incubation period and biochemical and neuropathologic properties of the BSE/JP24 prion between the first and second passages in cattle.

Adiposity, adult weight change and breast cancer risk in postmenopausal Japanese women: the Miyagi Cohort Study.

BACKGROUND: The role of adult weight change in breast cancer (BC) risk is unclear in Japanese women. METHODS: A total of 10,106 postmenopausal women aged 40-64 years (the Miyagi Cohort) were followed from 1990 to 2003, and 108 BC cases were identified. Hazard ratios (HRs) were estimated according to body mass index (BMI) at the current age and at the of age 20 years, and weight change since age 20 years. RESULTS: Higher current BMI was associated with an increased risk of BC (P for trend=0.02), whereas higher BMI at the age 20 years was inversely associated with this risk (P for trend=0.002). There was a significant association between weight change since age 20 years and BC risk (P for trend=0.0086). Compared with stable weight, HR was 0.35 for weight loss of 5 kg or more (P for weight loss trend=0.04) and 1.55 for weight gain of 12 kg or more (P for weight gain trend=0.05). CONCLUSION: Adiposity at younger and current age has differential effects on BC risk among postmenopausal women; weight gain in adulthood being associated with an increased, and weight loss with a decreased risk.

The role of inhibitory neurotransmission in locomotor circuits of the developing mammalian spinal cord.

Neuronal circuits generating the basic coordinated limb movements during walking of terrestrial mammals are localized in the spinal cord. In these neuronal circuits, called central pattern generators (CPGs), inhibitory synaptic transmission plays a crucial part. Inhibitory synaptic transmission mediated by glycine and GABA is thought to be essential in coordinated activation of muscles during locomotion, in particular, controlling temporal and spatial activation patterns of muscles of each joint of each limb on the left and right side of the body. Inhibition is involved in other aspects of locomotion such as control of speed and stability of the rhythm. However, the precise roles of neurotransmitters and their receptors mediating inhibitory synaptic transmission in mammalian spinal CPGs remain unclear. Moreover, many of the inhibitory interneurones essential for output pattern of the CPG are yet to be identified. In this review, recent advances on these issues, mainly from studies in the developing rodent spinal cord utilizing electrophysiology, molecular and genetic approaches are discussed.

Fish consumption and the risk of colorectal cancer: the Ohsaki Cohort Study.

BACKGROUND: Evidence from laboratory and animal studies suggests that high fish consumption may reduce the risk of colorectal cancer, but the results of studies in humans have been inconsistent. The objective of this study was to prospectively examine the association between fish consumption and the risk of colorectal cancer incidence in Japan, where fish is widely consumed. METHODS: We analysed data from 39 498 men and women registered in the Ohsaki National Health Insurance Cohort Study who were 40-79 years old and free of cancer at the baseline. Fish consumption was assessed at the baseline using a self-administered food frequency questionnaire. RESULTS: During 9 years of follow-up, we identified 566 incident cases of colorectal cancer (379 men and 187 women). The hazard ratios and 95% confidence intervals (CIs) for colorectal cancer incidence in the highest quartile of fish consumption compared with the lowest quartile were 1.07 (95% CIs; 0.78-1.46, P-trend=0.43) for men, and 0.96 (95% CIs; 0.61-1.53, P-trend=0.69) for women. CONCLUSION: The results of this prospective cohort study revealed no association between fish consumption and the risk of colorectal cancer.

Sleep duration and the risk of breast cancer: the Ohsaki Cohort Study.

In a prospective study of 23 995 Japanese women, short sleep duration was associated with higher risk of breast cancer (143 cases), compared with women who slept 7 h per day, the multivariate hazard ratio of those who slept

Green tea consumption and lung cancer risk: the Ohsaki study.

We examined the risk of lung cancer in relation to green tea consumption in a population-based cohort study in Japan among 41,440 men and women, aged 40-79 years, who completed a questionnaire in 1994 regarding green tea consumption and other health-related lifestyle factors. During the follow-up period of 7 years (from 1995 to 2001), 302 cases of lung cancer were identified, and the Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The multivariable-adjusted HRs of lung cancer incidence for green tea consumption of 1 or 2, 3 or 4, and 5 or more cups/day as compared to less than 1 cup/day were 1.14 (95% CI: 0.80-1.62), 1.18 (95% CI: 0.83-1.66), and 1.17 (95% CI: 0.85-1.61), respectively (P for trend=0.48). This cohort study has found no evidence that green tea consumption is associated with lung cancer.

Sleep duration and the risk of prostate cancer: the Ohsaki Cohort Study.

In a prospective study of prostate cancer incidence (127 cases), among 22 320 Japanese men, sleep duration was associated with lower risk; the multivariate hazard ratio of men who slept >or=9 h per day compared with those who slept less was 0.48 (95% confidence interval: 0.29-0.79, P for trend=0.02).

A simple HPLC method to determine urinary phenylmercapturic acid and its application to gasoline station attendants to biomonitor occupational exposure to benzene at less than 1 ppm.

The objective of this study was to establish a hand-saving method to measure phenylmercapturic acid (PMA) and to examine urinary PMA as a marker of occupational exposure to benzene at levels less than 1 ppm. A simple HPLC method was developed to analyse PMA by monitoring absorption at 195 nm of the ef? uent from an ODS-3 column with acetonitrile-methanol-perchloric acid-water as a mobile phase. The detection limit of the method was 0.2 µg l(-1) with sufficient reproducibility. The method was applied to end-of-shift urine samples from 70 gasoline station attendants exposed to up to 107 ppb benzene, and 20 non-exposed controls of both sexes. Time-weighted average (TWA) exposure to benzene was measured by diffusive sampling. A regression analysis was applied to examine the quantitative relationship between the intensity of exposure to benzene and PMA in the end-of-shift urine samples. Multiple regression analysis showed no effects of age, sex, smoking and co-exposure to toluene and xylenes on urinary PMA. There was a linear relationship between TWA benzene exposure and urinary PMA (r = 0.60-0.67, P < 0.01). Background PMA in urine of the non-exposed controls was low and scattering of PMA around the regression line was narrow so that those with 20 ppb benzene exposure can be separated from the non-exposed by urinalysis for PMA. Thus, urinary PMA is sensitive enough for biological exposure monitoring of those exposed to less than 1 ppm benzene.

Two actions of frabin: direct activation of Cdc42 and indirect activation of Rac.

Frabin is an actin filament-binding protein which shows GDP/GTP exchange activity specific for Cdc42 small G protein and induces filopodium-like microspike formation and c-Jun N-terminal kinase (JNK) activation presumably through the activation of Cdc42. Frabin has one actin filament-binding (FAB) domain, one Dbl homology (DH) domain, first pleckstrin homology (PH) domain adjacent to the DH domain, one cysteine-rich FYVE domain, and second PH domain from the N-terminus to the C-terminus in this order. Different domains of frabin are involved in the microspike formation and the JNK activation, and the association of frabin with the actin cytoskeleton through the FAB domain is necessary for the microspike formation, but not for the JNK activation. We have found here that frabin induces the formation of not only filopodium-like microspikes but also lamellipodium-like structures in NIH3T3 and L fibroblasts. We have analysed the mechanism of frabin in these two actions and found that frabin induces filopodium-like microspike formation through the direct activation of Cdc42 and lamellipodium-like structure formation through the Cdc42-independent indirect activation of Rac small G protein. The FAB domain of frabin in addition to the DH domain and the first PH domain is necessary for the filopodium-like microspike formation, but not for the lamellipodium-like structure formation. The FYVE domain and the second PH domain in addition to the DH domain and the first PH domain are necessary for the lamellipodium-like structure formation. We show here these two actions of frabin in the regulation of cell morphology.

Urinary phenylmercapturic acid as a marker of occupational exposure to benzene.

A hand-saving HPLC method to measure urinary phenylmercapturic acid (PMA) was developed which allows about 35 PMA determinations per day. The method involves conversion of pre-PMA to PMA by the addition of sulfuric acid to a urine sample, extraction into an ether-methanol mixture followed by condensation under a nitrogen stream. The condensate was introduced to a ODS-3 column in a HPLC system, and PMA in the column was eluted into a mobile phase of acetonitrile: methanol: perchloric acid: water. The elution of PMA was monitored at 205 nm. One determination will be completed in 40 min. The method was applied to analysis of end-of-shift urine samples from 152 workers exposed up to 210 ppm benzene, 66 workers exposed to a mixture of benzene (up to 116 ppm) and toluene + xylenes (up to 118 ppm), and 131 non-exposed controls of both sexes. A linear regression was established between time-weighted average intensity of exposure to benzene and urinary PMA. From the regression, it was calculated that urinary PMA level will be about 6.4 mg/l after 8-hour exposure to benzene at 100 ppm, and that PMA in urine accounted for about 0.1% of benzene absorbed. No effects of sex, age, and smoking habit of individuals were detected, and the effect of co-exposure to toluene + xylenes at the levels comparable to that of benzene was essentially nil, which indicates an advantage of PMA as a benzene exposure marker over monoto tri-phenolic metabolites or t,t-muconic acid.

Molecular cloning of mXCR1, the murine SCM-1/lymphotactin receptor.

Single C motif-1 (SCM-1)/lymphotactin is a C-type member of the chemokine superfamily. Previously, we identified its specific receptor XCR1. Here we isolated the murine homologue of XCR1 (mXCR1). To demonstrate its biological activity, we produced recombinant mouse SCM-1 by the baculovirus expression system. B300-19 murine pre-B cells expressing mXCR1 responded to mSCM-1 in chemotactic and calcium-mobilization assays. mXCR1 mRNA was weakly expressed in spleen and lung of normal C57BL/6 mice. In spleen, CD8+ cells and NK1.1+ cells were found to express mXCR1. Identification of mXCR1 will now allow us to study the role of this unique cytokine system in the mouse models of inflammation and immunity.

Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine.

Helper T cells are classified into Th1 and Th2 subsets based on their profiles of cytokine production. Th1 cells are involved in cell-mediated immunity, whereas Th2 cells induce humoral responses. Selective recruitment of these two subsets depends on specific adhesion molecules and specific chemoattractants. Here, we demonstrate that the T cell-directed CC chemokine thymus and activation-regulated chemokine (TARC) was abundantly produced by monocytes treated with granulocyte macrophage colony stimulating factor (GM-CSF) or IL-3, especially in the presence of IL-4 and by dendritic cells derived from monocytes cultured with GM-CSF + IL-4. The receptor for TARC and another macrophage/dendritic cell-derived CC chemokine macrophage-derived chemokine (MDC) is CCR4, a G protein-coupled receptor. CCR4 was found to be expressed on approximately 20% of adult peripheral blood effector/memory CD4+ T cells. T cells attracted by TARC and MDC generated cell lines predominantly producing Th2-type cytokines, IL-4 and IL-5. Fractionated CCR4+ cells but not CCR4- cells also selectively gave rise to Th2-type cell lines. When naive CD4+ T cells from adult peripheral blood were polarized in vitro, Th2-type cells selectively expressed CCR4 and vigorously migrated toward TARC and MDC. Taken together, CCR4 is selectively expressed on Th2-type T cells and antigen-presenting cells may recruit Th2 cells expressing CCR4 by producing TARC and MDC in Th2-dominant conditions.

High-pressure liquid chromatographic determination of toluene in urine as a marker of occupational exposure to toluene.

OBJECTIVE: To establish a convenient method by high-pressure liquid chromatography (HPLC) to measure toluene in urine as a marker of occupational exposure to toluene. METHODS: As soon after sampling as possible, 1 ml of urine was mixed with an equal volume of acetonitrile in a 2.2-ml HPLC glass bottle, and the bottle was tightly sealed and stored at 4 degrees C. Immediately before HPLC determination, 100 microl methanol was added to the mixture to prevent confounding effects of glycosuria, and the bottle was spun to remove any suspended matter. An aliquot of the supernate was introduced into the HPLC system and analyzed on a PRODIGY column, with an acetonitrile - perchloric acid phosphoric acid - water mixture serving as the mobile phase. The effluent was monitored at 191 nm. RESULTS: The method can measure toluene in urine every 20 min, the detection limit was 2 microg/l, the coefficient of variation was less than 5%, and the recovery rate was 100%. No significant reduction in toluene concentration was observed for 1 week after storage at 4 degrees C. When the method was applied to end-of-shift urine samples from 13 male workers exposed to toluene at 18-140 ppm and also to urine samples from 10 nonexposed male controls, toluene in urine was linearly related to toluene exposure concentration, with a regression line passing close to the origin. The correlation coefficient was as high as 0.97 (n=23). No toluene was detected in control urine samples. Calculations suggest that urinary toluene accounts for as little as less than 0.01% of the toluene absorbed via inhalation and that the absorbed toluene is converted almost quantitatively to hippuric acid and, by less than 0.1%, to o-cresol.

Identification of single C motif-1/lymphotactin receptor XCR1.

Single C motif-1 (SCM-1)/lymphotactin is a member of the chemokine superfamily, but retains only the 2nd and 4th of the four cysteine residues conserved in other chemokines. In humans, there are two highly homologous SCM-1 genes encoding SCM-1alpha and SCM-1beta with two amino acid substitutions. To identify a specific receptor for SCM-1 proteins, we produced recombinant SCM-1alpha and SCM-1beta by the baculovirus expression system and tested them on murine L1.2 cells stably expressing eight known chemokine receptors and three orphan receptors. Both proteins specifically induced migration in cells expressing an orphan receptor, GPR5. The migration was chemotactic and suppressed by pertussis toxin, indicating coupling to a Galpha type of G protein. Both proteins also induced intracellular calcium mobilization in GPR5-expressing L1.2 cells with efficient mutual cross desensitization. SCM-1alpha bound specifically to GPR5-expressing L1.2 cells with a Kd of 10 nM. By Northern blot analysis, GPR5 mRNA of about 5 kilobases was detected strongly in placenta and weakly in spleen and thymus among various human tissues. Identification of a specific receptor for SCM-1 would facilitate our investigation on its biological function. Following the set rule for the chemokine receptor nomenclature, we propose to designate GPR5 as XCR1 from XC chemokine receptor-1.

Field and Electroantennogram Responses of the Pine Sawfly, Diprion nipponica, to Chiral Synthetic Pheromone Candidates.

(1S, 2R, 6RS)-1,2,6-Trimethyldecyl propionate, a lower homolog of the sex pheromone of known sawflies, strongly attracted Diprion nipponica, a popular species in Japan.

Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion.

Leukocyte trafficking at the endothelium requires both cellular adhesion molecules and chemotactic factors. Fractalkine, a novel transmembrane molecule with a CX3C-motif chemokine domain atop a mucin stalk, induces both adhesion and migration of leukocytes. Here we identify a seven-transmembrane high-affinity receptor for fractalkine and show that it mediates both the adhesive and migratory functions of fractalkine. The receptor, now termed CX3CR1, requires pertussis toxin-sensitive G protein signaling to induce migration but not to support adhesion, which also occurs without other adhesion molecules but requires the architecture of a chemokine domain atop the mucin stalk. Natural killer cells predominantly express CX3CR1 and respond to fractalkine in both migration and adhesion. Thus, fractalkine and CX3CR1 represent new types of leukocyte trafficking regulators, performing both adhesive and chemotactic functions.