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Japanese Subjects (japanese + subject)
Selected AbstractsPharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western subjectsEPILEPSIA, Issue 8 2009Peter Zannikos Summary Purpose:, To compare the pharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western adults, and to comparatively assess carisbamate safety and tolerability between the two populations. Methods:, An open-label study was conducted in 24 Japanese and 24 Caucasian healthy subjects. Subjects received a single oral dose of 250 mg carisbamate on day 1 followed by a 3-day washout period; twice-daily dosing of 250 mg carisbamate on days 5,8; subsequently, 500 mg on days 9,12 and a single dose of 500 mg on day 13. Plasma samples were collected for a pharmacokinetic analysis on days 1, 8, and 13. Plasma and urine samples were analyzed for carisbamate and its urinary metabolites by liquid-chromatography-mass-spectrometry. Results:, Following a single dose, carisbamate Cmax and area under the curve (AUC) geometric mean ratios were 16.4% and 28.8% higher in Japanese than in Caucasians, respectively; these differences were statistically significant and their 90% confidence intervals (CIs) fell outside of the 80,125% limits, which are considered not to be of clinical significance. With dose,body weight normalization, Cmax and AUC were similar in Japanese and Caucasian subjects and the 90% CIs were within the 80,125% boundaries. Carisbamate was well tolerated, and its mean oral clearance and half-life were similar in both groups, ranging from 35.1,41.4 ml/h/kg and 11.5,12.8 h. Discussion:, Carisbamate plasma exposure (AUC) and Cmax in Japanese subjects is ,20,25% higher than in Caucasians due to a higher mg/kg dose. After body weight normalization, carisbamate pharmacokinetics was similar between Japanese and Caucasian subjects following single and multiple dosing, and showed the same dose proportionality. [source] Validation of the oral glucose insulin sensitivity index to assess insulin sensitivity in Japanese subjects for use in clinical practiceEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2003M. Kanauchi No abstract is available for this article. [source] Brief screening tool for mild cognitive impairment in older Japanese: Validation of the Japanese version of the Montreal Cognitive AssessmentGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2010Yoshinori Fujiwara Aim: The Montreal Cognitive Assessment (MoCA), developed by Dr Nasreddine (Nasreddine et al. 2005), is a brief cognitive screening tool for detecting older people with mild cognitive impairment (MCI). We examined the reliability and validity of the Japanese version of the MoCA (MoCA-J) in older Japanese subjects. Methods: Subjects were recruited from the outpatient memory clinic of Tokyo Metropolitan Geriatric Hospital or community-based medical health check-ups in 2008. The MoCA-J, the Mini-Mental State Examination (MMSE), the revised version of Hasegawa's Dementia Scale (HDS-R), Clinical Dementia Rating (CDR) scale, and routine neuropsychological batteries were conducted on 96 older subjects. Mild Alzheimer's disease (AD) was found in 30 subjects and MCI in 30, with 36 normal controls. Results: The Cronbach's alpha of MoCA-J as an index of internal consistency was 0.74. The test,retest reliability of MoCA, using intraclass correlation coefficient between the scores at baseline survey and follow-up survey 8 weeks later was 0.88 (P < 0.001). MoCA-J score was highly correlated with MMSE (r = 0.83, P < 0.001), HDS-R (r = 0.79, P < 0.001) and CDR (r = ,0.79, P < 0.001) scores. The areas under receiver,operator curves (AUC) for predicting MCI and AD groups by the MoCA-J were 0.95 (95% confidence interval [CI] = 0.90,1.00) and 0.99 (95% CI = 0.00,1.00), respectively. The corresponding values for MMSE and HDS-R were 0.85 (95% CI = 0.75,0.95) and 0.97 (95% CI = 0.00,1.00), and 0.86 (95% CI = 0.76,0.95) and 0.97 (95% CI = 0.00,1.00), respectively. Using a cut-off point of 25/26, the MoCA-J demonstrated a sensitivity of 93.0% and a specificity of 87.0% in screening MCI. Conclusion: The MoCA-J could be a useful cognitive test for screening MCI, and could be recommended in a primary clinical setting and for geriatric health screening in the community. Geriatr Gerontol Int 2010; 10: 225,232. [source] Interleukin-2 Gene Polymorphisms Associated with Increased Risk of Gastric Atrophy from Helicobacter pylori InfectionHELICOBACTER, Issue 3 2005Shozo Togawa ABSTRACT Background., Gastric atrophy induced by Helicobacter pylori is thought to predispose patients to noncardiac gastric cancer development. However, the host genetic factors that influence the progression of gastric atrophy have not been elucidated. In this study, we examined the effects of cytokine polymorphisms on H. pylori -induced gastric atrophy. Methods., Blood samples were taken from 454 Japanese subjects. The interleukin-2 (IL-2; T-330G), IL-4 (C-33T), and IL-13 (C-1111T) polymorphisms were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Anti- H. pylori IgG antibody and pepsinogen I and II were measured to diagnose H. pylori infection and atrophic gastritis. Results., The odds ratios (ORs) for the association between IL-2 polymorphism [OR = 2.78, 95% CI (confidence interval) = 1.26,6.17 (T/T to G/G)] or IL-4 polymorphism [OR = 2.22, 95% CI = 1.01,4.89 (T/C to C/C)] were increased significantly with gastric atrophy, whereas the corresponding OR of IL-13 polymorphism was decreased with gastric atrophy [OR = 0.61, 95% CI = 0.39,0.96 (C/T and T/T to C/C)]. There were no significant H. pylori seropositivity-related differences between these polymorphisms. We examined the relationship between these polymorphisms and gastric atrophy separately in H. pylori -seropositive and -seronegative groups. In the H. pylori -seropositive group, the IL-2 T/T (OR = 2.78, 95% CI = 1.12,6.93) had a significant association with gastric atrophy. Conclusions., These results reveal that the IL-2 gene polymorphism is associated with an increased risk of gastric atrophy induced by H. pylori infection and might predispose to gastric cancer. [source] Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis,,HEPATOLOGY, Issue 3 2009Koji Fujita The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1) lipid inflow in the liver, (2) lipid outflow from the liver, (3) very-low-density lipoprotein (VLDL) synthesis in the liver, (4) triglyceride (TG) metabolites in the liver, and (5) lipid changes and oxidative DNA damage. Most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, VLDL synthesis and lipid outflow from the liver were impaired, and surplus TGs might have been produced as a result of lipid oxidation and oxidative DNA damage in the NASH group. Conclusion: A growing body of literature suggests that a deterioration in fatty acid oxidation and VLDL secretion from the liver, caused by the impediment of VLDL synthesis, might induce serious lipid oxidation and DNA oxidative damage, impacting the degree of liver injury and thereby contributing to the progression of NASH. Therefore, dysfunctional VLDL synthesis and release may be a key factor in progression to NASH. (HEPATOLOGY 2009.) [source] Analysis of a non-functional HNF-1, (TCF1) mutation in Japanese subjects with familial type 1 diabetesHUMAN MUTATION, Issue 4 2001Issei Yoshiuchi Abstract Mutations in the transcription factor hepatocyte nuclear factor-1, (HNF-1,; gene symbol TCF1) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic ,-cell dysfunction. Recent genetic studies, however, also found mutations in patients diagnosed with idiopathic (non-autoimmune based) type 1 diabetes. We identified a novel frameshift mutation (142delG) in the TCF1 gene in a family with a strong family history of type 1 diabetes and examined the functional properties of the mutant HNF 1,. The expression of the mutant protein was not detected in COS-7 cells by Western blot analysis after transfection of the mutant cDNA. This is the first case of an unstable mutant HNF-1, protein. Reporter gene analysis indicated that the mutant HNF-1, had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF-1, may lead to severe forms of diabetes like type 1 diabetes. Hum Mutat 18:345,351, 2001. © 2001 Wiley-Liss, Inc. [source] Beta-cell function and insulin sensitivity contribute to the shape of plasma glucose curve during an oral glucose tolerance test in non-diabetic individualsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2005M. Kanauchi Summary To clarify whether beta-cell function and/or insulin resistance contributes to the shape of plasma glucose curve during an oral glucose tolerance test (OGTT), we investigated 583 Japanese subjects with normal glucose tolerance (NGT, n = 306) or impaired glucose tolerance (IGT, n = 277). Each subject was subdivided into three shapes of plasma glucose curve as follows: monophasic pattern (M type), biphasic pattern (B type) and two peaks (T type). Homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and insulinogenic index were assessed by plasma glucose and insulin concentrations obtained at fasting or during an OGTT. There was a greater proportion of M type in the IGT group (M = 80.9%, B = 15.5% and T = 3.6%), whereas the prevalence of B and T types was much higher in the NGT group (M = 66.6%, B = 26.5% and T = 6.9%). There were significant differences in the proportions of shape types between the NGT and IGT groups (p = 0.0006). Among the NGT category, insulin sensitivity was significantly higher in the B type than in the M type, and beta-cell function adjusted for insulin resistance was significantly higher in the B and T types than in the M type. Among the IGT category, no significant differences were seen among the three shape types with respect to insulin sensitivity, but the beta-cell function adjusted for insulin resistance was significantly lower in the M type than in the B and T types. In conclusion, both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of the shape of plasma glucose curve in Japanese subjects. [source] Beliefs of chronically ill Japanese patients that lead to intentional non-adherence to medicationJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2004N. Iihara BS Summary Objective:, To identify factors, associated with personal beliefs, involved in intentional non-adherence to prescribed medication of Japanese patients with chronic diseases. Methods:, A cross-sectional study of Japanese subjects with chronic, primarily liver, gastrointestinal, or nervous system diseases who had been prescribed oral medicines for regular use, was performed. The subjects were admitted to a university hospital and were interviewed face-to-face on admission. Intentional non-adherence was defined as experience of deliberate adjustment of self-managed prescription medicines during the few months prior to hospital admission. Patients' beliefs about taking medicines were assessed from the perspective of what the patient valued in order to take medicines without anxiety; whether the patient valued information about the medication such as its function and side-effects and/or mutual reliance on doctors. Using logistic multivariate regression analyses, factors associated with intentional non-adherence were identified. Results:, Among 154 subjects, 51 showed intentional non-adherence. Intentional non-adherence was associated with the following three factors: (a) the patients' beliefs with respect to taking medicines without anxiety, especially putting no value on mutual reliance on the patient,doctor relationship (P < 0·001) and putting great value on knowing the drug's side-effects (P < 0·001), (b) poor comprehension of general aspects of medication (P for trend <0·001), and (c) being in the prime of life (40,59 years) (P = 0·011). Comprehension of the function of each medicine, experience of side-effects, anxiety about taking medicines, and the number of types of medicines taken, were not associated with non-adherence. Conclusions:, Beliefs on which individual Japanese patients with chronic diseases attach value in order to take medicines without anxiety were potential factors for intentional non-adherence. This emphasizes the necessity of a patient-oriented approach to take account of patients' personal beliefs about medicines to increase adherence rate in Japan. [source] Detection of serotype k Streptococcus mutans in Thai subjectsMOLECULAR ORAL MICROBIOLOGY, Issue 5 2009J. Lapirattanakul Introduction:,Streptococcus mutans, known to be a pathogen of dental caries as well as bacteremia and infective endocarditis, is classified into four serotypes, c, e, f and k, based on the structures of serotype-specific polysaccharides. Serotype k was recently designated using blood isolates from Japanese subjects and such strains are considered to be virulent in the bloodstream. The purpose of the present study was to analyse the serotype distribution of strains isolated from Thai subjects and determine whether serotype k strains were present. Methods:, A total of 250 S. mutans strains were isolated from 50 Thai subjects, and serotypes of all strains were determined. Then, molecular and biological analyses were carried out for serotype k strains. Results:, Immunodiffusion and polymerase chain reaction analyses showed that serotype c was the most prevalent (70%), followed by serotypes e (22.8%), f (4.4%) and k (2.8%), which indicated that serotype k S. mutans strains occurred in Thai individuals at a similar rate to that previously reported for Japanese and Finnish populations. Molecular analyses of the seven serotype k strains showed extremely low expression of rgpE, which is related to glucose side-chain formation in serotype-specific rhamnose-glucose polymers, similar to previous reports for those other populations. In addition, analysis of the biological properties of the seven serotype k strains demonstrated low levels of sucrose-dependent adhesion, cellular hydrophobicity, dextran-binding activity and phagocytosis susceptibility by human polymorphonuclear leukocytes, which are characteristics similar to those of serotype k strains previously isolated in Japan. Conclusion:, Our results indicate the possibility of a worldwide prevalence of serotype k strains with properties in common with those of previously reported strains. [source] Prevalence of restless legs syndrome in a rural community in Japan,MOVEMENT DISORDERS, Issue 16 2008Takashi Nomura MD Abstract To assess the prevalence and clinical significance of restless legs syndrome (RLS) in a Japanese population, we carried out a community-based survey in a rural area of Japan. We sent questionnaires requesting information on demographics, the Center for Epidemiological Studies Depression scale, the Short Form-8, the Pittsburgh Sleep Quality Index, the National Institutes of Health/International RLS Study Group (IRLSSG) consensus questionnaire, and the IRLSSG severity scale for RLS (IRLS) to 5,528 eligible adult residents in the town of Daisen in the Tottori prefecture of Japan. Next, we performed telephone interviews to identify subjects with probable RLS. Of the 2,812 subjects (51.1%) who gave complete answers on the IRLSSG questionnaire, 50 (1.8%) were judged as RLS positive. The prevalence of RLS was significantly higher in women than in men, and significantly lower in individuals 60 years of age or older. Multiple logistic regression analysis revealed that the existence of RLS was significantly associated with depression, lowered mental quality of life, and sleep disturbances. The prevalence of RLS in adult Japanese populations may be lower than that reported in Caucasian populations. However, in a group of Japanese subjects, RLS had a significant impact on daytime functioning as well as subjective sleep quality. © 2008 Movement Disorder Society [source] Relationship between late-life depression and life stressors: Large-scale cross-sectional study of a representative sample of the Japanese general populationPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2010Tatsuhiko Kaji MD Aim:, The purpose of the present study was to clarify the relationship between late-life depression and daily life stress in a representative sample of 10 969 Japanese subjects. Methods:, Data on 10 969 adults aged ,50 who participated in the Active Survey of Health and Welfare in 2000, were analyzed. The self-administered questionnaire included items on 21 reasons for life stressors and the magnitude of stress, as well as the Japanese version of the Center for Epidemiologic Studies Depression Scale (CES-D). The relationship between the incidence of life stressors and mild,moderate (D16) and severe (D26) depressive symptoms was examined using logistic regression analysis. Results:, A total of 21.9% of subjects had D16 symptoms, and 9.3% had D26 symptoms. Further, increased age and being female were associated with more severe depressive state. Logistic regression analysis indicated that the strongest relationship between both the incidence of D16 and D26 symptoms and life stressors stemmed from ,having no one to talk to' (odds ratio = 3.3 and 5.0, respectively). Late-life depression was also associated with ,loss of purpose in life', ,separation/divorce', ,having nothing to do', ,health/illness/care of self', and ,debt'. Conclusion:, There is a relationship between late-life depression and diminished social relationships, experiences involving loss of purpose in life or human relationships, and health problems in the Japanese general population. [source] No association between polymorphism in tyrosine hydroxylase and personality traits in healthy Japanese subjectsPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2010Shoko Tsuchimine MSc The aim of the present study was to investigate whether there is an association between the (TCAT)n repeat polymorphism in the tyrosine hydroxylase (TH) gene and personality. The (TCAT)n repeat polymorphism in the TH gene was genotyped in 898 healthy Japanese subjects. Personality traits were evaluated using the Temperament and Character Inventory (TCI). There was no significant difference in the TCI scores of subjects with and without the T9 allele. Furthermore, no significant association was found between each genotype and the TCI scores, even when the TCI scores were compared with the homozygous genotype. These findings suggest that the (TCAT)n repeat polymorphism in the TH gene does not contribute to the personality traits evaluated on the TCI in healthy Japanese subjects. [source] Factors associated with the development of panic attack and panic disorder: Survey in the Japanese populationPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2005HISANOBU KAIYA md Abstract, Environmental factors, in addition to genetic factors, may be related to the development of panic attack (PA) and panic disorder (PD). Previous studies suggested that there may be seasonal variation in the onset of PA/PD and possibly a higher prevalence of PA/PD in colder areas. Also observed were lactate-induced PA and elevated serum cholesterol in PD patients. These suggest that living environment and lifestyle, such as weather conditions, preference of food and physical exercise, might play a role in the occurrence of PA and PD. The present study explored the association of such candidate factors with the development of PA and PD in 4000 Japanese subjects, using a questionnaire. The subjects were recruited from the general population of Japan, using stratified random sampling. Logistic regression with stepwise selection of variables was employed for statistical analysis. Variables including ,dislike of physical exercise', mostly in female subjects, and ,living in areas with longer winter', in male subjects, were suggested for associations with PA and PD among the candidate factors. The result is preliminary but indicates that lifestyle such as like/dislike of physical exercise and environmental factors including weather conditions could play a partial role in the development of PA and PD. Further investigations are required before firm conclusions can be reached. [source] Polymorphism of the promoter region of prostacyclin synthase gene in chronic thromboembolic pulmonary hypertensionRESPIROLOGY, Issue 2 2004Shinya AMANO Objective: Decreased expression of prostacyclin synthase (PGIS) is observed in the lung vasculature of patients with pulmonary arterial hypertension and the biosynthesis of prostacyclin (PGI2) may be impaired in chronic thromboembolic pulmonary hypertension (CTEPH). Whether it is genetically determined or develops as the disease progresses is unclear. A variable-number tandem repeat (VNTR) polymorphism has been detected in the 5,-upstream promoter region of the PGIS gene. It has been demonstrated that the alleles vary in size from three to seven repeats of nine base pairs, and transcriptional activity increased with the number of repeats. The purpose of the present study was to elucidate the association between the VNTR polymorphisms of the PGIS gene and CTEPH in Japanese subjects. Methodology: Ninety patients with CTEPH and 144 control subjects were investigated for the presence of VNTR polymorphisms. Sixty-two blood samples were obtained from CTEPH patients and the plasma concentrations of prostacyclin and thromboxane A2 metabolites were measured. Results: VNTR polymorphisms in the prostacyclin synthase gene were grouped into L alleles (five, six and seven repeats) and S alleles (three and four repeats). The overall distribution of the alleles and genotypes were not significantly different between CTEPH patients and the control subjects. The patients with the LL genotype had higher plasma concentrations of 6-keto-prostaglandin F1, than patients with the LS and SS genotypes. Conclusions: Our results suggested that the specific VNTR polymorphism in the 5,-upstream promoter region of the PGIS gene regulated prostacyclin production, but did not seem to be associated with the development of CTEPH in this patient population. [source] Randomized clinical trial comparing 5% and 1% topical minoxidil for the treatment of androgenetic alopecia in Japanese menTHE JOURNAL OF DERMATOLOGY, Issue 8 2009Ryoji TSUBOI Abstract Minoxidil is efficacious in inducing hair growth in patients with androgenetic alopecia by inducing hair follicles to undergo transition from the early to late anagen phase. Although the efficacy of 1% topical minoxidil has been confirmed in Japan, no controlled study of 5% topical minoxidil has been conducted using male Japanese subjects. The objective of this trial was to verify the superiority in clinical efficacy of 5% topical minoxidil to 1% topical minoxidil in a double-blind controlled study with male, Japanese androgenetic alopecia patients as the subjects. The trial included 300 Japanese male patients aged 20 years or older with androgenetic alopecia who were administered either 5% topical minoxidil (n = 150) or 1% topical minoxidil (n = 150) for 24 weeks. The mean change from the baseline in non-vellus hair/cm2, the primary efficacy variable, was 26.4 (n = 142) in the 5% topical minoxidil group and 21.2 (n = 144) in the 1% topical minoxidil group at 16 weeks, the main time point for the evaluation. The difference between the groups was significant (P = 0.020). The incidence of adverse events was 8.7% (13/150) in the 5% group and 5.3% (8/150) in the 1% group, with no significant difference between the groups (,2 -test: P = 0.258). Our findings confirmed the superiority of 5% topical minoxidil to 1% topical minoxidil in treating Japanese men with androgenetic alopecia. [source] The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese populationARTHRITIS & RHEUMATISM, Issue 2 2010Kenichi Shimane Objective Genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Caucasian populations have independently identified risk variants in and near the tumor necrosis factor , (TNF,),induced protein 3 gene (TNFAIP3), which is crucial for the regulation of TNF-mediated signaling and Toll-like receptor signaling. The aim of this study was to assess the role of TNFAIP3 in the development of SLE and RA in Japanese subjects. Methods We selected 2 single-nucleotide polymorphisms (SNPs) from previous GWA studies. Rs2230926 is a nonsynonymous SNP in TNFAIP3 and is associated with SLE, while rs10499194 is an intergenic SNP associated with RA. We then performed 2 independent sets of SLE case,control comparisons (717 patients and 1,362 control subjects) and 3 sets of RA case,control comparisons (3,446 patients and 2,344 control subjects) using Japanese subjects. We genotyped SNPs using TaqMan assays. Results We observed a significant association between rs2230926 and an increased risk of SLE and RA in the Japanese population (for SLE, odds ratio [OR] 1.92, 95% confidence interval [95% CI] 1.53,2.41, P = 1.9 × 10,8; for RA, OR 1.35, 95% CI 1.18,1.56, P = 2.6 × 10,5). The intergenic SNP rs10499194 was also associated with SLE and RA, while the risk allele for RA in Caucasians was protective against the diseases in our population. Conclusion We demonstrated a significant association between the nonsynonymous variant in TNFAIP3 and the risk for SLE and RA in the Japanese population. TNFAIP3, similar to STAT4 and IRF5, may be a common genetic risk factor for SLE and RA that is shared between the Caucasian and Japanese populations. [source] Role of interleukin-17F in chronic inflammatory and allergic lung diseaseCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2006N. Hizawa Summary IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case,control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures. [source] Individual variations in aging of the male urethral rhabdosphincter in JapaneseCLINICAL ANATOMY, Issue 4 2002Gen Murakami Abstract Although the degenerative changes with aging of the male urethral rhabdosphincter (URS) have been investigated, its individual morphological variations are still unclear. To provide an anatomical basis for clinical evaluation of the individual URS function in the aged, we investigated the structural differences in the URS of 25 elderly Japanese men using semiserial sections stained immunohistochemically and by hematoxylin-eosin. Before removal of the histological specimens, we dissected the ischioanal fossa and labeled several structures by carbon particles to allow proper orientation during the histological observations. In addition, macroscopic slices (10 mm thickness) made from five other male pelves were examined and, when necessary, followed by routine histological procedure to confirm the gross observations. An extended circular URS (over ½ circumferential configuration) was found in 15/25 cadavers, but showed very limited height (proximal-distal length) and thickness. A more restricted URS, including even a thin, arc-like pattern, was observed in the remaining cadavers. The attachment of the URS to the smooth muscle layer was loose and usually clearly separated. Continuation between the URS and deep transverse perineal muscle was sometimes observed. The thick fascia of the levetor ani, with high content of smooth muscles, usually provided the lateral or dorsal insertions of the URS. Our results in elderly Japanese subjects suggest that the sphincteric action is weak or incomplete. We suggest that the elderly URS maintains continence by retracting the urethra backward and upward with the aid of the levator sling, rather than the real sphincteric action expected in younger men. Clin. Anat. 15:241,252, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||