Japanese Black (JB) calves are more susceptible to infectious diseases compared to Holstein (Hol) calves. To clarify the immunological differences between JB and Hol calves, expression of cytokine ...messenger RNA (mRNA) was examined using peripheral CD4⁺, CD8⁺ and γδ T cells. Healthy calves, 24 from each species, were examined. Blood samples were obtained from calves at 1 week, 1 month and 3 months old, eight calves for each age of each species. Peripheral blood mononuclear cells were stimulated with phytohemagglutin (PHA), and T cell subsets were isolated by positive selection using magnetic cell sorting (MACS). Levels of interlekin (IL)‐2, IL‐4, IL‐10 and interferon (IFN)‐γ mRNA in three T cell subsets were analyzed. WC1‐N1⁺ γδ T cell percentages were significantly lower in JB calves at 1 week and 1 month of age compared to Hol calves. In addition JB calves had significantly lower IL‐2, IL‐10 and IFN‐γ mRNA in WC1‐N1⁺ γδ T cells at 1 and 3 months of age, whereas there were no significant differences in cytokine mRNA of CD4⁺ and CD8⁺ cells between the two groups. Decreased cytokine mRNA and cell number of peripheral γδ T cells may affect negatively on the immune system of JB calves.
The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of ...dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.
Non‐Hodgkin's lymphoma (NHL) has a wide biological heterogeneity and shows extremely variable responses to therapeutic measures. However, markers that indicate disease activity and determine ...treatment strategies for this malignancy are little recognized. Using the differential display method, we have identified Aurora2/BTAK/STK15, a centrosome‐associated serine/threonine kinase, whose overexpression leads to centrosome amplification, chromosomal instability and transformation of mammalian solid tumours. Northern analysis with mRNA from a single tumour cell suspension of NHL confirmed that Aurora2/BTAK/STK15 was highly expressed in histologically aggressive types. To elucidate the function of Aurora2/BTAK/STK15 in NHL, Aurora2/BTAK/STK15 sense or antisense genes were transfected to B‐cell lymphoma cell lines to generate overexpressed or under‐regulated tumour cells. Aurora2/BTAK/STK15 antisense transfectant was barely established compared with a sense or vector‐only transfectant. Two clones were finally established that exhibited a low proliferation rate and significantly increased G1 arrest compared with vector‐only transfectants. Moreover, antisense oligo treatment in vitro showed that restriction of cell growth appeared in proportion to antisense oligo concentration. These results suggest that Aurora2/BTAK/STK15 is an effective candidate to indicate not only disease activity but also tumorigenesis of non‐Hodgkin's lymphoma. Retardation of tumour cell growth resulting from the restriction of this gene's functions may be a novel therapeutic approach for non‐Hodgkin's lymphoma.
CYP2C8 plays important roles in metabolizing therapeutic drugs and endogenous compounds. Although genetic polymorphisms of CYP2C8 were reported, there is little information on CYP2C8 polymorphisms in ...the Japanese population. In the present study, we screened for previously described polymorphisms in the coding region of this gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism or allele specific-PCR analyses. Eleven polymorphisms of CYP2C8*2 (I269F), CYP2C8*3 (R139K, K399R), CYP2C8*4 (I264M), CYP2C8*5 (frameshift), T130N, E154D, N193K, K249R, L390S, P404A, and H411L have been comprehensively investigated in at least 200 Japanese individuals. A single subject was heterozygous for CYP2C8*5, and the allele frequency was calculated as 0.0025. The other single nucleotide polymorphisms (SNPs) were not found in the Japanese subjects in the present study. Thus, it appears that the frequencies of these alleles in Japanese are extremely low. In addition, concerning the SNPs of T130N, E154D, N193K, K249R, and H411L, it remains clear that these alleles exist as polymorphisms or represent sequence errors or cloning artifacts. Although several SNPs such as CYP2C8*2, CYP2C8*3, CYP2C8*4, and P404A have been reported to reduce the enzymatic activity, pharmacokinetic abnormalities of drugs metabolized by polymorphic CYP2C8 might be rare in Japanese.
Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased uric acid (UA) levels are associated with MetS and its components. High-sensitivity ...C-reactive protein (hsCRP) levels are also associated with MetS, and hsCRP levels could be modulated by UA. We investigated whether combining UA and hsCRP levels are independently associated with MetS and insulin resistance in Japanese community-dwelling women. From a single community, we recruited 1,097 women (63 ± 12 years) during their annual health examination, and examined the cross-sectional relationship between UA, hsCRP, and MetS and insulin resistance, which was evaluated by homeostasis of minimal assessment of insulin resistance. Of these subjects, 218 women (19.9 %) had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS and insulin resistance, both UA and hsCRP as well as age and alcohol consumption, were independently and significantly associated with MetS and insulin resistance. The adjusted-odds ratios (95 % confidence interval) for MetS across tertiles of UA and hsCRP were 1.00, 1.45 (0.95–2.22), and 2.61 (1.74–3.93), and 1.00, 1.80 (1.18–2.74), and 3.23 (2.15–4.85), respectively. In addition, the combination increased UA, and hsCRP was also a significant and independent determinant for MetS and insulin resistance. In direction associations, we also observed a synergistic effect between these two molecules (
F
= 2.76,
P
= 0.027). These results suggested that combined assessment of UA and hsCRP levels provides incremental information for risk stratification of patients with MetS, independent of other confounding factors in community-dwelling women.
Pulse wave velocity (PWV) is a simple and noninvasive method of measuring arterial stiffness for the assessment of cardiovascular disease in high-risk populations. This association may be further ...confounded by hemoglobin status, which is involved in the development of atherosclerosis. We randomly recruited 120 men and 223 women aged 69 ± 9 and 68 ± 7 years, respectively, during their annual health examination in a single community. Arterial stiffness was evaluated by brachial-ankle PWV (baPWV). The value of baPWV was different from men and women. In men, baPWV was not related to hemoglobin levels (r = 0.013, P = .886), but in women baPWV increased significantly and progressively with increased hemoglobin levels (r = 0.276, P < .001). Stepwise multiple regression analysis using the baPWV as objective variables, adjusted for confounding factors as explanatory variables, showed that only in women, hemoglobin levels (β = 0.165, P = .001) as well as age (β = 0.268, P < .001), body mass index (BMI; β = −0.165, P < .001), systolic blood pressure (SBP; β = 0.429, P < .001), prevalence of antihypertensive (β = 0.154, P = .002), heart rate (HR; β = 0.108, P = .017), and antilipidemic medication (β = 0.094, P = .036), and estimated glomerular filtration rate (eGFR; β = −0.147, P = .003) were significantly and independently associated with baPWV. Multivariate-adjusted baPWV was significantly higher in hemoglobin groups of ≥12.7 g/dL (Group-2, Group-4) than in the lowest hemoglobin group (10.0-12.6 g/dL; P = .032). A slightly low hemoglobin level was beneficially associated with arterial stiffness in community-dwelling women but not men.
Alcohol consumption is associated with a decreased risk of type II diabetes and cardiovascular diseases. However, there is a great deal of controversy concerning the relationship between alcohol ...consumption and insulin resistance. This association may be further confounded by an increase in body weight levels. The aim of this study was to determine whether alcohol consumption promotes insulin resistance according to body weight levels in community-dwelling men. Study participants without a clinical history of stroke, transient ischemic attack, myocardial infarction, angina or diabetes were randomly recruited from a single community at the time of their annual health examination (678 men aged 59 ± 14 years). They were classified into never drinkers, light drinkers < 1 unit (22.9 g ethanol)/day, moderate drinkers (1-1.9 unit/day), and heavy drinkers (≥ 2 unit/day), and further divided into underweight body mass index (BMI) < 23 kg/m2 or overweight (BMI ≥ 23.0 kg/m2). Insulin resistance was estimated on the basis of the homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-IR and potential confounders were compared between the groups. The confounders included age, BMI, smoking status, serum gamma glutamyltransferase, and high molecular-weight adiponectin. In the overall, HOMA-IR is significantly correlated with age, BMI, serum gamma glutamyltransferase, and high molecular-weight adiponectin. After adjustment for potential confounders, mean log HOMA-IR is significantly lower in the heavy drinkers irrespective of BMI categories. In conclusion, alcohol consumption is associated with decreased insulin resistance independent of BMI in Japanese community-dwelling men.
A total of 45 different mutations of methyl-CpG-binding protein 2 gene (
MECP2) were identified in 145 of 219 Japanese patients with typical or atypical Rett syndrome (RTT) (66.2%). A missense ...mutation, T158M was the most common mutation of MECP2, identified in 22 (19.1%) patients, followed by four nonsense mutations, R168X (14.8%), R270X (13.0%), R255X (9.6%), and R294X (6.1%) in 115 patients with classical RTT. Two missense mutations, R133C (33.3%) and R306C (23.3%), and a nonsense mutation, R294X (13.3%), were common in 30 patients with atypical RTT, including the preserved speech variant (PSV). Frameshift mutations due to nucleotide deletion or insertion were identified in 22 patients with
MECP2 mutations, and one of them had a 3.6
kb deletion encompassing exons 3 and 4. Three patients with classical RTT had a splicing anomaly. The wide spectrum of phenotypic variability in patients with RTT has been considered to be correlated with the mutation type and location in MECP2, and X-inactivation. However, most patients showed a random X-inactivation pattern evaluated by an androgen receptor gene polymorphism in this study, suggesting that a skewed X-inactivation might not be a main modification factor on clinical phenotypes of RTT. In addition, three new missense mutations, P176R, A378V and T479M, were identified in patients with RTT, but also in healthy Japanese, indicating that these mutations are non-pathogenic in Japanese. Information about rare polymorphic variations is very important for the molecular diagnosis of RTT, although rare polymorphic variants might differ among ethnic groups.
Aims: Renal dysfunction is a major public health problem, but there have been few investigations of the relationship between serum high molecular weight (HMW) adiponectin and renal function in ...Japanese community-dwelling adults. Methods: We randomly recruited a sample of 1,849 adult Japanese (793 men aged 60±14 (mean±standard deviation; range, 20-89) years and 1,056 women aged 62±12 (range, 21-88) years) during their annual health examination in a single community. Participants with an eGFR of ≥ 60 mL/ min/1.73 m2 were divided into four groups based on quartiles of serum HMW adiponectin levels, and it was investigated whether serum HMW adiponectin is independently associated with eGFR. Results: Mean eGFR was significantly higher in the highest quartile than the lowest quartile of serum HMW adiponectin levels. Stepwise multiple linear regression analysis using eGFR as an objective variable, adjusted for confounding factors as explanatory variables, showed that serum HMW adiponectin (β=0.068) as well as age (β=-0.361), prevalence of antihypertensive medication (β=-0.115), triglycerides (β=-0.063), low-density lipoprotein cholesterol (β=-0.094), and fasting plasma glucose (β=0.148) were independently associated with eGFR. The multivariate-adjusted odds ratio for mild renal dysfunction of an eGFR < 70 mL/min/1.73 m2 was 0.62 (95% CI, 0.42-0.91) for the highest quartile compared with participants with the lowest serum adiponectin quartile. Conclusions: We conclude that a higher serum HMW adiponectin level is associated with a reduced odds ratio of mild renal dysfunction in Japanese adults.
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