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Objectives: Glucocorticoids (GCs) are effective treatments for rheumatoid arthritis (RA) but long-term use has adverse effects. This study aimed to elucidate whether GCs can be discontinued by intr...

Hepatic insulin signalling involves insulin receptor substrates (Irs) 1/2, and is normally associated with the inhibition of gluconeogenesis and activation of lipogenesis. In diabetes and obesity, insulin no longer suppresses hepatic gluconeogenesis, while continuing to activate lipogenesis, a state referred to as ‘selective insulin resistance'. Here, we show that ‘selective insulin resistance' is caused by the differential expression of Irs1 and Irs2 in different zones of the liver. We demonstrate that hepatic Irs2-knockout mice develop ‘selective insulin resistance', whereas mice lacking in Irs1, or both Irs1 and Irs2, develop ‘total insulin resistance'. In obese diabetic mice, Irs1/2-mediated insulin signalling is impaired in the periportal zone, which is the primary site of gluconeogenesis, but enhanced in the perivenous zone, which is the primary site of lipogenesis. While hyperinsulinaemia reduces Irs2 expression in both the periportal and perivenous zones, Irs1 expression, which is predominantly in the perivenous zone, remains mostly unaffected. These data suggest that ‘selective insulin resistance' is induced by the differential distribution, and alterations of hepatic Irs1 and Irs2 expression., Type 2 diabetes and obesity are associated with increased hepatic gluconeogenesis and lipogenesis, known as selective insulin resistance. Here Kubota et al. explain selective insulin resistance in the liver with the zonal distribution and selective insulin-mediated regulation of Irs1 and Irs2.

TGF-β family members are multipotent cytokines that are involved in many cellular processes, including cell differentiation, organ development, wound healing and immune regulation. TGF-β has pleiotropic effects on adaptive immunity, especially in the regulation of CD4(+) T cell and B cell responses. Furthermore, identification of CD4(+) T cell subsets that produce TGF-β3 revealed unexpected roles of TGF-β3 in the control of adaptive immunity. In contrast to TGF-β1, which induces extensive fibrosis, TGF-β3 induces non-scarring wound healing and counteracts tissue fibrosis. Recent progress in the understanding of the activation mechanism of TGF-β may enable us to develop novel biologic therapies based on advanced protein engineering.

The purpose of the present study was to assess the effects of social capital on mental health among the Japanese population with or without natural disaster experience. A nationwide cross-sectional study was performed in the population aged 15 to 79 years old. We collected data on psychological status, social capital, disaster experience in ten years prior to the survey, and socio-demographic information. We assessed cognitive social capital (perceptions of support, reciprocity and trust), social support (support from individuals in the community), and social participation (participation in social activities) as components of social capital. The study outcome was mild mood or anxiety disorder (hereafter mood/anxiety disorder), defined as the score of 5 or higher in the Kessler Psychological Distress Scale (K6). Using logistic regression models, we tested whether each component of social capital was associated with mood/anxiety disorder with or without disaster experience. Out of 1,200 participants, 1,183 had available K6 score data and were considered. Among three components of social capital, only social support significantly interacted with disaster experience (p = 0.019). In the population without disaster experience, those with high social support were less likely to have mood/anxiety disorder (OR 0.45, 95% Cl 0.28-0.73); however, no such association was observed among those with disaster experience (OR 1.11, 95% CI 0.64-1.90). Thus, the protective effects of social support against mood/anxiety disorder vary in the Japanese population depending on disaster experience. The present study provides important insight into the role of social capital on mental health after natural disaster.

Objective Biologic disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) treatment have several mechanisms of action. Interleukin-6 inhibitors (IL-6i) block the production of acute-phase reactants (APRs), which are some of the composite measures of disease activity. We undertook this study to examine the agreement between the European League Against Rheumatism (EULAR) response based on the erythrocyte sedimentation rate (ESR) or C-reactive protein level, the Simplified Disease Activity Index 50% response measure (SDAI50), and the Clinical Disease Activity Index 50% response measure (CDAI50) in patients treated with IL-6i and other bDMARDs. Methods We enrolled 306 patients with RA who started or switched bDMARDs. Treatment response at 6 months was analyzed. Kappa statistics were used to evaluate the agreement between different response measures. The contribution of APRs to improvement in disease activity scores was examined. The change of Health Assessment Questionnaire (HAQ) score was analyzed in IL-6i-treated patients. Results Good agreement was achieved between response measures, with κ >0.6 in patients treated with tumor necrosis factor inhibitors or cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein. In IL-6i-treated patients, the agreement was low between the EULAR response (ESR) and the SDAI50 or the CDAI50 (κ = 0.43 and 0.37, respectively). Under IL-6i treatment, APR improvement accounted for 56.0% of total improvement of the Disease Activity Score in 28 joints (DAS28) using the ESR. When discordance was found between the CDAI50 and EULAR response in IL-6i-treated patients, all patients were classified as EULAR-only responders; there was no HAQ improvement in EULAR-only responders. Conclusion EULAR response criteria overestimate the response under IL-6i treatment because the APR improvement largely contributes to the DAS28 improvement.

M2a-subtype macrophage activation is known to be impaired in obesity, although the underlying mechanisms remain poorly understood. Herein, we demonstrate that, the IL-4/Irs2/Akt pathway is selectively impaired, along with decreased macrophage Irs2 expression, although IL-4/STAT6 pathway is maintained. Indeed, myeloid cell-specific Irs2-deficient mice show impairment of IL-4-induced M2a-subtype macrophage activation, as a result of stabilization of the FoxO1/HDAC3/NCoR1 corepressor complex, resulting in insulin resistance under the HF diet condition. Moreover, the reduction of macrophage Irs2 expression is mediated by hyperinsulinemia via the insulin receptor (IR). In myeloid cell-specific IR-deficient mice, the IL-4/Irs2 pathway is preserved in the macrophages, which results in a reduced degree of insulin resistance, because of the lack of IR-mediated downregulation of Irs2. We conclude that downregulation of Irs2 in macrophages caused by hyperinsulinemia is responsible for systemic insulin resistance via impairment of M2a-subtype macrophage activation in obesity., Obesity is associated with low-grade chronic inflammation. Here the authors show that the activation of anti-inflammatory M2a-subtype macrophages requires the IL4/Irs2/Akt pathway. Due to decreased Irs2 expression this pathway is impaired in obese mice thus leading to a defect in M2a activation.

Introduction: M2a-subtype macrophage activation is known to be impaired in obesity, although the underlying mechanisms remain poorly understood. Methods: We found that the phosphorylation levels of Irs2 by IL-4 were significantly reduced along with decreased Irs2 expression in macrophages of high-fat (HF) diet-fed mice. To investigate the role of Irs2 in the macrophages, we then generated myeloid cell-specific Irs2-deficient (MIrs2KO) mice. Results: HF diet-fed MIrs2KO mice showed impairment of IL-4-induced M2a-subtype macrophage activation, resulting in insulin resistance. Expressions of the maker genes for M2a-subtype macrophages were downregulated by stabilization of the FoxO1/HDAC3/NCoR1 corepressor complex via impairment of the IL-4/Irs2 pathway. Furthermore, Irs2 expression was significantly suppressed by insulin treatment in macrophages, suggesting that chronic hyperinsulinemia downregulates macrophage Irs2 expression via insulin receptor (IR). Indeed, in myeloid cell-specific IR-deficient mice, the IL-4-Irs2 pathway was preserved in the macrophages due to the lack of IR-mediated downregulation of Irs2, resulting in a reduced degree of inflammation and insulin resistance. Conclusion: These data suggest that in obesity, downregulation of macrophage Irs2 is induced by hyperinsulinemia, resulting in impaired IL-4-induced M2a-subtype macrophage activation, and insulin resistance. Disclosure T. Kubota: None. M. Inoue: None. N. Kubota: None. I. Takamoto: None. K. Ueki: Speaker's Bureau; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., MSD K.K., Novo Nordisk Inc., Mitsubishi Tanabe Pharma Corporation, Kyowa Hakko Kirin Co., Ltd., Takeda. Research Support; Self; Takeda, Astellas, Novo Nordisk Inc. T. Yamauchi: Research Support; Self; Novo Nordisk Inc., Daiichi Sankyo Company, Limited, Sanofi, Takeda, Tanabe-Mitsubishi. T. Kadowaki: Consultant; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sanofi, Kyowa Hakko Kirin Co., Ltd., Novo Nordisk A/S, Astellas Pharma, Daiichi Sankyo Company, Limited, Takeda, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Astellas Pharma, AstraZeneca, Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Takeda, Eli Lilly and Company, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk A/S.

Background Reduction in neonatal deaths has been a major challenge globally. To prevent neonatal deaths, improvements in newborn care have been promoted worldwide. The World Health Organization Western Pacific Regional Office has been promoting the Early Essential Newborn Care (EENC), a package of specific simple and cost-effective interventions, in their region. However, mere introduction of EENC cannot reduce neonatal deaths unless quality of care is ensured. In Lao PDR, the government introduced self-managed continuous monitoring as a sustainable way to improve the quality of care described in the EENC. Methods A clustered randomized controlled trial was designed to compare the effectiveness of self-managed continuous monitoring with external supervisory visits to monitor health workers’ satisfactory EENC performance and their knowledge and skills related to the EENC in Lao PDR. Determinants of EENC performance will be measured with a structured questionnaire developed based on the Theory of Planned Behaviour, which predicts future behaviour. During self-managed continuous monitoring activities, health workers in each district hospital will conduct periodical peer reviews and feedback sessions. Fifteen district hospitals will be randomly allocated into the self-managed continuous monitoring (intervention) and the supervision (control) groups. Fifteen health workers routinely involved in maternity and newborn care including physicians, midwives and other health staff will be recruited from each hospital (effect size 0.6, intra-cluster correlation coefficient 0.06, 5% alpha error and 80% power). We will compare the change in the mean score of the determinants before and one year after randomisation between the two groups. We will also compare the retention of knowledge and skills related to the EENC between the two groups. The expected enrolment period is July 20th, 2017 to July 20th, 2018. Discussion This is the first cluster randomized trial to evaluate a self-managed continuous monitoring system for quality maintenance of newborn care in a resource-limited country. This research is conducted in collaboration with the Ministry of Health and international organizations; therefore, if effective, this intervention would be applied in larger areas of the country and the region. Trial registration This trial was registered at UMIN-CTR on 15th of June, 2017. Registration number is UMIN000027794. Electronic supplementary material The online version of this article (10.1186/s12913-018-3311-7) contains supplementary material, which is available to authorized users.

Purpose Interleukin-32 (IL-32) is an inflammatory cytokine that is associated with the pathogenesis of several connective tissue diseases. We measured serum IL-32γ concentrations of systemic lupus erythematosus (SLE) patients. Methods Serum samples were obtained from SLE patients ( n = 51), and healthy controls ( n = 15). Serum IL-32 concentrations were measured using ELISA. Clinical information was obtained from medical records. Results Serum IL-32γ was detectable in three cases of SLE patients, whereas it was not detected in any healthy controls. Case 1: a 44-year-old female with lupus nephritis (LN) (Class II) and antiphospholipid antibody syndrome. Serum IL-32γ was 5.1 pg/ml. Case 2: a 30-year-old female with a history of diffuse proliferative LN (Class IV G (A/C)) and pulmonary hemorrhage. Serum IL-32γ was 8.9 pg/ml. Case 3: a 45-year-old female with chronic LN. Serum IL-32γ was 9.1 pg/ml. All three cases of IL-32γ-detectable patients had histories of LN and one had an active disease. In the context of LN, serum IL-32γ was detectable in 18.8% (three of 16) of SLE patients with histories of LN. Conclusion We suppose that IL-32γ could contribute to the pathogenesis of renal diseases in some LN patients.

Common genetic variations of the transcription factor 7-like 2 gene (encoded by TCF7L2), one of the T cell factor/lymphoid enhancer-binding factor transcription factors for the converging wingless-type MMTV integration site family (Wnt)/β-catenin signalling pathway, are known to be associated with type 2 diabetes. Individuals with at-risk alleles of TCF7L2 exhibit impaired insulin secretion. Although previous studies using animal models have revealed the existence of a relationship between the Wnt/β-catenin signalling pathway and glucose homeostasis, it remains unclear whether TCF7L2 in the pancreatic beta cells might be causally involved in insulin secretion in vivo. In this study, we investigated the role of TCF7L2 expressed in the pancreatic beta cells in glucose homeostasis. Three independent groups of genetically engineered mice (DN mice) were generated, in which expression of the dominant-negative form of Tcf7l2 was driven under a rat insulin promoter. Phenotypes of both adult and newborn mice were evaluated. The levels of genes and proteins expressed in isolated islets were determined by reverse transcription-quantitative PCR and western blot analysis, respectively. Adult DN mice showed impaired glucose tolerance and decreased insulin secretion in both oral and intraperitoneal glucose tolerance tests. Marked reduction of the beta cell area and whole-pancreas insulin content was observed in both the adult and newborn DN mice. Islets from the DN mice showed decreased gene expressions of Ccnd1, Ccnd2, Irs1, Irs2, Ins1, Ins2 and Mafa, consistent with the deleterious effects of the dominant-negative form of Tcf7l2 on beta cell proliferation and insulin production. TCF7L2 expressed in the pancreatic beta cells plays a crucial role in glucose metabolism through regulation of the beta cell mass.

Pioglitazone (PIO) is widely used as an insulin-sensitizing agent in the treatment of type 2 diabetes, but it also causes an increase in body weight in a dose-dependent manner. Beraprost sodium (BPS), a stable prostaglandin I2 analog, is used clinically for the treatment of peripheral arterial disease and primary pulmonary hypertension. BPS has recently been demonstrated to promote insulin-induced glucose uptake by skeletal muscle. In this study, we examined whether low-dose PIO (PIO-L; 3 mg/kg/day) plus BPS treatment might exert antidiabetic effects without causing body weight gain in obese/diabetic KKAy mice. Treatment with PIO-L plus BPS tended to improve the hepatic insulin resistance and significantly improved the skeletal muscle insulin resistance, yielding a similar degree of hyperglycemia improvement to that obtained with high-dose PIO (PIO-H; 30 mg/kg/day) treatment. Moreover, the increase in body weight observed following PIO-H treatment was not observed following PIO-L plus BPS treatment. An increase in plasma adiponectin levels, which have been shown to be negatively correlated with hepatic glucose production, but not with the glucose disappearance rate during hyperinsulinemic-euglycemic clamp, was observed in the animals treated with PIO-L, PIO-L plus BPS, and PIO-H. This suggests that the improvement in hepatic insulin resistance was associated, at least in part, with an increase in the plasma adiponectin levels observed during PIO treatment. In contrast, treatment with BPS, which failed to increase the plasma adiponectin levels, ameliorated skeletal, but not hepatic insulin resistance. PIO-L plus BPS treatment may represent efficacious treatment for insulin resistance and type 2 diabetes without causing body weight gain.

(2012). The natural history of asymptomatic positron emission tomography: positive giant cell arteritis after a case of self-limiting polymyalgia rheumatica. Modern Rheumatology: Vol. 22, No. 6, pp. 942-946.

Objective: This study aimed to investigate the association between periodontal disease and peptic ulcers in a working population. Methods: Self-administered questionnaires were distributed to all employees of a large insurance company in Japan. The questionnaire asked about their health status and lifestyle habits. Peptic ulcer was defined as either stomach ulcer, duodenal ulcer, or both. For the evaluation of periodontal disease, three indices were used: (a) loss of five or more teeth, (b) having been told of having periodontitis, and (c) periodontal risk score. Results: Of the eligible 28 765 subjects analyzed, peptic ulcer was present in 397 (1.4%). The results of bivariate analyses showed that a significantly higher proportion of subjects with peptic ulcer reported that they lost five or more teeth (35.3 vs. 17.4%, p

Aims/Introduction: The therapeutic effectiveness against type 1 diabetes mellitus (DM) of the novel immunomodulator FTY720 (fingolimod), alone and in combination with insulin glargine, was examined in the non‐obese diabetic (NOD) mouse model. Materials and Methods: Female NOD mice that had developed DM spontaneously were divided into four groups: (i) an FTY720 (0.1 mg/kg, p.o., twice weekly)‐treated group; (ii) an insulin glargine (1.0 IU, s.c., once daily)‐treated group; (iii) a combination FTY720 + insulin glargine (0.1–1.0 IU, s.c., once daily)‐treated group; and (iv) a placebo (vehicle)‐treated group. Treatment was initiated at the time of onset of DM and continued for 70 days or until death. The therapeutic efficacy of FTY720, insulin glargine and FTY720 + insulin glargine was evaluated by measuring the ratio of insulin‐positive β‐cells/total islet area, the extent of islet inflammation (insulitis score), blood glucose levels, and serum C‐peptide levels. Results: Therapeutic administration of FTY720 to NOD mice with hyperglycemia (i.e. overt DM) significantly prolonged survival (P

A focus exclusively on waist circumference, the main component used in the diagnosis of metabolic syndrome (MetS), may lead to ignoring non-obese individuals with other MetS components, including high levels of blood pressure, fasting blood glucose, and triglycerides and low levels of high-density lipoprotein. This study investigated lifestyles and eating behaviors among non-obese individuals with components of MetS. Of the 918 Japanese male workers, 151 subjects (16.4%) had a waist circumference < 85 cm with more than one MetS component. This non-obese high-risk group for MetS gained weight in adulthood, consume alcohol, and engage in less leisure-time physical activity compared to 317 subjects (34.5%) with a waist circumference < 85 cm and without MetS components (p < 0.05). The remaining 450 subjects (49%) were obese with a waist circumference ≥ 85, including 93 men with MetS. A lack of leisure-time physical activity was associated with the non-obese high-risk group for MetS [odds ratio 1.59, 95% confidence interval 1.02 - 2.49] compared to the 317 non-obese men without MetS (reference group). Such a difference in physical activity was not found between the 450 obese subjects and the reference group. Instead, eating behaviors, such as eating rapidly, preference for fatty foods, and eating out for dinner, were significantly associated with MetS. Thus, men with smaller waist circumferences and any MetS component should be carefully monitored for physical activity to prevent further development of MetS, while men with larger waist circumferences including MetS need to be monitored for unfavorable eating behaviors.

Rapidly progressive interstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM) is often lethal despite corticosteroid therapy combined with cyclophosphamide and cy...

Background Recent studies on the association between the metabolic syndrome (MetS) and depression have reported conflicting findings. This 1-year cohort study aims to evaluate the association of MetS with the development of both depression and anxiety. Methods The cohort comprised 956 Japanese male employees of an enterprise (mean age, 42.7 years; SD, 10.2 years). MetS was diagnosed according to the International Diabetes Federation criteria. The psychological conditions of depression and anxiety were assessed in 2 successive years by using the profile of mood states (POMS) questionnaire and by conducting clinical interviews as per the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). We evaluated the temporal and dose-response relationships between MetS and the development of depression and anxiety, controlling for potential confounding factors like age and lifestyle-related factors. Results We identified a positive relationship between MetS at baseline and new-onset depression in the subsequent year (OR 2.14, 95% CI 1.10–4.17). Of the five MetS components examined, only waist circumference was significantly related to new-onset depression (OR 2.08, 1.23–3.50). Trend analysis revealed a significant positive trend of association between the number of MetS components identified and new-onset depression (Ptrend < 0.01), but not between Mets and new-onset anxiety. Conclusions Our results suggest that MetS is a predictive factor for the development of depression, and that waist circumference largely contributes to the association between MetS and depression. Copyright © 2009 John Wiley & Sons, Ltd.

Autoantibodies induce various autoimmune diseases, including systemic lupus erythematosus (SLE). We previously described that CD4+CD25−LAG3+ regulatory T cells (LAG3+ Treg) are regulated by Egr2, a zinc-finger transcription factor required for the induction of T-cell anergy. We herein demonstrate that LAG3+ Treg produce high amounts of TGF-β3 in an Egr2- and Fas-dependent manner. LAG3+ Treg require TGF-β3 to suppress B-cell responses in a murine model of lupus. Moreover, TGF-β3- and LAG3+ Treg-mediated suppression requires PD-1 expression on B cells. We also show that TGF-β3-expressing human LAG3+ Treg suppress antibody production and that SLE patients exhibit decreased frequencies of LAG3+ Treg. These results clarify the mechanism of B-cell regulation and suggest therapeutic strategies., B cells reactive against self antigens can cause autoimmune disease, but are normally suppressed by regulatory T cells (Tregs). Here the authors show that a subset of Tregs can suppress lupus in a mouse model by making TGF-β3 cytokine and by engaging an inhibitory PD-1 receptor on B cells.

Pulse wave velocity (PWV) is known to represent arterial stiffness and is established as a marker for cardiovascular risk and a prognostic factor for mortality in the case of chronic renal failure or hypertension. The application of an automated apparatus for measuring brachial-ankle pulse wave velocity (baPWV) has made PWV measurement non-invasive, easier to screen for cardiovascular risk and as a result, baPWV measurements have become widely applied in clinical practice in recent years. We assessed the baPWV in 7 flank hypothyroidism patients and 28 subclinical hypothyroidism patients. In comparison with age matched healthy controls, 3 hypothyroid patients had advanced values and by replacement therapy, all 7 subjects showed improvement in their baPWV values (1531.2 +/- 242.7 to 1330.2 +/- 208.6 cm/s, p

We herein report two cases of myelodysplastic syndrome with rheumatic manifestations. (Case 1) A 70-year-old man presented with fever, arthritis and bone pain and developed cranial nerve palsy caused by an epipharyngeal mass. Steroid therapy led to a prolonged remission of the febrile condition and mass lesion. (Case 2) An 82-year-old male was treated for intractable polyarthritis and fever with steroid therapy, and serious side effects resulted in lethal pneumonia. We herein describe the entire course of steroid therapy in these two cases. Various rheumatic manifestations in myelodyaplastic syndrome often require empirical steroid therapy. It was effective for the soft tissue mass in Case 1, in which indolent lymphoma could not be denied, and was only partially effective for Case 2 of the febrile and putatively benign conditions, suggesting heterogeneous nature of rheumatic complications in myelodysplastic syndrome.

The therapeutic efficacy of the novel immunomodulator FTY720 (Fingolimod), alone and in combination with betamethasone ointment, was examined in the NC/Nga mouse model of spontaneous steroid-resistant dermatitis. Male NC/Nga mice which had developed severe dermatitis were divided into six groups: 1) a biweekly betamethasone group (betamethasone ointment, twice a week), 2) a daily betamethasone group (betamethasone ointment, six times a week), 3) an FTY720 group (FTY720, orally, three times a week), 4) a biweekly combination group (oral FTY720 plus betamethasone ointment, twice a week), 5) a daily combination group (oral FTY720 plus betamethasone ointment, six times a week) and 6) a placebo group (vehicle alone). The therapeutic efficacy was evaluated in terms of severity of dermatitis, epidermal hypertrophy, accumulation and degranulation of mast cells and infiltrated CD3+ T cells into the dermis after 4 weeks of treatment. Biweekly and daily betamethasone treatments had little effect, confirming that the dermatitis was steroid-resistant. In the FTY720 and biweekly combination groups, the dermatitis showed no marked improvement. In the daily combination group, the dermatitis was significantly (p

1 , In the last 10 yr, a new dental field called "periodontal medicine 1) " has been proposed, which draws attention to the relationship between periodontal disease and systemic diseases. There have been reports of an association between periodontal disease, which are chronic inflammatory diseases, and heart diseases. Epidemiological studies of the association between periodontal disease and heart diseases have been reported in the last 10 or so years 2-10) . So far, however, no clear conclusions have been reached. The objectives of our cross-sectional study of a large group of Japanese workers were to examine the association between the state of oral health such as the presence of periodontitis and two CHDs, myocardial infarction and angina pectoris. We here define CHD as myocardial infarction or angina pectoris, or a combination of both. The investigation was implemented using results of a baseline investigation of the "MY Health Up Study," which was conducted at a large insurance firm for the purpose of health maintenance of its workers.

The objective of this study was to assess the degree of agreement between body mass index (BMI) and weight perception of Japanese office workers between the ages of 20 and 65. We sent 43,064 self-administered health-related questionnaires to all employees of a financial firm in Japan in October 2004. The questionnaire asked the respondents for their height, weight, and their weight perception. The kappa coefficient was calculated to investigate the degree of agreement between the BMI calculated using the self-reported data and weight perception for three categories. Of the questionnaires, 34,921 (81.1%) were returned and 33,514 responses (77.8%) were used for the analysis. Based on Japanese obesity criteria, 2,202 men (31.2%) and 5,145 women (19.5%) were obese; and 179 men (2.5%) and 2,769 women (10.5%) were underweight. The kappa coefficient was 0.374 for men and 0.297 for women. The kappa coefficients for different age groups-twenties, thirties, forties, fifties, and sixties (up to 65)-were respectively as follows: 0.315, 0.355, 0.374, 0.406, and 0.425 for men; and 0.194, 0.275, 0.285, 0.334, and 0.355 for women. In conclusion, the degree of agreement between BMI and weight perception differed by age and sex. The degree of agreement was smaller among women than among men and the degree of agreement among younger women was weaker than among older women.

Intrinsic reactive oxygen species (ROS) in a rat model of human minimal change nephropathy were detected directly using an in vivo electron paramagnetic resonance (EPR) method with 1-acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (ACP) in real time. The nephrosis was induced by the intravenous administration of 75 mg/kg of puromycin aminonucleoside (PAN). It was found that ROS in the kidney were increased 1 h after the administration of PAN. This increased oxidative stress declined at 24 h and returned to a normal level 3 days after PAN administration. This is the first non-invasive in vivo detection and quantification of specific ROS in an experimental nephrosis model.

A 50-year-old woman was transferred to our hospital because of acute renal failure and thrombocytopenia. Due to rapid enlargement of the kidney, we first suspected that she had diffuse renal invasion of anaplastic carcinoma or lymphoma of the kidney. Anti-bacterial treatment for complicated urinary tract infection and hemodialysis treatment resulted in recovery of both renal function and thrombocytopenia. Serial CT study demonstrated disappearance of kidney swelling and multiple masses within the kidney. We finally made a diagnosis of acute multifocal bacterial nephritis. Timely initiation of dialysis therapy and appropriate anti-bacterial treatment was essential to rescue this case.

Oxidative stress during ischemia-reperfusion acute renal failure (IR-ARF) was noninvasively evaluated with in vivo electron paramagnetic resonance (EPR) imaging. Female ICR mice underwent left nephrectomy and 30-min ischemia-reperfusion of the right kidney. Oxidative stress was evaluated as organ reducing activity with the half-lives of the spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) using 1) conventional L-band EPR, which showed organ-reducing activity in the whole abdominal area; and 2) EPR imaging, which showed semiquantitative but organ-specific reducing activity. The results were compared with the reducing activity of organ homogenate and phosphatidylcholine hydroperoxide (PC-OOH) concentrations. Half-lives of carbamoyl-PROXYL in the whole upper abdominal area, measured by L-band EPR, were prolonged on day 3 after ischemia-reperfusion and recovered to the level of nontreated mice on day 7. This trend resembled closely that of serum creatinine and blood urea nitrogen concentration. The EPR imaging-measured carbamoyl-PROXYL half-life was also prolonged on day 3 in both the kidney and the liver. However, in the kidney this showed only partial recovery on day 7. In the liver, this convalescence was more remarkable. The ex vivo studies of organ reducing activity and PC-OOH agreed with the results from EPRI, but not with those from L-band EPR. These results indicate that renal reducing activity shows only partial recovery on day 7 after ischemia-reperfusion, when serum creatinine and blood urea nitrogen have recovered. EPR imaging is an appropriate and useful method for the noninvasive evaluation of oxidative stress in the presence of renal injury.

s / Placenta 35 (2014) A1eA23 A18 determined to identify what kind of cells produce IL-6 in placentae complicated with CAM and analyze the potential of targeting IKKb signaling to suppress IL-6 production, using a novel IKKb inhibitor, IMD0560 (IMMD Inc. Tokyo, Japan). Methods and Results: First, we examined the expressional pattern of IL6 in placentae complicated with severe CAM and found that IL-6 is mainly expressed in amniotic mesenchymal stromal cells (hAMSCs). Primary hAMSCs were collected and the strong expression of IL-6 as well as IL-6 receptor was confirmed by RT-PCR. In hAMSCs, treatment of inflammatory cytokines such as TNF-alpha and IL-1-beta drastically induced IL-6 production followed by the phosphorylation of IKK as confirmed by western blotting. The pretreatment of IMD-0560 to hAMSCs almost abolished IL-6 production enhanced by proinflammatory cytokines. Conclusion: IL-6 was strongly expressed mainly in amniotic mesenchymal stromal cells in placentae complicated with CAM. Targeting IKK-beta signaling could be a promising option for the prevention of preterm delivery and needs to be further explored for future clinical application. O-069. TWO CASES OF PLACENTAL MESENCHYMAL DYSPLASIA: CASE REPORTS Mariko Inoue , Usui Hirokazu , Akiko Omoto , Jun Okayama , Michio Sanada , Hirokazu Tanaka , Hisao Osada , Makio Shozu . Department of Obstetrics and Gynecology, Chiba University Hospital, Japan; Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Japan Introduction: Placentae with placental mesenchymal dysplasia (PMD) are typically larger than average, show cystic changes similar to those seen in moles on ultrasound. Fetal outcomes are variable and are often associated with growth restriction, sometimes intra uterine fetal death. We present two cases of PMD. Case 1: 29 years of age, secundipara. Ultrasonography at 18 weeks of gestation showed multiple small cysts in placenta, and was diagnosed as PMD. At 34 weeks, she was admitted with FGR and oligohydramnion, and had cesarean section due to NRFS. The neonate was male weighing 1620g with hypospadias. He was admitted in NICU, and was treated on RDS and PPHN. The placenta was 830g with multiple cysts and enlarged umbilical vessels, was diagnosed as PMD histologically. The karyotype of placenta was 47, XY, +13/47, XXY and that of the neonate was 47, XXY. Case 2: 22 years of age, primipara. At 9 weeks of gestation, she came to our hospital with doubt of partial mole, was diagnosed as PMD by ultrasonography. At 34 weeks, she was admitted with FGR and threatened premature labor, and had cesarean section due to fetal cardiac dilatation, fetal anemia, elevated maternal level of CPK. The neonate was female weighing 1610g. She was admitted in NICU, needed blood transfusion due to anemia (Hb8.6). The placenta was enlarged weighing 1650g, was diagnosed as PMD histologically. The karyotype of placenta was 46, XX, 1qh+1 supposed to be familial variation. Conclusion: Both of cases diagnosed as PMD by ultrasonography and confirmed the diagnosis by histologically. Both neonates showed FGR in their period of gestation, was treated on PPHN in case1 and fetal anemia in case2 after birth. It is necessary cases of PMD are followed carefully at the hospitals providing advanced neonatal care. O-070. PROFILING ANALYSIS FOR GENE EXPRESSION AND GLYCAN STRUCTURE IN EXTRAVILLOUS TROPHOBLAST CELLS WITH NEOPLASTIC TRANSFORMATION Yusuke Kobayashi , Kenta Masud , Eiichiro Tominaga , Kouji Banno , Kanako Nakamura , Masataka Adachi , Miho Iida , Kiyoko Umene , Yuya Nogami , Hiroyuki Nomura , Takatsune Shimizu , Hideyuki Saya , Daisuke Aoki . Department of Obstetrics and Gynecology, School of Medicine, Keio University, Japan; Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Japan Objectives: It has been cleared that the reregulation of extravillous trophoblast cells (EVT) invasion to the deciuda and its related disease. However, it is still remained that the alteration of gene expression and glycan structure in extravillous trophoblast cells with neoplastic transformation. We established a new choriocarcinoma cell line, induced choriocarcinoma cell-1 (iC3-1), from EVT. In this study, the alterations of gene expression and glycan structures in the development of choriocarcinoma were examined by conventional microarray and the recently introduced lectin microarray. Methods: iC3-1 cells were generated from HTR8/SVneo retrovirally transduced with activated HRASV12. We compared the gene expression and glycan structure of iC3-1 and control HTR8/SVneo cells by microarray analysis, quantitative RT-PCR and lectin microarray. Results: Gene expression study revealed that epithelial-mesenchymal transition related genes, matrix metalloproteinase family genes, HAS2 andCD44 were upregulated in iC3-1 cells. Lectin microarray analysis detected increased Helix pomatia agglutinin (HPA) and decreased Sambucus sieboldiana agglutinin (SSA), showing upregulation of Tn antigen and downregulation of alpha-2-6 sialic acids. Conclusions: With neoplastic transformation, some interested genes in proliferation, metastasis, angiogenesis and cancer stem cell marker were upregulated. In addition, glycan structure was partially altered with upregulation of Tn antigen and downregulation of alpha-2-6 sialic acids. O-072. A CASE OF CONGENITAL CUTANEOUS CANDIDIASIS FOLLOWING INTRAUTERINE INFECTION Akihisa Katayama, Fumitake Ito, Miyoko Waratani, Tadahiro Yasuo, Kazuhiro Iwasaku, Jo Kitawaki. Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Japan Introduction: Candida vaginalis has a high incidence of 10-35% during pregnancy; in contrast, congenital cutaneous candidiasis is a very rare disease with less than 100 cases published in the medical literature, because it is estimated that less than 1% of women develop chorioamnionitis that could be a cause of fetal infection. In this report, we present a case of threatened premature delivery due to Candida chorioamnionitis that caused congenital cutaneous candidiasis. Case report: A 34-year-old woman who was admitted for fetal membrane bulging at 20 weeks of gestati on underwent McDonald cervical cerclage. Since uterine contraction had occurred regularly at 22 weeks, the patient was transferred to our hospital. On admission, the uterine cervix shortened and showed funneling. Although blood examination did not reveal inflammatory reactions, the results for cervical neutrophil elastase reaction were positive. The vaginal suppository of ulinastatin was administered and the dose of ritodrine hydrochloride was increased up. At 23 weeks, the uterus recontracted regularly, and blood examination revealed severe inflammatory reaction. We diagnosed threatened premature delivery due to intrauterine infection, and then terminated the gestation by cesarean section. The patient delivered a living 604 g male infant in poor condition with an Apgar score of 2. The amniotic fluid was yellowish-stained and turbid. The infant had a prominent systemic desquamation on the skin. Intravenous administration of antifungal agent was given after the birth for the possibility of fungal infection. Candida albicans was detected in the infantile auricle, and neck. Histopathological examination of the placenta revealed infiltration of neutrophils and profound necrosis in the field and that Candida albicans mycelium invaded the placenta. Conclusion: In case intrauterine infection is suspicious, an appropriate antibacterial treatment is needed as soon as possible with the consideration of fungal infections as well as bacterial infection.

Background Temporary employment, a precarious form of employment, is recognized as social determinant of poor health. However, evidence supporting precarious employment as a risk factor for health is mainly obtained from subjective data. Studies using objective clinical measurement data in the assessment of health status are limited. This study compared body mass index (BMI), lipid and glucose metabolism, and health-related lifestyle factors between permanent workers and fixed-term workers employed in the manufacturing industry. Methods Data of 1,701 male manufacturing industry workers

SummaryIn obese patients with type 2 diabetes, insulin delivery to and insulin-dependent glucose uptake by skeletal muscle are delayed and impaired. The mechanisms underlying the delay and impairment are unclear. We demonstrate that impaired insulin signaling in endothelial cells, due to reduced Irs2 expression and insulin-induced eNOS phosphorylation, causes attenuation of insulin-induced capillary recruitment and insulin delivery, which in turn reduces glucose uptake by skeletal muscle. Moreover, restoration of insulin-induced eNOS phosphorylation in endothelial cells completely reverses the reduction in capillary recruitment and insulin delivery in tissue-specific knockout mice lacking Irs2 in endothelial cells and fed a high-fat diet. As a result, glucose uptake by skeletal muscle is restored in these mice. Taken together, our results show that insulin signaling in endothelial cells plays a pivotal role in the regulation of glucose uptake by skeletal muscle. Furthermore, improving endothelial insulin signaling may serve as a therapeutic strategy for ameliorating skeletal muscle insulin resistance.