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Congenital mutations of the Wilms' tumor 1 (WT1) gene can lead to various abnormalities, including renal/gonadal developmental disorders and cardiac malformations. Although there have been many reports of somatic WT1 mutations in patients with acute myeloid leukemia and myelodysplastic syndrome, congenital WT1 mutations have not been reported in hematological disorders. We herein report a patient with early-onset clonal cytopenia of undetermined significance that was associated with a congenital mutation of WT1 and an acquired mutation of DNMT3A [encoding DNA (cytosine-5)-methyltransferase 3A].

COVID-19 is a viral infection characterized by a cytokine storm similar to that in acute respiratory distress syndrome (ARDS). Neutrophils and monocytes are known to play an important role in tissue damage in ARDS. COVID-19 has been reported to be more severe in patients with hematological malignancies; however, there are few reports of COVID-19 in patients with aplastic anemia. Moreover, how aplastic anemia affects COVID-19 remains unclear. Here, we report the case of a COVID-19 patient with aplastic anemia who had high serum IL-6 levels but did not progress to the severe form of COVID-19. We inferred that severe neutropenia and monocytopenia due to aplastic anemia could contribute to a mild form of COVID-19, although a risk of more severe secondary bacterial infections exists.

Aim To examine the efficacy of abatacept in patients with rheumatoid arthritis (RA) using magnetic resonance imaging (MRI) of bilateral hands. Method This prospective study included 35 RA patients. MRI of bilateral hands was performed at baseline and after 12 months of treatment with intravenous abatacept. MRI images were scored for synovitis, osteitis, erosion and joint space narrowing (JSN) according to the RA MRI Scoring System (RAMRIS). The primary endpoint was the change in RAMRIS score from baseline. Repair of erosion was defined as a negative change in the erosion score that was greater than the smallest detectable changes (SDCs). Results Thirty-one patients completed the study. Median synovitis and osteitis scores showed statistically significant reductions at Month 12 when compared to baseline (synovitis score, −5.5 [P

Tempei Otsubo,1 Yoshinori Watanabe,2,3 Seiji Hongo,3 Mikichika Inoue,4 Kimiko Akimoto,4 Ken Murakami,5 Ryutaro Takahashi,6 Toshiaki Kikuchi7 1Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan; 2Himorogi Psychiatric Institute, Tokyo, Japan; 3Nanko Clinic of Psychiatry, Shirakawa, Japan; 4Ikebukuro Internal Medicine, Tokyo, Japan; 5Murakami Hospital, Tokyo, Japan; 6Takahashi Clinic, Tokyo, Japan; 7Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Aim: To assess the effectiveness and safety of switching the antidepressant formulation from immediate-release (IR) to controlled-release (CR) paroxetine in patients with major depressive disorder (MDD). Patients and methods: A total of 113 outpatients with MDD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and treated with a stable dose of IR paroxetine for at least 6 months were enrolled. Patients were then switched to CR paroxetine for 8 weeks. Effectiveness was evaluated by scores on the Himorogi Self-Rating Depression/Anxiety Scales (HSDS/HSAS) and the Clinical Global Impression – Severity (CGI-S). Safety was evaluated based on the reported adverse drug reactions (ADRs). Medication satisfaction and preference were assessed based on questionnaire responses using Likert-type scales. Results: The overall patient HSDS/HSAS scores significantly improved after switching from IR to CR paroxetine (P

Polyethyleneimine (PEI) complexed with chiral D- (or L-) tartaric acid (tart) in water can self-organize into chiral and crystalline PEI/tart assemblies. It has been previously confirmed that the complexes of PEI/tart could work as catalytic/chiral templates to induce the deposition of SiO2 nanofibres with optical activity but without outwards shape chirality such as helices. In this work, we found that the templating functions of PEI/tart were still effective to prompt the deposition of TiO2 to form chiral PEI/tart@TiO2 hybrid nanofibres under aqueous and room temperature conditions within two hours. Furthermore, the co-deposition of TiO2 and SiO2 was also fulfilled to yield chiral PEI/tart@TiO2/SiO2 nanofibres. These TiO2-containing hybrid nanofibres showed non-helical shapes on the length scale; however, chiroptical signals with mirror relation around the UV-Vis absorption band of TiO2 remarkably appeared on their circular dichroism (CD) spectra. By means of the protocols of XRD, TEM, SEM, UV-Vis, CD and XPS, structural features and thermoproperties of the chiral TiO2 and SiO2/TiO2 were investigated.

Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries of rats with an ectopic cardiac allograft. Some studies have shown that expression of AIF-1 increased in a mouse model of trinitrobenzene sulfonic acid-induced acute colitis and in acute cellular rejection of human cardiac allografts. These results suggest that AIF-1 is related to acute inflammation. The current study used bleomycin-induced acute lung injury to analyze the expression of AIF-1 and to examine its function in acute lung injury. Results showed that AIF-1 was significantly expressed in lung macrophages and increased in bronchoalveolar lavage fluid from mice with bleomycin-induced acute lung injury in comparison to control mice. Recombinant AIF-1 increased the production of IL-6 and TNF-α from RAW264.7 (a mouse macrophage cell line) and primary lung fibroblasts, and it also increased the production of KC (CXCL1) from lung fibroblasts. These results suggest that AIF-1 plays an important role in the mechanism underlying acute lung injury.

Bone destruction at inflamed joints is an important complication associated with rheumatoid arthritis (RA). Interleukin-10 (IL-10) may suppress not only inflammation but also induction of osteoclasts that play key roles in the bone destruction. If IL-10-producing osteoblast-like cells are induced from patient somatic cells and transplanted back into the destructive bone lesion, such therapy may promote bone remodeling by the cooperative effects of IL-10 and osteoblasts. We transduced mouse fibroblasts with genes for IL-10 and Runx2 that is a crucial transcription factor for osteoblast differentiation. The IL-10-producing induced osteoblast-like cells (IL-10-iOBs) strongly expressed osteoblast-specific genes and massively produced bone matrix that were mineralized by calcium phosphate in vitro and in vivo. Culture supernatant of IL-10-iOBs significantly suppressed induction of osteoclast from RANKL-stimulated Raw264.7 cells as well as LPS-induced production of inflammatory cytokine by macrophages. The IL-10-iOBs may be applicable to novel cell-based therapy against bone destruction associated with RA.

Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries in a rat ectopic cardiac allograft model. We previously reported that AIF-1 is associated with the pathogenesis of rheumatoid arthritis and skin fibrosis in sclerodermatous graft-versus-host disease mice. Here, we used an animal model of bleomycin-induced lung fibrosis to analyze the expression of AIF-1 and examine its function in lung fibrosis. The results showed that AIF-1 was expressed on lung tissues, specifically macrophages, from mice with bleomycin-induced lung fibrosis. Recombinant AIF-1 increased the production of TGF-β which plays crucial roles in the mechanism of fibrosis by mouse macrophage cell line RAW264.7. Recombinant AIF-1 also increased both the proliferation and migration of lung fibroblasts compared with control group. These results suggest that AIF-1 plays an important role in the mechanism underlying lung fibrosis, and may provide an attractive new therapeutic target.

In this paper, a high frequency ring oscillator with low power consumption is proposed.The proposed ring oscillator is based on GRO by applying boot strap technique. Simulation resultsindicate that the FoM(Power Consumption/Oscillation Frequency) of the proposed ring oscillator isless than that of the conventional ring oscillator.

Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. The role of MDSCs in autoimmune diseases remains controversial, and little is known about the function of MDSCs in autoimmune arthritis. In this study, we clarify that MDSCs play crucial roles in the regulation of proinflammatory immune response in a collagen-induced arthritis (CIA) mouse model. MDSCs accumulated in the spleens of mice with CIA when arthritis severity peaked. These MDSCs inhibited the proliferation of CD4+ T cells and their differentiation into Th17 cells in vitro. Moreover, MDSCs inhibited the production of IFN-γ, IL-2, TNF-α, and IL-6 by CD4+ T cells in vitro, whereas they promoted the production of IL-10. Adoptive transfer of MDSCs reduced the severity of CIA in vivo, which was accompanied by a decrease in the number of CD4+ T cells and Th17 cells in the draining lymph nodes. However, depletion of MDSCs abrogated the spontaneous improvement of CIA. In conclusion, MDSCs in CIA suppress the progression of CIA by inhibiting the proinflammatory immune response of CD4+ T cells. These observations suggest that MDSCs play crucial roles in the regulation of autoimmune arthritis, which could be exploited in new cell-based therapies for human rheumatoid arthritis.

Background Patients with glucocorticoid-induced osteoporosis (GIOP) are at very high risk of fracture, and patients with severe GIOP often experience fractures during treatment with bisphosphonates. Teriparatide (TPTD) is the only currently available anabolic agent expected to be effective for GIOP. Once-weekly TPTD decreased bone resorption marker with primary osteoporosis different from daily TPTD, but it has not yet been tested with GIOP. Objectives To evaluate the efficacy of once-weekly TPTD for patients with GIOP and inadequate response to bisphosphonates. Methods Patients with GIOP and collagen diseases treated with prednisolone for at least 6 months with inadequate responses to bisphosphonates were administered once-weekly TPTD. Bone density of the lumbar spine and femoral neck, measured as percent young adult mean (YAM); serum concentrations of cross-linked N-terminal telopeptides of type I collagen (NTx), bone alkaline phosphatase (BAP), and calcium; and FRAX were measured at baseline and 6, 12 and 18 months after starting TPTD. Results Of the 12 GIOP patients with collagen diseases enrolled, nine (seven females, two males; mean age 57.4 ± 11.1 years) completed treatment, including six with systemic lupus erythematosus, two with rheumatoid arthritis, and one with adult onset still disease. Only one new fracture event, a lumbar compression fracture, occurred during the study period, although seven patients experienced eight fracture events within 18 months before starting TPTD (p = 0.04). Lumbar spine YAM significantly improved at 18 months (p = 0.04), whereas femoral neck YAM did not (p = 0.477). Serum NTx, BAP, Ca, and FRAX were not significantly affected by TPTD treatment. Conclusions Once-weekly TPTD reduces fracture events and increases bone density of the lumbar spine of GIOP patients with inadequate response to bisphosphonates.

We report a case of rheumatoid vasculitis (RV) that responded well to abatacept, a cytotoxic T lymphocyte-associated antigen 4 (CTLA4)-immunoglobulin fusion protein. A 38-year-old woman developed RV despite treatment with methotrexate and tumor necrosis factor (TNF) inhibitors. The effects of steroid therapy, immunoabsorption plasmapheresis, and interleukin-6 inhibitor were insufficient, however, administration of abatacept rapidly improved her clinical symptoms with almost normalization of the immunological findings. This is the first published case report of the successful treatment of RV with abatacept.

In this research, optical fiber sensors and shape memory alloys (SMA) were incorporated into sandwich panels for development of a smart honeycomb sandwich structure with damage detection and shape ...

The analysis of the sound field of a hall including the effect of audience seats has difficulties in computing time and memory. Although extensive investigations have been conducted for analyzing sound fields, there is scarcely any report dealing with the sound field including this effect. The main cause may be the complex shape and amount of materials of the audience seats. However, there is a possibility that periodical grooved structures like seat rows can be replaced by an appropriate imaginary boundary with an impedance of quasi-local reaction at the top of seats. The purpose of this research is to reduce the calculation load of acoustical analysis by treating the seat rows as an imaginary-impedance boundary which is almost equivalent to the characteristics of audience seats. The SDE filter, which can express excess attenuation caused by seat rows, is proposed and some applications to both the geometrical and wave theoretical methods are presented. To examine the validity of this method, some numerical examples calculated using an image method are discussed in comparison with the measured data. Furthermore, the numerical results of its application to the boundary element method are presented and discussed in terms of its effectiveness and validity.

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.

Obliteration of portal-systemic shunts is effective for portosystemic encephalopathy but is often associated with complications such as retention of ascites and worsening of esophageal varices. Selective embolization of the splenic vein was performed on six patients with hepatic encephalopathy and splenorenal shunts. Hepatic encephalopathy was not observed in four patients after the procedure. Neither retention of ascites nor rupture of esophageal varices was observed because postoperative elevation of portal venous pressure was not as great as that seen when shunt obliteration is performed. This procedure can be an effective and safe treatment option for hepatic encephalopathy with a splenorenal shunt.

A 55-year-old man developing transfusion-dependant anemia was diagnosed with autoimmune hemolytic anemia (AIHA). Although he received prednisolone (PSL) (daily 60 mg), his hemoglobin level continued to decrease. After 3 weeks of treatment, he presented with a distension of the abdomen. Cytological examination of ascitic fluid revealed large, immunoblastic lymphocytes with plasmacytoid features and abundant IgM chains on the cellular surface; this was diagnosed as primary effusion lymphoma (PEL). Administration of CHOP (cyclophosphamide, Adriamycin, vincristine, and PSL) chemotherapy elicited regression of ascites as well as recovery of hemoglobin level. We hypothesize that PEL cells generated antibodies against red blood cells, resulting in AIHA resistance to PSL.

This study investigated the relationship between binge-purge episodes and the affective state by analysing the changes in affective states during the binge-purge cycle. Thirty-seven Japanese patients with bulimia nervosa were surveyed for 22 types of affective states. Some negative affects were alleviated by bingeing or purging, while others were exacerbated by these behaviours. These findings suggest that one has to differentiate the temporal situations in the binge-purge cycle in considering the relationship between the affective states and binge-purge behaviours. The escape hypothesis and hopelessness hypothesis proposed by Beebe (1994) suggest some possible mechanisms. Binge and purge behaviours should be examined separately as defence functions to regulate negative moods and as acting out in response to intense negative affects.

Most research studies of stress and coping in a person's life utilize only one or two measures. As scientists, therefore, we become accustomed to seeing these topics in a limited perspective. As health care practitioners, however, we profit from a broader view of these fields. Practitioners of health promotion strive to alert patients and clients to several areas of life adjustment pertinent to health and disease. The Stress and Coping Inventory (SCI) was designed for this kind of health promotion, primarily as an educational instrument and secondarily as a research tool. Reliability testing, using Cronbach alpha correlations, was performed utilizing a sample of 1772 individuals. Intercorrelations run between SCI stress and coping indicators were all in the predicted direction and several were at moderately high orders of magnitude. Analysis of variance was carried out for stress and coping measures according to subjects' reports of recent health problems. Finally, stepwise multiple regression analysis was done, including validation, cross-validation. Copyright © 2000 John Wiley & Sons, Ltd.

Following our preceding study on thick target neutron yields by He and C, we measured angular and energy distributions of neutrons produced by 100, 180 and 400 MeV/nucleon Ne ions stopping in thick carbon, aluminum, copper and lead targets using the heavy ion medical accelerator of the National Institute of Radiological Sciences. The neutron spectra in the forward direction have broad peaks which are located at about 60 to 70% of the incident particle energy per nucleon due to break-up process and spread up to almost twice as much as the projectile energy per nucleon. The neutron spectra at all angles consist of two components of cascade neutrons and evaporation neutrons. The phenomenological hybrid analysis of the moving source model for these two components and the Gaussian fitting of break-up process could well represent the measured thick target neutron spectra. The experimental results are also compared with the calculations using the HIC code, and the calculated results generally agree with the meas...

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cellular processes, including proliferation, migration, and angiogenesis, through interaction with a family of five G protein–coupled receptors (S1P1–5). Some reports have implicated S1P as an important inflammatory mediator of the pathogenesis of airway inflammation, but the role of S1P3 in the pathogenesis of lung diseases is not completely understood. We used S1P3-deficient (knockout (KO)) mice to clarify the role of S1P3 receptor signaling in the pathogenesis of pulmonary inflammation and fibrosis using a bleomycin-induced model of lung injury. On the seventh day after bleomycin administration, S1P3 KO mice exhibited significantly less body weight loss and pulmonary inflammation than wild-type (WT) mice. On the 28th day, there was less pulmonary fibrosis in S1P3 KO mice than in WT mice. S1P3 KO mice demonstrated a 56% reduction in total cell count in bronchoalveolar lavage fluid (BALF) collected on the seventh day compared with WT mice; however, the differential white blood cell profiles were similar. BALF analysis on the seventh day showed that connective tissue growth factor (CTGF) levels were significantly decreased in S1P3 KO mice compared with WT mice, although no differences were observed in monocyte chemotactic protein-1 (MCP-1) or transforming growth factor β1 (TGF-β1) levels. Finally, S1P levels in BALF collected on the 7th day after treatment were not significantly different between WT and S1P3 KO mice. Our results indicate that S1P3 receptor signaling plays an important role in pulmonary inflammation and fibrosis and that this signaling occurs via CTGF expression. This suggests that this pathway might be a therapeutic target for pulmonary fibrosis.

Background Tocilizumab, anti-IL-6 receptor monoclonal antibody, is widely used for patients with rheumatoid arthritis. IL-6 is essential for production of C-reactive protein (CRP). Tocilizumab fully inhibit the production of CRP. Therefore, we have difficulty in objective assessment of infection and disease activity because the level of CRP is suppressed under tocilizumab therapy. The development of new biomarker alternative to CRP is needed for daily practice. Objectives To discover new biomarkers alternative to CRP under tocilizumab therapy for rheumatoid arthritis. Methods We registered patients with rheumatoid arthritis treated with tocilizumab. We collected serum samples from those patients at baseline, 4 weeks after the first tocilizumab administration when patient9s CRP level is almost normal, and 1 year later. And we measured CRP, ESR and clinical disease activity index (CDAI) score.Serum peptidomic analysis was conducted by newly-established one-step direct transfer technology (BLOTCHIP-MS analysis), a rapid quantitative technology for peptidomic analysis. All sample measurements were repeated four times. Statistical analyses of MS spectral data were conducted using ClinProTools version 2.2 (Bruker Daltonics). Results We registered 14 patients and their background is shown in Table 1. The levels of CRP were 1.16±0.99 mg/dl at baseline, 0.02±0.01 mg/dl at 4 weeks and 0.01±0.01mg/dl at 1 year, respectively. Their CDAI score were 22±9.2 at baseline, 15±8.9 at 4 weeks and 3±2.6 at 1 year, respectively. CRP titer decreased to almost normal level at 4 weeks regardless whether CDAI score did not fully decrease. We detect 6 biomarkers, named as PRSJ01 to PRSJ06, by the peptidomic analysis (Table 2). The AUC of diagnostic value of these markers is from 0.742 to 0.858. For example, the level of PRSJ06 significantly decreased 4 weeks (Wilcoxon singed-rank test, p=0.02) and 1 year (Wilcoxon singed-rank test, p=0.003) after first tocilizumab administration (Figure 1). and it was inversely-correlated with CDAI score. Conclusions We detect new disease activity biomarkers alternative to CRP under tocilizumab therapy for rheumatoid arthritis. It is useful for exact evaluation of disease activity and infection during tocilizumab therapy. Disclosure of Interest None declared

Due to rapid industrialization and the concentration of the population shifting towards large cities starting from the 1950s, Japan experienced severe water pollution problems throughout the country. In order to cope with these problems, the legal system has been refined and various measures to control water pollution have been taken. This paper summarizes the current institutional structure, legal system, as well as plans and programs, for water pollution control and river basin management in Japan.

We produced a Japanese version of the Eating Disorder Inventory-2 (EDI-2) and investigated its reliability and validity.EDI-2 Japanese version was administered to 246 patients with eating disorders and 100 control subjects. The internal consistency as well as discriminant validity were examined.The alpha reliability coefficients were high (0.71 to 0.92) in all subscales except the asceticism subscale which was rated 0.61. The anorexia nervosa binge-purging type and bulimia nervosa showed significantly higher scores in all the EDI-2 subscales when compared to the controls, and also significantly higher scores in seven EDI-2 subscales compared to anorexia nervosa restricting type (AN-R). AN-R showed significantly lower scores in the body dissatisfaction subscale. Lower scores in Japanese than Western patients for drive for thinness as well as marked difference in perfectionism and maturity fears suggested cross-cultural issues between Japan and western countries.Japanese version of EDI-2 is a measure instrument that can be expected to have a satisfactory level of internal consistency except the asceticism subscale as well as high validity as a tool for the evaluation of the psychopathology of eating disorder.

We report a patient with advanced carcinoma of the pancreatic body and tail with multiple liver metastases who showed a complete response to hepatic and splenic arterial infusion chemotherapy (HSAIC) with gemcitabine and 5-fluorouracil, following transcatheter peripancreatic arterial embolization (TPPAE) and partial splenic embolization (PSE). Nonresectable advanced pancreatic carcinoma tends to have a low response to medical treatment, with the median survival time being 6 months or less for stage IV cases. We disclose herein that the median survival time of patients receiving HSAIC after TPPAE is more than three times longer than the survival time attained with conventional treatments. However, in patients with advanced carcinoma of the pancreatic tail, for which TTPAE is not applicable, survival times remain low. Thus, in the patient described here, we also performed embolization of the left gastric and short gastric arteries as well as PSE to increase the flow within the great pancreatic and caudal pancreatic arteries via the splenic artery, and gemcitabine and 5-fluorouracil were administered via the splenic artery. As a result of these procedures, marked reduction in the advanced carcinoma of the pancreatic body and tail and of liver metastases was attained.