Search

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].

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.

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.

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 ...

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.

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.

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.

Two controversial issues regarding p53 are whether it is involved in apoptosis induction of tumor cells by a histone deacetylase (HDAC) inhibitor and, given that p53 is indeed involved, which genes of acetylated p53 targets are responsible for giving rise to apoptotic death. We, in the present study, first confirmed that some substantial extent of apoptotic cell death was seen when p53-deficient cells (KATO-III) were transfected with wild-type p53 and treated with sodium butyrate (SB) or trichostatin A. By Western blotting, using specific antibodies, we then demonstrated that residues 320, 373, and 382 lysines of p53 were acetylated in KATO-III cells transfected with wild-type p53 (KATO-III/p53) treated with a HDAC inhibitor. However, as revealed by terminal deoxynucleotidyl transferase-mediated nick end labeling staining, only those KATO-III cells transfected with K320R p53 or K373R p53 became insensitive to the HDAC inhibitor, suggesting that these two residues of p53 may be essential for HDAC inhibitor-induced apoptosis, whereas others such as K382R p53 may not. Furthermore, reverse transcription-PCR demonstrated that among various p53-related proapoptotic genes, expression of PIG3 and NOXA were clearly enhanced by SB treatment in KATO-III/p53 cells but not in KATO-III/K320R or KATO-III/K373R cells. Finally, we revealed that apoptosis could be evoked by SB even in cells where p53 mutations occur at residues other than 320 lysine or 373 lysine (TMK-1 and HSC-39 cells) and that this apoptosis was significantly, although not totally, suppressed by the anti-p53 antisense. It was, therefore, concluded that acetylation of the p53 molecule at residues 320 and 373, giving rise to up-regulation of PIG3 and NOXA, is one of the mechanisms for induction of apoptosis by HDAC inhibitors in cancer cells.

Three case studies of research applications in the field of wastewater treatment technology in Japan are presented. The technologies being dealt with in the case studies are the two-stage dewatering of sewage sludge, the use of prefabricated panels for the construction of oxidation ditches and the multi-stage reversing-flow bioreactor (MRB) process. The main organizations in charge of development of these technologies are a city, a public corporation and a national research institute, respectively. The processes of research application as well as the associated problems are described and discussed through the case studies. The technology evaluation system that started in 1986 is also described here. This system was established in order to promote the actual use of new technologies, particularly those developed by the private sector.

A small quantity of Rhodamine WT dye was injected at the headwater of the Muddy Creek estuary and concentration of the dispersed dye was measured with a uniform time interval at a number of fixed locations in the lower portion of the estuary. By the use of the superposition principle of a linear system, the builtup concentration of the dye is found to range from 8 ppb at 1,900 feet downstream from the confluence of the north and south forks of Muddy Creek to 2 ppb near the Smithsonian Institution’s pier in the Rhode River, provided that the dye is continuously injected at the headwaters at the rate of one pound per two tidal cycles.