Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE.

Background: Risks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented.

Methods: Subgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6-12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors.

Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study.

Background: Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA.

Serum starvation activates NF-κB through G protein β2 subunit-mediated signal.

Several cell stresses induce nuclear factor-kappaB (NF-κB) activation, which include irradiation, oxidation, and UV. Interestingly, serum-starving stress-induced NF-κB activation in COS cells, but not in COS-A717 cells. COS-A717 is a mutant cell line of COS cells that is defective of the NF-κB signaling pathway.

Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription.

Mice deficient for interferon regulatory factor (Irf)2 (Irf2(-/-) mice) exhibit immunological abnormalities and cannot survive lymphocytic choriomeningitis virus infection. The pancreas of these animals is highly inflamed, a phenotype replicated by treatment with poly(I:C), a synthetic double-stranded RNA. Trypsinogen5 mRNA was constitutively up-regulated about 1,000-fold in Irf2(-/-) mice compared with controls as assessed by quantitative RT-PCR.

Interferon regulatory factor-4 activates IL-2 and IL-4 promoters in cooperation with c-Rel.

Interferon regulatory factor (IRF)-4 is a member of the IRF transcription factor family, whose expression is primarily restricted to lymphoid and myeloid cells. In T-cells, IRF-4 expression is induced by T-cell receptor (TCR) cross-linking or treatment with phorbol-12-myristate-13-acetate (PMA)/Ionomycin, and IRF-4 is thought to be a critical factor for various functions of T-cells. To elucidate the IRF-4 functions in human adult T-cell leukemia virus type 1 (HTLV-1)-infected T-cells, which constitutively express IRF-4, we isolated IRF-4-binding proteins from T-cells, using a tandem affinity purification (TAP)-mass spectrometry strategy.

Aberrant expression of interferon regulatory factor 3 in human lung cancer.

We analyzed the subcellular distributions and gene structures of interferon regulatory factor 3 (IRF3) transcription factor in 50 cases of human primary lung cancer. The immunohistochemical analyses revealed substantially aberrant IRF3 expression specific to the cancer lesions (2 and 6 tumors with nuclear staining, and 4 and 5 tumors with negative staining, in adenocarcinoma and squamous cell carcinoma, respectively), while the morphologically normal region around the tumors exhibited only cytoplasmic staining. In addition, we determined the sequence of the entire IRF3 coding region, and found two novel variants with the amino acid changes (S(175)(AGC)-->R(175)(CGC) and A(208)(GCC)-->D(208)(GAC)).

Long-term study of indolent adult T-cell leukemia-lymphoma.

The long-term prognosis of indolent adult T-cell leukemia-lymphoma (ATL) is not clearly elucidated. From 1974 to 2003, newly diagnosed indolent ATL in 90 patients (65 chronic type and 25 smoldering type) was analyzed. The median survival time was 4.

Hippocampal Fyn activity regulates extinction of contextual fear.

Contextual fear memory is attenuated by reexposure of animals to a context alone without pairing it with an unconditioned stimulus, a phenomenon referred to as fear extinction. Here, we report that Fyn tyrosine kinase in the hippocampus is involved in the extinction of contextual fear. We inhibited Src-family tyrosine kinases in the dorsal hippocampus by stereotaxic injection of an inhibitor, PP2, and observed facilitation of extinction.

Aberrant expression of BAFF receptor, a member of the tumor necrosis factor receptor family, in malignant cells of nonhematopoietic origins.

The acquired capability of evading apoptosis is one of the prerequisites for cancer development, and NF-kappaB plays a critical role by inducing anti-apoptotic molecules. In this study, we firstly carried out an expression-cloning approach to isolate the responsible molecules in the NF-kappaB activation pathway with the defective mutant cell line, COS-A717. This cell line shows reduced constitutive basal activity of NF-kappaB as compared with the parental COS cells.

Activation of Fyn tyrosine kinase in the mouse dorsal hippocampus is essential for contextual fear conditioning.

Fyn-tyrosine-kinase-deficient mice exhibit defects in the Morris water maze test and long-term potentiation (LTP) induction in the hippocampus, and given that LTP has been postulated as the neural basis for memory formation, Fyn may be required for hippocampus-dependent memory formation. However, how Fyn is involved in the process of memory formation is unclear. To investigate the role of Fyn in hippocampal memory formation, we first tested the behavior of Fyn-deficient mice by contextual fear conditioning.

Inactivation of p14ARF as a key event for the progression of adult T cell leukemia/lymphoma.

The INK4a/ARF locus encodes two different proteins, p16INK4a and p14ARF, which are crucial for two tumor suppressor pathways. We found that p14ARF mRNA expression was suppressed in 13 of 37 cases, among which 9 cases showed the inactivation of both of p14ARF and p16INK4a, and 4 cases showed the inactivation of p14ARF alone. The inactivation of p14ARF and the mutation of p53 are mutually exclusive.

Tgat, a Rho-specific guanine nucleotide exchange factor, activates NF-kappaB via physical association with IkappaB kinase complexes.

Constitutive activity of NF-kappaB is associated with various human cancers including adult T-cell leukemia (ATL). In this study, we have found Tgat that activates NF-kappaB by screening a cDNA expression library derived from ATL cells. We previously identified Tgat as the oncogene, which consists of the Rho-guanine nucleotide exchange factor (Rho-GEF) domain and the unique C-terminal region, as a consequence of alternative splicing of the Trio transcript.

Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS.

A member of the IFN regulatory factor (IRF) family of transcription factors, IRF-4 is expressed in lymphocytes and macrophage/dendritic cells. Studies using IRF-4-deficient mice have revealed the critical roles of IRF-4 in lymphocyte responses. However, the role of IRF-4 in innate immune responses is not clearly understood.

Active repression of IFN regulatory factor-1-mediated transactivation by IFN regulatory factor-4.

IFN regulatory factor-4 (IRF-4) is a transcription factor that is involved in the development and the functions of lymphocytes, macrophages and dendritic cells. Despite their critical roles in immune system regulation, the target genes controlled by IRF-4 are poorly understood. In this study, we determined the consensus DNA-binding sequences preferred for IRF-4 by in vitro binding site selections.

Possible origin of adult T-cell leukemia/lymphoma cells from human T lymphotropic virus type-1-infected regulatory T cells.

Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder caused by human T lymphotropic virus type 1 (HTLV-I). Although ATLL cells display an activated helper/inducer T-cell phenotype, CD4+ and CD25+, they are known to exhibit strong immunosuppressive activity. As regulatory T cells (Treg cells) express CD4+ and CD25+ molecules and possess potent immune response suppressive activity, we investigated a possible link between ATLL cells and Treg cells.

A novel immunomodulator, FTY720, prevents development of experimental autoimmune myasthenia gravis in C57BL/6 mice.

Prophylactic oral administration of a novel immunomodulator (immunosuppressant), FTY720 (1 mg/kg, three times a week), completely prevented the development of experimental autoimmune myasthenia gravis (EAMG) in C57BL/6 mice. EAMG has been used as an animal model for human myasthenia gravis, and was established by immunizing the mice with acetylcholine receptor (AChR) from Torpedo californica. FTY720 also suppressed the production of both anti-Torpedo californica AChR antibody and anti-mouse AChR autoantibody by the mice, which were observed in mice in which EAMG had become established.

Induction of epithelial cell apoptosis in the uterus by a mouse uterine ischemia-reperfusion model: possible involvement of tumor necrosis factor-alpha.

Menstruation in primates is preceded by a period of intense vasoconstriction, with resultant ischemia-reperfusion. Although apoptosis is involved in endometrial breakdown, the relationship between ischemia-reperfusion and apoptosis in the female genital tract has not been determined. To investigate the relationship between ischemia-reperfusion and apoptosis in the uterus, we analyzed a uterine ischemia-reperfusion model using BDF1 and C57BL/6 mice.

Regulation of hepatocyte growth factor by basal and stimulated macrophages in women with endometriosis.

Background: The different macromolecules as secreted by macrophages in the pelvic environment are believed to enhance the growth of endometriosis. However, the possible mediator that stimulates macrophages for the production of different growth factors is not well described. Therefore, we investigated the possible production of hepatocyte growth factor (HGF) by the basal and lipopolysaccharide (LPS)-stimulated macrophages derived from women with or without endometriosis.

Near reflex substituting for acquired horizontal gaze palsy: a case report.

Background: Some patients with acquired horizontal gaze palsy overcome the adduction palsy by utilizing convergence. This substitution phenomenon is very rare. We report a patient with horizontal gaze palsy who was able to use convergence to compensate for the lack of adduction in the left eye.

Comparison of dental students selected as student clinicians by Japanese dental schools.

The aim of this study was to determine if students selected from Japanese dental schools for competition at the Japan Dental Association meeting and who subsequently won awards were different from students who did not win. Eighty abstracts submitted from 1995 to 2001 by dental students for the Japan Student Clinician Program (SCP) award were evaluated. Multiple logistic regression analysis using backward stepwise selection was completed with the dependent variables.

A novel immunomodulator, FTY720, prevents spontaneous dermatitis in NC/Nga mice.

Oral administration of a novel immunomodulator, FTY720 (0.1 mg/kg, once a week), completely prevented the spontaneous development of dermatitis in NC/Nga mice. It also strongly suppressed hyper IgE production in serum, as well as hypertrophy of the epidermis and the degranulation of granulocytes in the skin, all of which were observed in mice in which the dermatitis had become established.

Identification of a novel GC-rich binding protein that binds to an indispensable element for constitutive IRF-4 promoter activity in B cells.

Interferon regulatory factor-4 (IRF-4) is a lymphoid-specific transcription factor that plays crucial roles in the development and the functions of immune cells. B lymphocytes express IRF-4 constitutively. In this report, we investigated the transcriptional control of IRF-4 in B lymphocytes.

Changes in response properties of periodontal mechanoreceptors after experimental orthodontic tooth movement in rats.

Using an in vitro preparation, we investigated chronological changes in response properties of periodontal mechanoreceptors (PMRs) in the rat right mandibular first molar (M1) after experimental orthodontic tooth movement. Orthodontic force was applied to M1 for 14 days by activating 24.5 mN superelastic titanium-nickel alloy closed coil springs anchored to the mandibular incisors.

Brain-derived neurotrophic factor-dependent unmasking of "silent" synapses in the developing mouse barrel cortex.

Brain-derived neurotrophic factor (BDNF) is a critical modulator of central synaptic functions such as long-term potentiation in the hippocampal and visual cortex. Little is known, however, about its role in the development of excitatory glutamatergic synapses in vivo. We investigated the development of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-only synapses (silent synapses) and found that silent synapses were prominent in acute thalamocortical brain slices from BDNF knockout mice even after the critical period.