A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans

On the Magnetic Anisotropy of a Pyrrhotite Crystal

Measurement of the magnetic anisotropy energy of a single crystal of natural pyrrhotite in c-plane was made by means of the torque method at room temperature up to a magnetic field of 20000 Oe and at low temperature in a constant field. It was found that the easy axis lay along [210] direction above -80℃ which, however, changed to [100] direction below that temperature. The torque curves in c-plane were composed of two- and six-fold symmetric parts. It was also found that in the range of strong magnetic fields the six-fold symmetric part at room temperature decreased with the inverse square of the applied field ; such a field dependence is explained assuming a triad structure for the single crystal of pyrrhotite. A remark is also given on the origin of the two-fold symmetric torque

Development and characterization of IL-21–producing CD4+ T cells

It has recently been shown that interleukin (IL)-21 is produced by Th17 cells, functions as an autocrine growth factor for Th17 cells, and plays critical roles in autoimmune diseases. In this study, we investigated the differentiation and characteristics of IL-21–producing CD4+ T cells by intracellular staining. Unexpectedly, we found that under Th17-polarizing conditions, the majority of IL-21–producing CD4+ T cells did not produce IL-17A and -17F. We also found that IL-6 and -21 potently induced the development of IL-21–producing CD4+ T cells without the induction of IL-4, IFN-γ, IL-17A, or IL-17F production. On the other hand, TGF-β inhibited IL-6– and IL-21–induced development of IL-21–producing CD4+ T cells. IL-2 enhanced the development of IL-21–producing CD4+ T cells under Th17-polarizing conditions. Finally, IL-21–producing CD4+ T cells exhibited a stable phenotype of IL-21 production in the presence of IL-6, but retained the potential to produce IL-4 under Th2-polarizing conditions and IL-17A under Th17-polarizing conditions. These results suggest that IL-21–producing CD4+ T cells exhibit distinct characteristics from Th17 cells and develop preferentially in an IL-6–rich environment devoid of TGF-β, and that IL-21 functions as an autocrine growth factor for IL-21–producing CD4+ T cells

Evaluation of complex physical therapy for lymphedema of the unilateral lower limbs

We evaluated the effectiveness of the complex physical therapy (CPT) for lymphedema of the unilateral lower limbs of eleven patients who had been admitted to Tokushima Rehabilitation Hospital. Ten patients were of secondary lymphedema, nine of which were after treatment of uterine cancer and one was of primary lymphedema. Our CPT consited of skin care, manual lymph drainage (MLD), compression therapy with elastic bandages or elastic stockings, and exercise therapy under compression. MLD functionally operates to enhance the lymph drainage more proximally in both contralateral and ipsilateral truncal quadrants of the torso, then in the proximal limb, and only thereafter from the distal to proximal portion of the edematous extremity. Swelling ratio of all patients on admission was 26.9± 11.8% and that at discharge was 16.8±9.4%. Edema reduction ratio (ERR) of the entire patients was 41.5± 16.5%, and 81.8% of cases were recognized as effective, in which ERR showed more than 30% at discharge. In a consensus document about the diagnosis and treatment of peripheral lymphedema in 1995, the International Society of Lymphology Executive Committee reported that most operations designed to alleviate peripheral lymphedema have not as yet been perfected or usually are still inferior to combined physiotherapy. At present lymphedema should be accurately diagnosed in the early stage and be treated with CPT correctly by clinicians who understand lymphedema thoroughly and are well trained

Clinical Outcome of Patients with Pelvic and Retroperitoneal Bone and Soft Tissue Sarcoma : A Retrospective Multicenter Study in Japan

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan

Experimental investigation and micropolar modelling of the anisotropic conductive adhesive flip-chip interconnection

A conductive adhesive is a promising interconnection material for microsystem packaging. The interconnect features are of great importance to system responses under various loading conditions. The flip-chip packaging system with anisotropic conductive film (ACF) joint under thermal loadings has been investigated both experimentally and theoretically. The displacement distributions have been measured by an interferometer, which could provide the in-plane whole-field deformation observation. The interconnection is of much smaller scales compared with the neighbouring components such as the chip and substrate, and there are even finer internal structures involved in the joint. The wide scale range makes both experimental observation and conventional simulation difficult. A micropolar model is thus developed. Utilizing the homogenization, this model requires low computation resource. Combination of this model with a secondorder model was able to produce a highly efficient and valid prediction of the packaging system response under thermal and mechanical loadings. Comparison of the micropolar model simulation and experimental data shows good agreement

Experimental Investigation and Micropolar Modelling of the Anisotropic Conductive Adhesive Flip-Chip Interconnection

A conductive adhesive is a promising interconnection material for microsystem packaging. The interconnect features are of great importance to system responses under various loading conditions. The flip-chip packaging system with anisotropic conductive film (ACF) joint under thermal loadings has been investigated both experimentally and theoretically. The displacement distributions have been measured by an interferometer, which could provide the in-plane whole-field deformation observation. The interconnection is of much smaller scales compared with the neighbouring components such as the chip and substrate, and there are even finer internal structures involved in the joint. The wide scale range makes both experimental observation and conventional simulation difficult. A micropolar model is thus developed. Utilizing the homogenization, this model requires low computation resource. Combination of this model with a second-order model was able to produce a highly efficient and valid prediction of the packaging system response under thermal and mechanical loadings. Comparison of the micropolar model simulation and experimental data shows good agreement