Small GTP-binding protein Rho-mediated signaling promotes proliferation of rheumatoid synovial fibroblasts

Rho is a major small GTP-binding protein that is involved in the regulation of various cell functions, including proliferation and cell migration, through activation of multiple signaling molecules in various types of cells. We studied its roles in synovial fibroblasts (SFs) in patients with rheumatoid arthritis (RA) and clarified its relevance to RA synovitis, with the following results. 1)We found that the thrombin receptor was overexpressed on RA synovial fibroblasts (RA SFs) and that thrombin induced a marked proliferation and progression of the cell cycle to the S phase in these cells. 2)We also found that thrombin efficiently activated Rho. 3)Rho activation and proliferation and the progression of the cell cycle to the S phase were completely blocked by p115RGS (an N-terminal regulator of the G-protein signaling domain of p115RhoGEF) and by the C-terminal fragments of Gα13 (an inhibitor of the interaction of receptors with G13). 4)Thrombin induced the secretion of IL-6 by RA SFs, but this action was blocked by p115RGS or Gα13. Our findings show that the actions of thrombin on the proliferation of RA SFs, cell-cycle progression to the S phase, and IL-6 secretion were mainly mediated by the G13 and RhoGEF pathways. These results suggest that p115RGS and Gα13 could be potent inhibitors of such functions. A rational design of future therapeutic strategies for RA synovitis could perhaps include the exploitation of the Rho pathway to directly reduce the growth of synovial cells

Hemorrhagic infarction at 33 days after birth in a healthy full-term neonate

Intraparenchymal hemorrhage in the full-term neonate rarely occurs more than 2 weeks after birth, and its definitive cause remains unclear. In the present report, a case of a patient with intraparenchymal hemorrhage occurring 33 days after birth is described. Histological examination of the brain tissue obtained during hematoma evacuation through craniotomy showed hemorrhagic infarction. Patent foramen ovale may have been present and this may have led to spontaneous paradoxical cerebral embolism followed by hemorrhagic infarction

Endoscopic sphincterotomy assisted by percutaneous transhepatic choledochal tube: a preliminary report

We report a method of endoscopic retrograde sphincterotomy in patients in whom the optimal viewing of the papilla of Vater is hardly obtained. Percutaneous transhepatic cholangiodrainage (PTCD)-tube is placed under ultrasonographic guidance. PTCD-tube coming out of the papilla of Vater is observed by the endoscope and the guide wire inside the shpincterotome is inserted into the PTCD-tube. Sphincterotome is advanced into the common bile duct by the guidance of the guide wire and PTCD-tube. Sphincterotomy is performed in a usual fashion. Two patients with previous history of gastrectomy underwent this procedure with successful results. This method should be tried when usual method of EST is difficult and unsuccessful.</p

A monoclonal antibody which recognizes the inner and outer segments of the photoreceptor cells in the vertebrate retina.

A monoclonal antibody (MAb-1E7), generated against bovine retinal homogenate, labeled the outer and inner segment layers of the vertebrate retina. Immuno-electron microscopic observation clearly demonstrated that antigen(s) bound by MAb-1E7 was localized in the cell membrane of the outer segment and the distal portion of the inner segment. Western blot analysis revealed that MAb-1E7 recognized 40 kD- and 27 kD-polypeptides. Mouse retina with hereditary photoreceptor degeneration (C3H/He and CBA strains) did not involve the MAb-1E7 immunoreactive structures. The present immunocytochemical observation demonstrated that MAb-1E7 was highly specific to the outer segment of the photoreceptor cells and, therefore, can be a useful marker for the cells.</p

機械工学科における設計製図教育の取組み

Design and drawing is a core courses in mechanical engineering. Fourth grade student designs a two-stage gear reducer for 1 year. Performing design calculations using C language. It's modeled by 3D-CAD and the safety factor is confirmed using a CAE analysis. Then shaped it using three-dimensional printers. Finally the students have a presentation using the PowerPoint and video for each group. In this paper, based on the curriculum of courses that they are exercises, we will introduce our efforts in the lecture

Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development

Follistatin-related gene (FLRG) encodes a secretory glycoprotein that has characteristic cysteine-rich follistatin domains. FLRG protein binds to and neutralizes several transforming growth factor-β (TGF-β) superfamily members, including myostatin (MSTN), which is a potent negative regulator of skeletal muscle mass. We have previously reported that FLRG was abundantly expressed in fetal and adult mouse heart. In this study, we analyzed the expression of FLRG mRNA during mouse heart development. FLRG mRNA was continuously expressed in the embryonic heart, whereas it was very low in skeletal muscles. By contrast, MSTN mRNA was highly expressed in embryonic skeletal muscles, whereas the expression of MSTN mRNA was rather low in the heart. In situ hybridization and immunohistochemical analysis revealed that FLRG expressed in smooth muscle of the aorta and pulmonary artery, valve leaflets of mitral and tricuspid valves, and cardiac muscles in the ventricle of mouse embryonic heart. However, MSTN was expressed in very limited areas, such as valve leaflets of pulmonary and aortic valves, the top of the ventricular and atrial septa. Interestingly, the expression of MSTN was complementary to that of FLRG, especially in the valvular apparatus. Biochemical analyses with surface plasmon resonance biosensor and reporter assays demonstrated that FLRG hardly dissociates from MSTN and activin once it bound to them, and efficiently inhibits these activities. Our results suggest that FLRG could function as a negative regulator of activin family members including MSTN during heart development

Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease

IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed

Effect of Sb and Zn Addition on the Microstructures and Tensile Properties of Sn&ndash;Bi-Based Alloys

The tensile behavior of Sn&ndash;Bi&ndash;Cu and Sn&ndash;Bi&ndash;Ni alloys has been widely investigated. Reportedly, the addition of small amounts of a third element can refine the microstructures of the eutectic Sn-58mass% Bi solder and improve its ductility. However, the superplasticity mechanism of Sn-based alloys has not been clearly established. Therefore, in this study, the effects of Sb and Zn addition on the microstructures and tensile properties of Sn&ndash;Bi-based alloys were investigated. The alloys were subjected to tensile tests under various strain rates and temperatures. We found that Zn- and Sb-added Sn&ndash;Bi-based alloys demonstrated superplastic deformation at high temperatures and low strain rates. Sb addition significantly affected the elongation of the Sn&ndash;Bi&ndash;Sb alloys because the metal dissolves in both the primary Sn phase and the eutectic Sn&ndash;Bi matrix. The segregation of Zn and formation of needle-like Zn particles at the eutectic Sn&ndash;Bi phase boundary affected the superplastic deformation of the alloys. The deformation of the Sn&ndash;40Bi-based alloys at high temperatures and low strain rates led to dynamic recovery, dynamic recrystallization, and/or grain boundary slip because of the accumulation of voids