Shinichi Itoh

Suppression of hepatic lesions in a murine graft-versus-host reaction by antibodies against adhesion molecules

BACKGROUND/AIMS The injection of parental CD4+ T cells into major histocompatibility complex (MHC) class II disparate F1 hybrid mice induced an autoimmune graft-versus-host reaction (GVHR) which is analogous to autoimmune liver diseases. The interaction of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) has been known to be profoundly involved in the trafficking of lymphocytes into the inflammatory tissues. The aim of this study was to clarify the role of VLA4 or VCAM-1 in the development of GVHR-induced hepatic lesions in our model. METHODS B6 T spleen cells were injected into (B6.C-H-2bm12xB6) F1 mice intravenously. Anti-VLA-4 mAbs and/or anti-VCAM-1 mAbs were injected intraperitoneally at a dose of 2.5 mg/kg of each mAbs per body weight of mouse. We examined the changes in GVHR-induced hepatic lesions, serum levels of antimitochondrial antibodies (AMA) and cytokine mRNA expressions of liver-infiltrating lymphocytes using H.E. and immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS Hepatic lesions of anti-VLA-4 mAbs-treated mice were inhibited compared with those of GVHR mice. However, the administration of mAbs did not interfere with the induction of splenomegaly, the invasion of CD4+, CD8+, B220+, or Mac-1+ cells around bile ducts, nor the production of AMA. Liver-infiltrating CD4+ T cells obtained from these treated mice did not alter the expression of T helper (Th)1 and Th2 cytokine mRNA. CONCLUSION The results suggest that treatment with antibodies against these adhesion molecules could inhibit the infiltration of lymphocytes without affecting the Th1/Th2 balance. The blockade of VLA-4-mediated cell infiltration into the liver in this model may have a possible novel therapeutic role of VLA-4 mAbs.

Cytokine profile of liver-infiltrating CD4+ T cells separated from murine primary biliary cirrhosis-like hepatic lesions induced by graft-versus-host reaction

Background and Methods : We have previously reported that CD4+ T cells induced primary biliary cirrhosis (PBC)‐like hepatic lesions in mice with graft‐versus‐host reaction due to major histocompatibility complex class II disparity. To clarify the relationship between the cytokine profile produced by CD4+ T cells and the formation of hepatic lesions, we sorted CD4+ T cells from the liver by using flow cytometry and examined their cytokine mRNA expression at various times after GVHR induction. We also examined the associated changes in the serum levels of antimitochondrial antibodies (AMA).

Brillouin linewidth and anomalous damping of acoustic phonons near the phase transition in Gd2(MoO4)3

Abstract Anomalous damping of acoustic phonons has been observed from the measurements of the linewidths of Brillouin components near the transition temperature in Gd2(MoO4)3 and the temperature dependence of damping constants has been fitted by a power law. Just below T0, the phonons propagating along the x-axis can only travel one wavelength in their relaxation time.

Brillouin scattering study of Gd2(MoO4)3 using a double Fabry-perot interferometer

Abstract Brillouin shifts by longitudinal phonons propagating along orthorhombic x and y axes were measured using a double Fabry-Perot interferometer. The observed phonons show softening near its phase transition point.

Progression of autoimmune-mediated hepatic lesions in a murine graft-versus-host reaction by neutralizing IL-10

C57BL/6 (B6) spleen T cells which were injected into major histocompatibility complex (MHC) class II-disparate (B6.C-H-2(bm/2)xB6) F1 hybrid mice induced autoimmune graft-versus-host reaction (GVHR). Early production of interferon (IFN)-gamma and delayed production of interleukin (IL)-10 might play an important role in the formation of GVHR hepatic lesions. To clarify whether blocking of IL-10 deteriorate autoimmune-mediated hepatic lesions induced by GVHR, and to elucidate the change of the T helper (Th)1/Th2 cytokines in the liver, anti-IL-10 monoclonal antibodies (mAbs, 500 &mgr;g) were given 4 h before the induction of GVHR. We evaluated the change of splenomegaly and GVHR-induced hepatic lesions. The changes of the expressions of IFN-gamma and IL-4 mRNA isolated from liver-infiltrating lymphocytes were measured by real-time polymerase chain reaction (PCR). In GVHR with anti-IL-10 mAbs mice splenomegaly and periportal cellular infiltration was significantly increased compared with those of GVHR mice. In these mice, both IFN-gamma and IL-4 mRNA expression levels were significantly elevated by the neutralization of IL-10. These findings suggest an important role of IL-10 in murine GVHR due to MHC class II disparity. IL-10 may play a crucial role in down-regulating autoimmune-related hepatic lesions.

Novel murine autoimmune-mediated liver disease model induced by graft-versus-host reaction and concanavalin A

Background and Aims: We have previously reported that cluster of differentiation (CD)4+ T cells induced autoimmune liver diseases in mice with graft‐versus‐host reaction (GVHR) because of major histocompatibility complex (MHC) class II disparity. To analyze the progression of the autoimmune‐related mechanism in the liver, concanavalin A (Con A) was injected in mice undergoing GVHR. The aim of this study is to clarify whether Con A deteriorates murine hepatic lesions induced by GVHR, and to elucidate the participation of the cytokines of liver‐infiltrating CD4+ T cells.

Simulation Study of Phase-Shift Dependence of the Phase Conjugate Wave Intensity in a Photorefractive Medium

Based on the exact solutions of the coupled-wave equations in the degenerated four-wave mixing process, the behavior of the phase-conjugate wave (PCW) intensity in a photorefractive medium was calculated with varying phase shift O between the light interference pattern and the refractive index grating, and coupling strength of the wave interaction. The behavior of the PCW intensity was examined in a wider range of O than the previous reports by other authors. It was found that a multiple-solution region exists at specific values of O. The fidelity of image reconstruction was discussed based on the results of the dependence of the PCW intensity on the probe beam intensity

Brillouin Scattering Study of Gd2(MoO4)3 Using a Double Fabry-Perot Interferometer

To improve the contrast of a single Fabry–Perot interferometer, a double Fabry–Perot interferometer was designed. The contrast of this system is ~7×104 which is ~30 times as large as that of a single Fabry-Perot interferometer. Using this system, the Brillouin spectrum of gadolinium molybdate crystal, which has a very strong central component, could be observed. The temperature dependence of Brillouin shifts and Brillouin linewidths was measured. Brillouin shifts show softening and Brillouin linewidths show anomalous broadening near the structural phase transition point.

A Study on Decomposition of Dioxin Analogues by FEL

Abstract Decomposition of dioxin analogues by infrared (IR) laser irradiation occurs by ways of thermal destruction and multiple-photon dissociation. It is necessary for the decomposition to choose the laser wavelength which is strongly adsorbed. The thermal decomposition takes place by the irradiation of the low IR laser power. Considering the model of thermal decomposition, it is proposed that the adjacent water molecules assist the decomposition of dioxin analogues. PACS codes: 33.80.-b

Decomposition of Dioxin Analogues by IR Laser

The decompositions of dioxin analogues by infrared (IR) laser irradiation were caused by thermal destruction for the low laser fluence. It is important for the effective decomposition to choose the proper laser wavelength. In this paper, the results of irradiation at 7 µm of FEL are compared with those at 10.6 µm of CO2 laser. It was also presented that the adjacent water molecules assist the decomposition of dioxin analogues.