Role of endothelial damage in the pathogenesis of interstitial pneumonitis in patients with polymyositis and dermatomyositis

OBJECTIVE: Polymyositis and dermatomyositis (PM/DM) are often complicated by interstitial pneumonitis (IP), which is an important cause of death. It has been reported that blood concentration of transforming growth factor-beta (TGF-beta), which is produced by a wide range of cells including endothelial cells and enhances the fibrotic changes in various tissues, is increased in PM/DM with IP. Endothelial damage is likely to exist in PM/DM. We studied the relationship between endothelial damage and IP in PM/DM. METHODS: Blood levels of sialylated carbohydrate antigen KL-6, TGF-beta, endothelin-1 (ET-1), thrombomodulin (TM), and plasminogen activator inhibitor-1 (PAI-1) were determined in 43 patients with PM or DM with or without IP, and the relationship between these measures was analyzed. RESULTS: Blood levels of KL-6 and TGF-beta were higher in the patients with IP than those without, and these measures were well correlated with each other. Levels of ET-1, TM, and PAI-1, all known to reflect the extent of endothelial damage, were also increased in patients with IP, and these measures correlated well with TGF-beta. CONCLUSION: Our data suggest that endothelial damage might play an important role through the production of fibrosis-enhancing factors such as TGF-beta or ET-1 in PM/DM.     

Two cases of lupus cystitis with no bladder irritation symptoms

Lupus cystitis is a rare manifestation in systemic lupus erythematosus (SLE); it usually occurs in association with gastrointestinal manifestations. We report two cases of lupus cystitis without bladder irritation symptoms. Both cases developed severe abdominal pain, nausea, and diarrhea and showed no bladder irritation symptoms. The diagnosis of lupus cystitis was made by abdominal ultrasonography and bladder biopsy. The patients were treated with intravenous methylprednisolone pulse therapy followed by oral prednisolone. Their symptoms were ameliorated, and hydroureteronephrosis improved. Thus, when a patient with SLE shows gastrointestinal symptoms, further examinations are required to determine whether the patient has lupus cystitis.     

A case of systemic lupus erythematosus that manifested in the course of schizophrenia

A case of schizophrenia is presented in which SLE was diagnosed after 14-year duration. Antibodies to single and double-stranded DNAs, but not to histone. were detected. This case suggests that similar immunological abnormalities as SLE are associated with the pathogenesis of a group of schizophrenia and that class-switch of anti-dsDNA antibodies are important in the pathogenesis of SLE.     

Interferon-gamma inhibition of interleukin 4-induced hyperproliferation of resting B cell from NZB/NZW F1 mice.

To characterize B cell hyperactivity in autoimmune NZB/NZW (B/W) F1 mice, we studied the effects of murine recombinant interferon gamma (IFN-gamma) on interleukin 4 (IL-4) induced resting B cell growth and differentiation. The number of resting B cells of B/W F1 mice were decreased, with more sensitivity to IL-4 than normal mice. Thus, resting B cell hyperresponsiveness to IL-4 was in a dose-dependent manner suppressed by IFN-gamma. This action was most noticeable when IFN-gamma was added to the culture system simultaneously with IL-4. As well, IFN-gamma did not exhibit cytotoxicity. These results suggest that IFN-gamma may have regulatory effects on IL-4 mediated B cell triggering.     

A case of limb-girdle muscular dystrophy with serum anti-nuclear antibody which led to a mistaken diagnosis of polymyositis

A 45-year-old woman had first been diagnosed with polymyositis because of the presence of focal necrosis, regeneration and inflammatory infiltration in the muscle fibers, and elevated creatinine phosphokinase levels. However, a pathological re-evaluation and family history led to the definite diagnosis of limb-girdle muscular dystrophy (MD). This case suggests that MD should be taken into consideration in the differential diagnosis of the inflammatory myopathies and genetic surveys including dystrophin molecule may be necessary if the condition manifests during or after adolescence, or when the family history is uninformative. In this case, the serum anti-nuclear antibody was positive, and it may represent the first time that ANA positivity has been found in limb-girdle MD.     

Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis

OBJECTIVE: To determine whether all-trans-retinoic acid (ATRA) improves the destruction of joints and the effect of cytokines on DBA/1J mice with collagen-induced arthritis (CIA). METHODS: Starting from the time of type II collagen injection, DBA/1J mice were injected intraperitoneally with PBS or 0.5 mg of ATRA 3 times per week for 35 days. The effects of treatment were monitored by determining arthritis and histological scores and measuring cellular proliferation, production of cytokines (IL-2, IL-10, IL-12, IL-6, IFN-gamma, and TNF-alpha) and IgG, and the expression of mRNAs for inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), and CXCR3. RESULTS: The arthritis score and incidence of arthritis were lower in the mice treated with ATRA than in those treated with PBS. Histopathologic evidence of joint damage was 34% lower, and the infiltrations of macrophages were reduced in the mice treated with ATRA compared with those treated with PBS. Type II collagen- and ConA-stimulated proliferation of spleen cells, the production of cytokines (IL-6, IL-12, and TNF-alpha), the serum levels of total IgG and IgG1 anti-collagen antibodies, and the expression of mRNAs for MCP-1 were significantly reduced in the mice treated with ATRA than in those treated with PBS. CONCLUSION: ATRA improved the clinical course and reduced the production of inflammatory cytokines, immunoglobulin, and chemokines in murine CIA. These data suggest that ATRA might be also effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.     

A case of Vibrio cholerae non-O1 septicemia with liver cirrhosis]

A case of Vibrio cholerae non-O1 septicemia is described in this paper. A 45-year-old male with a three year history of liver cirrhosis, was admitted to our division with hematemesis, abdominal pain, high fever and a loss of consciousness. Three days before onset of symptoms, he traveled to Ishigaki Island and ate a raw lobster. Two days after, his temperature rose to 39.7 degrees C and the blood pressure dropped to 36/- mmHg. By endoscopic examination, an ulcer was found in the stomach, and the bleeding was stopped by electrical coagulation. Blood culture showed growth of V. cholerae non-O1. The organism was found to be sensitive to OFLX, CZX, MINO, LMOX and CP. Although DIC, infections of fungus and MRSA occurred as complications, he recovered by adequate procedures. Subsequently, he left this division after eight weeks. There are various reports related to V. cholerae non-O1 septicemia in foreign countries, but few cases have been reported in Japan. And these cases had severe underlying diseases such as leukemia and liver cirrhosis.     

Massive bone reconstruction with heat‐treated bone graft loaded autologous bone marrow‐derived stromal cells and β‐tricalcium phosphate composites in canine models

Bone marrow‐derived stromal cells (BMSCs) contain mesenchymal stem cells that are capable of forming various mesenchymal tissues. We hypothesized that BMSCs and β‐tricalcium phosphate (β‐TCP) composites would promote the remodeling of large‐sized autologous devitalized bone grafts; therefore, the aim of this study was to evaluate the effects of the composites on the remodeling of autologous devitalized bone grafts. Autologous BMSCs cultured in culture medium containing dexamethasone (10^?7 M) were loaded into porous β‐TCP granules under low‐pressure. Theses BMSC/TCP composites were put into the bone marrow cavity of autologous heat‐treated bone (femoral diaphysis, 65‐mm long, 100°C, 30 min) and put back to the harvest site. In the contralateral side, β‐TCP without BMSC were used in the same manner as the opposite side as the control. Treatment with the BMSC/TCP composites resulted in a significant increase in thickness, bone mineral density, and matured bone volume of the cortical bone at the center of the graft compared to the control. Histological analysis showed matured regenerated bone in the BMSC loaded group. These results indicate that BMSC/TCP composites facilitated bone regeneration and maturation at the graft site of large‐sized devitalized bone. This method could potentially be applied for clinical use in the reconstruction of large bone defects such as those associated with bone tumors. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1308–1316, 2013