To identify protein biomarkers linking to disease activity and treatment responses of patients with rheumatoid arthritis (RA), proteomic study using mass spectrometric analysis of plasma proteins was performed. Proteomic profiling technologies can simultaneously resolve and analyze multiple proteins in plasma. Evaluation of multiple proteins of the plasma will be essential to discover protein biomarkers. In this study, we used protein chip surface enhanced laser desorption/ionization time of flight mass spectrometry approach (SELDI-TOF MS). Through differential profiling of plasma proteins, we selected two prospective candidate biomarkers. One mass spectrometric peak distinguished patients with RA from healthy controls was transthyretin (TTR) and the other distinguished inactive patients with RA from patients with active RA was Serum Amyloid A (SAA). This study demonstrates that proteomic profiling using mass spectrometry of plasma greatly facilitates global discovery and verify clinically relevant sets of disease biomarker directly links to disease activity and treatment responses.

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  Many autoantibodies associated with nucleic acids are found in autoimmune diseases, and are important for analyzing pathophysiologic mechanisms. Toll-like receptors (TLRs) are receptor molecules for innate immunity and some of them recognize nucleic acids. Nucleic acids in autoantigens may stimulate TLR and activate antigen presenting cells as adjuvants. The Wa antigen was found as a transfer RNA (tRNA)-binding protein by RNA immunoprecipitation and identified as NEFA/Nucleobindin-2. Although the function of NEFA/Nucleobindin-2 is still not clear, it may be involved in secretion of proteins along with calcium metabolism and in protein translation by tRNA-binding ability.

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  In vasculitis, dermatologists generally examine two kinds of patient who present with small-vessel vasculitis as defined by the Chapel Hill Consensus Conference nomenclature, and idiopathic cutaneous polyarteritis nodosa (CPN). CPN is a vasculitis of small and medium-sized arteries within the skin that does not involve internal organs. When these patients visit my clinic, I characterize the cutaneous manifestations at initial presentation and assess the histopathological findings. In systemic antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, the characteristic cutaneous clinical pattern of microscopic polyangiitis is livedo reticularis, whereas Churg-Strauss syndrome presents as purpura and petechiae with paresthesias on the lower extremities. When a patient presents with nodules on the elbows with histological palisading granuloma, diagnosis of three ANCA-associated vasculitis including Wegener's granulomatosis should be considered. In immune-complex-mediated vasculitis, Henoch-Schönlein purpura (HSP) is characterized by palpable non-thrombocytopenic purpura on initial clinical presentation. These clinical cutaneous investigations in vasculitis patients may allow us to refine our earlier diagnostic strategies. On the other hand, histological examination in a cryoglobulinaemic vasculitis patient revealed microvascular thrombus and leucocytoclastic vasculitis in the dermis. From these findings, I speculated that the presence of thrombosis may be somehow related to the pathogenesis of the vasculitis process and investigated the association between vasculitis, especially immune-complex-mediated vasculitis, and antiphospholipid antibodies (Abs). Serum levels of IgA anticardiolipin antibody (aCL) are elevated in the initial active stage of adult HSP, suggesting that the IgA aCL may play some role in the onset of adult HSP. We also suggest that CPN could be dependently associated with the presence of anti-phosphatidylserine-prothrombin complex Abs.

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  Platelet-derived growth factor (PDGF) is a topic in the pathophysiology of various systemic rheumatic diseases. For example, autoantibody against PDGF receptor was identified in patients with systemic sclerosis. Imatinib mesylate has been well tolerable and widely used for chronic myeloid leukemia and gastrointestinal stromal tomor. Imatinib also inhibits the activation of c-Abl, which is a key downstream molecule of transforming growth factor-beta signaling, and PDGF receptors. Thus, imatinib effectively suppresses the activation and proliferation of fibroblasts, mesangial cells and smooth muscle cells. Therefore, imatinib may overcome the limitation of current therapeutic strategy with corticosteroids and immunosuppressive agents for refractory diseases.

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  The growing numerical gap between the number of patients and available human donor organs have led to a revival interest in xenotransplantation. This review will mainly focus on the clinical affairs of xenotransplantation and the project of producing the gene modified pigs.
  Trials, designed to overcome xenogenic rejection by the expression of human complement regulatory protein (CRP), such as DAF (CD55), on the pig organ and knocking out the α-Gal epitope(Galα1-3Galβ1-4GlcNAc-R), which is biosynthesized by the action of α1,3 galactosyltransferase (α1,3GT), were accomplished in several institutes, such as Harvard University, Pittsburgh University, Mayo Clinic, and BresaGen. We have also produced the [DAF(CD55)+GnT−III+a-Gal KO] pigs in last year.
  On the other hand, the clinical pig islets transplantation was done in many countries, such as Russia, Sweden, Mexico and China, until 2005. In addition, the new clinical trials of pig islets transplantation will be started in USA within three years.
  In addition, as the current studies in the xenotransplantation field, the strategies for the downregulation of the glycoantigen, complement activation, NK cell, and other immuno responces on the xenografts, are reviewed. The studies for the infectivity of porcine endogenous retrovirus (PERV) to human cells are also introduced.

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  To determine risk factors for pregnancy and fetal outcomes in patients with lupus nephritis during pregnancy and postpartum, 26 patients with 34 pregnancies between 1986 and 2004 were reviewed retrospectively. Of the 34 pregnancies, we observed 23(67.6%) live births at term, 5(14.7%) premature births, 2(5.9%) spontaneous abortions and 4(11.8%) artificial abortions. After exclusion of artificial abortions, live birth rate was 93.3%; it was not significantly difference versus 88.1% in 197 pregnancies without nephritis. But in pregnancies with active nephritis, there were an increased number of pre-term deliveries (57.1% vs. 4.8%). Frequency of flare was analyzed in 30 pregnancies with lupus nephritis by trimester and postpartum. In addition to 7 flares that occurred in the postpartum, 8 flares occurred during pregnancy (3[20%] in the first trimester, 3[20%] in the second trimester, 2[13%] in the third trimester). There was higher rate of flare compared to that 115 lupus patients with 129 pregnancies between 1986 and 2001 (50% vs. 22.5%). Renal flare in 29 pregnancies was 6(20.7%), three flares occurred in the first trimester, 3 in the second trimester. In the analysis of laboratory data of 28 pregnancies at onset of pregnancy, fetal gestational age significantly associate with proteinuria, plasma creatinine level and SLEDAI, fetal birth weight significantly associate with proteinuria and plasma creatinine level. Of the 34 pregnancies, 11 underwent renal biopsy prior to pregnancy, pregnancy and fetal outcomes were poorly in the class IV patients. In conclusion, pregnancy is safe for the majority of mothers if it is planned when lupus nephritis is quiescent.

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  We report a case of 58-year-old woman with a ruptured dissecting aneurysm of the middle colic artery (MCA). Her initial manifestation was sudden and severe right-sided abdominal pain, followed by hemorrhagic shock and acute anemia. Abdominal CT showed a right retroperitoneal hemorrhage. Emergency catheter angiography and therapeutic coil embolization of the middle colic artery were performed and micro aneurysms were enhanced in the jejunal branch. Immunological tests showed nothing abnormal. Follow-up angiography after 3 months showed that the micro aneurysms had disappeared. The patient was diagnosed as having segmental arterial mediolysis (SAM), because no definitive evidence of atherosclerosis and polyarteritis nodosa were observed. SAM is a rare disease of unknown etiology. The arterial lesions developing in elderly patients are characterized by segmental lysis of the abdominal splanchnic arteries resulting in aneurysms, and acute bleeding in a skip pattern. Multiple aneurysms and abdominal pain due to the rupture of these lesions in SAM resemble the clinical findings in polyarteritis nodosa. Differential diagnosis of the two diseases is important because steroid therapy is not beneficial for SAM.

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  A 14-year-old girl with aortitis syndrome in the early pre-pulseless phase was admitted to our hospital because of slight fever, neck bruit, asymmetrical blood pressure, stenosis or dilatation of the main branch arteries in aorta on chest computed tomography. Laboratory examination revealed a high level of C-reactive protein and an elevated erythrocyte sedimentation rate, as well as hypergammaglobulinemia, and ¹⁸F-FDG-PET revealed an accumulation of 18 fluorodeoxyglucose in the great vessels. She was first given pulse therapy with a combination of methylprednisolone and intravenous cyclophosphamide, and then maintenance therapy with oral prednisolone and azathioprine. All the abnormal laboratory parameters improved to normal levels within a month. We suggest that early diagnosis of aortitis syndrome may permit early treatment in the early pre-pulseless phase and could possibly prevent progression to the occlusive phase.

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