We measured soluble interleukin-2 receptor (sIL-2R) in serum samples from 57 patients with idiopathic thrombocytopenic purpura (ITP). The sIL-2R level was significantly increased in the ITP patients (481.3±378.5 U/ml) compared with controls (176.2±66.9 U/ml) (p<0.001), and was significantly higher in 8 patients positive for hepatitis C virus (HCV) antibody positive (1, 140.7±194.3 U/ml) than in 49 HCV-antibody negative patients (378.9±278.6 U/ml) (p<0.0001). There was also a significant difference between the HCV-antibody negative ITP patients and the controls (p<0.01). Elevated sIL-2R levels correlated with the CD 4/8 ratio (p<0.05), but not with the platelet count or the level of platelet-associated IgG. The increase of sIL-2R in ITP may be related to the immunological abnormalities underlying this disease.

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It has not been clarified that the anti-platelet antibodies are related to thrombocytopenia in systemic lupus erythematosus (SLE). We evaluated the presence of anti-platelet antibodies in sera from patients with SLE using immunoblot analysis. In this study, 19 of 65 cases (29.2%) in SLE had anti-platelet antibodies in their sera, wheras no anti-platelet antibodies were detected in 16 cases of rheumatoid arthritis, 16 cases of progressive systemic sclerosis, 2 cases of polymyositis-dermatomyositis and 10 healthy controls. Six bands of 200kDa, 140kDa, 120kDa, 95kDa, 80kDa and 65kDa molecular weight were detected using immunoblot analysis. The platelet antibodies to 95kDa and 80kDa proteins were frequently detected in 12.3% and 16.9% respectively of SLE. These 2 antibodies were adsorped with the platelet pellet derived from healthy person. Therefore, it was suggested that the antibodies to 90kDa and 80kDa platelet antigens were specific to platelet membrane protein. Although we could not find any correlation between clinical and laboratory manifestions of SLE and these platelet antibodies, these antiplatelet antibodies were specifically detected in sera from patients with SLE by immunoblot analysis.

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Raynaud's phenomenon is an important clinical manifestation in patients with systemic sclerosis (SSc). No effective therapy, however, has been established for this phenomenon. Beraprost sodium, a stable prostacycline (PGI₂) analogue, has been reported to improve hemorrheological impairment in patients with rheumatic diseases. In this study, we, therefore, examined the efficacy of beraprost sodium on Raynaud's phenomenon in 30 patients with SSc.
Sixty μg per day of beraprost sodium was found to be effective in 14 patients (47%) in the period of 15.0±12.5 weeks. Raynaud's phenomenon inpatients who responded to beraprost sodium was characterized by infrequent nail fold thrombosis and narrower hand areas affected by Raynaud's phenomenon, with mild secondary symptoms such as pain.
These results indicate that beraprost sodium is effective for mild forms of Raynaud's phenomenon in patients with SSc.

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To analyze the abnormality of natural killer (NK) cells in childhood hemophagocytic syndrome (HPS), we investigated the numbers, cytolytic functions of circulating NK cells, and responsiveness to cytokines by flow cytometry, ⁵¹Cr-releasing and single-cell assay in 13 patients. In the active phase, the relative number of CD 16⁺ cells was decreased in 3 patients. NK activity was depressed in 6 patients but normal in the remaining 7 in the active phase. Lymphokine-activated killer (LAK) activity showed the similar tendency. The responsiveness of NK cells to IFN-γ was absent, but that to IL-2 was normal in the active phase. Single-cell assay showed depressed maximal recycling capacity (MRC) and killing capacity values in the active phase and in remission phase, respectively. From these results, NK cells have such functional abnormalities as the absence of responsiveness to IFN-γ and depressed recycling capacity in the active phase of childhood HPS. Further, abnormality of killing capacity of NK cells may exist even in the remission phase.

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We here report fourteen patients diagnosed as adult-onset Still's disease (AOSD) in our hospital. Seven patients were males (mean age at onset was 26.6 years), and seven were females (30.6 years). All of the cases had spiking fever (>39°C) and joint symptoms. Hepatomegaly, splenomegaly, and lymphadenopathy were noted in 50% of the patients, respectively. Skin eruption was seen in twelve patients (85.7%). Among them, nine patients (64.3%) exhibited typical rash. Pleuritis or pericarditis was seen in one case each. Only one patient revealed neurological disorder. Abdominal pain was present in 50% of the cases. The ratio of occurrence of secondary amyloidosis was 14.3%. Four patients (28.6%) were diagnosed to have the apophyseal narrowing at the cervical spine (C2-C3). Two patients (14.3%) accompanied by Sjögren's syndrome were women over 40 years of age. The levels of soluble interleukin-2 receptor were significantly elevated in the sera obtained from seven patients with AOSD and four patients with juvenile-onset Still's disease, compared with normal controls. It seems to support the notion that immunopathologic processes via T cell activation play an important role in the pathogenesis of AOSD.

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Liver disease in 193 patients (17 male and 176 female) with systemic lupus erythematosus (SLE) at Kawasaki Municipal Hospital were analyzed. Abnormal transaminase levels were found in 78 case (40.4%). Among them, there were 35 patients whose liver disease were identified. There were 12 patients whom no cause could be found other than SLE. Other liver disease were as follows: fatty liver in 9 cases, virus infection in 5 cases, gall stone and/or cholecystitis in 3 cases, drug allergy in 2 cases, autoimmune hepatitis 2 cases, primary biliary cirrhoses in 1 case. Liver disease with systemic lupus erythematosus was frequentry, but there was no severe case.

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We examined proliferation of natural killer (NK) cells in 10 day mixed culture of peripheral blood mononuclear cells (PBMC) from healthy subjects with irradiated bone marrow mononuclear cells (BMMC) with multiple myeloma. In culture, NK cells increased with 9.5-fold. However, no increase was observed in T cells. The NK cell proliferating activity of PBMC stimulated with BMMC was higher than that of IL-2. NK cells at a purity of 90% or higher purity were collected from 10 day culture. Proliferation of these NK cells was stimulated by the addition of IL-2 but was suppressed by the addition of antibody coated erythrocyte (EA). IFN-γ production was negligible in cultures of these NK cells alone but was marked in cultures with EA stimulate IFN-γ production. Next, the NK cell obtained as above showed marked NK activity against K 562 cells, and this activity was further enhanced by the addition of IL-2. Also, While NK cells, these NK cells had some activity against Daudi cells and it was enhanced by the addition of IL-2. These results also suggest the presence of unknown cytokines with NK cell proliferating activities in the bone marrow of patients with multiple myeloma.

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A fifty-six-year old man complained of arthralgia and swelling of both feet, morning stiffness in both hands and finger joints in March 1987, and was treated with non-steroidal anti-inflammatory agents at another hospital. He has been treated for chronic myelogenous leukemia (CML) since May 1990. He was admitted to our hospital in March 1991 because of worsening of his multiple arthralgias, and a diagnosis of rheumatoid arthritis (RA) (Stage I, Class 2) was made on the basis of gait disturbance, arthralgia persisting for more than 6 weeks, the presence of subcutaneous nodules and X-ray findings. CML was confirmed by peripheral blood and bone marrow findings and the presence of the Philadelphia chromosome and bcr gene rearrangement. High fever and dyspnea developed suddenly 3 days after administration of interferon in May 1991. In addition to pneumonia, a leucostasis was suspected and he was treated with high dose steroids and antibiotics. After improvement, the steroids were tapered and he was discharged from hospital in July 1991.

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We report a sixty-year-old woman with transverse myelitis who had suffered from rheumatoid arthritis since age of 52. She was admitted to our department because of muscle weakness and painful tonic spasm in the bilateral lower extremities, sensory disturbance below the mamillary level and bladder disturbance. She had sicca symptoms. As a result of sialography, Sjögren's syndrome was diagnosed. Antineuronal antibody was found in the sera of the patient. She had no symptom of systemic vasculitis. Lupus anticoagulant and anticaldiolipin antibody were negative. The pathogenesis of transverse myelitis in rheumatic disease is still uncertain. Vasculitis and the immunological reaction of antineuronal antibody have been suggested as possible causes. This report suggests the influence of direct immunological reaction on the central nervous system.

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A 22-year-old woman, who had been diagnosed as having rheumatoid arthritis (RA) 2 years before, was admitted to our hospital complaining of watery diarrhea (several times/day). She had been treated with low dose prednisolone (PSL) and auranofin in out-patient clinic. On admission, laboratory data showed moderate proteinuria (0.3g/day) and positive CRP (2.7mg/dl). Although the activity of RA was controlled by the administration of low dose methotrexate (7.5mg/week) in addition to PSL, watery diarrhea and proteinuria did not improve.
The biopsy of the stomach, rectum and kidney revealed the deposition of AA type amyloid protein, resulting in the diagnosis of secondary amyloidosis. Secondary amyloidosis has been reported as one of the common complications in RA patients, especially in old patients with a long history of RA. To our knowledge, however, there have been few reported cases who developed secondary amyloidosis so early during the course of RA as our case. We should be careful for the development of secondary amyloidosis even in young RA patients with short history of RA, when the disease is active.

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This case involves a 41-year-old women with SLE. The patient began having symptoms of arthralgia in 1978 and developed fever, pleuritis and lupus psychosis in 1986. Laboratory exams showed positive antinuclear-antibody, LE-cell phenomenon, hypocomplementemia and lupus anticoagulant. Echo cardiography demonstrated mitral regurgitation and stenosis. She was treated with 50mg of prednisolone and these manifestations subsided. In 1989, she developed dyspnea on exertion and echo cardiography revealed severe mitral stenosis. Pulmonary infarction was detected by MAA lung scintigraphy. At this time, she was diagnosed as SLE associated with antiphospholipid syndrome (APS). A mitral valvular replacement operation was performed in 1991. Pathological studies of mitral valve demonstrated Libman Sacks endocarditis. APS is known occasionally to complicate with leftsided valvular diseases, mitral stenosis is quite rare in both SLE and APS. This patient reveals a rare case of SLE associated with APS and mitral stenosis. It is suggested that this patient developed mitral stenosis with Libman Sacks endocarditis, associated with the presence of antibody against phospholipids.

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Our report concerns a 53 year-old woman with pure red-cell aplasia (PRCA) accompanied by neutropenia. In July 1992, she experienced palpitations and came to our hospital. A peripheral blood examination demonstrated severe anemia and neutropenia, and an analysis of bone marrow cells revealed a marked decrease in the erythroid series. She was therefore diagnosed as PRCA. Sixteen percent of her peripheral lymphocytes had azur granules, which were considered to be a T-cell lineage based on surface marker analysis. However, gene analysis of T-cell receptors indicated no clonality. Administration of prednisolone (PSL) improved the subject's neutropenia but not her anemia. However, administration of cyclophosphamide (CPM) was effective in reducing the granular lymphocyte count, and finally improved the anemia. In this case, the granular lymphocytes presumably participated in the pathogenesis of anemia and neutropenia. While PSL did not yield sufficient effects on anemia and neutropenia, CPM was effective, suggesting that each drug may have different effects on these disorders.

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A woman of 79 years was admitted to our hospital because of headache and high erythrocyte sedimentation rate (ESR). Temporal artery biopsy demonstrated giant cell arteritis and nonsteroidal antiinflammatory drugs were effective. Another woman of 69 years was admitted because of headache, high ESR, and polymyalgia. Temporal arteritis (TA) with polymyalgia rheumatica (PMR) was established in biopsy of the temporal artery, and steroid therapy was effective. In our hospital, a third patient of 81 years was also suffering from TA with PMR, but temporal artery biopsy was not performed. Those three cases were followed for several years after the diagnosis of TA. Two years later, cancer in cervix of uterus was diagnosed in first case, and acute myelogenous leukemia in second case. However, such symptoms were not observed in third case. These findings and recently described reports suggest that the patients with biopsy-proven TA may have an increased risk of developing malignancy.

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A 57-year-old man was admitted because of hypergammaglobulinemia which was initially pointed out by annual complete physical examination. No significant abnormal findings were observed except polyclonal hypergammaglobulinemia at that time (IgG; 2, 662mg/dl, IgA; 422mg/dl). Seven months later, he has progressed to show thrombocytopenia. The laboratory data showing the reduction of peripheral CD 4-positive T cells (CD 4; 0.2×10⁹/l, CD 4/8 ratio; 0.19) and positive serum HIV antibody revealed that his hypergammaglobulinemia and thrombocytopenia were resulted from HIV infection. The peripheral platelet count decreased to 28×10⁹/l at minimal point, however, it recovered to 160×10⁹/l within 7 months without treatment. His good performance status has been still maintained over 4 years. His whole clinical course suggests that there is no significant correlation between peripheral platelet counts, serum gammaglobulin levels or the amounts of PAIgG in this case. This case proposes that we should also consider a possibility of HIV infection for the patients showing hypergammaglobulinemia.

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A 64 year-old woman with rheumatoid arthritis was admitted to our hospital because of general fatigue. She noticed polyarthralgia 8 months prior to the admission and diagnosis of rheumatoid arthritis was made. Administration of salazosulfapyridine (1.0g/day) was started 6 months before the admission. Complete remission of rheumatoid arthritis was obtained in 2 months and blood cell counts showed normal values at that time.
The results of laboratory tests included hemoglobin; 8.6g/dl, white blood cell count; 1, 900/mm³ with a differential of 19% neutrophils, 77% lymphocytes, and 4% moeocytes; platelets were 21, 000/mm³. A bone marrow aspiration and biopsy were performed. There were reduced numbers of myelocytes, erythroblasts, and megakaryocytes indicating aplastic anemia. Salazosulfapyridine was discontinued. Prednisolone, anabolic steroid and granulocyte-colony stimulating factor (G-CSF) were administrated. In spite of these therapy, recovery of peripheral blood cell counts have not been observed and supporting therapy including red cell and platelets transfusion have been continued.
To our knowledge, this is the first case report which describes occurrence of aplastic anemia in patients with rheumatoid arthritistreated by salazosulfapyridine.

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Here we report a case of primary Sjören's syndrome with hilar lymphadenopathy, interstitial pneumonitis and interstitial tubulo-nephritis. A 60-year old man was admitted to our hospital in May 1993 because of general fatigue and fever.
He was noted to have hypergammaglobulinemia and had positive antibodies to nuclear antigens since 1990 in the absence of clinical manifestations. Since 9 months before admission, he presented with general fatigue, low grade fever and uveitis.
On admission, chest X-ray and CT scan showed bilateral hilar lymphadenopathy and interstitial pneumonitis. The negative results for both serum angiotensin converting enzyme and histological findings of the cervical lymph node and the lung excluded the diagnosis of sarcoidosis. Serological examination exhibited marked elevation of polyclonal IgG level and anti-nuclear antibody, but neither anti-SS-A (Ro) nor anti-SS-B (La) antibody was detected. He did not have symptoms of xerophthalmia and xerostomia. Keratoconjunctivitis sicca was diagnosed by positive Schirmer's and rose bengal tests. His labial gland biopsy demonstrated severe mononuclear cell infiltration around the ducts. MRI findings of the parotid glands revealed heterogenous and dotted high signal intensity similar to those in fat tissues in the T 1-and T 2-weighted images. These findings depicted that bilateral parotid gland was extensively destructed and was replaced by lipid tissue. Renal biopsy showed interstitial tubulo-nephritis. Ort the basis of the above findings, he was diagnosed to have primary Sjögren's syndrome and uveitis. Therefore, MR image of the parotid gland is considered to be a noninvasive and useful method for diagnosis of Sjögren's syndrome.

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