In hemodialysis using 3 types of dialysis membrane materials [regenerated cellulose (RC), cellulose triacetate (CTA), and polysulfone (PS)], activation of the complement, reduction of white blood cells, and variation of vitronectin (VN) were observed.
RC membrane caused a significant reduction of white blood cells and elevations of Bb and soluble membrane attack complex (S-MAC), indicating a strong activation of the alternative complement pathway. Especially, the increase of S-MAC persisted for a long time during hemodialysis. Because reduction of VN was transient, it was assumed that the S-MAC escaping removal by VN receptors might have persisted in the circulation. These findings suggested that S-MAC would become useful as an index for evaluating biocompatibility of various artificial organs including dialysis membranes.

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The role of anti-ssDNA and dsDNA antibody in preeclampsia were studied. Serum samples were taken from 38 pregnants with preeclampsia including 19 cases of severe type. Also, 26 normal pregnant women were studied as the control. Anti-ssDNA and dsDNA antibody were measured by enzyme-linked immunosorbent assay (ELISA). Anti-phospholipid antibody (APA), was measured by ELISA. Anti-dsDNA antibody was positive in 1 of the 38 preeclampsia. Anti-ssDNA antibody was positive in 15 out of the 38 cases (39.4%) in preeclampsia. Incidence of anti-ssDNA positive preeclampsia is related to it's severity of symptom as following: Six of 19 mild preeclampsia (26.3%) were positive. In severe cases, 10 of 19 (52.6%). However, the relationship between anti-ssDNA antibody and IUGR in preeclampsia, was not confirmed, although the antiphospholipid antibody was related to the IUGR.
From these results, we concluded that the autoantibody, such as anti-DNA antibody, might be produced in preeclampsia and the B cell activation might play a role of exaggeration of preeclampsia.

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In this study, we examined the effects of IL-10 and vIL-10 on the production of superoxide anion (O₂^-) and nitric oxide (NO) by human monocytes and mouse macrophages.
At an optimal concentration, human IL-10 (hIL-10) and vIL-10 significantly inhibited the production of interferon (IFN)-γ by stimulated human peripheral blood mononuclear cells (PBMNCs). They also efficiently inhibited the production of O₂^- by both unstimulated and IFN-γ-activated human monocytes. Mouse IL-10 (mIL-10) also significantly inhibited the production of NO by lipopolysaccharide (LPS) and IFN-γ-stimulated mouse peritoneal macrophages. Moreover, the production of O₂^- and NO was effectively suppressed whether the IL-10 was added before or together with the stimulus, indicating that this cytokine acts primarily at an early stage of monocyte/macrophage activation by IFN-γ and LPS. We also examined the effects of IL-4 and transforming growth factor (TGF)-β on the production of O₂^- and NO by human monocytes and mouse macrophages, and found that they significantly inhibited both the production of O₂^- by human monocytes and the production of NO by mouse macrophages. Moreover, a combination of any two of IL-10, IL-4 and TGF-β caused an additive effect on the inhibition of O₂^- production by human monocytes.
These results indicated that IL-10 suppresses monocyte/macrophage activation either indirectly via an inhibition of the synthesis of IFN-γ, a potent monocyte/macrophage activator, by PBMNCs, or directly via the deactivation of monocytes/macrophages. Moreover IL-10 may act in concert with IL-4 and TGF-β to suppress monocyte/macrophage activation in vivo.

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We established the system to detect superoxide produced by Epstein Barr virus lymphoblastoid cell line (EB-LCL). Superoxide production of EB-LCL was evaluated by measuring chemiluminescence (CL) enhanced with addition of horseradish peroxidase (HRP).
Using this system, we measured CL of EB-LCL established from 13 patients with chronic granulomatous disease (CGD) and 8 normal individuals. Significant elevation of CL was observed in all control EB-LCLs, however, no remarkable CL was seen in any patients' EB-LCLs. We examined the effect of recombinant human interferon gamma (rh-IFN-γ) and granulocyte colony stimulating factor (G-CSF) on CL of EB-LCL in vitro. With addition of rh-IFN-γ, CL of normal control EB-LCL was significantly enhanced (p<0.05), on the other hand, G-CSF was shown to have no effect. No significant CL was observed in any CGD patients' EB-LCLs even with addition of rh-IFN-γ or G-CSF.
It was suggested that superoxide produced by EB-LCL detected in this system was dependent on the same NADPH oxidase system which presents in phagocyte.

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The distribution and localization of collagen types were studied immunohistochemically in resected tissues obtained from gastric cancer patients. The expression of transforming growth factor (TGF)-α, TGF-β₁ and TGF-β₂ on cancer cells as well as the aggregation of T lymphocytes in the cancer tissue were also studied, in order to determine the differences between differentiated and undifferentiated type cancer. The interstitial tissues of differentiated type cancer showed intense staining for types I and III collagen, while those of undifferentiated type cancer showed intense staining for types I and III collagen, in addition to the stronger staining for types IV, V and VI collagen. Characteristically, type IV collagen was intensely stained in the interstitium in 18 of 20 undifferentiated type cancer (90%), but was stained in only one of 15 differentiated type cancer (6%). CD 3⁺ T lymphocytes were aggregated in the interstitial tissue of both the tumors, where the density of CD 4⁺ cells and the ratio of CD 4 to CD 8 were significantly higher in undifferentiated type cancer than in differentiated type cancer. TGF-α was detected in cancer cells in 80% of the differentiated cases and in 45% of the undifferentiated cases. The staining of TGF-β₁ was also detected in 80% of the undifferentiated cases, which was significantly higher than 47% in differentiated cases. There were no differences in the incidences of staining for TGF-β₂ between differentiated (33%) and undifferentiated type cancer (40%). These results suggest that there exist different mechanisms in the regulation of collagen production between differentiated and undifferentiated types of gastric cancer.

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We studied the effects of cytokines such as IL-1 α, IL-6 and TNFα, and lipopolysaccharide (LPS) on cultured human monocytes. Increased fibronectin (FN) production, as a indicator of the activation of monocytes, was observed with any cytokines or LPS stimulation those were added in the culture medium. These increased FN production by cytokines showed a dose dependent fashon, and 4 hours culture with these cytokines was enough to obtain the amount of FN measured with radioimmumoassay. The combination of sub-optimal dose of cytokines (IL-1 α+IL-6, IL-1 α+TNFα, IL-6+TNFα), that could not induce substantial amount of FN with any single cytokine, also could induce FN by cultured monocytes. The specificity of cytokines for the FN production by cultured monocytes was confirmed by the neutralization using monoclonal antibodies specific for each monokines. Northern blot analysis with cDNA specific for FN confirmed the expression of FN mRNA in cultured monocytes stimulated with cytokines or LPS.
Cytokine network plays an essential role for immune and inflammatory reaction, and FN has been shown to induce monokines through VLA-5 receptor on cultured monocytes. Our data suggests that monocytes may not always require high concentration of cytokines for the activation of monocytes in vitro, and that the synergistic action of low concentration of cytokines for the activation was enough for the progression of immune or inflammatory reaction.

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We determined islet cell cytoplasmic antibodies (ICA) using rat pancreatic sections as a test substrate substitutive for human pancreatic sections by indirect immunoflorescent technique. ICA were measured in sera from 58 patients with insulin-dependent diabetes mellitus (IDDM), 456 with non-insulin-dependent diabetes mellitus (NIDDM), 50 patients with autoimmune diseases, and 110 healthy controls. Seventeen of 58 patients with IDDM showed recent-onset (within 3 months). ICA were also measured in some samples using blood group 0 human pancreatic sections, and the ICA titers were compared with those measured using rat pancreatic sections.
The prevalence of ICA was 55.2% (32/58) in patients with IDDM, 1.5% (7/456) in those with NIDDM, 0% (0/50) in those with autoimmune diseases, and 0.9% (1/110) in the healthy controls. Of the 17 recent-onset IDDM ICA were positive in 14 (82.3%).
In comparative study of titers for ICA using rat pancreatic sections or human pancreatic sections, rat pancreatic sections yielded ICA titers as high as human pancreatic sections did.
These results demonstrate that ICA assay using rat pancreatic sections was diseasespecific, and that antigenicity of the substrate was favorable to ICA. Rat pancreas presents the advantage of greater availability, while providing an identical substrate for ICA.
In conclusions, rat pancreatic sections are useful substrate for detecting ICA.

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NK and LAK activities of a patient who recovered from bladder transitional cell carcinoma were determined. He was diagnosed in 1980 and operations, radiations and chemotherapies were repeated until 1986. Since 1987, a relapse has not been recognized, and he is now in a tumor free state. Recently, his very high NK and LAK activities were found. The percentage of CD 16⁺ in his peripheral blood lymphocytes (PBL) was 52.9%, the CD 4^-CD 8^-CD 16⁺ was 26.6% (17.5% and 12.1% in control, respectively). It seems likely that his tumor free condition may be related to these high killer activities. As a high number of CD 4^-CD 8^- cells were included in his PBL, it was possible to generate a CD 4^-CD 8^--LAK and compare it with the CD 8⁺-LAK. The CD 4^-CD 8^--LAK exhibited higher killer activity which was maintained for a long period of the culture, and a strong adherence property against the cultured tumor cells. Whereas, the CD 8⁺-LAK did not show such a high level of killer activity which decreased after two weeks into the culture. However, the CD 8⁺-LAK in this patient demonstrated higher killer activity against the auto-tumor cell line compared to what occurred with the control. A type of specific killing against auto-tumor cells may be contained in his CD 8⁺-LAK, although the MHC-restrictive killing was not confirmed. It remains unclear why the killer activities increased in this patient.

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A 71 year-old man with adult onset Still's disease was admitted to our hospital because of fever, sore throat, myalgia and macular nonpruritic salmon pink eruption. He was treated with prednisolone, 40mg daily and these symptoms disappeared. When the dose of prednisolone was reduced to 30mg daily, he began to notice fever. 5 days later he developed adult respiratory distress syndrome (ARDS). The dose of prednisolone was increased to 50mg daily and oxygen administration was started. All symptoms began to improve immediately and the dose of prednisolone was decreased to 40mg daily. 10 days later he noticed fever and skin rash. Laboratory investigation showed platelet counts of 69, 000/mm³, a ferritin of 37, 000ng/ml, and increased fibrinogen degradation product, indicating increased activity of adult onset Still's disease associated with disseminated intravascular coagulation (DIC). The dose of prednisolone was again increased to 60mg daily, and 100mg of nafamostat mesilate was administrated intravenously. All above symptoms associated with adult onset Still's disease and DIC disappeared. The dose of prednisolone was gradually decreased and the clinical course was uneventful with daily administration of 10mg of prednisolone.
Although there are a couple of case report which described the association of adult onset Still's disease with either ARDS or DIC, the association of adult onset Still's disease with both ARDS and DIC have not been reported yet.

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A 42-year-old woman presented in 1992 with Raynaud's phenomenon, polyarthralgia and morning stiffness and next year developed xerostomia and xerophthalmia. Investigations revealed 20mm/hr of ESR, positive test for RAPA (1:320), ANF (1:1280), anti-SS-A antibody and anti-Wa antibody, and positive Schirmer tear test. A biopsied specimen of minor salivary gland of lip showed lymphocytic infiltration around the ducts and fibrotic changes and a sialogram demonstrated diffuse dilatations of the peripheral ducts. Resulting from the data shown above, the diagnosis of Sjören's syndrome was made.
Anti-Wa antibody, which recognizes a 48kD tRNA associated protein was identified in serum from a patient with systemic sclerosis by Yamagata in 1985. So far the antibody has been specific for systemic sclerosis, because all of six patients with anti-Wa antibody previously reported were diagnosed as having systemic sclerosis. However, we here described the first case of Sjören's syndrome with anti-Wa antibody.

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A 68-year-old woman had been complained of xerostomia since she was 30 years old. Further symptoms of polyuria, polyposia and insomnia had been developed since she was 35 years old. The biopsy material from a minor salivary gland demonstrated the infiltration of lymphocytes into mesenchyme which was compatible with Sjören's syndrome. She admitted to our hospital because of myalgia in bilateral gastrocnemius and petechiae in both lower extremities in addition to the complaints described above. Complete blood cell counts on admission revealed hemoglobin 9.7g/dl, platelet count 12.5×10⁴/μl, and white blood cell count 3, 300/μl. Marked polyuria, polyposia (more than 5, 000ml/day, respectively) and low urine gravity (1.005) were observed, although the serum creatinine level showed normal value. Serologic examination showed that the elevation of total serum protein concentration (9.5g/dl) with marked elevation of serum IgG level (6, 190mg/dl). Her immunoglobulins contained cryoglobulin (cryocrit 20%), and immunoelectrophoresis demonstrated the existence of IgG-κ monoclonal protein. A positive anti-nuclear antibody at 1:320 dilution, a positive rheumatoid factor and a positive antibody to SS-A (Ro) were also observed. The serial studies of blood gas analysis could not demonstrated the presence of metabolic acidosis. Together with the result of elevated plasma antidiuretic hormone level and results of vasopressin test, Fishberg's concentrating test and the tests of the overload of NH₄Cl or bicarbonate, she was diagnosed Sjögren's syndrome with both diabetes insipidus and subclinical renal tubular acidosis. She was initially medicated with prednisolone (40mg/day, orally), then she was given six courses of intravenous cyclophosphamide (750mg/body/month). These treatments, however, did not change her complaints nor change the laboratory examination. It is generally accepted that interstitial nephritis induced by the infiltration of lymphocytes may contribute to the renal tubular acidosis and diabetes insipidus seen in Sjören's syndrome. Taking to the resistance of these treatments, the large amount of cryoglobulin in her serum might responsible for the pathogenesis of renal disorders as well as the infiltration of lymphocytes.

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Felty's syndrome is diagnosed when a patient shows both splenomegaly and leukocytopenia of various degree during the course of rheumatoid arthritis (RA). The accompanying immunologic abnormalities (e.g., antinuclear antibody, antiplatelet antibody, and hypocomplementemia) also characterize Felty's syndrome, but some authors may regard these abnormalities as a transitional form into overlap syndrome [RA+systemic lupus erythematosus (SLE)].
Here we reported a female case of Felty's syndrome who showed marked thrombocytopenia and severe hypocomplementemia. Thrombocytopenia had been refractory against several forms of therapies including high-dose methylprednisolone. Simultaneously, she had various autoantibodies (i.e., antiplatelet antibody, positive Coombs' test, antithyroglobulin antibody, antimicrosome antibody and anti-RNP antibody). Although she did not fulfill the ARA diagnostic criteria for SLE, the degree of thrombocytopenia as well as that of hypocomplementemia argued in favor of the overlap of SLE in this patient. Low-dose cyclosporin A (CsA) combined with small dose of prednisolone could increase both platelet count and level of complement. Notably, the titers of several autoantibodies dropped after CsA was started. These findings might suggest that CsA could normalize the underlying immunologic abnormalities in this patient. However, the disease activity of RA could not be decreased without a help of low-dose methotrexate.

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A 76-year-old man was admitted to Kisen hospital because of lumbago and chest pain. Laboratory examinations revealed a chronic renal failure with marked elevation of the serum BUN (48.8mg/dl) and creatinine levels (8.2mg/dl). The serum electrophoresis demonstrated a hypergammaglobulinemia with M peaks. An immunoelectrophoresis demonstrated monoclonal IgD-λ and IgG-κ proteins in the serum, and λ-type Bence Jones protein in the urine (0.4g/day). Bone marrow smears revealed an abnormal proliferation of atypical plasma cells (43%). A systemic X-ray examination of the skeletal system showed systemic osteoporosis without punched out lesion. The patient was diagnosed as having IgD-λ type multiple myeloma and IgG-κ type benign monoclonal gammopathy by quantifing concentration of two M proteins (1, 160mg/dl in IgD, 1, 179mg/dl in IgG, respectively). A combination chemotherapy with melphalan and prednisolone was administered monthly for multiple myeloma, and hemodyalysis for the renal failure was performed 3 times a week. A marked improvement of his laboratory findings including a diminution of the serum IgD-λ M-protein was obtained. Ort the other hand, IgG-κ M-protein level was unchanged. Two M-protein levels showed a different behavior after the combination chemotherapy. Although the patient died of congestive heart failure, the partial remission of multiple myeloma has been maintained for 16 months with chemotherapy.

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62-year old man who had small cell lung carcinoma (SCLC) with subacute sensory neuropathy had an antibody (IgM) recognizing the antigen on peripheral nerves. The antibody in the serum recognized cell surface antigen on small cell carcinoma cell lines and also reacted with peripheral nerves simultaneously, but not with central nervous system. Two months before admission, he felt difficulty in walking because of paresthesias in the extremities. He was found to have a tumor shadow in chest X-ray, and was diagnosed as SCLC by biopsy of right supraclavicular lymph node. Western blot analysis demonstrated that auto-antibody (IgM) in the serum recognizing the antigen on the neuronal axon with single band at 29kD. Pathogenesis of carcinomatous neuropathy is still unexplained, but the findings presented here have given rise to the possibility that anti-SCLC antibody may crossreact with neuronal antigen, primarily resulting in neuronal disorder.

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We describe an 8-year-old boy with CVID and chronic CMV infection. Although at onset he was diagnosed as IgA deficiency, 4 years after his clinical manifestations because compatible to CVID. During his clinical course he had suffered from various disorders as follows; AIHA, interstitial pneumonia, hemophagocytic syndrome, chronic gastroenterocolitis and so forth. At the age of 8 the PCR of CMV-DNA of biopsy specimen from colon, lung and bone marrow were confirmed to be positive. Hematological examinations revealed abnormal cellular immunity such as decreased CD 4/8 ratio with increased HLA-DR⁺CD 8⁺ T cell, decrease of absolute blood lymphocytes count and reduced responce of lymphocytes to blastogenetic agents. These findings brought us to diagnose him as having CVID complicated with chronic CMV infection. This case gives us some impact to speculate what role CMV infection plays in CVID, Whose etiology is unknown.

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We report a 20 year-old woman with hemophagocytic syndrome. In February 1993, she developed high fever, arthralgia, salmon-like pink eruption, leukocytosis and splenomegaly. She was diagnosed as adult Still's disease and successfully treated with intravenous immunoglobulin and oral prednisolone. In September 1993, she was re-admitted to our hospital complaining of general fatigue and low grade fever and treated with oral prednisolone at a daily dose of 15mg. On October 2, 1993, she suddenly developed high fever and salmon-like pink eruption on her leg followed by the marked increase of serum transaminase and LDH levels (GOT 3, 270IU/l, GPT 1, 880IU/l, LDH 5, 480IU/l) on October 7. Since hepatic failure progressed, we started methylprednisolone pulse therapy and plasmapheresis. However, because of the progression of pancytopenia caused by hemophagocytosis, the treatment with VP-16 was initiated. However, she died of DIC on November 2, 1993. Autopsy revealed submassive necrosis of the hepatocytes with moderate infiltration of histiocytes. She was retrospectively diagnosed as hemophagocytic syndrome whose manifestations are very similar to those in adult Still's disease and acute viral hepatitis.

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