Complement split products C3d in the plasma taken serially from the patients suffering from SLE in active stage were measured using anti-human C3d coated plate and peroxidase labelled anti-human C3. The titers of C3d were compared with those of CH50, C3 protein and immune complexes.
Mean O. D. values (0.260±0.091) of C3d of SLE patients were higher than that (0.210±0.104) of healthy subjects. In plasma of SLE patients, C3d levels and serum-CH50 correlated inversely (r=-0.509, P<0.05). Moreover, C3d levels (0.280±0.098) at the stage with high titers of immune complexes more than 20μg/ml were significantly higher than that (0.191±0.063) of less than 20μg/ml (P<0.05). Along the recovery of the disease activity of SLE patients, serum levels of various components improved in order of C3d, C3, immune complex and lastly CH50.
The present studies would suggest that complement consumption and split could be related to immune complexes. Therefore, the measurement of C3d in plasma taken serially from SLE seemed to be a useful marker to evaluate the activation of complement in vivo.

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Dendritic cells (DC) were successfully isolated from human peripheral blood and investigated for cluster formation by co-culturing them with autologous T cells at 37°C.
Cluster formation was recognized in the presense of anti-CD4, anti-OKDR antibody and γ-interferon (IFN). However, the proliferative response of clusters as measured by ³H-thymidine incorporation was depressed in a dose-dependent manner in the presense of anti-CD4 and anti-OKDR antibody. On the other hand, non-clustered cells showed slight ³H-thymidine incorporation in the presense or absense of anti-CD4 and anti-OKDR antibody. The proliferative response of clusters was augmented by pretreating DC with interleukin 1 (IL-1) and depressed by pretreatment with γ-IFN.
These results suggested that IL-1 has a stimulatory effect on the proliferative reponse of the cluster while anti-CD4, anti-OKDR antibody and γ-IFN have an inhibitory effect, even though these factors exhibited no effect on cluster formation.

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A preliminary study of recombinant human interleukin 2 therapy was made in 8 patients with chronic hepatitis B. They received 250 to 1, 000 units per day of interleukin 2 for 28 consecutive days. Fever, fatigue, and anorexia were the major side effects, although all of them were resolved after interleukin 2 administration was discontinued. Serum deoxyribonucleic acid (DNA) polymerase activity decreased in all patients during the administration of interleukin 2. There was an abrupt rise in serum alanine aminotransferase level associated with a fall in serum DNA polymerase level in 5 of the patients. One patient had sustained losses of hepatitis B e antigen and DNA polymerase. Recombinant interleukin 2 therapy may be of benefit in some hepatitis B virus carriers, although further development of this approach and additional patient follow-ups are required.

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It has been reported that the active form of vitamin D3, 1, 25 (OH)₂D₃(VD3), acts on activated T cells, especially on CD4 cells, and consequently suppresses DNA synthesis and the helper function. On the other hand, the effect of VD3 on CD8 cells is still unclear. We previously reported the suppressive effect of VD3 on both functions of CD4 and CD8 cells against immunoglobulin production in B cells. However, another report contracted our results on CD8 cells so we desired further information to define the effect of VD3 on CD8 cells compared to that on CD4 cells.
We assessed the DNA synthesis, interleukin 2 (IL 2) production and surface membrane antigen of CD8 cells as compared with those on CD4 cells. VD3 suppressed DNA synthesis of PWM-stimulated CD8 cells, as well as those of PWM-stimulated CD4 cells, in a dose-dependent manner. The DNA synthesis and IL 2 production of PHA-stimulated CD8 cells and CD4 cells were also suppressed by VD3 in a dose-dependent manner. These suppressive effect of VD3 were not observed on both subsets of cells unstimulated with mitogen. The expression of the IL 2 receptor on PHA-stimulated CD4 and CD8 cells was slightly suppressed at the middle or late phases of the culture. However, at the early phase of the culture, VD3 did not suppress the expression of the IL 2 receptor on both cells. In addition, VD3 failed to suppress DNA synthesis in CD4 and CD8 cells when cultured with IL 2, suggesting that VD3 intrinsically has no effect on IL 2-receptor expression and that the IL 2-receptor expressed in the culture with VD3 is functionally intact. The expression of the transferrin receptor on PHA-stimulated CD4 and CD8 cells decreased with the addition of VD3. Furthermore, this report states that VD3 suppressed the expression of Ia antigen on CD4 and CD8 cells, implying that, with reduced IL 2 production and DNA synthesis, this could be one possible cause of the deterioration of helper or suppressor activity in CD4 and CD8 cells by VD3.
Taken together, these results are reasonably in accord with our previous report, indicating that VD3 acts not specifically on CD4 cells, but on both CD4 and CD8 cells. Probably VD3 suppresses functions of CD4 and CD8 cells, via VD3 receptor, when activated and entered into a certain proliferative state. Thus our results suggest that, in the immune system in vivo, VD3 might play an important role in negative feedback regulation.

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Ciclosporin has great immunosuppressive potency and it has become the immunosuppressive agent of first choice in most transplant centers. But its therapeutic index is very narrow, the individual therapeutic response and the bioavailability are both very variable. Therefore, regular monitoring of ciclosporin blood level is required.
Ciclosporin is chiefly metabolised by cytochrome p-450 in liver. So, in liver transplantation, ischemic damage, surgical complications and graft rejection are direct and severe to the most important organ of ciclosporin metabolism. The optimal use of ciclosporin is more difficult, and the study of ciclosporin metabolism is very important issue.
The effect of ischemic liver damage on ciclosporin metabolism in dogs was examined. Liver ischemia was made by total vascular occulusion of porta hepatica, and the ciclosporin concentration in whole blood and in bile were measured by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA).
The concentration of ciclosporin in whole blood study increased only a little, also increased in bile study, but the amount of ciclosporin excretion in bile decreased with ischemic damage. RIA was not efficient method to measure ciclosporin metabolites and more specific method such as HPLC should be used.
Three peakes on the chromatograph of bile samples were successfully quantitated. These are probably ciclosporin metabolites (M1, M17 and M21). The concentration and the biliary excretion of two peaks (M17 and M1: hydroxylated) markedly increased and those of one peak (M21: N-demethylated) markedly decreased. Possibly the severerity of ischemic damage is not equal to each metabolic pathway.

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When heat-killed Propionibacterium acnes (P. acnes) was intravenously injected into mice, a remarkable infiltration of mononuclear cells, mainly macrophages, in the liver tissue was observed a week later, and when lipopolysaccharide (LPS) was additionally injected, massive hepatic cell necrosis was induced. In order to clarify the mechanism by which P. acnes caused the infiltration of mononuclear cells, ¹⁴C-labeled P. acnes was intravenously injected into mice, and its distribution among the organs was studied. In addition, various fractions of P. acnes were injected into mice, and their effects on the infiltration of mononuclear cells were examined. As a result, ¹⁴C-labeled P. acnes remained for a longer period of time in the liver compared to be lung, kidney and spleen. Furthermore, the chloroform insoluble fraction of the P. acnes cell wall caused the infiltration of mononuclear cells into the liver tissue, and massive hepatic cell necrosis was subsequently induced in these mice by the intravenous injection of LPS.

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Human T-cell lymphotropic virus type 1 (HTLV-I) has been associated originally with adult T-cell leukemia (ATL). It is thought to be transmitted by sexual contact, from mother to child by milk, and by transfusion of infected blood. We measured anti-HTLV-I antibodies (particle agglutination; PA, Western blotting; Wb), and IgG subclasses (IgGs.), β₂-microglobulin (β₂-m), and fibronectin (FN) in sera from 5 cases with leukemia that anti-HTLV-I antibody changed from seronegative to positive by blood transfusion and studied these course. The results were following;
1) In serum IgGs., IgG1 and IgG3 levels increased transiently or continuously compared with the blood transfusion before.
2) Serum β₂-m increased transiently at PA positive conversion. Moreover, serum FN decreased transiently at the same phase.
3) PA titer changed to seropositive within about one month after the blood transfusion.
4) By Wb, the IgM type antibodies to p19, p24 and p53 were expressed at the begining, and switched subsequently to the IgG type antibodies.
5) These parameters are considered to be important in order to clarify the early response in the host defence mechanisms to HTLV-I infection.

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The effector cell function and immunological phenotype of peripheral blood lymphocytes (PBL) and cultured PBL in the presence of rIL 2 with or without rIFNγ for 14 days were investigated in 20 patients with advanced gastric carcinoma (10 resectable and 10 nonresectable cases).
PBL cultured with HL 2 in experimental groups acquired a higher cytolytic activities against K 562 and Daudi cells detected even at lower effector/target cell ratio as compared with that of PBL. However, rIL 2-activated PBL obtained from patients with nonresectable cancer showed a siginificantly decreased lytic activities as compared with those of patients with resectable cancer and normal healthy controls (p<0.05). rlL 2-activated PBL (LAK cells) were analyzed to investigate the phenotypic characterization by two-color flow cytometry. The LAK cells from patients showed markedly increased proportion of CD4⁺Leu 8^- cells which were believed as helper T cells, and decreased proportion of CD8⁺CD11^- cells which were considered as killer T cells. Thus, a more likely possibility based on the data presented here is that CD4⁺Leu 8^- cells from healthy donors and patients might be mainly active as LAK-effector cells.
Depressed LAK cell activities in patients with nonresectable carcinoma were restored tonormal level by additional cultivation of exogeneous rIFNγ. However, there was not augmented phenomenon of LAK cell activities with rIL 2 plus rIFNγ in normal healthy controls and patients with resectable carcinoma. The augmented LAK cell activities by rIL 2 with rIFNγ were accompanied with increase in the proportion of CD8⁺CD11^- cells and Leu 7⁺CD16^- cells, but not CD4⁺Leu 8^- cells. Thus, cell population responsible for augmented LAK cell activities showed a phenotype of CD8⁺CD11^- and Leu 7⁺CD16^-. The results suggest that LAK-effector cells are heterogeneous nature with respect to immunological phenotype.

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Anti-idiotypic (anti-Id) antibody to anti-DNA antibody in the serum of patients with systemic lupus erythematosus (SLE) was studied. Thirty-five samples from 11 patients with SLE were tested for anti-Id antibody activity by using the inhibition of standard anti-DNA antibody activity. Anti-DNA antibody and anti-Id antibody to anti-DNA antibody were measured with ELISA in 25 samples and with Farr's assay in 14 samples.
It was suggested that there were two types of anti-idiotypic antibodies: the one was to anti-ssDNA antibody or anti-DNA antibody with low avidity and the other was to anti-dsDNA antibody or anti-DNA anti-body with high avidity.
There were 12 samples without anti-idiotypic activity to anti-DNA antibody. Five of 12 samples were accompanied with high titer of anti-DNA antibody, and the other 7 samples were not. These 7 samples without high titer of anti-DNA antibody were all associated with central nervous system lupus (CNS lupus). The correlationship between CNS lupus and anti-idiotypic antibody activity to anti-DNA antibody was suggested.

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We experienced a case of carcinoembryonic antigen (CEA)-producing lung cancer associated with polyarteritis nodosa (PN). A 62-year-old man admitted to the Shimane Medical University Hospital because of cough, sputum and fatigability. He was diagnosed as having pulmonary fibrosis and squamous cell carcinoma in the right hilar region. Serum CEA was elevated to 200 ng/ml. He underwent subtotal pneumonectomy of right lung. He had noticed motor weakness of extremities since before the operation. Fever, diarrhea and pleural effusion continued after the operation, although antibiotics were administered. Skin ulcer then occurred on the lower legs and sensory disturbance of extremities appeared. Laboratory examinations revealed elevated erythrocyte sedimentation rate, hyper-gammaglobulinemia, and positive C reactive protein. Auto-antibodies, cryoglobulin and hepatitis B antigen were all negative. Serum complements such as CH₅₀, C₃ and C₄ were decreased and circulating immune complexes were detected by C_1q, precipitation method. Muscle biopsy revealed necrotizing vasculitis of PN type. Using peroxidase-antiperoxidase method, CEA present in the affected vessel walls as well as in the cancerous tissue of the lung was demonstrated. The deposition of IgG was also observed in the affected vessel walls, suggesting a role of the immune complexes in the development of PN in this case. Prednisolone and cyclophosphamide were administered with temporary effect but the patient died of metastic liver cancer two months later. This case provided possible evidence that cancer-associated antigens and their immune complexes could play crucial role in the pathogenesis of PN.

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Although pleuro-pulmonary involvement commonly occurs in systemic lupus erythematosus (SLE), pulmonary hypertension is a rare condition documented in patients with SLE. Improvement of prognosis was achieved by therapeutic progress in patients with SLE. However pulmonary hypertension is still a serious complication, which often results in sudden death. Diagnosis of pulmonary hypertension in early stage is essential for subsequent successful treatment. We describe a woman with SLE in whom pulmonary hypertension developed insidiously during over four years. We noted that electrocardiogram was helpful for earlier detection of pulmonary hypertension. The treatment of pulmonary hypertension is generally unsatisfactory, but various vasodilators are reported to be helpful. In our case, nitroglycerin and prazosin had an acute effect for the improvement of pulmonary hypertension in addition to the treatment with prednisolone.

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A 26-year-old female patient of mixed connective tissue disease (MCTD) associated with urticarial vasculitis was reported here. Early symptoms of the case were Raynaud's phenomenon, sausage fingers, slight fever, facial eruption and abnormal high levels of CPK 401 U/ml and anti-ENA antibody (312, 500) in February 1978.
While she had been treated with 10mg prednisolone a day, she noticed systemic urticarialike eruption associated with hypocomplementemia in September 1984. She was readmitted for further examination of skin eruptions. Skin biopsy findings showed the leucocytoclastic vasculitis.
Then 60mg prednisolone a day could control urticarial vasculitis for the first month.
It is well known that urticarial vasculitis is usually complicated with systemic lupus erythematosus, but urticarial vasculitis would be scarcely associated with MCTD. High titer of anti-RNP antibody has been suggested for the significant pathogenesis. As the case present here was not clinically active, more detailed studies are required to know the pathogenesis of coexistence of urticarial vasculitis and MCTD.

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The author experienced a case of panniculitis accompanied by OKT 4 epitope deficiency. The patient was a 47-year-old female. Panniculitis was found in the epigastrium, and it was removed and a skin transplantation operation was performed on the area. However, an ulcer formed on that area. Clinical tests revealed leucocytopenia and hyper-gamma globulinemia. Studies using a monoclonal antibody as a peripheral blood T lymphocyte surface marker revealed OKT 4 antigen deficiency. Biopsy of ulcerated skin revealed lymphocyte infiltration in the periphery of adipose tissue and blood vessels. The patient was therefore diagnosed as a case of skin ulcer accompanying vasculitis. When steroid therapy was initiated, juvenescence reactions due to PHA stimulation, which showed low values at the beginning, improved, and there was a tendency for the skin ulcer to heal. The present case is different from those reported in many clinicians' papers, in that OKT 4 deficiency was sccompanied by lymphocyte dysfunction. This is why the author regards it as an interesting case.

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A 52 year old man with Behcet disease complicated with mononeuritis multiplex is reported. Having been suffering from Behçet disease without uveitis for 15 years, he was admitted to our hospital because of pain and hypesthesia of fingers with an aggravation of inflammatory symptoms. Muscle weakness and hypesthesia were observed in distal parts of the four extremities, but no abnormality was found in cranial nerves or central nervous system. EMG examination revealed not only neurogenic changes of distal muscles but also reduced nerve conduction velocity of peripheral nerves. Skin temperature of finger tips was demonstrated to be decreased by a thermographic examination, although his large arteries and veins seemed intact on an RI angiography. Biopsies of sural nerve and sural muscle revealed mononeuritis multiplex due to vasculitis of small-sized arteries. After treatments with NSAIDs, colchicine and prostaglandin E₁, the general inflammatory symptoms and pains of the fingers were reduced with an improvement of the peripheral neuropathy.
This case shows that Behçet disease can be associated with peripheral neuropathy without any other involvement of nervous system. Moreover, vasculitis of small arteries, which is commonly observed in skin or intestinal lesions of this disease, can be a cause of the peripheral neuropathy.

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The immunological study on a case of Waldenström's macroglobulinemia with the elevation of suppressor T cell activity is presented.
A 73-year-old male was admitted to Ehime University Hospital, because of general malaise and low grade fever. Hematological examination showed pancytopenia and myelogram revealed an increase of mature B cells. Serum immunoelectrophoresis disclosed a marked increase of the monoclonal IgM. A diagnosis of primary macroglobulinemia was made on the basis of these findings.
Two color analysis of peripheral blood lymphocytes revealed the excess of CD3⁺, CD8⁺, CD11⁺ and Ia⁺ lymphocytes that were supposed activated suppressor T cells. The effects of patient's T cells on PWM-induced polyclonal immunoglobulin (Ig) production by B cells were examined. The patient's CD8⁺ T cells showed marked suppressor activity for Ig production by B cells from a normal individual. On the other hand, the amount of Ig secreted by the coculture of patient's B cells and normal T cells was not decreased.
The results of these phenotypic and functional studies suggested that the impaired production of normal Ig in this case was due to the activated suppressor T cells.

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