Membraneous nephritis can be induced by cationized antigens. The method to detect antibodies to cationized antigens is needed to analyse the mechanism of onset of membraneous nephritis. Rabbits (IgG allotype is b 4) were injected with either cationized rabbit IgG (c-RbIgG) b 4 or b 9 allotype. They developed renal lesions in which complement and IgG deposited in granular form along basement membrane. Passive hemagglutination tests were successfully performed, without considering the interaction between positive and negative charge, to detect the antibodies to c-RbIgG. The titers of antibodies to c-RbIgG antibodies were higher in rabbits injected with c-RbIgGb 9 than with c-RbIgGb 4. Because rabbits injected with c-RbIgGb 9 also developed antibodies to RbIgGb 9, cationized antigens are considered to be strong immunogens.

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Changes in kinetics of blood coagulation and fibrinolysis factors, when assayed with endothelium by the venous occlusion (VO) test, were studied in patients with SLE and PSS, especially seeking any discrepancies between those with and without lupus anticoagulant (LA).
There was no significant difference in the blood concentration of plasminogen activator inhibitor-1 (PAI-1) between patient and control groups both before and after VO test. On the other hand the tissue plasminogen activator (tPA) in patient group showed a relatively smaller increment than in control group before versus after the test, and the Factor VIII related antigen (FVIIIR: Ag) in the former group was statistically higher than in control group both before and after the test (p<0.01). The tPA in LA positive patients was remarkably lower than in LA negative SLE patients and control group both before and after the test (p<0.01), but no significant difference was found in the FVIIIR: Ag between the two subpopulations at either monitoring.
These results suggest that the major causes of thrombosis frequently observed in patients with collagen diseases, especially in those with LA, could involve depressed production of tPA from the endothelium.

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Neopterin has been recently known as one of the new makers for activated cell-mediated immunity. We studied serum neopterin levels in 114 controls and 83 patients in childfood. Neopterin levels of serum were measured with radioimmunoassay. The group under one year age showed significantly higher serum neopterin levels than the group from the elder. Significantly higher serum neopterin levels were detected in sera of patients with acute bacterial infection, acute viral infection, subacute necrotizing lymphadenitis and active SLE. Particularly in subacute necrotizing lymphadenitis cases and SLE cases, neopterin represented a sensitive marker for the active stage. It seemed that measurement of serum neopterin levels are useful as indicators of these disease states.

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Properties of IL-1 inhibitor present in the urine of febrile patients were examined. The molecular weight of IL-1 inhibitor was estimated to be about 21 KD by high pressure liquid chromatography (HPLC). IL-1 inhibitor was inactivated by incubation at 56°C for 30min or treatment with acid at pH3.0, but its activity was not affected at pH5_??_11. It was also unaffected by treatment with neuraminidase.
IL-1 inhibitor suppressed not only thymocyte proliferation induced by IL-1 but also in vitro plaque forming cell (PFC) formation and the development of fever after intraperitoneal administration of IL-1 in mice. These data suggest that IL-1 inhibitor acts not only in vitro but also in vivo.

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Raynaud's phenomenon is easily affected by environmental temperature and the patient's own physical and emotional stress. In order to study the peripheral circulatory dynamics of such patients, we applied the vasoconstrictive stimuli by means of ice immersion and vasodilatory stimuli by means of topical nitroglycerin (NG) or an intravenous administration of prostaglandine E₁ in a lipid microsphere (LipoPGE₁). The digital temperature was monitored for a total of 170 minutes by an autonomic temperature monitoring system. The subjects consisted of 25 patients with Sjögren's syndrome, 8 with progressive systemic sclerosis, 6 with systemic lupus erythematosus, and 6 with other various connective tissue diseases, in addition to 5 with Raynaud's disease and another one with vibration disease. There were 7 control subjects. The digital temperature was automatically recorded by a core temperature monitor (Core Temp Model CTM-205, Thermo Co Ltd, Tokyo). The core temperature and surface temperature probes were attached to the left middle finger and the temperature was recorded for 20 minutes. The probes were then detached and both hands were immersed into an ice bath for one minute. After drying the hands the probes were reattached and the temperature was recorded for 60 minutes. Then, a 2% ointment of NG was rubbed on the surface of the fingers and hands or, alternatively, 5μg of LipoPGE₁ was injected intravenously. After recording the temperature for 30 minutes by the same method the hands were immersed in an ice bath and the temperature was monitored for another 60 minutes. Digital temperature patterns were categorized into 4 types based on the resting, cooling, and rewarming temperatures and recovery time patterns before and after treatment: normal (N), moderately improved (I), markedly improved (II), and exacerbation (III). In the patients treated with NG ointment, 37 (62.7%) out of 59 patients came under category I or II. In those treated with intravenous LipoPGE₁, 11 (57.9%) out of 19 patients came under categories I or II, while 9 patients (17.3%) out of the NG group and 5 patients (15.3%) out of the LipoPGE₁ group came under category III. These results suggest that continuous monitoring of the digital temperature to demonstrate the effects of vasoconstrictive and vasodilatory stimuli is a useful test because it is highly sensitive to monitoring these changes and it has a high reproducibility to evaluate the Raynaud's phenomenon. Additionally, topical NG as well as intravenous LipoPGE₁ treatment improved digital circulation in most patients. But for those patients who showed adverse effects, they should be treated cautiously by the oral administration of vasodilatory drugs.

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We generated human monoclonal immunoglobulins secreted by human-mouse heterohybridomas. When EB virus transformed B lymphoblastoid cells were used as fusion partner, IgM secreting heterohybridomas were generated. After culturing cell lines for longer time, hybridization produced more clones. When pokeweed mitogen stimulated lymphoblastoid cells were used as fusion partner, IgM, IgG, and IgA secreting heterohybridomas were generated. These human monoclonal immunoglobulins library can be useful for analysis of human immunoglobulin allotypes.

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The quality of life (QOL) in patients with systemic sclerosis (SSc) was studied.
Thirty-eight patients with SSc answered a questionnaire or were interviewed about their QOL. Four main factors, physical, social, psychological, and economic factors, were evaluated.
The functional disability index (FDI) was examined as an assessment of the physical factor. The FDI was significantly lower in patients with diffuse scleroderma than in those with limited scleroderma. Moreover, the FDI was significantly correlated with the specific scores of the severity of patients with SSc described by Ishikawa.
It was suggested that the quality of well-being score (QWB score) as a social factor and the face scale score as a psychological factor were lower in patients with diffuse scleroderma than in patients with limited scleroderma. Patients who had discomforts of having SSc felt the economic loss, regardless of a high or low medical cost.
However, the patients with better QWB score showed better face scale score even if they had poor FDI.
These data indicate that the analysis of QOL in patients with SSc is valuable in managing them.

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A case of adult Still's disease occurred during pregnancy was reported. A 30-year-old woman in the 18th week of pregnancy was admitted because of fever and polyarthralgia. She had an episode of unknown fever suggesting adult Still's disease at the age of 19. Physical examinations revealed lymphadenopathy, hepatosplenomegaly and swelling of many joints in decreased motion. A macular rash which had appeared with fever was present on the legs. Laboratory data revealed rapid ESR, neutrophilia, mild liver dysfunction, positive CRP and elevation of serum ferritin. A diagnosis of probable adult Still's disease was made because other febrile diseases were denied. After admission, she was treated with aspirin, resulted in exacervation of liver dysfunction, but was much improved with naproxen. Intrauterine growth retardation was suggested at one time, but at the 38th week of gestation, she delivered a healthy baby with no problems and no recurrence has been occurred till now. Six cases of adult Still's disease occurred during pregnancy are reported including the present case and discussions were made on such cases in the present paper.

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A 21-year-old male came to the Hokkaido University Hospital complaining high fever and cervical lymph node swelling in October 1989. Laboratory findings showed proteinuria of 300mg/dl, anti-nuclear antibody with a homogeneous pattern at a titer of 1:160, and anti-DNA antibody of 827U/ml. From these findings the diagnosis of systemic lupus eryth-ematosus (SLE) was made. Because of persisting high fever and progression of anemia, he admitted to our hospital on December 1989. His peripheral blood count was as follows; RBC 169×10⁴/μl, Hb5.2g/dl, reticulocyte 1‰, WBC 14, 300/μl (neutrophils 80%, eosinophils 2%, lymphocytes 11%, monocytes 7%) platelets 45.5×10⁴/μl. The marrow aspirate was of normal cellurality but showed marked depletion of erythroblastic series (6%). A diagnosis of pure red cell aplasia (PRCA) associated active SLE was made. He was treated with prednisolone at a dose of 60mg/day, but failed to respond. In order to control the activity of SLE and to increase the erythroid cells, pulse therapy with 1g/day methylprednisolone was administered for 3 days. After the pulse therapy, fever, skin eruption, high anti-DNA antibody level, and reticulocyte count were improved, and a bone marrow aspiration revealed increased nucleated red blood cells (26%).
In this case, colony-forming units-erythroid (CFU-E) increased about twice compared with normal control, and few erythroblast cells were found in his bone marrow. This results indicate that the level of damage in erythropoiesis in this case is at the point between CFU-E and proerythrocyte.
Steroid pulse therapy was considered to be effective in this patient. When PRCA was complicated with active SLE, sufficient amount of steroid administration was important in order to control the activity of SLE itself. If ordinary conventional doses of steroid is not effective, steroid pulse therapy is considered as one of the useful method against PRCA with SLE.

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The patient (a 56-year-old male) had no subjective symptoms, although mild proteinuria had been observed in 1986. He gradually started to notice bilateral pitting edema of the lower extremities, general fatigue, night sweating, and Raynaud's phenomenon in around August 1988. He visited a hospital with an episode of acute tonsillitis and a profound amount of proteinuria with nephrotic syndrome and serological abnormalities such as positive antinuclear antibody, high titer of anti-DNA antibody and hypocomplementemia were recognized. At that time, he was referred to our hospital for further detailed examinations.
Renal biopsy revealed typical histopathological findings compatible with lupus nephritis, i.e. mesangial cell proliferation, IgG and C1q deposits on the glomerular capillary wall by immunofluorescence and electron-dense deposits on subepithelial lesions by electron microscopy. His white blood cell count was increased (16, 000/mm³), with marked lymphocytosis (66%, absolute number of Ly: 10, 560/mm³). The analysis of lymphocyte subpopulations showed that the majority of lymphocytes (53%) were surface Ig positive lymphocytes (i.e., B-cells) with monoclonality of IgM, IgD and κ light chain.
The myelogram also showed an increased percentage of lymphocytes (48.6%) with the same surface marker. According to the criteria of the NCI-sponsored workshop (1988), CLL (Rai stage 0) was diagnosed. Proteinuria disappeared in response to prednisolone (40mg/day) therapy, but there was the persistence of lymphocytosis. Thus, it is speculated that in this case autoimmune phenomena associated with CLL might have caused renal damage in morphology to that of lupus nephritis.

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Hepatic manifestations of systemic lupus erythematosus (SLE) have been reported to be less common than renal involvement and confined to mild biochemical or histological abnormalities. Since a concept of “autoimmune hepatitis”, characterized by the presence of chronic active hepatitis (CAH) concomitant with positive LE cells, was proposed by Mackay in 1956, discrimination between hepatic involvement of SLE (“hepatic lupus”) and autoimmune hepatitis (or “lupoid hepatitis”) has become important on occasion. However, many epidemiological or immunopathological studies hasn't be able to disclose significant differences between two diseases.
We reported a case of CAH associated with typical profiles of immunological abnormalities in SLE. Although this case certainly fulfilled the proposed criteria for lupoid hepatitis, observations listed below raised the possibility that CAH might be accompanied by SLE in some occasions; 1) More than four of the manifestations listed in ARA's criteria for SLE were definitely present in our patient. 2) Anti-ds DNA, anti-Sm and anti-RNP antibodies were present in his serum. 3) Neither anti-smooth muscle antibody nor anti-mitochondria antibody was present. 4) Marked reduction of hemolytic complement activity was associated with depressed serum complement components (C 3, C 4), indicating the activation of classical complement pathway.
Clinicoimmunological difference between two diseases should be further investigated and elucidated not only by hepatologists but by immunologists.

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Three cases of antibiotic-induced granulocytopenia were examined for their etiology using the GM colony formation technique. Examined in two cases were the effect of the drugs, convalescent serum, and peripheral blood mononuclear cells on their GM colony formation. Also examined in one case were the effect of the drug, acute phase serum and IgG on normal human GM colony formation.
Two principal results were derived. First, the coexistence of the drug, convalescent serum and mononuclear cells markedly suppressed the patient's GM colony formation. Second, the patient's IgG purified from acute phase serum suppressed normal human GM colony formation without the drug. These results suggest that the granulocytopenia developed via an immunological mechanism involving the drug, patient's serum and mononuclear cells.

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A 41-year-old Japanese man was admitted with dyspnea, fever and general fatigue on January 23 rd 1990. He was found to suffer from pneumonia and thought to have a lover of the man who cared gently for him at his bed side. He was diagnosed as AIDS on the basis of a homosexual history, marked lymphopenia, markedly decreased T 4/T 8 ratio and positive HIV antibody. But he died from pnemocystis carinii (PC) pneumonia shortly after the diagnosis.
The autopsy findings disclosed cytomegalovirus (CMV) infection in the adrenal gland and PC pneumonia.

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A 42-year-old man with Behçet's disease was admitted because of visual loss in his right eye. He had been suffering from recurrent genital ulcer, uveitis, folliculitis and oral ulcer. On admission, studies using a monoclonal antibody as peripheral blood T lymphocyte surface marker, revealed OKT 4 antigen deficiency. His Leu 3 a and PHA, ConA response was normal. Examination of the family tree indicated that the hereditary type of OKT 4 epitope deficiency was imcomplete dominant.
The association of Behçet's disease and OKT 4 epitope deficiency has not been reported.
Oral administration of cyclosporin A (CYA) 400mg per day for severe uveitis was initiated. Some days later, his uveitis condition improved, but the patient noticed muscle weakness and muscle pain in proximal limbs. After the laboratory examinations, the serum levels of CPK, aldolase and transaminase were markedly elevated. The electromyograms revealed typical myogenic pattern. These findings gradually improved after administration of prednisolone. Only one case of CYA induced myopathy has been reported.
It is not clear whether the myopathy in this case was a common side effect of CYA, or if it occurred on the basis of OKT 4 epitope deficiency.

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