To study the clinical significance of complement system in diabetics, fragments of complement (C4d, iC3b, & Bb) in plasma samples of 72 patients were measured.
Diabetic subjects were divided into four groups as follows. Patients without complications (group F n=35), with retiropathy (group R n=14), with nephropathy (group N n=12), under hemodialysis (group DHD n=11) and normal healthy controls (group H n=25).
The results were summarized as following four points.
1) In group F, the values of C4d, iC3 & Bb were significantly increased compared with those of group H. These results suggested that complements were activated through classical and alternative pathway in diabetics.
2) Complement fragments levels of group R showed significantly higher than those of group H.
3) In group N, the values of C4d and iC3b were higher than those in both group F and R. From these facts, increase of complement activation through classical pathway might be related to the diabetic nephropathy.
4) In group DHD, C4d, iC3b & Bb were significantly higher than those in group H. It was suggested that both classical and alternative pathway of complement system were activated in this group.

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A distinct antinuclear antibody reacting with a celluler component which showed a characteristic expression pattern is reported. In immunofluorescence, the new antibody, termed anti-Na, stained approximately 20_??_30% of HEp-2 cells with a varigated speckled pattern. Anti-Na was differentiated from anti-PCNA by 1) discrete speckling on mitotic cells, 2) staining of the anaphase cells and 3) a negative immunodifusion test: and from ACA (Anti-Centromere Antibodies) by discrete speckling observed only on mitotic cells. Although the preliminary study showed that approximately 1% of SLE patients had anti-Na, exact frequencies of the anti-Na antibodies in rheumatic diseases and their clinical significances remain to be clarified.

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We performed extracorporial immunoadsorption therapy for anti-DNA antibodies (anti-DNA) in 4 active SLE patients with nephritis. The dextran sulphate column (SL-01, Kanegafuchi chemical) introduced to remove anti-DNA from the plasma of the subjects. The mechanism underlying the process is based on the cross reactivity of the anti-DNA antibodies with dextran sulphate, which has negatively charged units. Each patient received 4 to 7 times of this treatment with 2, 500ml of treated plasma per times.
After the course of the treatments, the titers of anti-DNA in all patients were remarkably decreased. The data of creatinine clearance were improved in 2 patients, while those remained unchanged in the other 2 patients. The treatment diminished the urinary protein more rapidly than the corticosteroid therapy alone.
In two cases, the doses of predonisolone (18mg/day, and 20mg/day, respectively) didn't seem to be enough to suppress the anti-DNA production, because the effects of immunoadsorption were not sustained for more than one month. Our experiments suggest that the extracorporeal immunoadsorption therapy using SL-01 may be benificial for patients with lupus nephritis and could give us stronger effect to suppress lupus activity when moderate to large doses (more than 0.5mg/kg/day) of steroid is combined.

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We determined CD5 antigen, interleukin-2 receptors (IL-2R) and transferrin receptors (TfR) on circulating B-cells in Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) by two-color flowcytometry.
The proportions of total B-cells were significantly higher in 15 SLE patients and were relatively higher in 17 patients with primary (I°)-SS, 20 patients with secondary (II°)-SS and 24 patients with RA as compared with 22 controls. The proportion of CD5⁺ B-cells was also higher in I°-SS and RA than controls, although the cells were significantly decreased in SLE patients. However, the proportions of CD5⁺ B-cells in total B-cells were significantly low in II°-SS, RA and SLE. Most of the patients with SLE were receiving prednisolone (PSL) treatment, and the dosage of PSL administered was negatively correlated with the CD5⁺ B-cells in II°-SS patients.
IL-2R⁺ B-cells were few and were within negligible range in any patients' groups, but the proportions of TfR⁺ B-cells were significantly high in the patients' groups, except for RA. TfR⁺ B-cells seemed to reflect the activity of diseases, since they positively correlated with the dosage of PSL in the patients.
Among the B-cells determined, the increase of total B-cells, CD5⁺ B-cells and TfR⁺ B-cells was proportional in only RA patients.
Our results, therefore, did not support the previous reports showing increased CD5⁺ B-cells in RA, SS or SLE patients. In addition, the results indicate that CD5 antigen might not be an activation antigen of B-cells, although the stimulations to B-cells might be different among patient's groups.

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19 year old woman was admitted to our hospital because of the psychiatric manifestations. She was well until one month before entry, when schizophrenia like psychosis and disturbance of behavior developed. She was admitted another hospital and administered haloperidol without symptomatic improvement. She was referred to our hospital because of leukopenia and spastic seizures on August 10, 1989. On admission she was severely depressed and became frankly schizophrenic. Active synovitis in the small joints of hand and ankles, skin rash and fever were observed. Laboratory studies revealed leukopenia and positive antibodies against n-RNP which was detectable to a serum dilution of 1 in 128. Antibodies against neither ds-DNA nor Sm were detected. She was started on high dose methylprednisolone pulse therapy of three courses. After three months of maintenance steroids therapy, she was fully orientated and improved.
Enough items were present in criteria for systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) in this patient, and it was suggested that the psychiatric manifestations may be one of the clinical signs of the patient with antibodies against n-RNP positive connective tissue disease and bolus methylprednisolone should be attempted for these patients as a therapy.

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Mononuclear cells in 30 patients with esophageal cancer, resectable cases 21 and nonresectable cases 9, were harvested from peripheral blood by Ficoll Hypaque gradient. Peripheral blood mononuclear cells (PBMC) were incubated with rIL-2 for 5 days. After incubation, sensitivity of these cells for rIL-2 was examined by LAK activity and cell proliferation. PBMC in patients with esophageal cancer exhibited 48.1±25.2% in cytotoxicity against NK sensitive tumor cell, K 562, while PBMC in healthy donors did 64.5±8.8%. In regard to LAK activity against NK resistant tumor cell, Raji, 18.9±18.2% in patients with esophageal cancer was significantly lower than 29.2±14.9% in healthy donors (p<0.05).
Cell proliferation rate after incubation with rIL-2 was calculated by deviding post-incubated cell number by preincubated. Cell proliferation rate in patients with esophageal cancer was 53.2±30.2%, while that in healthy donors was 93.8±49.3%.
Moreover, nonadherent cells, acquired by removing adherent cells from PBMC by means of adherence to plastic dish, displayed higher LAK activity and cell proliferation rate after incubation with rIL-2 than PBMC.
The ratio (L/M) of number of peripheral lymphocytes (L) to monocytes (M) was compared between patients with esophageal cancer and early gastric cancer. L/M in patients with esophageal cancer was significantly lower than with early gastric cancer (p<0.01).
We suggested that sensitivity of PBMC in patients with esophageal cancer for rIL-2, LAK induction and cell proliferation, was depressed due to increase of monocytes in PBMC, whereas sensitivity of lymphocytes itself for rIL-2 was preserved to some degree.

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Plasma immune complexes (IC), especially IC fixing either C 3b or iC 3b/C 3dg to form C 3b-IC or iC 3b/C 3dg-IC, and the level of C 3b receptor (complement receptor 1, CR 1), factor H and factor I, were studied in patients with liver cirrhosis (IC), chornic hepatitis (CH) and normal subjects (NS). Elevation of C 3b-IC were observed in patients with LC compared with CH oh NS, while no differences of iC 3b/C 3dg-IC were found among patients with LC, CH and NS. The expressione of CR 1 on erythrocytes patients with LC was increased compared to CH or NS. The values of factor I were very low while factor H were very high in patients with LC compared to CH or NS. These results suggested the presence of hyperproduction of C 3b-IC as well as abnormalities in the C 3 cascade for the clearance of IC in patients with LC, probably be due to impaired-production of factor I neccessary to cleave C 3b to C 3dg. The increase of CR 1 on the erythrocytes and the increase of plasma factor H in patients with LC might be an effort to compensate the diminution of the cleavage of C 3b to C 3dg.

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A case of rheumatoid arthritis with leukocytoclastic vasculitis was reported. The patient, a 52-year-old woman, had developed polyarthralgia in June 1982, and had been treated with several drugs such as gold sodium thiomalate, d-penicillamine, lobenzarit and prednisolone. However, her joint symptoms became worse. She was hospitalized to our center in June 1987 for further evaluation. On physical examination, swelling and tenderness of right wrist joint and bilateral knee joints, and subcutaneous nodules on her occiput were noted, but she had no skin ulcer or eruption. Her erythrocyte sedimentation rate was 168mm/hr, C-reactive proteins (CRP) was positive in a high titer, and rheumatoid factor elevated. In October, new skin lesions developed on her bilateral legs, which were slightly pruritic and painful. A biopsy specimen taken from the lesions showed leukocytoclastic vasculitis. The combination therapy with prednisolone (10mg/day) and methotrexate (7.5mg/week) was started. After the therapy the skin lesion and arthralgia were improved without adverse effects.
Low-dose methotrexate therapy seems to be useful in the treatment of leukocytoclastic vasculitis associated with rheumatoid arthritis.

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This report describes a patient with chronic fatigue syndrome (CFS) with persisting endotoxemia defined with limulus lysate test. A 30-year-old female was admitted to our hospital because general fatigue continued for a long time. She had been treated with anti-inflammatory drugs, steroids and immunosuppressive drugs at another hospital. But these treatments did not improve the symptoms and sign completely. The symptom of swollen lymph nodes and muscle weakness, and the sign of general fatigue, low grade fever, sore throat, myalgias, headaches, althralgias, difficulty thinking and inability to concentrate have been lasted for these ten years. A diagnosis of chronic fatigue syndrome was made based on clinical criterion proposed by Holmes GP et al. Serological studies revealed an elevation of titer of serum antibodies to measles, herpes simplex, herpes zoster, epstein-barr virus and human herpesvirus-6 (HHV-6). HHV-6 specific DNA was not detected in the peripheral blood lymphocytes. Endotoxin defined by limulus lysate test and endospecy was positive. Reduced natural killer cell activity was found in the patient. Phenotypic analysis revealed that the CD57⁺ population was exist (19.7%), but the CD16⁺ population was extremely diminished (2.3%). With psychological approach of explanation alone, her symptoms improved one month later.
There has been growing interest in CFS in Europe and America, and supporting organizations for patients with CFS are at work today. On the other hand, little attention has been focused on CFS in Japan. Clinical diagnosis of the collagen diseases, climacteric psychosis or depression were made for the patients with CFS. It is necessary to make adequate diagnosis and treatment for the patients with CFS in Japan.

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Two cases of systemic lupus erythematosus (SLE) complicated with intestinal perforation were reported. One patient was 27-year-old female suffering from SLE for about 9 years. She recently developed various symptoms due to SLE, followed by sudden onset of abdominal pain. Steroid-pulse therapy was performed and later antibiotics were administered. In spite of intensive treatment she died from sepsis and disseminated intravascular coagulation syndrome. Histopathological study demonstrated sigmoid colon perforation and numerous vasculitis in the small vessels of the intestinal wall. The other patient was 34-year-old female who developed SLE just before 10 months. She complained of unspecific abdominal illness for 2 months and suddenly got severe abdominal pain. Intestinal perforation was diagnosed immediately and she received surgical operation. After operation her clinical course was good.
Only 8 cases of SLE with intestinal perforation have been reported in Japan, and we believe these two cases are of great importance to discuss.

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Patients with DiGeorge syndrome, which is characterized by idiopathic hypoparathyroidism, hypogenesis or agenesis of thymus and cardiovascular abnormality, usually die in newborn or infant period. We experienced a patient with partial DiGeorge syndrome at age of 30 years old. He had been suffered from seizures and mental retardation from age of 3 years old. At age of 22 years old, he was diagnosed to be suffered from idiopathic hypoparathyroidism because of hypocalcemia (2.8mEq/l), hyperphosphatemia (5.4mg/dl), and high responses in urinary inorganic phosphate and cyclic AMP to Ellsworth-Howard test. He was administered with 1 α-hydroxyvitamin D₃, At age of 30 years, he was referred to our hospital because of development of cataracta, when he was found to have right aortic arch with characteristic features of ocular hypertelorism, micrognasia and microtia. Immunological examination revealed normal values of circulating numbers of lymphocytes and T cells, of T cell blastogenesis by PHA, ConA SAC and PWM. However, analysis of T cell subsets revealed slight increases in the population of immature T cells, OKT 9 and OKT 10. He is thought to be a case of partial DiGeorge syndrome with slight abnormalities in the cardiovascular system and thymic function, which may permit his escape from early death usually seen in this syndrome.

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We report a young female case of multiple sclerosis (MS) associated with mixed connective tissue disease (MCTD) and aseptic meningitis. The case is a 27-year-old woman who had a sudden onset of visual disturbance at the age of twelve. The diagnosis of acute retrobulbar optic neuritis was made by an ophthalmologist. Two months later she had headache, fever, neck rigidity and finger tremor, and was admitted. She was diagnosed as having MS because of neurological findings and her clinical course. At the age of twenty-two she had arthralgia, swelling of fingers, Raynaud's phenomenon and morning stiffness, and was readmitted. Two years later, facial butterflyrash and muscle weakness of the neck, upper and lower extremities were manifested. Anti-nRNP antibody showed a high titer and she was diagnosed as having MCTD. She had had aseptic meningitis three times during last five years.
Several reports have suggested that MS may be one of autoimmune diseases. Association of MS, MCTD and aseptic meningitis was interesting in terms of immunological mechanism and development of these diseases.

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We report a case of the incomplete type of Behçet's disease with diffuse ulcerations of the esophagus.
In December, 1986, a 59-year-old woman was diagnosed as having incomplete type of Behcet's disease because of oral ulcers, folliculitis and uveitis. In September, 1987, She was admitted to our hospital with a complaint of dysphagia. Hematological tests showed anemia, and occult blood was present in the stool. The upper GI series and endoscopic examinations revealed diffuse ulcerations ranging from the upper portion to the lower portion of the esophagus. The histology of the biopsied tissue showed non-specific inflammation. The esophageal ulcers failed to respond to the combination therapy of antacid drugs, colchicine and salazosulfapyridine. Thus 30mg/day of prednisolone was given orally to the patient with dramatic response. One month later, these ulcers became healed by the use of corticosteroid.
Diffuse ulcerations of the esophagus in Behçet's disease are extremely uncommon and its therapy is not established.
Our case seems to valuable to the study of esophageal ulcerations in Behçet's disease.

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A 54-year-old woman with a 15-year history of Sjögren's syndrome presented with xerostomia, keratoconjunctivitis sicca, and hypergammaglobulinemia. She was admitted to our hospital in February 1989, for evaluation of high fever, dyspnea on exertion and easy fatiguebility. Velcro rales was heard in bilateral lower lung fields. The platelet counts was 6.9×10⁴/μl and PAIgG was 184.2ng/10⁷ cells.
Megakaryocyte count was increased in bone marrow. Anti-nuclear antibody, anti-SS-A antibody and anti-SS-B antibody were positive. Chest roentgenography showed reticulonodular infiltrates in bilateral lower lungs. Arterial blood gases were: PaO₂ 54mmHg, PaCO₂ 22.7mmHg.
We diagnosed as a case of Sjögren's syndrome involving thrombocytopenia and interstitial pneumonitis. Steroid therapy was started by 50mg/day. A dramatic improvement of the interstitial pneumonitis and the thrombocytopenia was occured instantly after this corticosteroid therapy.
Only 24 cases of Sjögren's syndrome involving thrombocytopenia were reported in Japan. In this case, however, the involvement of severe interstitial pneumonitis made the case much more characteristic and significant among others. No other cases involving both thrombocytopenia and severe interstitial pneumonitis have been previously described.

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Rheumatoid arthritis (RA) was associated with generalized as well as periarticular osteoporosis. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry in 53 female patients with RA. We investigated BMD of lumbar (II-IV) and radius, the BMD corrected by age-matched female, total bone mineral (TBM) and TBM/total lean mass. The BMD of lumbar did not correlate with the disease stage, the activities and the laboratory findings. But the BMD of radius and total body was lower in stage IV than in stage I-III and it was also lower in patients with low grasping score. In laboratory findings, the BMD was lower in patients with decreased CD45RA+CD4 cells and/or increased CD8+HLA•DR cells. This data suggested that there was a association between the abnormal function of lymphocytes and the osteoporosis in RA.

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