Persistent hypocomplementemia is often recognized in patients with systemic lupus erythematosus (SLE) even in cases of a clinical remission. To elucidate the pathogenesis of persitent hypocomplementemia, we measured plasma C3a and C4a, catabolic products of C3 and C4, respectively, by radioimmunoassay.
Fifteen SLE patients were divided into three groups based on clinical activity and the presense of hypocomplementemia as follows, group I-inactive disease without hypocomplementemia, group II-inactive disease with hypocomplementemia, group III-active disease with hypocomplementemia. Nineteen healthy volunteers were also chosen as control.
Mean value of plasma C3a in group II was 699±200ng/ml, significantly higher than that of group I (p<0.01). Therefore it was suggested that the complement activation played an important role in persistant hypocomplementemia in inactive SLE patients.
Mean values of plasma C3a and C4a in group I were 254±158 and 377±75, compared with 89±58 and 207±69 in control group (p<0.05, p<0.01), suggesting that the potential complement activation was constantly present in SLE patients.
Mean values of plasma C3a and C4a in group III (918±79, 1, 728±730ng/ml) were markedly elevated, compared with those of group II (p<0.10, p<0.01), although there was no significant difference in the serum complement levels between these two groups.
We conclude that the measurement of plasma C3a and C4a may be very useful for themanagement of SLE patients.

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As to the patients of pulmonary alveolar proteinosis, the fall of ability in pulmonary alveolar macrophage (PAM) has been often indicated. The authors studied the phagocytosis of PAM and peripheral blood monocytes (PBMo) of both healthy subjects and the patients of pulmonary alveolar proteinosis, using FITC labelled latex beads and flow cytometry. This method has advantages of that the measurement is possible by a small amount of cells without a separation of PAM and the phagocytic reaction can be observed dynamically.
The results of this research have shown that opsonin was necessary for the phagocytic action of PBMo. On the other hand, activation of opsonin was unnecessary for the phagocytic action of latex beads. It was suggested that the presence of opsonin suppressed the phagocytic action of PAM.
PAM phagocytosis of the patients of pulmonary alveolar proteinosis have been recognized to be much inferior to those of healthy subjects. However, the reaction to the opsonin was the same with that of the healthy subjects. Also, no fall in phagocytic ability of PBMo was observed.
The results of this research lead to the conclusion that there is a possibility of fall in the ability to treat foreign bodies of PAM which plays an important role in the foreign body clearance mechanism in the pulmonary area of the patients of pulmonary alveolar proteinosis.

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The serum IgD level in patients with multiple myeloma was measured by ELISA.
There was no difference in the serum IgD level between myeloma patients and normal donors. In contrast, other class of serum immunoglobulin levels were remarkably depressed in multiple myeloma patient. The characteristics of periferal mononuclear cells from myeloma patients were in vestigated by flow cytometry using monoclonal antibodies against CD 8 and CD 11b antigen. The ratio of suppressor T cells with both CD 8 and CD 11b antigen in myeloma patients was ramarkably increased compared to normal donors.
The increase in the suppressor T cells ratio was higher, especially in myeloma not accompanied by Bence-Jones protein.
This depression of the serum immunoglobulin except IgD was related to the increase of suppressor T lymphocyte in multiple myeloma. Our observations suggest that the mechanism of the regulation of the serum IgD levels and the roles of the serum IgD are quite different from other classes of immunoglobulins.

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Aseptic meningitis has been reported in association with the administration of non-steroidal anti-inflammatory drugs, including ibuprofen, tolumetin and sulindac. Most of the patients reported have had connective tissue diseases, as SLE and MCTD.
In this report, we described a case of aseptic meningitis caused by sulindac in a patient of rheumatoid arthritis with Raynaud's phenomenon and pulmonary fibrosis. In July 1983, a 58 years old woman who had a history of Raynaud's phenomenon for two years and pulmonary fibrosis for one year, complained polyarthralgia. She was diagnosed as rheumatoid arthritis based on morning stiffness, polyarthritis, and positive rheumatoid factors. Since August, arthritis had been controlled by a dose of 75mg of diclofenac and 50mg of indomethacin. In December, because of epigastric pain, she began taking sulindac of 300mg per day instead of indomethacin. But after 13 days, she was hospitalised because of fever, headache and meningeal signs. Lumbar puncture yeilded cerebrospinal fluid with 257/3 cells, glucose value of 58mg/dl, and protein value of 152mg/dl. She also had pleuropericarditis and disseminated intravascular coagulation syndrome during the hospital course. Discontinuation of sulindac resolved these above symptoms in the next 4 days. She had not been rechallenged with sulindac.
Although the mechanism of the meningitis is far from clear, past history of drug allergy, eosinophilia, positive findings of lymphocyte stimulation test for slindac and the rapid resolution of meningeal symptoms after cessation of the drug suggest that allergic or immunological mechanisms induced by sulindac might be involved in our patients.

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The antibodies to 2 types of intermediate filaments (IFs), vimentin and cytokeratin filaments, were assayed by western blotting in sera from 148 patients with connective tissue diseases and from 36 patients with infectious diseases. IFs were isolated from human embryonic lung fibroblast, HEL-299 and epithelial cell line, PtK-2. The antibodies to vimentin filament from HEL-299 cell were found in 29% of 82 patients with rheumatoid arthritis (RA), 54% of 35 patients with polymyositis-dermatomyositis (PM-DM) and 39% of 31 patients with progressive systemic sclerosis (PSS). The frequencies of antibodies to cytokeratin filament from PtK-2 cell were 30%, 46% and 45% in RA, PM-DM and PSS, respectively. The frequencies of those antibodies detected by western blotting were higher than those by immunofluorescence using PtK-2 cells as substrate. The frequencies of antibody to vimentin and cytokeratin in 36 patients with infectious diseases were 58% and 22%, respectively. These antibodies belonged mainly to the IgG class. No healthy volunteer had anti-IFs antibody. The vimentin antibodies positive patients with RA and PSS had frequently lung fibrosis. The presence of IFs antibodies in patients with both connective tissue diseases and infectious diseases might suggest the relationship between these two disorders.

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A family including a grandmother with CREST syndrome, SLE, and chronic thyroiditis, mother with SLE and Sjögren syndrome, and a daughter with SLE was reported.
Clinical signs, HLA and laboratory findings were studied in this three patients and 17 of their relatives.
1. All three patients and 3 symptomatic relatives were female, and had a same haplotype, HLA A11, B 39 (16), CW 7, DRW 8.
2. Study of asymptomatic relatives.
Autoantibodies were found in 14% in male, and 57% in female. Decreased levels of CH 50 were found more frequently in 43% than control population in 5%, significantly (p<0.05). Autoantibodies were also found more frequently in 36% than normal control group (5%).
3. Study of all 20 relatives including the patients.
Decreases of CH 50 level were found more frequently in 40% than normal control group (5%), significantly (p<0.05).
Hematological abnormalities were found more frequently in 25% than normal control group.

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The effects of iron and iron-binding proteins on Fc- and C3-receptor function of human monocytes were examined. Human peripheral blood monocytes were obtained as adherent cells on a cover glass after isolation of peripheral blood mononuclear cells (PBMC) from heparinized venous blood by Conray-Ficoll gradients. Human O type red cells coated with anti-D antibody (IgG) or with third complement component were used as indicator cells for EA or EC rosette formation. The co-culture of human monocytes with 1mM concentration of ferric citrate for 7 days but not for 1 hour gave rise to the significant decrease of both Fc- and C3-receptor function of the cells. None of the other concentrations of ferric citrate (0.01, 0.1mM) and iron-binding proteins (transferrin and lactoferrin, 10^-6M) had any effect on both of receptor function of monocytes cultured for 1 hour or 7 days.

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We have experienced two cases (Case 1; 30-year-old female, Case 2; 46-year-old female) of rheumatoid arthritis (RA) associated with Graves' disease. Case 1 was diagnosed to have Graves' disease in another hospital in 1977 and was treated with methimazole for approximately 2.5 years. With the treatment, she became euthyroid, however, arthralgia and general fatigue which appeared 5 years ago have not been improved. She admitted Gifu University Hospital for the further evaluation and treatment of RA and Graves' disease. In addition to Graves' disease and RA, she had diabetes mellitus which required insulin treatment.
Case 2 who had been diagnosed as RA in the orthopedic department of Takayama Red Cross Hospital was referred to the Department of Internal Medicine for the evaluation of palpitation, leg edema, and muscle weakness of lower extremities. She was diagnosed as Graves' disease and was started to treat with methimazole.
High prevalence of the association of Hashimoto's thyroiditis and RA has been reported, however, so far only two cases of RA associated with hyperthyroidism have been reported. Significance of the association of both diseases of autoimmune origin is discussed.

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48 year-old man was suffered from polyarthritis since 1981 and myalgia, muscle atrophy, gait disturbance since 1983. In 1984, he complained of numbness of extremities and poor appetite and he was admitted to our clinic in February 1984. His laboratory data showed elevated ESR, 6 (+) CRP and high value of immune complexes and rheumatoid factors. The biopsy of his femoral skin showed PN type vasculitis with fibrinoid degeneration. From these results, he was diagnosed as malignant rheumatoid arthritis and has been treated with prednisolone.
He developed abdominal pain and tarry stool on the 25th day after admission, and 2 days later, abdominal roentgenogram revealed a free air shadows. He received surgical operation as his perforation of gastro-intestinal tract. Multiple lesions of perforation were observed in the ileum. The pathohistological findings showed vasculitis of submucosal or mesenteric arteries with PN, EA or RA type. The immunohistological examination revealed a deposition of IgG and C₁q on the intima of the mesenteric artery. He was expired on June 24, 1984 bacause of re-perforation of G-I tract and pneumonia. The autopsy findings revealed multiple ulcerations in the small intestine, perforating lesion in the rectum, and EA type vasculitis in many organs. Through his clinical course, types of the vasculitis changed from PN type in the skin vessel on admission to PN, EA and RA type in the mesenteric artery on operation, and to EA type in the mesenteric artery on autopsy. It was suggested that adrenocortical steroid hormone might affect the natural histcry of vasculitis.

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A seventeen-year-old girl with insulin dependent diabetes mellitus (IDDM) had also selective IgA deficiency and No.9 chromosome aberration. The onset of IDDM was at the age of seven, and it happened that selective IgA deficiency and No.9 chromosome aberration were found out at the age of nine and twelve respectively.
Secretory IgA level in the serum and saliva was reduced because of selective lgA deficiency, however she had rarely suffered from infectious diseases. In addition, she had no IgG subclass deficiency. According to the study of immunoglobulin synthesis of lymphocytes in vitro, the impediment of maturity of B lymphocytes producing IgA was suspected as one of the causes of selective IgA deficiency in this case.
This case had No.9 chromosome aberration, and the karyotype was 46, XX, inv (9p+q-) both in G-band stain and C-band stain. Mother of this case had the same abnormality in No.9 chromosome.
This case had HLA-Cw 1 and Bw 54 which were frequently observed in Japanese IDDM patients, but did not have HLA-B 8 which was frequently observed in Caucasian IDDM patients with selective IgA deficiency.

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We report a case of mixed connective tissue disease (MCTD) who had necrotizing lymphadenitis and aseptic meningitis in the clinical course. The patient was thirteen year old boy. He visited our hospital with chief complaint of fever of unknown origin and clinical studies revealed liver disfunction. After that he showed Raynaud's phenomenon, swollen hands and arthralgia. The titer of antibody to antinuclear antigen (ANA) and nuclear ribonucleoprotein (nRNP) elevated gradually and the diagnosis of MCTD was made.
It was suspected that necrotizing lymphadenitis had some relation to MCTD, but aseptic meningitis occured by chance owing to a viral infection.

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The patient, 39 year-old female, started to have polyarthralgia on both hand fingers in Oct. 1985, extending to bilateral wrist and shoulder joints with morning stiffness in Dec. 1985. Laboratory data showed elevated erythrocyte sedimentation rate, hyper-γ-globulinemia, positive rheumatoid factor, positive anti-nuclear antibody with speckled pattern and marked hypocomplementemia. Typical urticarial skin eruption on face and extremities with slight itching appeared on Mar. 1986. The histological findings in skin biopsy revealed neutrophil infiltration around the small vessels in epidermis. She began to have high fever, pain and swelling on bilateral upper arms and right side of thigh, macrohematuria, abdominal pain on Apr. 1986. For the first moment, the diagnosis of hypocomplementemic urticarial vasculitis syndrome was made according to preliminary diagnostic criteria proposed by Schwartz et al. in 1982. Prednisolone at initial dosage of 60mg per day was used for therapy, followed by marked improvement of clinical symptoms. Hypocomplementemia was, however, continued during clinical remission.

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The authors described a patient with primary non-familial amyloidosis who showed remarkable peripheral and autonomic neuropathy. Sixty five years old man developed orthostatic hypotension, severe polyneuropathy, nephrotic syndrome and cardiomegary 20 years after hypotension was noted. He died of sinus arrest despite of the treatment with dimethylsulfoxide (DMSO).
1. Peripheral nerve biopsy and autopsy revealed that Congo red positive and potassium permanganate resistant fibril was abundant deposited in interstitial space in multiple organs.
2. Amyloid protein isolated from the kidney was chiefly composed of the molecular weight of 10 kilodalton, and was identified as AL (λ) type.
3. The immunological tests showed decreased amount of IgG, IgA and IgM, poor response of lymphocytes to PHA, Con A mitogens, and increased ratio of OKT 4+/OKT 8+T cells.
While polyneunopathy is one of the common clinical features in familial amyloidosis, only 14% of the patients with primary non-familial amyloidosis have this manifestation. Properties of the amyloid protein was probably related to immunological and neurological abnormalities in this patient.

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Bone destructins in the wrist and MCP joints were observed in two patients with systemic lupus erythematosus (SLE) 6 and 10 years after the onset of the disease, respectively. They fulfilled the diagnostic criteria for both SLE and rheumatoid arthritis (RA) by American Rheumatism Association. However, joint involvements were restricted to the hands and fingers only, so that the disease activities as RA were low. SLE was also mild, being controlled by prednisolone of less than 30mg daily. The clinical course, therefore, has been favorable without renal dysfunction or apparent hypocomplementemia. These facts suggest that SLE with destructive arthritis may be not simply the overlap of SLE and RA.

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An enzyme-linked immunosorbent assay (ELISA) was developed to detect polypeptides coded by the pre-S (1) and pre-S (2) region of hepatitis B virus (HBV) DNA with monoclonal antibody in 100 sera containing hepatitis B surface antigen particles. There can be seen a close correlation between the titer of pre-S (1) polypeptide and HBV-DNA level (HBV-asymptomatic carrier; n=40, r=0.800, p<0.01, chronic hepatitis type B; n=60, r=0.730, p<0.01). Ten patients with chronic hepatitis type B was devided into two groups (group 1: serum transaminase normalized after acute exacerbation (AE), group 2: abnormality of serum transaminase continued after AE). The titer of pre-S (1) polypeptide as well as HBV-DNA level was significantly reduced after AE in group 1 and group 2. But the titer of pre-S (2) polypeptide was more significantly reduced after AE in group 1 than in group 2. These results suggest that the detection of serum pre-S (2) polypeptide is more useful as a prognostic test for chronic hepatitis type B than pre-S (1) polypeptide.

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