Supernates of thymic epithelial cell culture (STEC) strongly inhibit the aggregation induced by the addition of adenosine diphosphate (1 μM) or thrombin (0.5 unit per ml) to washed platelet suspensions. At the same time, STEC increased the levels of adenosine 3', 5'-cyclic monophosphate (cyclic AMP) and guanosine 3', 5'-cyclic monophosphate (cyclic GMP) in platelets in a dose-dependent manner. In contrast the supernates from Chang, Hela or HCC-M cells did not affect platelet aggregation induced by ADP and intracellular cyclic nucleotide levels. Within 2 min after the treatment with STEC, more than 50% of the maximum inhibitory activity on platelet aggregation and increases in intracellular cyclic AMP were observed. These activities were not altered when STEC was boiled for 5 min, but disappeared following STEC treatment with pronase E. These activities were found predominantly in the fraction>1, 000 daltons. The level of prostaglandin E derivertives in STEC was about two times that found in the control culture medium. In these data suggest that the biological activity of STEC in the platelets might be attributed to thymosin-like polypeptides and prostaglandins.

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Effect of oral administration of OK-432 on the immune reactivities of regional lymphnode (RNLs) and peripheral blood lymphocytes (PBLs) in colon cancer patients were investigated. Twenty KE of OK-432 was given orally on 7 days prior to the operation, and peripheral blood and regional lymphnodes were collected at the time of operation. As for the immune reactivities of PBLs such as lymphocyte proliferative response to phytohemagglutinin (PHA), natural killer (NK) cell activity and Concanavalin A (Con-A) induced suppressor cell activity, there were no significant differences between patients with oral OK-432 (OK-432 (+) group) and those without OK-432 (OK-432 (-) group). NK cell activity of RLNs was significantly higher in OK-432 (+) group than in OK-432 (-) group. Furthermore, the decline of Con-A induced suppressor cell acivity was found in OK-432 (+) group. T cell subsets in regional lymphnode tissues were identified with the use of monoclonal antibodies and immuneperoxidase technique. Both of Leu-2 a and Leu-7 positive cells distributed more frequently in lymphnodes from OK-432 (+) group than in those from OK-432 (-) group. Thus, these results suggested that immune reactivities of regional lymphnodes were en-hanced by oral administration of OK-432 in colon cancer patients.

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We intended to analyze the mechanism of polyclonal B cell activation in patients with Sjögren's syndrome (SS). We examined the abilities of peripheral blood lymphocytes from SS to respond to B cell stimulatory factors (BSF). Peripheral B cells from SS showed a marked IgG synthesis with BSF alone, in the absence of anti-IgM antibody, measured with Enzyzme Linked Immunosorbent Assay (ELISA). Moreover, SS B cells responded vigorously to the stimulation by BSF associated with anti-IgM antibody compared to normal controls. Furthermore, the hyperactivity of SS B cells to BSF correlated with IgG levels in their sera. By contrast, B cell response to Staphylococcus aureus Cowan 1 (SAC) and expression of B cell differentiation antigens on SS B cells were not different from normal controls.
In addition, one B cell line, spontaneously established from the peripheral blood and positive for EBNA, produced IgG in the culture. It also responded to BSF resulting in augmentation of IgG synthesis.
These data highly suggest that SS B cells are polyclonally activated in vivo and SS B cells have hyperresponsiveness to BSF. These abnormalities might be responsible to perturb immunoregulatory system which result in polyclonal gammopathy and/or production of various autoantibodies in SS.

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A soluble suppressive factor (or factors) was demonstrated in the supernate from a 72-h mixed lymphocyte culture (MLC) that exhibited suppressive activity toward the natural killer (NK) activity of allogeneic as well as autologous lymphocytes in vitro, as detected in a 4-h ⁵¹Cr release assay on K562 target cells. Suppression of the NK activity reached significant levels when the MLC-supernate was added to the medium at a concentration of 30% (v/v). The percent suppression on NK activity of healthy controls was 23.7±8.7% (mean±SD). The activity of alloactivated lymphocytes to produce a suppressive factor was poor in prostatic cancer (M1 stage) and renal cancer, but not in bladder cancer and prostatic cancer (M0 stage). On the other hand, the NK activity of the lymphocytes from any type of cancers tested was not suppressed by the addition of MLC-supernates from normal individuals. The unresponsiveness was observed even in the early stage of cancer, thus suggesting that a qualitative abnormality might exist in NK cells even from an early stage of Carclnogenesis.

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In order to clarify the pathogenesis of lupus dermatoses and lupus nephritis, histamine degrading-enzyme activities in the skin and the kidney of MRL/Mp-lpr/lpr (MRL/l) mice were investigated, since the mice with lupus nephritis are the most attractive among several murine models from a dermatopathological point of view because their skin lesions resemble very well to those of human SLE.
In the dorsal lesional skin of MRL/l mice, the specific activity of histamine-N-methyltransferase (HMT), the major histamine metabolizing enzyme in murine skin and kidney, was markedly lower than that in abdominal uninvolved skin. In addition, age-related analysis of HMT activity in the dorsal skin of MRL/l mice revealed that the activity increased by age and was maximum at 1 or 2 months, and then decreased at 4 or 5 months when skin lesion appeared. However, HMT activity of the abdominal skin increased almost linearly by age. In contrast, histamine degrading-enzyme activity in kidney of MRL/l mice increased almost linearly by age. There were no differences between the HMT activities of perfused kidney and non-perfused one. Whole blood and serum had little enzyme activities.
In vivo administration of corticosteroid (betamethasone) restored the HMT activity in the dorsal lesional skin of MRL/l mice, although no significant macroscopic or histological differences were present in skin lesion of corticosteroid-treated mice when compared with non-treated mice. However, in vivo administration of corticosteroid had no significant effect on the enzyme activities of the kidney. Corticosteroid did not recover the HMT activity when added directly to the enzyme preparation obtained from the skin lesion.
Based on these findings, the effects of released histamine at least in the lesional skin of MRL/l mice are considered to last much longer than in the normal skin, which may contribute significantly to the development of the lupus dermatoses.

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Spleen cells (SC) obtained from gastric and esophageal cancer patients were tested for natural killer (NK) cell activity against K562 cells and non-specific suppressor cell activity, in compasiron with those of splenic venous blood (SVL) and peripheral venous blood lymphocytes (PBL). NK cell activitites of PBL in cancer patients were significantly depressed as compared to those of normal control PBL. NK cell activity of SVL was either higher than or comparable to that of PBL in the same patients. In both PBL and SVL, the NK cell activities declined with the advance of the disease. However, high NK cell activity of SC was observed in many cases, even in advanced cancer patients. Positive suppressor cell activities were recorded in SC, SVL and PBL of advanced cancer patients. The patients with the positive suppressor cell activities in SC showed low NK cell activities in SC. Similar results were obtained in SVL and PBL. Moreover, NK cell activitites of SVL and PBL were low in the patients with the positive suppresser cell activities in SC. These results suggested that NK cell activity might be regulated by non-specific suppressor cells, and suppressor cell activity was dominantly present in the spleen, although NK cell activity was maintained even in the spleen of advanced cancer patients.

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Serum anti-ribonucleoprotein (RNP) antibody levels were measured using an enzyme linked immunosorbent assay (ELISA) technique. Paper discs, activated by CNBr and coupled covalently with rabbit thymus extract (RTE), were used for the solid phase of ELISA.
Twenty serum samples containing antibodies specific only to the RNP antigen, determined by double immunodiffusion, were examined by ELISA. The sera were obtained from patients with MCTD, SLE and PSS. The samples were measured for anti-RNP antibody levels in each immunoglobulin class. It was found that most of the anti-RNP antibodies were IgG class and the rest were IgA class. No IgM or IgE anti-RNP antibodies were detected in this study.
To determine the absolute concentration of anti-RNP antibodies in sera, the IgG fraction of a sample from a patient with MCTD was labelled with N-succinimidyl [2, 3-³H] propionate ([³H] NSP). Then, Sepharose 4B coupled with RTE was reacted with the [³H] NSP-labelled IgG, and non-binding [³H] NSP-labelled IgG was removed by washing. The radioactivity of the Sepharose 4B obtained was measured and the absolute concentration of anti-RNP antibodies in serum was calculated from the binding ratio of the radioactivities of the entire [³H] NSP-labelled IgG to that bound with Sepharose 4B. Thus, the IgG anti-RNP anibody concentration of the IgG fraction was determined. The IgG fraction was sequentially diluted, and the anti-RNP antibody levels of the fractions were measured by ELISA. A dose response cure was obtaned from these values. The concentration of anti-RNP antibodies of twenty serum samples was determined from each antibody level by ELISA, using the dose response curve. The concentration of anti-RNP antibodies in sara tested ranged from 0.16 to 3.98mg/ml.

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High molecular weight glycoprotein (HMWGP) isolated from bovine red blood cells (BRBC) contains two antigenic determinants of H-D complexes. One is N-glycolyl neuraminic acid (NGNA) ganglioside, of which antigenic determinants are destroyed by treatment with neuraminidase and another is asialo-HMWGP, of which antigenic activities are resistant to neuraminidase. Using HMWGP and asialo-HMWGP as antigen, H-D antibody activities in sera of patients with liver diseases were examined by enzyme immunoassay (EIA) and trypsinized BRBC hemagglutination.
Four of ten sera showed high O. D. values of antibodies in EIA against both HMWGP and asialo-HMWGP and BRBC hemagglutinating activities in these sera were similarly inhibited by these two antigens. On the other hand, two sera showed extremely low O. D. values against asialo-HMWGP but high O. D. values against HMWGP. Subsequently, hemagglutination activites of these two sera were inhibited by HMWGP but not by asialo-HMWGP.
The results would indicate that antigenic determinants to which H-D antibodies in liver disease sera reacted were asialo-HMWGP and/or NGNA ganglioside.

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The effect of Platonin on human peripheral blood lymphocytes (PBL) was studied in vitro. Platonin showed proliferative effect on PBL. When PBL was stimulated with T cell mitogen Phytohemagglutinin (PHA) and B cell mitogen Staphylococcus aureus Cowan I (Cowan I), it showed enhancing effect on the former and suppressive effect on the latter. In Pokeweed mitogen (PWM) induced immunoglobulin (Ig) productive system, both of the T.B cells, T cells only, or B cells only were pretreated with Platonin and then co-cultured. The Ig secreting cells were demonstrately decreased than that of the absent Platonin pretreated in any groups. However, the ³H-thymidine incorporation failed to give a significant variation in any groups. In the experiment of T cell subsets detected with monoclonal antibodies and by Fluorescent Activaed Cell Sortor (FACS), the OKT8⁺ T cells showed a high proportion in the Platonin treated groups. In summary, B cells were directly suppressed by Platonin and concerning T cells, the T cell subsets showed a high proportion of suppressor/killer T cells. So it is suggested that Platonin suppressed Ig prodution through suppressing B cells and enhancing suppressor/killer T cells.

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Trigeminal neuropathy is seldom noted to accompany connective tissue disease. We found that nine of 267 patients with connective tissue diseases had clinical evidence of trigeminal neuropathy. These 9 patients were all women whose mean age at onset was 39.2 years. Six cases were classified as having MCTD, and the others were overlap syndrome between PSS and probable SLE. All the patients had Raynaud's phenomenon which was followed by trigeminal neuropathy. The mean interval between the onsets of these features was 20.1 months. In 7 cases out of nine, trigeminal neuropathy developed within 12 months. Scleroderma, polyarthritis, muscle involvement and leukopenia were found in 7, 5, 6 and 7 patients respectively. Anti nuclear antibody and anti-RNP antibody were positive in all patients. We examined blink reflex in all cases. Five patients revealed abnormal findings.
In summary, all 9 patients with trigeminal neuropathy had also Raynaud's phenomenon and anti-RNP antibody which were markers of MCTD. These findings suggested trigeminal neuropathy might be an important feature of MCTD.

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Seventy Japanese patients with systemic lupus erythematosus (SLE) were studied to define clinical and laboratory characteristics of lupus anticoagulant (LA). To detect LA activity, a mixing test of APTT was performed according to the method of Colaco et al., using the 1:5 diluted phospholipid reagent. As a result, LA was found in the plasma of 11 of 70 patients (16%) with SLE. The incidence of spontaneous abortion in LA-positive and LA-negative women were 7 of 18 pregnancies (39%) and 7 of 73 pregnancies (10%), respectively. The difference was highly significant (p<0.01). Cerebral infarction was observed in 2 patients of LA-positive SLE (18%) and was significantly associated with LA (p<0.05). There was no significant difference between LA-positive and LA-negative patients in frequencies of each manifestation of the 1982 ARA revised criteria for the classification of SLE. However, we found a tendency of lower incidence of serositis in LA-positive patients. The number of items of the revised criteria that LA-positive patients manifested was lower (p<0.05). LA was significantly associated with biological false positive seroreaction for syphilis (p<0.01). Platelet counts and anti-DNA antibody levels were significantly lower in LA positive-patients (p<0.05). We found a new evidence that platelet associated IgG levels were elevated significantly in LA-positive patients (p<0.05). It seems that LA-positive group includes atypical or mild SLE patients according to the fact that LA-positive patients have significantly low levels of anti-DNA antibodies, rare serositis and decreased number of manifestations of the revised criteria, compared with LA-negative patients.

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A 59-year-old man was admitted to the hospital because of polyarthralgia. After admission interstitial pneumonitis and pleuritis developed and a diagnosis of rheumatoid vasculitis was made. Treatment with steroids including pulse therapy was initiated and all symptoms went into remission. Three months after, cough, sputa and dyspnea developed. Invasive pulmonary aspergillosis was diagnosed based upon the findings of the culture of sputa and chest roentogenogram. Amphotericin B could not be used because of adverse reaction. For the treatment of opportunistic infection, the dosage of steroids had to be decreased, but the serum immune complex level went up and polyarthralgia reappeared, suggesting a relapse of rheumatoid vasculitis. Double filtration plasmapheresis (DFPP) was then started for the treatment of rheumatoid vasculitis. The clinical symptoms of the disease improved as the serum immune complex level decreased, while invasive aspergillosis turned to aspergilloma by the treatment of aspergillus and improvement of host immunity. After a series of 18 trials of DFPP, it could be discontinued and immunosupressants were administered instead.
Since DFPP does not affect normal immunity compared with immunosuppressants, although this method is costly, a limited period of DFPP trials is recommended as the treatment for rheumatoid vasculitis during the period of opportunistic infection.

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A case of systemic lupus erythematosus with portal hypertension due to multiple nodular hyperplasia of the liver was reported. A 30-year-old female with systemic lupus erythematosus for the past 7 years was admitted to Sapporo City General Hospital because of hematemesis. She had been receiving prednisolone (about 10mg/day, as a maintenance dose) for over 4 years. Physical examination showed severe anemia and marked splenomegaly. Endoscopic examination, computed tomography scan, echography and scintigraphy of her liver revealed esophageal varices due to portal hypertension.
ON the 8th hospital day, she was subjectted to splenectomy and esophageal transection. The pressure of her potal vein was 27cmH₂O in the operation. The surface of her liver was irregular shape. The surgical liver biopsy revealed multiple nodular hyperplasia of the liver. On the 23rd hospital day, she was died owing to the failure of the sutures and sepsis. The relation ships between multiple nodular hyperplasia of the liver and nRNP antibody was discussed.

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A case with typical lupoid hepatitis whose hepatic histology could be obtained prior to development of the disease, is described. The case was 46 years old female. Since her 32 year old age, she suffered from polyarthralgia. Hypergammaglobulinemia and antinuclear antibody were detected since her 40 year of age. At her 45 year old age, Hashimoto's disease developed. At the same time abnormalities in the liver function test were pointed out. Since then she had repeated acute exacerbation of the liver injury for these 5 years. Thereafter serum IgG concentration was raised, and liver cell membrane antibody and LE cell phenomena became positive. Number of peripheral OKT 4 positive lymphocyte was gradually increased while that of OKT 8 positive lymphocyte fell. By biopsy of the liver, the histological feature changed from chronic hepatitis inactive type to the active one, and finally typical lupoid hepatitis developed during this observation period.
As shown in the present case, immunological abnormalities may be observe preceding the development of lupoid hepatitis.

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A case of systemic lupus erythematosus (SLE) with interstitial pneumonitis developing concurrently with antibiotics administration is reported.
A 50-year-old woman was administered amoxicillin by a practitioner because of fever and arthralgia, but she remained febrile. On admission to our hospital, initial studies revealed leukopenia, positive LE cells, positive antinuclear antibody, high titer of anti-DNA antibodies, and hypocomplementemia. Chest X-ray films showed minimal interstitial changes. The diagnosis of SLE was made and prednisolone, 60mg daily, was started. Her symptoms and laboratory findings, including chest X-ray abnormalities improved, and the dose of prednisolone was tapered. When prednisolone was tapered to 35mg daily, she was given cephalexin for sinusitis. A few days following the antibiotics therapy, fever, cough and dyspnea gradually appeared, and diffuse interstitial changes developed on chest X-ray films. Prednisolone was tapered to 30mg, cephalexin was discontinued, and ampicillin, followed by cefmenoxime were administered. However, her clinical symptoms became progressively worse associated with densely infiltrative interstitial changes in both lungs. Combination therapy with INH and trimethoprim-sulfamethoxazole was added. About one week after the beginning of cefmenoxime, eosinophilia and high level of serum LDH appeared. Drug-induced pneumonitis was suspected and cefmenoxime was discontinued. Consequently, clinical symptoms, laboratory data, and interstitial pneumonitis on chest films improved promptly. Histopathologic examinations of a transbronchial biopsy specimen discolsed alveolar septal thickening with fibrosis, and perivascular lymphocytic infiltration, compatible with the diagnosis of interstitial pneumonitis in healing stage.
To our knowledge, this is the second case of histologically confirmed antibiotics-induced interstitial pneumonitis in SLE. Clinicians should be alerted to the possibility of such complication in SLE patients with pneumonitis being treated with antibiotics.

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