We examined soluble IL-2R in sera of patients with SLE by ELISA using two monoclonal anti IL-2R antibodies. When we examined sera of forty patients with SLE, soluble IL-2R in sera of them significantly increased as compared with normal controls, (SLE; 337.8±188.2U/ml, Normal control; 150.0±35.0U/ml). Sixteen patients (40%) had high titer of soluble IL-2R (more than mean+2 S. D. of normal controls). And then we investigated the clinical findings of patients with high titer of soluble IL-2R. Although in these patients, the peripheral pattern of anti nuclear antibody and pericarditis appeared more frequently than patients with normal titer of soluble IL-2R, there was no significance in anti DNA antibody, CH 50, renal involvement (proteinuria, urine cast), skin involvement, pleuritis, central nervous system involvement, hematological findings. It is known that soluble IL-2R appeared in the culture supernatant of normal peripheral blood lymphocyte stimulated by mitogen (PHA, anti OKT 3 etc.) or in sera of patients with adult T cell leukemia, it is said that soluble IL-2R relate to activated T cells. On the other hand, although it was reported that activated T cells appeared in peripheral blood lymphocytes of patients with SLE, the fact that many patients with SLE had soluble IL-2R in our examination may relate to activated T cells. And therefore, we confirmed them by using various activated T cell marker (HLA-DR positive T cell, HLA-DP positive T cell, IL-2R positive T cell). The patients with high titer of soluble of IL-2R tended to have high positive rate of HLA-DP positive T cells, HLA-DR positive T cells, but not so much IL-2R positive T cell. This results suggest the existence of activated T cells and the relationship between soluble IL-2R and activated T cells. It is said that patients with SLE have T cells abnormality (ex. the decrease of mitogen response, auto mixed lymphocyte reaction, IL-2 production, IL-2 response) and activated T cells, and it is suggested that these abnormality related to the pathogenesis of SLE. Our results confirm the existence of activated T cells, in patients with SLE and suggest the possibility that soluble IL-2R could be used as the marker of activated T cells or the new barometer of disease activity, although it is not clear how activated T cells relate to pathogenesis or clinical findings of SLE. And, although the immunological role of soluble IL-2R is not clear, it may be one of clue in the investigation of pathogenesis of SLE.

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When a streptococcal preparation OK-432 was intraperitoneally injected for the treatment of carcinomatous peritonitis, antitumor PMN accumulated in the peritoneal cavity. Increases of C5a, thromboxane B₂ and leukotriene B₄ were observed before the accumulation of PMN in ascitic fluid. Here, we examined mechanism of this PMN accumulation using an in vivo system in rats employing anticomplementary reagents and proteinase inhibitors. FUT-175, EDTA and K 76 inhibited C5a generation by OK-432 in vitro, but EGTA, FOY and urinastatin did not. In in vivo experiments, EDTA, FUT-175, anti-rat C3 serum, K 76, FOY and urinastatin reduced the accumulation of PMN onto filter membranes, when these reagents were reacted with OK-432 for 3hrs through filter membranes placed on the turned peritoneum in rats. EGTA did not inhibit PMN accumulation. This inhibition of PMN accumulation were confirmed by histological examination. It is suggested that complement-derived chemotactic factor C5a generated by OK-432 induces PMN accumulation in association with clotting, fibrinolytic and kinin systems.

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The natural killer (NK) activity of peripheral blood mononuclear cells in 144 patients with the colorectal carcinoma and 60 healthy individuals as control group was measured and evaluated.
NK activity was significantly lower in patients with lymphnodes metastasis or distant metastasis than in healthy control group. In contrast there was no significant difference of NK activity between the patients without any metastasis and healthy control group.
The serial monitarings of pre- and opst operative NK activity demonstrated almost unchanged level of the activity except for the temporal decrease of the activity during three weeks after the initial operation.
NK activity in colorectal carcinoma patients with lymphnodes metastasis was low throughout any period, although the curative resection of the carcinoma was made.
There was a significant positive correlation between the NK activity and T_γ% of peripheral lymphocyte subpopulation.
Among subpopulation of peripheral blood mononuclear cells classified by monoclonal antibody, NK activity showed the positive correlation with the cell percentage of OKM1⁺ or Leu7⁺ cells, and the negative correlation with the cell percentage of OKT4⁺ or OKT3⁺ cells.

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Lymphokine-activated killer (LAK) cells can be generated by the incubation of peripheral blood mononuclear cells (PBMC) in the presense of interleukin 2 (IL 2). However, activity of these cells are frequently deppressed in tumor bearing hosts. In order to analyze a mechanism inhibiting induction of LAK activity, the effect of adherent cells on induction of LAK activity was investigated in the patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC).
Though LAK activity from nonadherent PBMC of the patients with HCC was deppressed in the presense of low concentration of IL2, sufficient activity was induced by high-dose of IL 2.
Adherent cells of the patients with HCC inhibited induction of LAK activity and this suppression was prevented by adding indomethacin. High concentration of PGE₂ was detected in the culture medium of LAK induction system in the presense of adherent cells of the patients with HCC. The same concentration of PGE₂ added in LAK induction system of normal controls suppressed LAK induction from NK cells in the early phase.
These results suggest that PGE₂ produced by adherent cells inhibits LAK induction from NK cells in early phase in the patients with HCC.

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An enzyme-linked immunosorbent assay (ELISA) was developed to detect polypeptide coded by the pre-S (2) region of hepatitis B virus (HBV) DNA with monoclonal antibody in 120 sera containing hepatitis B virus surface antigen particles. Binding sites for polymerized human serum albumin (pHSA) have been found to be encoded by the pre-S (2) region of hepatitis B virus genome. There can be seen a close correlation between the titers of pre-S (2) polypeptide and those of HBV-pHSA receptor (HBV-pAR) (HBV-asymptomatic carrier: r=0.826, P<0.01, chronic hepatitis: r=0.787, P<0.01). The titers of pre-S (2) polypeptide of sera from 75 hepatitis B e antigen (HBeAg) positive carriers (mean±SD) was 92±9 in asymptomatic carrier (ASC), 78±21 in chronic persistent hepatitis (CPH), 66±31 in chronic aggressive hepatitis activity moderate (CAH2A), 44±28 in chronic aggressive hepatitis activity severe (CAH2B), 30±6 in liver cirrhosis (LC), and 21±30 in 15 anti-HBe positive ASC. Under interferon treatment in patient with CAH2B, the titer of pre-S (2) polypeptide as well as HBV-pAR activity was significantly reduced before HBeAg was reduced and the serum transaminase was normalized. These results suggest that the ELISA described for detection of pre-S (2) polypeptide might be useful as a prognostic test for HBV-carriers.

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In order to examine the immunological avidity of F (ab')₂ fragment of monoclonal antibody generated against a human renal cell carcinoma cell line (C5H), a binding assay was performed against human renal cell carcinoma cell lines using iodinated intact C5H and it's F(ab')₂ fragment. Stable production of F(ab')₂ fragments were obtained by pepsin digestion at pH3.5. The fragments were purified by affinity and gel-filtration chromatography in acceptable yield. This binding assay indicates that F(ab')₂ fragments retain almost the same immunological fraction (51.2%) and avidity (4.7×10⁵/cell) as the intact antibody (49.9%, 5.2×10⁵/cell), even after the enzyme digestion and iodinating procedures.
Based on these findings, it was concluded that the iodinated F(ab')₂ fragments can be applied for further in vivo radioimmunodetection assay.

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Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are known to be as enzymes of purine salvage pathway. ADA isoenzyme including ADA1 and ADA2, and PNP activities were measured in sera of 28 patients with adult T-cell leukemia (ATL). Nine cases with acute ATL, 6 lymphoma ATL, 10 chronic ATL and 3 smoldering ATL were subjected in this study. Sera of 21 healthy carriers with positive for anti-ATLA antibody and 86 normal individuals were also tested for the enzyme activity.
ADA isoenzyme and PNP activities were found uniformly higher in sera of the patients with ATL than that of the normal controls. In sera from the patients with acute (12.4±4.8, P<0.01)and lymphoma ATL (12.8±5.9, P<0.05), ADA1 activity was significantly elevated as compared with chronic ATL (5.1±2.3). No significant difference in ADA1 activity was noted in both smoldering ATL and healthy carriers as compared with chronic ATL. ADA2 activity was elevated in sera of ATL patients (P<0.05) as compared with healthy carriers. PNP activity was found to be increased in sera of patients with acute ATL (8.3±4.0, P<0.05) as compared with both lymphoma (3.2±2.9) and chronic ATL (5.1±2.3), respectively.
These data indicate that the ADA and PNP activities in sera of ATL patients reflect the condition of this disease. To measure of these purine metabolic enzyme activities may provide an additional parameter for distinguishing subtypes of ATL and may prove to be considerable prognostic and therapeutic monitors in ATL cases.

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When a streptococcal preparation OK-432 was i. p. injected for the treatment of carcinomatous pleuritis and peritonitis, anti-tumor polymorphonuclear leukocytes (PMN) accumulated into the cavity. We proved that PMN accumulated from the peritoneum into the peritoneal cavity and chemotactic factors derived from the complement played a significant role on the accumulation in rats. Here, we examined the association of arachidonic acid metabolites with the PMN accumulation using in vivo system in rats. When various kinds of inhibitors of arachidonic acid cascade were reacted with OK-432 for 3 hrs through filter membranes placed on the turned peritoneum of rats, prednisolone and indomethacin reduced the accumulation of PMN onto filter membranes. OKY 046, AA 861, and azelastine also inhibited PMN accumulation in a dose-dependent manner, and these inhibitions were confirmed by histological examination. On the other hand, STA₂ promoted PMN accumulation. These reagents did not inhibit C5a generation by OK-432 in vitro. It was concluded that chemotactic factors derived from arachidonic acid cascade such as TXA₂, HETEs, and LTB₂ were associated with PMN accumulation by OK-432.

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The production of interferon γ (IFN-γ) by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) was examined in 19 patients with uterine cervical cancer and 28 controls without cancer. The mean IFN-γ production of the cancer patients was significantly lower than that of the controls (P<0.05 in early cancer, P<0.01 in advanced cancer). The depletion of adherent monocytes from PBMC resulted in an increased IFN-γ production in 68% of the cancer patients and in 38% of the controls. The addition of indomethacin (1μg/ml) to PHA-stimulated cultures of PBMC enhanced IFN-γ production in both cancer patients and controls. However, this increase in IFN-γ production was significantly higher in cancer patients than in the controls (P<0.05).
These results suggest that depressed IFN-γ production in patients with uterine cervical cancer is due to monocytes which produce a mediator capable of suppressing INF-γ production, namely, prostaglandin E₂.

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NZB/W F₁ mice, animal models of systemic lupus erythematosus (SLE), have age dependent loss of interleukin-2 (IL-2) productions and response to IL-2. But it has not been known whether in vivo administration of IL-2 is effective on disease of NZB/W F₁ mice. The studies have been done in two protocols: one is short term (1 month) study and another is long term (6 month) study. We examined the effects of human recombinant IL-2 (rIL-2) on proteinuria, survival, syngeneic mixed lymphocyte reactions (SMLR), and autoantibody productions. We had following results:
1. In short term study, the administrations of rIL-2 have no effects on IL-2 productions and proliferative responses to IL-2. But, in vivo IL-2 administration recovered significantly SMLR in 16 week age of NZB/W F1 mice.
2. In long term study, IL-2 administration had no effects on production of IgM class anti-dsDNA antibody, but suppressed significantly IgG class anti-dsDNA antibody production. Reduction of profuse proteinuria and improvement of survival rate were also observed.
In conclusion, IL-2 treatment might have some beneficial effects on SMLR and anti-dsDNA antibody production in NZB/W F1 mice.

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Eosinophilic fasciitis was observed in a 43-year-old woman who developed subcutaneous induration of the distal extremities accompanying peripheral eosinophilia. This patient showed the decreased power of grasp and gait disturbance due to flexion contracture of the knees. On admission, laboratory examinations revealed peripheral eosinophilia, positive CRP, a slightly high titer of ANA, positive LE test and elevated level of immune complex. The deep fascias remarkable thickened with infiltrated mononuclear cells which were detected in the biopsy specimen of the lesion. Application of corticosteroid resulted in dramatic improvement on the mobility of her knee joints in two days. Laboratory data revealed normal level of eosinophils and immune complex, negative CRP, ANA and LE test after the treatment. Early diagnosis and steroid therapy are inevitable in such cases associated with progressive systemic sclerosis without involvement of internal organs as this case reported here. It was suggested that eosinophilic fasciitis might be included in one of the autoimmune disease according to the findings of butterfly rash, positive LE test and ANA observed in this case.

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The patient was a 55-year-old male, and had received intermittent hemodialysis due to renal failure since February 1985. He was admitted to our hospital on July 16, 1986 due to cough and high fever.
Chest X-rays showed pleural effusion of the right lung and Bone X-rays revealed compression fractures of the 12th thoracic and 2nd and 5th lumbar spines.
Bone marrow aspirates revealed sheets of abnormal plasma cells. Repeated serum protein electrophoresis showed a marked M-spike in the beta region, which was immunologically identified as IgE lambda type protein. Associated Bence Jones protein of lambda type in the urine was also found.
The patient was treated with cyclophosphamide and steroid, but pleural effusion increased bilaterally. He died of dyspnea on December 4, 1986.
The clinical and laboratory features of IgE myeloma were compared with those of the 23 cases previously reported as myeloma.

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An immunohistological examination of colonic mucosa was performed on a case of hypereosinophilic syndrome presenting eosinophilic gastroenterocolitis.
A 63-year-old male was admitted to our hospital because of watery diarrhea and cerebral infarction in July, 1986. One month earlier, watery diarrhea gradually developed and had persisted every day. On admission, the patient presented right hemiplegia, remarkable eosinophilia, and a great deal of diarrhea. A biopsy of the sigmoid colonic mucosa through the gastrointestinal endoscopy revealed the accumulation of eosinophils, lymphocytes, and plasma cells in the lamina propria. Treatment with corticosteroids resulted in clinical remission, then he was discharged in October, 1986. He again entered the hospital because of seizure in August, 1987. Examination of the blood and the bone marrow showed marked eosinophilia with a normal morphological appearance. During the hospitalization the patient suffered from chronic watery diarrhea and relapsing eczema, subsequently he had become emaciated. There were no evidences of parasitic infection nor possible food allergy. An immunohistological study of the colonic mucosa showed diffuse infiltration of eosinophils accompanied with numerous IgA-containing plasma cells and a small number of IgG- or IgM-containing cells. The composition of IgA-, IgG-, an IgM-containing cells was just same as the one of normal mucosa previously reported. The pulse therapy with methylprednisolone had completely removed the infiltrated eosinophils of colonic mucosa and he was relieved from the diarrhea.
Although we could get no direct evidence that the immunological mechanism had effects on the pathogenesis of his diarrhea, his course after corticosteroid-therapy suggested that the mechanism worked at the time.

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We report a 38-year-old female with Sjögren's syndrome associated with renal tubular acidosis. She was also complicated with psuedofracture due to osteomalacia. She was admitted to Sapporo City General Hospital because of pain in her right thigh and difficulty in walking. X ray film revealed pseudofracture of her neck of right femur. Bone scanning showed abnormal multiple accumulations of RI on the same parts and bilateral ribs. Laboratory data showed metabolic acidosis, hypocalcemia, hypophosphate and elevation of alkaline phosphatase.
Distal renal tubular acidosis was suggested by the sodium bicarbonate and the NH₄Cl loading test. Since Keratoconjunctivitis and chronic sialoadenitis was ascertained, a diagnosis of osteomalacia in Sjöbgren's syndrome secondary to renal tubular acidosis was made. The metabolic acidosis and bony pain improved by the treatment with sodium bicarbonate and 1α-OH-D3. Sjögren's syndrome with pseudofracture due to osteomalacia is very rare but we should be aware of these complications.

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We examined the activity of the hepatitis B virus (HBV) associated polymerized humanserum albumin receptor (HBV-pAR) and the antibody to HBV-pAR (anti-pAR) in the sera from 14 patients of chronic hepatitis B treated with interferon (IFN) by _??_enzyme-linked immunosorbent assay (ELISA). Seroconversion (SC) of HBeAg was observed in 4 cases at the end of the IFN therapy (treatment), and in 4 cases 6 months after treatment. These cases as above had low HBV-pAR activities before treatment or rapidly decreasing HBV-pAR activities during the treatment. In cases whose HBV-pAR activities decreased minimally during the treatment in spite of the temporal disappearance of HBeAg after the treatment, it reappeared with the exacerbation of S-GPT. On the other hand, S-GPT remained in normal range in the cases with low HBV-pAR levels and positive anti-pAR antibody at the time of SC.
These results indicate that HBV-pAR activity and anti-pAR antibody might be more useful markers for determing the outcome of hepatitis B patients treated with IFN.

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