Prostaglandins (PGs) are generated by the lung with physiologic stimuli. There are many evidences that PGs are involved in immediate hypersensitivity reactions and their pathophysiologic roles in bronchial asthma have been suggested. Even then, the significance of their roles has not yet been established at the in vivo level in clinical studies.
We describe here an efficient method for simultaneous and quantitative determinations of plasma PGs from bronchial asthmatic patients using reversed-phase HPLC.
An overnight reaction of plasma PGs with 9-anthryldiazomethane (ADAM) was performed at room temperature. The mixture was loaded on GPC column to avoid interferences for the assay and PG-ADAM fraction was collected. The fraction was loaded on ODS column and was eluted with water-methanol gradient at 40°C. Fluorescence of PG-ADAM was measured in fluorometer with excitation at 350nm and emission at 412nm. Detection and simultaneous quantitation of 20pg PGE₁, PGE₂ and 100pg 6-keto PGF₁α, thromboxane B₂ was possible.

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An advanced flowcytometric technique for measuring phagocytosis of the Leu-M3 positive cells was developed. A 500 micro-litters of heparinized blood sample was mixed with 200 microlitters of fluorescent latex beads suspension and incubated at 37°C. The sample was then hemolysed and stained with FITC labelled monocyte-specific monoclonal anti-Leu-M3 antibody. Two color analysis was then applied, and the cells were discriminated by the positivity of Leu-M3 and the number of beads taken. The cells of each group were then sorted, and collected for morphological observations with non-specific esterase staining and for fluorescent microscopic observations. This method has the advantages of less blood required and easy processing of many samples at one time. The mean values of the phagocytosis of peripheral blood monocytes from health were 22.5±8.1% (1 hr), and 43.3±14.8% (2 hr).

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Effects of lymphokines, OK-432 and indomethacin on EB-virus specific cytotoxic T lymphocyte (EBV-CTL) activity were tested, and the results were as follows. Recombinant interleukin 2 (RIL-2, 0.2U/ml) and recombinant interferon α (RIFN-α, 500IU/ml) enhanced the EBV-CTL activity when added 18 hours before CTL assay. Recombinant interferon γ (RIFN-γ, 500IU/ml), OK-432 (0.01KE/ml) and indomethacin (1μg/ml) did not enhance the EBV-CTL activity. RIL-2 and RIFN-α did not enhance either the EBV-CTL activity against allogeneic lymphoblastoid cell-line or K-562 cells, and also did not enhance the EBV-CTL activity of seronegative individuals.
RIL-2 and RIFN-α can enhance the EBV-CTL activity specific for EB-virus and enhanced EBV-CTL should be MHC restricted activity.

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It has been recognized that monocyte-macrophage lineages play an important role in host defense mechanism against neoplasia. This study was designed to compare the qualitative and quantitative function of tumor infiltrating and regional lymph node' macrophages with peripheral blood monocytes. For this purpose a rapid and reproducible system for macrophage phagocytosis assay using flow cytometry has been developed. With the progression of gastric cancer, the phagocytic activity of monocyte was significantly increased in stage 3 and stage 4 diseases, although the number of monocytes and serum levels of C3 and IgG values were within normal range. On the other hand, the number of macrophages in gastric lesions and regional lymph nodes increased gradually, and extensively in stage 3 disease, turned to decrease in stage 4 disease. Numbers of macrophages were increased in the order of gastric tumors, the first, and the second regional lymph nodes. However, there were no significant diferences in their phagocytic activities between macrophages located close to and apart from the tumors.

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We examined the antibodies to adult T-cell leukemia-associated antigen (anti-ATLA) in the sera from 858 cases of healthy residents, 302 cases with hematologic malignancies and 63 cases of autoimmune disease. Anti-ATLA was detected by the indirect immunofluorescence assay or enzyme linked immunosorbent assay.
The positive rate of anti-ATLA was 17.2% (148/858)in healthy residents, 98.3% (174/177) in the patients with adult T-cell leukemia-lymphoma (ATLL), 87.5% (7/8) mycosis fungoides, 53.3% (8/15) Hodgkin's disease, 15.0% (9/60) other lymphoproliferative disorders, 11.9% (5/42) myeloproliferative disorders and 22.2% (14/63) autoimmune disease. The positive rate of anti-ATLA in the patients with ATLL, mycosis fungoides and Hodgkin's disease were significantly differed from that of human T-cell leukemia virus (HTLV-1) healthy carriers in Kagoshima district. However, clinical and pathological diagnosis of mycosis fungoides and Hodgkin's disease was difficult in the ATLL endemic area such as Kagoshima district, so further investigation was needed. While the incidence of anti-ATLA in the patients with other lymphoproliferative disorders and myeloproliferative disorders were not differed from that of HTLV-1 healthy carriers.
In autoimmune disease, the positive rate of anti-ATLA in the patients with rheumatoid arthritis (RA) was 22.7% (5/22) and that of systemic lupus erythematosus (SLE) was 25.7% (9/35). Four out of 9 patients with RA and six out of 10 patients with SLE who were found to have had blood transfusion, were positive for anti-ATLA. Then, in these disease, the positive rate of anti-ATLA in the patients without blood transfusion were 7.7% (1/13) and 12.0% (3/25), respectively. From these deta, a possible role of HTLV-1 in the etiology of autoimmune disease was not established.

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Total hemolytic complement (CH 50) and the serum levels of C3 and C4 were measured in 9 healthy male subjects for three months every week, in order to demonstrate the intra-individual variation in healthy subjects.
The mean values of intra-individual physiological variations in 9 subjects were as follows; CH 50: Standard Deviation (SD) 2.0unit/ml and Coefficient of Variation (CV) 5.0%, C3: SD 14% and CV 10%, and C4: SD 15% and CV 12%.
There was no correlation between CH 50 and the serum levels of C3 and C4. Hypocomplementemia was not seen. Elevated levels of CH 50 were observed in 5 subjects when they showed signs of common cold.
It may be important in assessing alterations of complement value in various disease states to consider about such intra-individual variations of complement in healthy subjects.

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Fifty-five patients who showed increased number of atypical lymphocytes (over 10% of total white blood cell count) were classified into four groups according to their titers of anti-Epstein-Barr virus (EBV) antibodies. The clinical and hematological findings, serological tests liver chemistries, serum immunoglobulin levels and lymphocyto surface phenotype in peripheral blood were examined in each group to delineate the clinicopathological features of infectious mononucleosis (IM) and IM syndrome (IMS) in Japan.
1. Less than half of the cases of IMS studied here were defined as IM, which is caused by primary infection of EBV, although the early antigens of EBV specific antibadies, examined by immunofluorescence technique, were hardly detected in some cases.
2. Clinical features of IM in Japan are quite similar to those in western countries except for the age distribution, which has two incidence peaks, in the first and third decades.
3. As for liver chemistry in IM, serum γ-GTP and alkaline phosphatase are elevated in comparison to HA-related IMS in which GOT is markedly elevated. This suggests that the main lesion of IM in the liver is in periportal and sinusoidal areas.
4. The elevation of serum IgE levels in IM is noteworthy in view of the high incidence of drug allergies and an expression of Fcε receptor/CD 23 by EBNA.
5. The clinical features of non-EBV-related IMS in Japan are as follows. The causal agent was unknown in more than half of the cases. The disease was common in childhood. In such cases, signs and symptoms and abnormal liver chemistry and immunoglobulin levels were similar to those of definite IM cases, but were milder.
6. MST, which is a simple test for detection of heterophil antibodies, were positive in 82% of the definite IM cases and in one-third of non-EBV-related cases. This suggests that MST is of clinical use in diagnosing IMS but is not necessarily specific for EBV infection.
7. Lymphocyte surface phenotype assay in peripheral blood showed low OKT 4+/8+ ratio in all groups, and increase of OKTIa 1+ cell only in IM.

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Lymphokine activated killer (LAK) cells are generated by a culture of lymphocytes with interleukin 2 (IL 2) without the need for any additional antigenic stimulation. LAK cells can lyse a wide spectrum of allogeneic and syngeneic tumor cells regardless of whether the tumor target cells are sensitive or resistant to fresh natural killer (NK) cells. In these studies, the functional characteristics of LAK cells by using metabolic inhibitors were investigated. The following results were obtained:
(1) Human peripheral blood lymphocytes were cultured in the presence of 2units/ml of human recombinant IL 2 (TGP-3, Takeda, Osaka), the dose of which is routinely used for the activation of LAK cells in human pilot studies. The killing activity was generated within 4 days and continued for more than 14 days.
(2) LAK cells generated by a higher dose of rIL 2 (2units/ml), are resistant to inhibitors for lipid peroxidation such as dimethylsulfoxide, ethyl alcohol, and nordihydroguaiaretic acid, while NK lineage killers such as fresh NK cells and killer cells activated by a lower dose of rIL 2 (approximately 0.02unit/ml) according to the method of Itoh et al. are sensitive to those reagents.
It is concluded that LAK cells induced by a relatively higher dose of rIL 2 have different lytic pathways from killer cells of NK lineage, and LAK activity appears to be derived from phenotypically heterogenous population and confined to any single subpopulation.

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Pleural fluids obtained from 17 patients- 7 with malignant pleurisy, 6 with infectious pleurisy, 4 with transudative pleurisy were analyzed for total hemolytic complement titers (CH 50), levels of six complement (C) components (C1q, C1s, C4, C3, factor B and C5), conversion products of C3, immune complexes (IC) and anti-complementary activities. The mean levels of each CH 50, C4 and C3 in the malignant group were significantly reduced compared with those in the infectious group (P<0.001, P<0.01, P<0.1 respectively) and also those in the transudative group (P<0.01, P<0.1, P<0.05 respectively). The mean level of C1q in the malignant group was lower than that in the infectious group (P<0.001). The mean level of conversion products of C3 in the malignant group (P<0.05) as well as that in the infectious group (P<0.1) increased compared with the transudative group. Neither IC nor anti-complementary activities were found in the malignant group. The above results suggested that the binding of tumor-specific antibodies to tumor cells might activate classical C pathway mainly and cause C depletion in malignant pleural effusions.

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The effect of interleukin 2 (IL 2) on the primary antigen-specific immunoglobulin production of human peripheral blood mononuclear cells (PBMC) has been unknown yet. It has already been reported that human PBMC respond to sheep red blood cells (SRBC) in vitro and produce SRBC-specific immunoglobulin secreting cells (IgSC). Hence, it seems interesting to study how human recombinant IL 2 works in SRBC-specific immunoglobulin production of human PBMC.
Utilizing this in vitro system, we showed that human recombinant IL 2 increased antigen-specific IgSC at the moderate concentration (100 u/ml). However, it did not increase antigen-specific IgSC at the higher concentration (1, 000 u/ml). SRBC-specific IgM antibody produced in the culture was also assessed utilizing the enzyme-linked immunosorbent assay, and it was also shown that the moderate concentration of IL 2 (100 u/ml) augumented antigen-specific IgM antibody production, but the higher concentration of IL 2 (1, 000 u/ml) did not. The reason why IL 2 at the high concentration did not augment the immunoglobulin production was discussed in this paper.
Anti-Tac is a well-known IL 2 receptor antibody. When anti-Tac was added to the culture of PBMC and SRBC, anti-Tac markedly inhibited the expansion of IgSC (20μg/ml), and it was shown that endogenous IL 2 was required for the induction of SRBC-specific IgSC. When recombinant IL 2 was added to the cultures in the co-presence of anti-Tac (20μg/ml), immunoglobulin production and expansion of IgSC were restored at the high concentration of exogenous IL 2 (1, 000 u/ml). In the further experiment, IL 2 was added to the culture of PBMC and SRBC on day 0, day 3, or day 6, while anti-Tac was added to the other culture on day 0, day 2, day 4, or day 6. IL 2 augmented the number of IgSC when added to the culture by day 3, and anti-Tac inhibited the expansion of IgSC when added to the culture by day 4.
In this report, we demonstrated that the interaction between IL 2 receptor and IL 2 generated endogenously was required in the antigen-specific immunoglobulin production. The addition of exogenous IL 2 at the moderate concentration to the culture remarkably augmented the antigen-specific immunoglobulin production and increased the number of antigen-specific IgSC. The presence of IL 2 on day 3 and 4 in this 8-day culture was essential for the expansion of antigen-specific IgSC.

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We report a 47-year-old woman with Sjögren's syndrome associated with protein-losing enteropathy. She also complicated with chronic thyroiditis. She was admitted to our hospital because of anasarca. Serum albumin was 1.6g/dl and total serum cholesterol 252mg/dl. Renal and hepatic function tests were normal. Quantitative urinary proteins showed a 24 hour excretion of 200mg. A diagnosis of protein-losing enteropathy was made by abnormal excretion of ¹²⁵I-polyvinylpyrrolidone. Endoscopic intestinal biopsies revealed edema, mild mononuclear cell infiltration, mildly dilated lymphatic vessels and deposits of C3 and fibrinogen in the walls of capillaries in the lamina propria of villi. Her protein-losing enteropathy responded to high-dose corticosteroid therapy. Lymphatic vessels remained dilated after resolution of protein-losing enteropathy. These findings suggest that increased capillary permeability may be the cause of protein-losing enteropathy in this case.

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A family including a mother with SLE and daughter with PSS is reported. The mother developed multiple purpura in the legs at age 64. When she referred to a local hospital in July 1982, she had positive antinuclear antibody, leukopenia, thrombocytopenia, proteinuria and hematuria. She was diagnosed as SLE and treated with prednisolone 60mg per day.
Thrombocytopenia was quickly controlled, and purpura disappeared by her dischange in August. In January 1986, she had polyarthralgia and positive anti-DNA antibody.
The onset of the daughters disease was at age 37 in October 1983, when she noted polyarthralgia, Raynaud's phenomenon and sausage-like swelling of fingers. At admission to our hospital in September 1984, she had proxismal scleroderma, digital pitting scars, systemic hyperpigmentation and positive ANA. Both mother and daughter had HLA DR5.
Eleven families have been reported in international literature and 2 families in Japan. In these reports, most patients showed overlapping nature, and most primary patients were PSS. Two families including our patients in Japanese contained the same DRW 11 (5).

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