Develop-ment-mechanism of chronic glomerulonephritis (the contracted kidney) was discussed in this paper, on the basis of both clinical observations which has recently been accumulated especially from comparative studies on (a) vascular and glomerular changes of chronic glomerulonephritis, lupus nephritis, diabetic nephropathy and so on and (b) a new experimental animal model of adult human chronic glomerulonephritis, which is induced in homologous animals by a single footpads injection of nephritogenoside.
Nephritogenoside was isolated and purified from the glomerular basement membrane of normal and healthy rats. Nephritogenoside has no antigenic activity but has biologic activity that induces, chemically, chronic glomerulonephritis (the contracted kidney) . Chemical structure of the active portion of nephritogenoside (sugar portion) has already established as follows; Glc (α1→6) Glc (β1→6) Glc (α1→NHCO-peptide) (a synthesized compound (Glc (α1→6) Glc (β1→6) Glc (α1→NHCO-Asn or Gln) showed the same ¹³CNMR specrum with the sugar portion of nephritogenoside)

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α₁-antichymotrypsin (α₁AC) is known to specifically inhibit the activity of chymotrypsin-like proteases, and considered to be one of the acute phase reactants. In our previous study, the α₁AC level was increased in gastric juice from the patients with gastric cancer, when compared to those in benign gastrointestinal disorders or normal controls, α₁AC was purified from serum using the method of salting out and gel chromatography which was modified from the method of Travis, et al. The moleculer weight of the purified α₁AC was 58, 000 daltons by SDS-polyacrylamide gel electrophoresis, which was completely identical to the report by Lame and Hayem. The new highly specific and sensitive radioimmunoassay (RIA) was established for α₁AC. The RIA was prepared using the purified α₁AC and anti-α₁AC antibody commarcially available. The α₁AC level was first determined in some human body fluids, such as gastric juice, bile, ascitic, pleural, cerebrospinal and synovial fluids.

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The mefenamic acid is an acidic type of non-steroidal antiinflammatory drugs. In a new view, the effects in the complement system, parameters of inflammation, proteinogram and various serum proteins were studied before and after oral administration of 750 mg of it for 4 weeks. Statisfactorily significant decrease was obtained on C4, C3 and factor Bb as components of the complement, ESR, CRP, fibrinogen and IgG. On α₁-antitrypsin, α₁-acidglycoprotein, haptoglobin and IgA were found the tendency of decreasing. These data suggest the effect of antiinflammation and some correlation between complement and parameters of the inflammation, then the complicated network of the correlation with coagulation, fibrinolysis, kinin-kallikrein, prostaglandin, complement and renin-angiotensin systems is discussed.

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It has been studied if radical oxygen involves in the formation of a hemorrhagic inflammation in the testis of rats intoxicated with CdCl₂. H₂O₂ production in rats testis increased significantly at 24 hrs after CdCl₂ injection (5.0 mg/kg) and it reached the highest value at 48 hrs. The curve of H₂O₂ production was very similar to that of heme protein contents in the testis with time course. Enzyme activities of catalase, glutathione peroxidase and glutathione reductase increased simultaneously, whereas superoxide dismutase activity was convertly depressed in the testis of intoxicated rats. On the other hand, in the liver where no inflammatory change manifested in the testis was observed, there was no increase of radical oxygen production and the activity of catalase rather decreased. These results indicate that CdCl₂ administration increases the formation of radical oxygen, and it followed by the occurrence of tissue damage (lipid peroxidation and denaturalization of protein) . The difference in the occurrence of radical oxygen between liver and testis may have a significant meaning for interpreting the tissue difference against the injury of CdCl₂.

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The treatment of human peripheral lymphocytes with CCA (N- (2-carboxyphenyl) -4 chloranthrannilic acid disodium) or D-penicillamine (d-PC) in culture for 1 hour, 3 or 5 days could augument the natural killer (NK) activity of the lymphocytes at concentrations rangind from 0.1 to 10 μg/ml. However, both drugs could not augument the antibody-dependent cell cytotoxicity (ADCC) of the lymphocytes. The CCA but not D-PC could induced interferon production from the lymphocytes in co-culture for 3 or 5 days.

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In order to clarify the correlation between autoimmunological phenomena and coagulation/fibrinolytic reactions in systemic lupus erythematosus (SLE), coagulation/fibrinolytic functions were studied in 20 patients with SLE; 9 of whom were in active stage and 11 were in inactive stage. And in one of them serial changes of autoimmunological reactions and coagulation/fibrinolytic reactions were observed for about 2.5 years until today from the onset of SLE. The results obtained were as follows : 1) Significant increase of plasma β-thromboglobulin level and significant decrease of plasma plasminogen and antithrombin III (AT-III) levels were observed in active SLE compared with those in inactive SLE. 2) There was a significant positive correlation (r=0.77) between serum CH50 and plsma AT-III levels in 20 cases with SLE. And in one of them CH50 and AT-III changed in parallel with each other. 3) Plasma von Willebrand factor activity (FVIIIR: WF) level was mildly higher in active SLE than that in inactive SLE. And in one case with SLE FVIIIR: WF changed in opposition to CH50 and AT-III. These results indicate that disease activity, vasculitis and hypercoagulability of blood may be intensely related to one another in SLE, that is, in parallel to the disease activity thrombogenesis may be accelerated.

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Prednisolone is oftenly used for the treatment of chronic active hepatitis (CAH), but it's therapeutic effect and mechanism of action are still unclear. Recently antibody dependent cellmediated cytotoxicity (ADCC) has been proved to be an important mechanism of liver cell injuries. This paper reports the effect of prednisolone on K-cell (the effector cell of ADCC) in vivo and in vitro experiments. K-cell assay was performed by plaque method using S-RBC as a target cell. Oral administration of prednisolone decreased the number of K-cell of peripheral blood lymphocytes in CAH (P<0.01) and clinical improvement was observed at the same time. In vitro study, prednisolone suppressed the human K-cell (P<0.05) at a low pharmacologic concentration such as 0.1 μg per ml. And the suppression of K-cell by prednisolone showed a dose response and was more prominent in male than in female. This suppression of K-cell by prednisolone was observed only when the lymphocytes were preincubated with prednisolone before mixing with anti S-RBC antibody. Washing the lymphocytes free of prednisolone reduced the suppression. On the contrary prednisolone did not suppress the K-cell when it was added to the lymphocytes after mixing with anti S-RBC antibody.

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The immunoglobulin classes (Ig) /complement fixation (CF) of anti-dsDNA and immune complexes were studied in sera from 12 SLE patients with digital ulcer and/or gangrene. These immunological examinations were also done in sera from 41 SLE patients with other clinical manifestations of vasculitis including leg ulcer, livedo, thrombophlebitis, peripheral neuropathy, aseptic bone necrosis and Raynaud's phenomenon. The Ig classes and CF of anti-dsDNA in sera were assessed by Crithidia IF technique. The precipitation with polyethylene glycol and the C1q solid-phase enzyme immunoassay were used to detect circulating immune complexes. SLE patients with digital ulcer and/or gangrene had high titer and high positive rates of anti-dsDNA. IgG and IgA of anti-dsDNA were found to be significantly greater in the patients with digital ulcer and/or gangrene. The patients with digital ulcer and/or gangrene had also high titer of immune precipitates that included IgG and IgA. However, these patients had low incidences of CF of anti-dsDNA, low C1q binding activity, and nearly normal complement levels in sera. This result differed from the findings in active lupus nephritis. Almost all groups of clinical manifestations of vasculitis were normal or revealed high levels of complement in sera. Especially, in SLE patients with leg ulcer and livedo the complement in sera significantly increased more than that in sera from patients with other clinical manifestations of vasculitis.

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Peripheral polymorphonuclear leukocytes of patients with rheumatoid arthritisa (RA) showed stronger spontaneous cytotoxicity against synovial cells of patients with osteoarthritis than peripheral lymphocytes of the patients with RA.

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Anti-arthritic effect of a newly synthesized immunomodulating drug, Lobenzarit (CCA: 4-chloro-2, 2-imminodibenzoate), was evaluated in rat experimental arthritis, which was induced by the injection of antigen into the left knee joint cavity of the rat previously immunized with methylated bovine serum albumin in Freund's complete adjuvant. Pretreatment with 10 to 200 mg/kg of oral daily doses of CCA for 14 days suppressed the development of arthritis in terns of infiltration of the mononuclear cells into the synovium. However, continuation of CCA treatment after immunization abolished the inhibition of arthritis development. These findings indicate that CCA inhibits the immune response in normal rats, in contrast, CCA enhances it in immunosuppressed rats when they were sensitized with antigen.

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Concomitant effects of CCA, an immunomodulating agent, with one of the nonsteroidal antiinflammatory drugs, indomethacin were investigated in the preventive and curative experiments of rat adjuvant arthritis and the following findings were obtained. (1) No remarkable effect was found on the inhibition of suelling in hind legs. (2) In the prophylactic treatment, an increase of ESR was suppressed and the changes of wet weights of thymic and spleen tissues were inhibited. (3) Concomitant use of CCA with indomethacin improved the bone lesions of hind legs in both preventive and curative experiments.

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