Mammalian tissues or cells produce significant amounts of so called active oxygen species such as O^-₂, H₂O₂, ·OH, and ¹O₂ under certain physiologic and pathologic conditions. ClO^- and lipid peroxides are sometimes included in the same category. In polymorphonuclear leukocytes, an NADPH oxidase system present in the plasma membrane converts molecular oxygen (O₂) stoichiometrically into superoxide anion (O^-₂), which dismutates into hydrogen peroxide (H₂O₂) . Hydroxyl radical (·OH) and the rest of active oxygen species are produced from the two oxygen compounds either enzymatically or nonenzymatically. Recently, in vivo production of the active oxygen species was successfully demonstrated by detecting the oxyradical-dependent chemiluminescence from granulocytes sticking to venular endothelium in rat mesenteric microvascular bed (Suematsu, M. et al.: J. Biochem. 106: 350-355, 1989) . A similar but different NADPH oxidase system which produced O^-₂ from O₂ was also demonstrated in the plasma membrane fraction from porcine thyroid cells (Nakamura, Y. et al.: J. Biol. Chem. 264: 4759-4761, 1989) . Then our present knowledge on the constitution and properties of the NADPH oxidase system in polymorphonuclear leukocytes has been reviewed and discussed with special reference to cytochrome b₅₅₈, flavin-containing proteins and so called cytosolic factors.

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We compared the effect of leukotriene B₄ (LTB₄), one of 5-lipoxygenase (5-LO) products of arachidonic acid, with that of leukotriene B₅ (LTB₅), one of 5-LO products of eicosapentaenoic acid, on interleukin 1 (IL-1) production and calcium mobilizing activity in human blood monocytes. LTB₄ was significantly more active than LTB₅ in the enhancement of IL-1 production and calcium mobilization in human monocytes. IL-1 production in monccytes was reported to be dependent on cytosolic free calcium. These results, therefore, may indicate that the different activity between LTB₄ and LTB₅ in the enhancement of IL-1 production could be partly ascribed to the different potency in inducing calcium mobilization between LTB₄ and LTB₅ in human blood monocytes. Although effective concentrations of LTB on IL-1 production with LPS co-stimulation was shifted to the left as compared to those without LPS, effective concentrations of LTB in inducing calcium mobilization was nearly in the same range regardless of the presence or absence of LPS. Further, LPS itself could not induce a detectable calcium mobilization in fura-2-loaded monocytes. Therefore, LPS may enhance IL-1 production in human monocytes through a mechanism different from that of LTB.

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We compared the effects of polyethylene glycol conjugated superoxide dismutase (PEG-SOD, plasma t1/2≥30 hrs) to the native form of the enzyme (N-SOD, t1/2=6 min) in protecting the ischemic/reperfused canine myocardium. Anesthetized, open chest, male mongrel dogs (n=14) underwent 6 hrs of left circumflex coronary artery occlusion and reperfusion for 24 hrs. A single dose of either PEG-SOD (1, 000 U/kg) or N-SOD (1, 000 U/kg) was given via the left atrium 15 min before occlusion, followed by a continuous infusion of an additional 1, 000 U/kg of the respective enzymes for 6.5 hrs ending 15 min after reperfusion. The animals were sacrificed 24 hrs after reperfusion.
Mean infarct size, determined 24 hrs after reperfusion, in the PEG-SOD group was smaller than that observed in the N-SOD group (47.1±2.9% vs 63.5±2.2% of area-at-risk; P<0.001) with no observed difference in the size of area-at-risk. Hemodynamic parameters and calculated rate-pressure-product, as well as regional myocardial blood flow, during ischemia between the groups did not differ and could not account for the effect of PEG-SOD.
The results suggest that the sustained presence of oxyradical scavenger activity is necessary to prevent rather than delay myocardial necrosis due to oxyradicals produced during the ischemia as well as the during the period of reperfusion.

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The incidence of interstitial pneumonia (IP) after bone marrow transplantation (BMT) were decreased by; the fractionation of total body irradiation, anti-cytomegalovirus antibody negative platelet transfusion and prophylactic administration of anti-cytomegalovirus immunoglobulin. However, the establishment of much better prophylactic procedures and treatments for IP after BMT is essential when considering the mortality rate. On the other hand, it has been reported that superoxide and some protease released by neutrophils may be related to the progression of interstitial pneumonia.
Gabexate mesilate (FOY), a protease inhibitor, was used in two cases which were clinically diagnosed to be IP after BMT. Effects of FOY were remarkable with the improvement of clinical findings and recovery from IP. The inhibitory effect of FOY on superoxide production by neutrophils in vivo and in vitro was examined. FOY did not suppress the production of superoxide by the neutrophils in vitro, but did suppress in vivo. These results suggest that FOY improved the clinical findings of patients with IP after BMT by the indirect suppression of the production superoxide by the neutrophils.

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The clinical utility of propionic acid derivatives as an antipyretic agent was examined in the differential diagnosis of fever of undetermined origin in total twelve times of 8 cases with malignant neoplasm (Hodgkin's disease, non-Hodgkin lymphoma and leukemia) . Five cases (7 times) had dramatic responses on fever promptly and completely within 12 hours or 24 hours, and sustained lysis of fever was obtained. Moreover, there was no evidence of infection on careful physical examination, negative results of adequate blood, urine and other cultures and no response to the antibiotics. Complete remission and lysis of fever was obtained intensive chemotherapy for neoplasm. These results suggest specific effect of these drugs on neoplastic fever.
In contrast none of 5 cases (5 times) with infectious fever had responses to the same drugs.
Nonsteroidal anti-inflammatory propionic acid derivatives such as naproxen, pranoprofen and ketoprofen had similar antipyrotic property on neoplastic fever. Since such drugs are safe and used only for short-term, they may be of great value in the differential diagnosis of neoplastic fever and infectious fever.

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When trinitrophenylated hepatocytes and lipopolysaccharide are intravenously injected into trinitrophenylated liver protein sensitized guinea pigs, most of the guinea pigs die of massive hepatic cell necrosis within 24 hours of LPS injection. Using this experimental model, we studied the changes in the levels of leukotrienes (LTs) and prostaglandins (PGs) in the liver tissue of guinea pigs with experimentally-induced massive hepatic cell necrosis. As a result, both the levels of LTs and PGs in the liver tissue increased. These results suggest that the arachidonic acid metabolites may play an important role in the induction of liver cell injury.

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We analysed kinetics of phagocytosis by using the whole blood and fluorescent microspheres with flow cytometry. The rate of phagocytosis (y) was determined by the T/C (target particles-to-cell) ratio (x) (y=K1×log (x) +K2 K1, K2: constant) . We defined the Phagocytosis 50 (Ph 50) that indicated the value of T/C ratio in which 50% of phagocytes injested the particles. The Ph 50 might be the new general parameter of phagocytosis independent of several conditions.
The Ph 50 in cases of systemic lupus erythematosus (SLE) were statistically higher than in normal controls, which indicated the decreased phagocytic activity in SLE.

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Extracts of articular cartilage from patients with osteoarthritis were shown to contain plasminogen activators (PA) . Two types of PA were detected on SDS-polyacrylamide gel electrophoresis followed by fibrin overlay technique. Cartilage derived PAs with Mr 53 K and 33 K were immunologically identical to urokinase type PA, and PAs with Mr 67 K, 72 K and 95 K were immunologically identical to tissue type PA, for the lysis bands of these cartilage derived PAs were quenched by addition of specific antibodies to fibrin gels.

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