Transepidermal migration of leukocyte with resultant formation of microscopic or macroscopic sterile pustules is a phenomenon characteristically noted in psoriasis and related sterile pustular dermatoses such as pustular psoriasis, pustulosis palmaris et plantaris and subcorneal pustular dermatosis. We found that crude scale extracts of these dermatoses show remarkably high neutrophil chemotactic activity as compared with those of other non-psoriatic inflammatory dermatoses. We isolated psoriatic leukotactic factor (PLF) with a molecular weight around 12KD as a chemotactic peptide distinct from those common to other inflammatory changes involving the skin and from those released by bacteria. Further analysis of PLF identified C5 cleavage fragments together with other anaphylatoxins. Recently chemotactic peptides derived from monocyte are suspected to be also present in PLF. Likewise, potent cell membrane-derived lipid chemotactic factor leukotriene B₄ is also increased in these lesions, although its specificity to them is not clear because it is also increased in other inflammatory dermatoses not characterized by transepidermal leukocyte chemotaxis. Moreover, the peripheral blood leukocytes from active psoriatic patients show enhanced function in chemotaxis, phagocytosis, active oxigen production and enzyme release; their sera contain substances such as anaphylatoxins that activate leukocyte function.

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Plasma levels of thiol proteinase inhibitor and kininogen were determined in rat following the injection of Freund's complete adjuvant into hind-paw. Thiol proteinase inhibitor in plasma increased in the same profile with plasma kininogen levels as well as paw swelling. Either thiol proteinase inhibitor or kininogen in normal and adjuvant-treated rat plasma completely adsorbed on columns with ligands of anti-T-kininogen IgG and S-carboxymethylated papain. These results indicate that thiol proteinase inhibitor elevated in the inflammatory condition attributes to kininogen, especially T-kininogen.

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HL-60 human promyelocyic leukemia cells were treated with 10^-7M 1, 25-dihydroxy vitamin (VD₃) for 3-4 days. VD₃-treated cells expressed a NADPH-oxidase activity as evidenced by chemiluminescence, cytochrome C reduction and hexose monophosphate shunt activity. Furthermore, cytochrome b that is an essential component of electron transport chain in the respiratory burst appeared in the VD₃-treated cells. However, reduced-minus-oxidized spectrum of VD₃-treated cells was somewhat different from that of human blood neutrophils. The particulate fraction was prepared from the VD₃-treated cells that had been activated with phorbol myristate acetate. NADPH induced luminol mediated chemiluminescence (LMCL) in the fraction. The LMCL required halide and was susceptible to NaN₃. No luminescence occurred in the particule fraction of untreated HL-60 cells. It was suggested that NADPH-oxidase dependent H₂O₂ formaion and H₂O₂-halide-MPO system were involved in LMCL of the particulate fraction.

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This paper describes a sister and brother with recurrent infections resulting from an adhesion defect of neutrophils due to a deficiency in neutrophil membrane proteins.
Neutrophil function tests of both patients revealed a gross reduction in adhesion and chemotaxis and to a lesser extent in phagocytosis. Their parents' neutrophils showed a mild reduction in adhesion. Analysis of membrane proteins by conventional sodium dodecyl sulfate polyacrylamide gel electrophoresis disclosed a total deficiency of 110K glycoprotein (gp 110) in neutrophils of the siblings and a 50% reduction in those of the parents. These results indicate that the disease was inherited in an autosomal recessive fashion.
The patients' neutrophils attached on a glass surface showed a considerable reduction of pseudopods compared to a normal control, whereas when suspended in an aqueous solution, they showed normal morphological changes in reaction to a chemotactic factor, a finding indicating that their neutrophils have a normally functioning cytoskeleton. A polyclonal rabbit antiserum to the deficient membrane proteins identified yet another membrane protein, p98, in addition to gp 110, deficient in the patients' neutrophils. The polyclonal antiserum showed a strong inhibitory activity against adhesion and chemotaxis and to a lesser extent against phagocytosis of normal neutrophils, a finding indicating that the membrane proteins deficient in the patients' neutrophils are essential n adhesion of the neutrophils.

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The pathogenesis of anaphylactic shock is still a matter of speculation. In present investigation we measured blood level of leukotriene (LT) and thromboxane B₂ (TxB₂) in an anaphylactic shock induced by the intravenous infusion of ascaris antigen and studied the effect of OKY-046, thromboxane A₂ synthetase inhibitor, on the change of blood level of LT and TxB₂ in anesthetized dogs.
Mongrel dogs, weighing about 10 kg, were anesthetized with intravenous administration of 25mg/kg of sodium pentobarbital.
(1) Anaphylactic shock-induced fall in Psyst was inhibited, while the increase of Ptr was not inhibited by the pretreatment with OKY-046.
(2) Plasma level of TxB₂ showed a significant increase and reached a maximum value 30 min. after the antigen challenge, but such and increase was suppressed significantly by the pretreatment with OKY-046.
(3) Total amount of LTs in blood showed a significant increase and reached a maximum value 10 min. after the antigen challenge, and such an increase was not suppressed by the pretreatment with OKY-046.
Above results may suggest that TxA₂ did not show any significant role in the mechanism of Ptr increase in an ascaris antigen-induced anaphylactic shock.

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Plasma fibronectin (FN) binding to bacteria and its effect of the opsonic activity on the phagocytosis of them by human alveolar macrophages (AM) was investigated. The binding of ¹²⁵I-FN to Staphylococcus aureus (S. aureus: 209-P) was proportional to the amount of FN added, and was inhibited by adding non-ladiolabeled FN. Haemophilus influenzae (H. inf: 85-237) was less reactive than S. aureus. FN alone was a poor opsonin for S. aureus, but FN promoted the phagocytosis of S. aureus by AM in dose dependent manner on condition that the reactions were carried out with FN depleted serum at the higher bacteria to AM ratio. On the other hand, the phagocytosis of H. inf was not affected by FN at the higher bacteria to AM ratio. These results suggested that FN binding to bacteria might contribute to the promotion of the bacterial phagocytosis by AM in cooperation with serum factor.

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The effects of ketotifen on the chemiluminescence (CL) and chemotaxis of human neutrophils were studied in vitro. Stimulation of neutrophils by concanavalin A (Con A), calcium ionophore A 23187 (CI), zymosan treated serum, and formyl-methionyl-leucyl-phenylalanine (FMLP) were strongly suppressed in contrast with by zymosan, which was only slightly inhibited in CL assay: the inhibitory effect of ketotifen was dose dependent. The addition of ketotifen even after stimulations of CI or FMLP also inhibited CL response. The neutrophils which were activated by incubation with FMLP (10^-7M) or ZAS at 37°C for 60 min emitted much greater light in CI, con A, or zymosan-induced CL assays than those without the pretreatment with chemotactic factors. Such enhanced CL of treated cells was also markedly suppressed by ketotifen. On the other hand, ketotifen did not show any inhibitory effect on the direct movement of neutrophils by FMLP (10^-7M) at the concentrations which inhibited CL responses. Thesse unique pharmacological activities of ketotifen are encourageing for its potential clinical usage as an antiinflammatory agent in some disorders associated with neutrophils as well as for its experimental usefulness for the analysis of various functions of neutrophils.

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We evaluated the coronary vasoconstrictory action of intracoronary (i.c.) leukotriene D₄ (LTD₄) in anesthetized mongrel dogs (n=20) . Coronary blood flow (CBF), coronary arterial pressure (CAP), left ventricular enddiastolic pressure (LVEDP), aortic flow (AoF), coronary vascular resistance (CVR), and ST deviation on epicardial ECG were measured. Coronary sinus blood samplings were obtained in order to determine the influence of LTD₄ on prostanoids metabolism. In addition, to calarify whether the vasoconstrictory action of LTD₄ is primary or mediated by thromboxane A₂ (TXA₂), LTD₄ were administered after intravenous infusion of OKY-046 (a selective TXA₂ synthetase inhibitor) . Furthermore, to confirm the LTD₄-induced coronary spasm, coronary angiography (CAG) was performed. In results, LTD₄ 0.33μg i.c. administration caused a significant reduction of CBF (from 0.85±0.05 to 0.66±0.06ml/kg/min. mean±SEM, P<0.01) and a significant elevation of CVR (from 4.7±0.4 to 7.3±0.9×10³ dynes⋅sec⋅cm^-5, P<0.05) concomitant with a marked elevation of ST segment on epicardial ECG (peak voltage 1.8±0.2mv, duration time 46±6sec) . LVEDP elevated significantly (from 8.7±0.6 to 9.7±0.7 mmHg, P<0.01), meanwhile, AoF and coronary sinus thromboxane B₂ (TXB₂) level were not changed. OKY-046 did not influence these changes induced by LTD₄. Furthermore, LTD₄-induced coronary spasm was directly documented by CAG. It was concluded that the coronary vasoconstrictory action of LTD₄ is independent of TXA₂ and may play an important role in the pathogenesis of coronary spasm and ischemic heart disease.

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In Behçet's disease, thrombophlebitis of cutaneous veins is common and that of deep veins occurs occasionally. In order to study thrombus formation in twenty-eight patients who have Behçet's disease, their platelet function was measured by various methods and compared with the control group.
The number of platelets in Behçet's disease was not different from that of the control group. The maximum aggregation and the incidence of secondary aggregation induced by ADP were significantly higher than those in the control group. Platelet sensitivity was also higher in Behçet's disease. Increased tendency of platelet aggregation seems to be an etiological factor in thrombus formation.
The plasma concentrations of platelet factor 4 (PF4) and β-thromboglobulin (β-TG) were measured by RIA. The plasma PF 4 concentration in Behçet's disease is three times higher than that in the control group. However, plasma β-TG concentration in Behçet's disease was not different from that in control group. The reason why the increase of PF 4 was shown and that of β-TG wasn't in Behçet's group has not been investigated.
The plasma concentrations of prostaglandin I₂ (PGI₂) and thromboxane A₂ (TXA₂) were measured by RIA as 6-keto PGF_1α and TXB₂ respectively. The level of TXB₂ in Behçet's disease was not different from that of the control group. But the 6-keto PGF_1α level was significantly increased in Behçet's disease.
The increased plasma concentration of PGI₂ suggests a homeostatic reaction against thrombus formation in Behçet's disease.

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The effects of anti-inflammatory drugs on matrix degradation of articular chondrocytes of young rabbit were investigated by following methods; (1) release of ³⁵SO₄-labelled proteoglycans from cells and matrix layers into culture medium. (2) proteoglycanase and collagenase activities of the culture media of articular chondrocytes.
The anti-inflammatory drugs investigated were floctafenic acid, aspirin, dichlofenac Na, tiaprofenic acid, indomethacin and hydrocortisone. The results obtained were as follows; the decrease of proteoglycan release was observed with tiaprofenic acid, dichlofenac Na and indomethacin. The effects of anti-inflammatory drugs on proteoglycanase and collagenase activities were studied under the activated condition with interleukin 1. Hydrocorisone was found to inhibit these enzyme activities remarkably and NSAIDs except floctafenic acid and aspirin also inhibit these enzyme activities in moderate degree. From these results, some of anti-inflammatory drugs were recognized to inhibit degradating enzymes released from articular chondrocytes.

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Clinical studies in humans have shown that pranoprofen is an active anti-inflammatory, antipyretic, analgesic agent which is well tolerated by asthmatic patients with minimal side effects. This study was performed in animals in order to confirm its clinical superiority. Pranoprofen (1 mg/kg, i.v.) inhibited the SRS-A related phase in passive anaphylactic bronchoconstriction in guinea pigs pretreated with mepyramine. In IgE-mediated rat passive peritoneal anaphylaxis, pranoprofen (0.01-1mg/rat, i.p.) inhibited the release of SRS-A and histamine dose-dependently. Pranoprofen also inhibited the production of a prostaglandin E₂ like substance, but did not increase the SRS- (A) production from rat peritoneal leucocytes which phagocytize killed bacteria in vitro. On the other hand, indomethacin distinctly enhanced SRS- (A) related reactions in these models. These results indicate that the low adverse effects of pranoprofen seen in treating asthma may be related to its inability to potentiate SRS- (A) production.

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