岡山医学会Acta Medica Okayama0030-15581047-81992難治性喘息の発症に関する研究 第2編 フローサイトメトリーによる喘息患者抹梢血のリンパ球サブセット･表面抗原の検討863870ENMinoruTakataTo elucidate the role of lymphocytes in asthmatics, lymphocyte subpopulations were analyzed using monoclonal antibodies (CD2, CD3, CD4, CD8, CD16, CD19, CD25, and HLA-DR, all from Leu series) and flow cytometry (FACScan, Beckton-Dickinson). Blood samples were obtained when there was no attack unless otherwise stated. Patients were defined as intractable when they had been taking more than 5 mg of prednisolone for at least one year. (1) Non-intractable asthmatics had greater ％ of CD16＋NK cells as compared with agematched normal subjects. (2) No differences were observed between RAST or intradermal test-positive and negative patients, although the former had significantly higher serum IgE levels than the latter. (3) Intractable asthmatics showed an increased proportion of IL−2R＋lymphocytes as compared with normal subjects. (4) Patients on attack also had a higher ％ of IL−2R＋lymphocytes than patients without attack. These findings suggest that NK cells play an important role in bronchial asthma, and that activeted lymphocytes are involved in the pathogenesis of intractable asthma and asthmatic attack.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992難治性喘息の発症に関する研究 第1編 気管支喘息の発症における各種気道感染ウイルスの役割に関する検討853861ENMinoruTakataAllergen exposure leads to production of the specific IgE antibody and bronchospasm in atopic asthmatics. However, in adult cases with non-atopic asthma, the mechanism of asthma attack is still unknown. We observed that many adult asthmatics had fever and cold symptoms immediately before developing their first attack. Therefore, we measured the serum antibody titers against nine viruses (Influenza A and B, Adenovirus, RSV, Coxsackie B type 3, CMV, Parainfluenza type 1, 2, and 3), and analyzed their relationship with other clinical paremeters to elucidate the possible role of virus infection in inducing asthma attack. (1) No difference in antibody titers was observed between atopic and non-atopic asthmatics. (2) Steroid-dependent asthmatics had a higher antibody against CMV, and lower antibody against Coxsackie virus as compared with non-steroid dependent patients. (3) The anti-CMV antibody showed a significant correlation with the specific IgG antibody and lymphocyte blastogenesis to Candida antigen. (4) To examine the cross reactivity between Candida antigen and CMV, Candida antigen-specific-human monoclonal antibody was used but the result was negative. These findings suggest that the relationship between CMV and Candida is important in the pathogenesis of non-atopic adult asthmatics, although the mechanism is still unknown.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992長期リンパ球混合培養で誘導される抑制性T細胞の免疫学的解析843852ENKatsutoshiTsuboiSuppressor T cells (Ts) may play an important role in the regulation of immunological responses. Ts may play a role in the long-term acceptance of an allogeneic organ graft and the beneficial effects of donor-specific blood transfusions on subsequent transplant survival. The population of Ts induced in mixed lymphocyte culture (MLC) was analyzed, and the mechanism underlying the suppressor activity was examined. The Ts generated in 10-day MLC were found to belong to the OKT8(+) subset and inhibited both mixed lymphocyte reaction (MLR) and cell-mediated lympholysis. These Ts inhibited MLR in an antigen-specific manner, but failed to alter the kinetics of the MLR. Furthermore, these Ts inhibited the production of endogenous interleukin-2 and exerted a suppressive effect only when added early in the culture. In condition, the precise target of Ts generated in 10-day MLC might be the earliest responding T helper clone.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992気管支喘息の重症化要因に関する検討833842ENYasuoNambaThe allergic responses to mite and Candida antigen were analyzed in atopic and non-atopic asthmatics to clarify the mechanisms of severe bronchial asthma. Skin responses and serum level of antigen specific IgE to mite antigen were lower in severe atopic asthmatics, especially in intractable atopic asthmatics. The serum level of antigen specific IgG1 and responses of peripheral blood lymphocytes to mite antigen showed no difference with severity in either type of asthma. Atopic severe asthmatics had higher serum levels of antigen specific IgE antibodies to Candida antigen and higher serum levels of antigen specific IgG1 antibodies to Candida antigen than atopic mild and moderate asthmatics. Non-atopic severe asthmatics had higher serum levels of antigen specific IgG1 antibodies to Candida antigen and higher responses of peripheral blood lymphocyte to Candida antigen than non-atopic mild and moderate asthmatics. In atopic and non-atopic severe asthmatics, bronchial provocation tests by Candida antigen showed higher positive responses than mild and moderate asthmatics. These findings suggest that a common mechanism makes asthma severe in atopic and non-atopic asthma and that Candida antigen plays an important role in both types of asthma.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992虚血性脳浮腫に及ぼすロイコトリエンの影響821832ENNorikoTakasugiArachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. To examine the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured the concentration of leukotriene C4 in the gerbil forebrain following ischemia, and pretreated several animals with cyclooxygenase and lipoxygenase inhibitors. The leukotriene C4 concentration was significantly increased 1 hour after transient ischemia and cerebral edema. The incerase in the concentration of leukotriene metabolites was significantly suppressed by preteratment with the lipoxygenase inhibitors except for the cyclooxygenase inhibitor and phospholipase A2 inhibitor. Intracerebral cerebral injection of leukotriene C4 produced local intracerebral edema. Cycloxygenase inhibition may result in increased substrate availability for the lipoxygenase system. Studies of such an interaction help elucidate the pharmacological modification of detrimental vascular changes after transient cerebral ischemia.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992遅発型気道反応におけるIgG サブクラス抗体に関する研究 第2編 気管支肺胞洗浄液中抗原特異的 IgG サブクラス抗体と遅発型気道反応の関連について809820ENKazuroOgurusuImmunoglobulin classes which induce a non-immediate asthmatic response (non-IAR) in the case of low level of IgE antibody are still unknown, although IAR is mediated by IgE. To elucidate the relationship between antibodies and late asthmatic responses (LAR), antigen-specific IgG subclass antibodies in the serum and bronchoalveolar lavage fluid (BALF) of asthmatics were measured by avidin-biotin ELISA before provocation by antigen. The BALF levels of IgG and IgG1 antibodies to mite and Candida antigen in bronchial asthmatics were higher than those in healthy subjects (p<0.05). Followed by inhalation of house dust or Candida antigen, bronchial asthmatics were divided into group A (higher levels of BALF IgG1 antibody) and gourp B (lower levels of BALF IgG1 antibody). The percentages of LAR including DAR after inhalation of house dust antigen in group A were significantly higher than those in group B (p<0.05). The percentages of LAR including DAR after inhalation of Candida antigen in group A were significantly higher than those in group B (p<0.01). In asthmatics with LAR after inhalation of house dust antigen or Candida antigen, the BALF levels of antigen-specific IgG and IgG1 antibodies were significantly higher than those in asthmatics without LAR of healthy subjects (p<0.01). In asthmatics with LAR after inhalation of house dust antigen or Candida antigen, the BALF levels of antigen-specific IgG and IgG1 antibodies were significantly higher than those in asthmatics without LAR of healthy subjects (p<0.01). In asthmatics with LAR, the relative (to albumin) of coefficients of excretion (RCE) in the BALF of antigen-specific IgG and IgG1 antibodies were higher than those in asthmatics without LAR of healthy subjects. These findings suggest that local production of antigen-specific IgG and IgG1 antibodies incerases in asthmatics with LAR, and that these antibodies may induce LAR.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992遅発型気道反応におけるIgG サブクラス抗体に関する研究 第1編 血清中抗原特異的 IgG サブクラス抗体と遅発型気道反応の関連について797807ENKazuroOgurusuThe immediate asthmatic response is mainly induced by IgE-dependent mechanisms. However, the late asthmatic response (LAR) is induced by inhalation of antigens without the participation of antigen-specific IgE antibodies in some asthmatics, especially in intractable asthma induced by Candida antigen. To elucidate the relationship between antibodies and those bronchial responses, the antigen-specific IgG subclass antibodies in sera from asthmatics were measureed and compared with IgE antibody. The avidin-biotin ELISA (enzyme-linked immunosorbent assay) method was established for the measurement of specific IgG and IgG subclass antibodies to mite or Candida antigen. Serum levels of IgG and IgG1 antibodies to mite and Candida antigen in bronchial asthmatics were significantly higher than those in healthy subjects (p<0.01). Bronchial asthmatics who were tested with inhalation of house dust or Candida antigen were divided into group A (higher levels of serum IgG1 antibody) and group B (lower levels of serum IgG1 antibody). The percentage of LAR including DAR after inhalation of house dust antigen in group A were significantly higher than those in group B (p<0.01). The percentages of LAR and LAR including DAR after inhalation of Candida antigen in group A were significantly higherSerum levels of house du than those in group B(p<0.01). Serum levels of antigen-specific IgG and IgG1 antibodies in asthmatics with LAR after inhalation of house dust or Candida antigen were significantly higher than those in asthmatics with IAR or non-responders (p<0.01). The serum level of specific IgE antibody to these antigens in asthmatics with LAR after inhalation of house dust or Candida antigen was slightly lower than that in the asthmatics without LAR, though the difference was not significant. These findings suggest that high serum levels of specific IgG and IgG1 antibodies to adequate antigens play a role in inducing an attack in asthmatics with LAR.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992高校野球選手における形態と投能力の関係789795ENHayatoUchidaThere is little information on anthropometric measures (i. e., length, breadth and girth of body's parts) related to throwing ability. To clarify the influence of the physique on the throwing ability, the relationships between physique and throwing distance, as well as ball speed were investigated. The subjects were fourty-nine high school baseball players, and thirty-eight high school volleyball players, football players and canoeists served as a control group. The throwing distance was significantly related to lean body mass (r=.290), chest girth (r=.416), upper arm girth (r=.307), abdominal girth (r=.288), thigh girth (r=.327) and lower leg girth (r=.285) in baseball players group (p<0.05-0.01). A significant relationship between the throwing distance and foot length in control group (r=.329, p<0.05) was demonstrated. Significant relationships between ball speed and standing height in the baseball players group (r=.354, p<0.01) and that between ball speed and Impedance in the control group (r=-.288, p<0.05) were ovserved. These findings indicate that the throwing distance is influenced by quantity of body muscle in baseball players. There was no relation between physique and throwing ability in unskilled players.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992難治性喘息における好中球の役割に関する研究 第2編 好中球からの免疫学的刺激による Leukotrienes 産生能に関する検討777787ENIkkiShimizuPreviously, I reported that more leukotrienes (LTs) and superoxides were produced from the neutrophil-rich fraction by non-immunological stimulation with CaI in intractable asthmatics than in non-intractable asthmatics. This suggested that neutrophils are involved in the pathogenesis of intractable asthma. To investigate the process of neutrophil activation in intractable asthma, the LTs production from neutrophils by immunological stimulation was measured by high performance liquid chromatography (HPLC). LTs were produced from neutrophils by stimulation of anti-IgG and zymosan activated serum (ZAS), but not anti-IgE. However, there was no significant difference with each disease severity of asthma. The production from neutrophils was also detected by Candida antigen stimulation. Moreover, the production of LTC4 from neutrophils by this stimulation was higher in intractable asthmatics than in non-intractable asthmatics. These findings suggested that neutrophils are produced LTs by immunological stimulation such as by Candida antigen based on the IgG mediated allergy reaction, and play an important role in the pathogenesis of intractable asthma.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992難治性喘息における好中球の役割に関する研究 第1編 好中球からの Leukotrienes 産生能及び superoxide 産生能に関する検討763775ENIkkiShimizuThe role of neutrophils migrated in the sputum and bronchoalveolar lavage fluid of intractable asthmatics is not difficult to understand. The production of leukotrienes (LTs) and superoxide stimulated by the calcium ionophores (CaI) from neutrophil-rich fraction of 29 intractable, 70 non-intractable asthmatics and 18 healthy subjects was examined by high performance liquid chromatography and a cytochrome C reduction method. Significantly larger amounts of LTC(4) and LTB(4) were produced by CaI in the neutrophil-rich fraction from asthematics, than in that from the healthy subjects (p<0.01). Moreover, a significantly larger amounts of LTC(4) was producted in the fraction obtained from the intractable asthmatics than in that from the non-intractable asthmatics (p<0.05). However, there was no significant difference in LTB(4) production between the two groups of asthmatics. The production of superoxide by concanavalin A was significantly increased in the neutrophil-rich fraction from prednisolone-within-10mg-dependent asthmatics than in those from prednisolone-over-10mg-dependent patients (p<0.01). There were correlations between the LTC(4) and LTB(4) production, and also between LTB(4) and superoxide production. LTs and superoxide released from inflammatory cells, especially neutrophils, may play an important role in the pathgenesis of intractable asthma.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992実験的閉塞性黄疸および肝循環障害における血清と胸管リンパ液組成の変動に関する研究747761ENYuzoUedaA long-term study on the chemical and physiological changes of serum and thoracic-duct lymph in the dog with a ligated common bile duct and/or artificial liver circulation was performed. The influencee of ligation of the common bile duct appeared earlier in the thoracic-duct lymph than in the serum. The portal pressure did not increase in the dog with a ligated common bile duct, but the lymph flow of the thoracic duct was 3 times that before ligation, which would prevent the rapid stagnation of bile pigment in the liver. The portal pressure was not elevated after ligation of the hepatic artery. The cholesterol level in the thoracic-duct lymph was about half of that in the serum. In the dog with ligature of the common bile duct, the serum total cholesterol level was elevated with the elevation of serum bilirubin, whereas that in the lymph of the thoracic duct was not elevated with the elevation of the bilirubin level in the lymph. These findings suggested that cholesterol would not easily enter into the lymphatic route. The serum GPT level increased during the first week after ligation of the hepatic artery, and decreased thereafter. However, after ligation of the common bile duct, the GPT level increased for several weeks after the first week of ligation. The pattern of GPT by both ligations seemed to be cross-crossed. The marked change in the total bilirubin level in the lymph of the thoracic duct suggested its close relation with the lymphatic system. It was proved possible to secure a tube into the thoracic duct for over three weeks by the use of a U-type connector and jacket-type plaster cast.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992難治性喘息の病態と治療に関する研究 第2編 難治性喘息における細胞反応型アレルギーに対する選択的 Thromboxane A(2) 合成酵素阻害剤の抑制機序について735746ENArihikoKanehiroThe specific thromboxane A(2) (TXA(2)) synthetase inhibitor (OKY-046) seems to be a useful drug in the treatment of intractable asthmatics. In this study, to clarify the action mechanism of OKY-046 and the relationship between TXA(2) and prostaglandin E(2) (PGE(2)) in cell-mediated allergy, the effect of the TXA(2) receptor antagonist (AA-2414), TXA2 analogue (STA(2)) and PGE(2) for peripheral blood mononuclear cells in adult intractable asthmatics was studied. OKY-046 significantly suppressed TXB(2) production and increased PGE(2) production from the peripheral blood mononuclear cells stimulated by PHA and Candida antigen, but AA-2414 had no effect. AA-2414 suppressed lymphocyte blastgenesis, but did not suppress significantly interleukin-2 (IL-2) or neutrophil chemotactic factor (NCF) production. Furthermore, STA(2) increased lymphocyte blastgenesis stimulated by Candida antigen partially, but not dose-dependently. On the other hand, PGE(2) suppressed significantly lymphocyte blastgenesis and IL-2 and NCF production in a dose-dependent manner. These findings suggest that the action mechanism of OKY-046 is a suppressive effect of cell-mediated allergy, and that TXA(2) and PGE(2) play an important role in the mechanism of intractable asthma.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581047-81992難治性喘息の病態と治療に関する研究 第1編 難治性喘息患者のリンパ球および好中球機能に及ぼす選択的 Thromboxane A(2) 合成酵素阻害剤の効果721733ENArihikoKanehiroTo clarify whether thromboxane A(2) (TXA(2)) is involved in type III and IV allergy, so-called "cell-mediated allergy", the effects of a specific TXA(2) synthetase inhibitor, sodium ozagrel (OKY-046) on peripheral blood mononuclear cells and neutrophils in adult intractable asthmatics were studied. Lymphocyte blastogenesis and interleukin-2 (IL-2) production from peripheral blood mononuclear cells stimulated by PHA and Candida antigen in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. The neutrophil chemotactic factor (NCF) and eosinophil chemotactic factor (ECF) from peripheral blood nomonuclear cells stimulated by Candida antigen in intractable asthmatics tended to be suppressed by OKY-046. Furthermore, leukotriene C(4) (LTC(4)) and superoxide (O(2)(-)) production from peripheral blood neutrophils in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. These findings suggest that TXA(2) plays an important role in the development of intractable asthma and OKY-046, which has a suppressive effect on type IV allergy caused by lymphocyte activation and on mediator release from neutrophils, might be a useful drug in the treatment of intractalbe asthmatics.No potential conflict of interest relevant to this article was reported.