http://hdl.handle.net/10564/2107 1989-10 2026-04-09T03:47:14Z http://hdl.handle.net/10564/2157 タイトル: 慢性下気道感染症に対するErythromycin長期投与療法の作用機序に関する研究 ： 第2報 マウス好中球・免疫担当細胞などに及ぼす作用 著者: 柳生, 善彦 抄録: The present study was carried out to analyze the effects of erythromycin on functions of polymorphonuclear leukocytes (PMN) and immunocompetent cells in mice. Administration of erythromycin (EM) reduced phagocytic activity as determined by chemiluminescence, although chemotaxsis and elastase production of PMN were not affected. These were consistent with results obtained from PMN of EM-treated patients with chronic lower respiratory infections. However, serum of EM-treated mice exhibited suppressive activity to mitogenic activity of recombinant interleukin 1 (rIL-1), when serum was prepared from mice 2h after intravenous injection of heat-killed Pseudomonas aeruginosa. Inhibition of IL-1 activity by this serum was neutralized by anti-mouse α＿1-antitrypsin (α＿1-AT) antiserum to a significant extent. Furthermore, mouse splenocytes cultured with several concentrations of EM produced higher levels of IL-2 upon stimulation with concanavaline A (Con A). IL-2 production by splenocytes increased in proportion to increasing doses of EM (2-5 μg/ml), but EM suppressed IL-2 production at doses higher than 10 μg/ml. These results were consistent with the results of Con A-induced blastogenesis of splenocytes. Additionally, IL-1 production by PMN and alveolar macrophage was also enhanced by EM in the dose range of 2-5 μg/ml. To analyze the kinetics of production of IL-1 suppressive factor in serum, supernatant fluids from cultures of mouse hepatocytes with EM were tested for α＿1-AT activity and IL-1 inhibitory activity. Upon stimulation with IL-1, cultured hepatocytes produced α＿1-AT in the presence of EM (5-10 μg/ml) higher than did hepatocytes cultured without EM. Furthermore, supernatant fluids of hepatocytes cultured with EM exhibited suppressive activity to IL-1. These results suggest that EM can exert regulatory functions in host defense mechamsms. 1989-10-30T15:00:00Z http://hdl.handle.net/10564/2150 タイトル: 慢性下気道感染症に対するErythromycin長期投与療法の作用機序に関する研究 ： 第1報 ヒト好中球機能などに及ぼす作用 著者: 柳生, 善彦 抄録: The present study was carried out to analyze functions of polymorphonuclear leukocyte (PMN) in the peripheral blood of patients with chronic infections in the lower respiratory tract after long-term treatment with erythromycin (EM). The number of total leukocytes was significantly higher in patients than in healthy controls before treatment, and it returned to normal levels after a 3-month treatment. Phagocytic activity of PMN was determined by measuring the intensity of luminol-mediated chemiluminescence. EM treatment reduced chemiluminescence of PMN in patients to a significant extent, in proportion to the improvement of clinical symptoms. Intracellular production of elastase, which was recognized as one of the predisposing factors in tissue damage of the respiratory tract, did not increase in PMN of patients throughout observation, but extracellular release of elastase from PMN upon stimulation with interleukin 1 (IL-1) was much reduced by EM treatment. Furthermore, serum obtained from EM-treated patients exhibited significanty higher levels of anti-elastase activity as compared with serum of healthy controls. The anti-elastase activity in EM-treated patients was completely neutralized by monoclonal antibody to human α＿1-antitrypsin. These results suggest that EM can modify PMN functions and also increase the anti-elastase activity in serum. 1989-10-30T15:00:00Z http://hdl.handle.net/10564/2149 タイトル: 肝硬変における血中substance Pの変動と免疫学的意義 ： 特にIgA抗体産生の面より 著者: 狭間, 真澄 抄録: Serum levels of neuropeptide substance P (SP) were measured in patients with chronic liver diseases and its effect on the immunogloblin synthesis was investigated. Serum SP levels in patients with liver cirrhosis were significantly higher than those in patients with chronic hepatitis and in healthy subjects. Serum SP levels were positively correlated with ICG-R15 (r=0.82, P＜0.001), and were negatively correlated with cholinesterase (r=-0.69, p＜0.001), hepaplastin test (r=-0.68, p＜0.001) and thrombo test (r=-0.54, p＜0.01). Serum IgA levels in patients with liver cirrhosis were significantly higher than those in patients with chronic hepatitis and in healthy subjects. Serum IgA levels were positively correlated with serum SP levels. In vivo IgA antibody production in peripheral lymphocytes from patients with liver cirrhosis was increased, and it was positively correlated with serum SP levels. SP (10＾＜-9＞M) increased IgA antibody　production in peripheral lymphocytes. Its effect was significantly greater in healthy subjects than in patients with liver cirrhosis. However, SP results in a partial restoration of IgA antibody production in peripheral lymphocytes from the patients with liver cirrhosis, when the lymphocytes were precultured in SP free medium for three days. In conclusion, the elevation of serum SP levels related to the impairment of liver functions and SP in blood could modulate IgA synthesis in liver cirrhosis. 1989-10-30T15:00:00Z http://hdl.handle.net/10564/2142 タイトル: 高血圧の臓器循環 ： 低酸素負荷による検討 著者: 塩見, 直幸 抄録: In order to investigate the pathophysiological mechanism of hypertension, a comparative study was performed on the cardiovascular resposes to acute systemic hypoxia between two groups, hypertensive dogs (two-kidney, one-clip renovascular) and normotensive controls. During hypoxia induced by breathing a mixed gas of 5% O＿2 and 95% N＿2 with artificial ventilation, systemic and regional hemodynamics were measured using an electromagnetic flowmeter and a pressure transducer. The following results were obtained in hypertensive dogs. (1) Cardiac output and arterial blood pressure increased, but these increases were inhibited by the previous administration of hexamethonium (C＿6). (2) Carotid blood flow also increased, but was not affected by either previous administration of C＿6 or continuous infusion of captopril. (3) Renal blood flow almost did not change, but　increased by pretreatment with C＿6. (4) Femoral blood flow increased, but was suppressed by both previous administration of C＿6 and following administration of propranolol. These findings suggest that the cardiovascular responses to acute systemic hypoxia of the hypertensive group differ from those of the normotensive group, and interactions among the sympathetic nervous system, renin-angiotensin system, autoregulation of regional blood flow and β-adrenergic receptor activity may play an important role in the pathogenesis of hypertension. 1989-10-30T15:00:00Z