IL—2／LAK细胞对麻风杆菌感染巨噬细胞的溶解作用

观察了小鼠IL-2/LAK细胞体外对麻风杆菌感染巨噬细胞(Mφ)的溶解作用。结果显示,当麻风杆菌感染Mφ比率在1:1,10:1和50:1时,经体外培养1,3和5天后,效应细胞与靶细胞比例在10:1时,对麻风杆菌感染Mφ比率在10:1和50:1的靶细胞溶解作用比没有感染的Mφ或麻风杆菌与Mφ比率1:1的靶细胞显著增加。而且溶解百分率随着培养时间增加而提高。用放射性同位素标记麻风杆菌的代谢活力测定发现,LAK细胞能抑制麻风杆菌氧化(14)~C-棕榈酸产生(14)~CO_2。提示IL-2/LAK细胞在溶解麻风杆菌感染的巨噬细胞时,可能还具有影响胞内杀菌物质对麻风杆菌活力代谢的作用。     

Methacholine reactivity and asthma

Methacholine tests were used in an epidemiologic study of the prevalence of asthma and chronic bronchitis in northern Sweden. Of 6610 subjects in three age groups from eight representative geographic areas in the northernmost province of Sweden, 5698 (86%) completed a postal questionnaire on respiratory symptoms, and 1506 underwent a structured interview and a lung function test. A total of 292 (5%) were diagnosed as having asthma. A subsample of 284 subjects (of 320 invited) classified at the interview as having asthma ( n = 98) or as having respiratory symptoms that might be due to asthma but not fulfilling the interview criteria for the diagnosis of asthma ( n = 186) underwent a methacholine test. Subjects who, before the interview study, already had a well-defined asthma diagnosis were not invited to the methacholine testing. Of those 98 subjects classified as having asthma, 61 % reacted to methacholine doses ≤ 4 mg/ml and 79% to doses ≤ 8 mg/ml, while the corresponding figures in the symptomatic but nonasthma group were 20% and 34%, respectively. The results show that a carefully performed structured interview accurately diagnoses asthma in epidemiologic studies. The methacholine tests provide important diagnostic information primarily in subjects in whom the medical history is equivocal.     

Immediate hypersensitivity to penicillins. Studies on Italian subjects

The IgE response, the involvement of the different penicillins available for therapeutic use, and the specificity of the IgE antibodies found in a group of penicillin-allergic subjects from Italy were studied. Thirty subjects with a history of allergic reactions to penicillins were studied. In vivo and in vitro specific IgE antibodies were determined to different penicillin determinants. Fifteen subjects developed anaphylactic responses and the remainder urticaria and angioedema. The drug most frequently involved in the patients' allergic reactions was ampicillin (AMP). The benzylpenicilloyl (BPO) skin test was positive in 16 (53.3%) patients, whereas 23 (76.6%) patients were positive to minor determinant mixture (MDM), benzylpenicillin (PG), AMP, or amoxicillin (AX). When classified according to initial reaction type, most anaphylactic patients (93.3%) were associated with minor determinant reactivity, whereas most urticaria patients (80%) reacted to BPO. RAST results for the anaphylactic and urticaria subgroups were similar. RAST inhibition showed that most sera contained highly cross-reactive IgE antibodies. There was evidence of a specific response to AX and PG (one patient each). These data show that in a population of penicillin-allergic patients from Italy, AMP was the main drug inducing the allergic reaction. In skin tests and RAST, patients exhibited heterogeneous IgE responses with little indication of specific reactivity to AMP.     

CD28-dependent killing by human YT cells requires phosphatidylinositol 3-kinase activation

CD28/B7 interactions have been demonstrated to provide a co-stimulatory signal for the generation of CD8⁺ cytotoxic T lymphocytes in the absence of CD4⁺ T helper cells. The CD28 signals required for induction of cytotoxicity have yet to be described. To investigate further the biochemical signaling pathways associated with CD28-dependent cytotoxicity, we have studied the human thymic leukemia cell line, YT. YT cells kill B7⁺ targets in a non-major histocompatibility complex (MHC)-restricted, CD28-dependent manner. CD28 ligation on the surface of YT cells caused a rapid increase in the tyrosine phosphorylation of four major cellular substrates with masses estimated to be 110, 95, 85, and 44 kDa. The 110 and 85 kDa substrates were identified as the catalytic and regulatory subunits, respectively, of phosphatidylinositol 3-kinase (PI3-K). Engagement of CD28 caused the rapid receptor association and activation of PI3-K but did not activate phospholipase C_γ. CD28-induced tyrosine phosphorylation and PI3-K activation was independent of p56^lck protein tyrosine kinase (PTK) activity (previously reported to be associated with CD28) and was insensitive to inhibition by the PTK inhibitor herbimycin A. Two structurally and mechanistically dissimilar inhibitors of PI3-K, wortmannin and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) also failed to block CD28-dependent tyrosine phosphorylation events or the association of PI3-K with the CD28 receptor. However, both drugs inhibited CD28-dependent cytotoxicity and CD28 receptor associated PI3-K activity with IC₅₀ values similar to the reported IC₅₀ values for PI3-K inhibition. Although herbimycin A did not significantly block the observed CD28-dependent tyrosine phosphorylation or PI3-K activation, herbimycin did block CD28-dependent cytotoxicity in a dose-dependent manner. These data support a role for PI3-K activation in the CD28-dependent initiation of cytotoxic effector function and suggest that a herbimycin sensitive step(s) is either CD28-independent, resides within a PI3-K-independent CD28 signaling pathway, or is downstream of CD28-dependent PI3-K activation.     

Histamine concentrations in nasal secretion and secretory activity in allergic rhinitis

The prerequisites for using the assayed histamine concentration in nasal secretion as an objective measure of disease activity in allergic rhinitis were investigated. It was demonstrated that in histamine determination procedures the presence of quenching substances in the nasal secretion could lead to underestimation of the histamine concentration. This bias was eliminated in a modified spectrofluorometric assay. Only an insignificant fraction of the histamine in samples collected by nasal spray washing was bound to unfiltrable particles or cells. The mean histamine concentration in nasal secretions from 15 healthy subjects was 11.2 micrograms/ml and in a group of nine patients with allergic rhinitis out of season 3.36 micrograms/ml. The histamine concentration in the latter group decreased during the pollen season and after positive allergen challenge. It is suggested that this decrease is caused by the increase in volume of the secretion during the allergic response. The use of lithium as an exogenous marker permitted quantitation of the increase in the relative amount of nasal secretion recovered by washing in the symptomatic subjects.     

Acute renal dysfunction by cadmium injected with cysteine in relation to renal critical concentration of cadmium

In order to study the critical concentration of cadmium (Cd) in acute renal dysfunction following Cd, male mice were injected IV with Cd complexed with cysteine. The critical concentration was 10 g Cd/g wet weight in whole kidney and it was the same as that for Cdthionein (Cd-Th), which may suggest that the toxicity of Cd-Th is due to Cd ions liberated from Cd-Th in the kidneys. Renal Cd concentration was at first higher than the critical concentration, but decreased to the critical concentration by 24 h after administration. As an index for renal dysfunction, the uptake of p-aminohippurate (PAH) by renal cortical slices in vitro was sensitive, and showed the different time-course from those of urinary protein and glucose levels. The results suggest the usefulness of PAH uptake as an index. Incidental to the renal dysfunction, renal calcium levels exhibited a marked increase.     

新型补体抑制剂对同基因大鼠移植肾功能的长期影响

目的：观察新型补体抑制剂APT070对同基因大鼠移植肾功能的长期影响。方法：应用同基因大鼠肾脏移植模型,供肾移植前分别经观察药物APT070、对照药物APT898及肾脏灌注液灌注,测定术后4－20周移植肾功能及24h尿蛋白含量。结果：肾移植术后4－20周,APT070灌注组移植肾功能明显好于对照组,24h尿蛋白含量明显低于对照组,P＜0．01。结论：APT070作为一种可与肾脏组织结合的新型补体抑制剂,可改善同基因大鼠移植肾的长期功能。     

慢性阻塞性肺病大鼠模型的建立及药物干预的影响

目的：寻求建立慢性阻塞性肺病（COPD）大鼠模型的新方法,探讨吸入皮质激素布地奈德及抗胆碱能受体支气管扩张剂溴化异丙托品（异丙托品）对大鼠COPD模型干预的影响。方法：用两次气管内注入脂多糖（LPS200μg/次）及熏香烟4周的复合刺激法建立大鼠COPD模型（模型组）,药物干预组于制作模型后第8天起分别吸入布地奈德及异丙托品溶液。观察支气管病理学改变及支气管肺泡灌洗液（BALF）细胞计数与分类,检测有关呼吸功能指标。结果：模型组气管、支气管及肺组织有慢性支气管炎、阻塞性肺气肿的特征性病理改变;气管壁厚度及腺体厚度／气管壁厚度的比值显著高于对照组（P＜0．01－0．001）;BALF中白细胞总数及中性粒细胞数较对照组显著增高（P＜0．01）,静息分钟通气量（VE）、呼气峰流速（PEF）和“0．3s用力呼气容积”（“FEV0．3”）则显著降低（P＜0．05）。与模型组相比,布地奈德组白细胞总数及中性粒细胞数显著降低,单核－巨噬细胞所占构成比显著升高（P＜0．05）,异丙托品组则无显著差异（P＞0．05）。结论：采用两次气管内注入适量LPS和反复熏香烟的方法,可成功制备大鼠COPD模型,其病理及病生理改变与人类COPD类似,为人类COPD研究提供了一个新工具。皮质激素对大鼠COPD模型有一定保护作用。