卡介苗对体外培养膀胱癌细胞株的直接作用和形态学观察

我们用卡介苗（ＢＣＧ）直接作用于体外培养膀胱癌细胞株，用扫描电镜和相差显微镜观察，癌细胞形态学发生明显变化，癌细胞表面结构损伤严重，微绒毛和长突起消失，残存畸变，小球密集成片，肿瘤表面结构与胞体分离，癌细胞生长抑制曲线表明，癌细胞的生长抑制率随着时间延长和ＢＣＧ浓度增大而增高。实验证明，ＢＣＧ对膀胱细胞有直接损伤作用。     

斯奇康联合丝裂霉素顺铂胸腔内注射治疗肺癌恶性胸水的疗效观察

目的　探讨斯奇康联合丝裂霉素、顺铂胸腔内注射治疗肺癌恶性胸水的有效性和安全性。方法　对我科1999年以来确诊为肺癌恶性胸水的 5 3例患者 ,随机分为斯奇康组 ( 2 7例 )和对照组 ( 2 6例 ) ,进行胸腔内注药 ,观察治疗的有效率、Karnofsky评分及不良反应。结果　斯奇康组与对照组治疗有效率分别为 88 8%和 5 3 9%,两组比较有显著性差异 (P <0 0 1) ;两组治疗后生存质量均有改善 ,但Karnofsky评分 70分以上治疗组为 66 7%,对照组为 3 0 8%,两组比较差异显著 (P <0 0 1) ;两组均出现不同程度的白细胞、血小板减少 ,但治疗组与对照组相比反应明显较轻 ,有显著性差异 (P <0 0 5 )。结论　斯奇康联合丝裂霉素、顺铂胸腔内注射治疗肺癌恶性胸水疗效较好 ,毒副反应较轻。     

The value of pleural fluid anti-A60 IgM in BCG-vaccinated tuberculous pleurisy patients

Objectives   To determine if detection of IgM and IgG antibodies against mycobacterial antigen A60, together with the Mantoux tuberculin skin test (TST), could be used in the diagnosis of tuberculous pleurisy (TP) in BCG-vaccinated cases.
Methods   We investigated 125 BCG-vaccinated patients with pleural effusion. Of these, 88 had TP and 37 had non-tuberculous pleurisy (NTP). TST and anti-A60 IgM and IgG measurements by ELISA were performed in the sera and pleural effusions of both groups.
Results   Cut-off values, in optical density, for serum anti-A60 IgM, pleural fluid anti-A60 IgM, serum anti-A60 IgG and pleural fluid anti-A60 IgG were defined as 0.624, 0.614, 0.464, and 0.613, respectively. TP patients had higher IgG and IgM levels in the serum ( P  < 0.001 and P  < 0.05, respectively) and pleural effusion ( P  < 0.001 and P  < 0.001, respectively). Regardless of the diagnosis, IgG and IgM levels were higher in the sera ( P  < 0.001 and P  < 0.05, respectively) and pleural effusions ( P  < 0.001 and P  < 0.001, respectively) of TST-positive cases, and serum and pleural fluid IgM levels were higher ( P  < 0.001 and P  < 0.001, respectively) in the TST-positive TP cases. Sensitivity and specificity of TST were 65% and 68%, respectively. As a single parameter, pleural fluid anti-A60 IgM had the highest sensitivity (77%) and specificity (94%) in patients with negative TST.
Conclusion   We suggest that in populations where tuberculosis prevalence is high and BCG vaccination is common, pleural fluid anti-A60 IgM can facilitate the diagnosis of TP.     

Cytologic features of disseminated bacillus Calmette-Guérin (BCG) infection

Disseminated bacillus Calmette-Guérin (BCG) infection is an unusual complication of immunization against Mycobacterium tuberculosis with the bacillus Calmette-Guérin. We report on 4 such cases in which the diagnosis was suspected at the fine-needle aspiration biopsy (FNAB) procedure. Participants were 4 males (mean age, 21.5 mo; range, 8-36 mo) in good general condition, in whom epidemiology data favoring tuberculosis and presence of pulmonary tuberculosis were lacking. Cases 1 and 2 presented with a deep-seated subcutaneous nodule located near the left mamilla and lower aspect of the left scapula, respectively, resulting from lymph node involvement by BCG. Cases 3 and 4 presented as an osteolytic lesion of the ninth right rib and right iliac bone, respectively. FNAB findings showed poorly to moderately cellular smears. Epithelioid histiocytes in a granuloma pattern with occasional multinucleated Langerhans-type giant cells, lymphocytes, and polymorphonuclear leukocytes in a finely granular background with necrotic debris were found in all cases. The presence of isolated calcified spherules interspersed among the cells was found to be a useful finding for diagnosis. When dealing with disseminated BCG infections, clinical and cytological pictures must be evaluated as a whole in order to arrive at an accurate diagnosis.     

Immune biology of macaque lymphocyte populations during mycobacterial infection

Immune responses of lymphocyte populations during early phases of mycobacterial infection and reinfection have not been well characterized in humans. A non-human primate model of Mycobacterium bovis bacille Calmette-Guerin (BCG) infection was employed to characterize optimally the immune responses of mycobacteria-specific T cells. Primary BCG infection induced biphasic immune responses, characterized by initial lymphocytopenia and subsequent expansion of CD4+, CD8+ and gammadelta T cell populations in the blood, lymph nodes and the pulmonary compartment. The potency of detectable T cell immune responses appears to be influenced by the timing and route of infection as well as challenge doses of BCG organisms. Systemic BCG infection introduced by intravenous challenge induced a dose-dependent expansion of circulating CD4+, CD8+ and gammadelta T cells whereas, in the pulmonary compartment, the systemic infection resulted in a predominant increase in numbers of gammadelta T cells. In contrast, pulmonary exposure to BCG through the bronchial route induced detectable expansions of CD4+, CD8+ and gammadelta T cell populations in only the lung but not in the blood. A rapid recall expansion of these T cell populations was seen in the macaques reinfected intravenously and bronchially with BCG. The expanded alphabeta and gammadelta T cell populations exhibited their antigen specificity for mycobacterial peptides and non-peptide phospholigands, respectively. Finally, the major expansion of T cells was associated with a resolution of active BCG infection and reinfection. The patterns and kinetics of CD4+, CD8+ and gammadelta T cell immune responses during BCG infection might contribute to characterizing immune protection against tuberculosis and testing new tuberculosis vaccines in primates.     

Functional characterization of human natural killer cells responding to Mycobacterium bovis bacille Calmette-Guérin

The kinetics of activation and induction of several effector functions of human natural killer (NK) cells in response to Mycobacterium bovis bacille Calmette-Guérin (BCG) were investigated. Owing to the central role of monocytes/macrophages (MM) in the initiation and maintenance of the immune response to pathogens, two different experimental culture conditions were analysed. In the first, monocyte-depleted nylon wool non-adherent (NW) cells from healthy donors were stimulated with autologous MM preinfected with BCG (intracellular BCG). In the second, the NW cells were directly incubated with BCG, which was therefore extracellular. In the presence of MM, CD4+ T lymphocytes were the cell subset mainly expressing the activation marker, CD25, and proliferating with a peak after 7 days of culture. In contrast, in response to extracellular BCG, the peak of the proliferative response was observed after 6 days of stimulation, and CD56+ CD3- cells (NK cells) were the cell subset preferentially involved. Such proliferation of NK cells did not require a prior sensitization to mycobacterial antigens, and appeared to be dependent upon contact between cell populations and bacteria. Following stimulation with extracellular BCG, the majority of interferon-gamma (IFN-gamma)-producing cells were NK cells, with a peak IFN-gamma production at 24-30 hr. Interleukin (IL)-2 and IL-4 were not detectable in NK cells or in CD3+ T lymphocytes at any time tested. IL-12 was not detectable in the culture supernatant of NW cells stimulated with extracellular BCG. Compared to the non-stimulated NW cells, the NW cells incubated for 16-20 hr with BCG induced the highest levels of expression of apoptotic/death marker on the NK-sensitive K562 cell line. BCG also induced expression of the activation marker, CD25, and proliferation, IFN-gamma production and cytotoxic activity, on negatively selected CD56+ CD3- cells. Altogether, the results of this study demonstrate that extracellular mycobacteria activate several NK-cell functions and suggest a possible alternative mechanism of NK-cell activation as the first line of defence against mycobacterial infections.     

卡介苗对豚鼠实验性哮喘的预防性治疗作用

目的:观察卡介苗(BCG)对哮喘豚鼠的预防治疗作用。方法:采用31只豚鼠,分为3组进行处理,分别为对照组、卵蛋白(OVA)致敏组和BCG处理组。用OVA(Ⅲ级)致敏豚鼠复制豚鼠哮喘模型。结果:本模型采用10%的OVA致敏,1%的OVA激发,所有动物都表现有不同程度的过敏反应症状。实验动物在接受BCG注射后,表现为以下特点:一是外周血淋巴细胞和单核细胞增加;二是BALF中细胞分类的变化,支气管肺泡灌洗液(BALF)中以淋巴细胞的增加最为明显。 经过OVA致敏的动物BALF和肺组织中嗜酸性粒细胞(EOS)明显增加,BCG不同程度地降低肺组织EOS的气道浸润及减轻OVA致敏豚鼠的气道反应。结论:[HTSS]使用本实验体系BCG可以减轻实验性哮喘的气道炎症反应。     

重组卡介苗及猪苓多糖对荷瘤小鼠巨噬细胞NO释放量的影响

目的 观察重组卡介苗（rBCG)和中药猪苓多糖（PPS），对荷瘤小鼠空巨噬细胞释放NO的影响。方法 将黑色素瘤细胞株B16接种于小鼠左大腿外侧皮下，建立荷瘤小鼠模型，分别用rBCG－IL-2,rBCG-IL-2 PPSPPS进行局部治疗。于给药后第1，2，3和5wk处死小鼠，用NO酶法测定小鼠腹腔巨噬细胞释放NO的水平，并观察不同实验组瘤体的变化。结果 rBCG－IL－2组小鼠腹腔巨噬细胞释放NO的水平最高。与对照组相比较，PPS组小鼠腹腔巨噬细胞释放NO的水平在第1wk与第2wk增高，第3wk起与对照组释放的NO水平没有差异。rBCG－IL－2组小鼠随给药时间的延长，皮下瘤体逐渐缩小。PPS组小鼠瘤体在给药后第1wk和第2wk生长缓慢，第3wk起瘤体生长速度明显增加。结论 rBCG－IL－2与PPS能提高小鼠腹腔巨噬细胞释放NO的水平，rBCG－IL－2能明显抑制肿瘤生长。     

Cytotoxic action of macrophages activated by BCG on tumor target cellsin vitro

The activating action of liquid BCG vaccine, lyophilized BCG vaccine, and killed BCG cells on macrophages was studied. Activation of mouse peritoneal macrophages was identified by their cytotoxic actionin vitro on syngeneic tumor target cells labeled with⁵¹Cr. Macrophages obtained from mice two to three weeks after a single injection of liquid BCG vaccine were shown to have a cytotoxic action on tumor cells. A single injection of lyophilized BCG vaccine or killed BCG cells into mice did not cause activation of their macrophages. Two injections of liquid or lyophilized BCG vaccine caused activation of macrophages much earlier — three to five days after the second injection. Intraperitoneal injection of BCG activated macrophages to a greater degree than subcutaneous injection.Laboratory of Experimental Tumor Therapy, P. A. Gertsen Moscow Oncologic Research Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Timofeevskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 1, pp. 36–39, January, 1979.