Epitope focus, clonal composition and Th1 phenotype of the human CD4 response to the secretory mycobacterial antigen Ag85

Lymphoproliferation of healthy donors was tested against mycobacterial antigens (PPD, Ag85, Ag85 peptides). All PPD responders recognized the secretory antigen Ag85 and the peptide specificity for Ag85B was defined. Peptide 91-108 was recognized by 85% of donors. In addition, all CD4 T cell lines generated from 12 donors against PPD or Ag85 responded to 91-108. When this peptide was used to generate T cell lines, the cells responded also to tuberculins from atypical mycobacterial species. Thus the cross-reactive peptide behaved as quasi-universal. The analysis of TCR-BV gene usage by cell lines showed that most Ag85-specific T cells correspond to 91-108-specific clonotypes. Intracytoplasmic staining of cell lines after phorbol myristate acetate stimulation resulted in dominance of interferon-gamma (IFN-gamma)-IL-4 double-positive cells, whereas antigen stimulation resulted in production of IFN-gamma only. The data show that peptide 91-108 is the major focus of the CD4 response to mycobacterial antigens in peripheral blood mononuclear cells and in T cell lines from PPD responders.     

Alpha-adrenoceptors, 5-hydroxytryptamine receptors and the action of dihydroergotamine in human venous preparations obtained during saphenectomy procedures for varicose veins

Summary Changes in tension were monitored isometrically on spiral strips from human saphenous veins obtained during surgical removal of varicose veins. Concentration-response curves for noradrenaline and 5-hydroxytryptamine (5-HT) were established by cumulative administrations, curves for dihydroergotamine were constructed from the mean responses to single concentrations. The use of the antagonists prazosin, yohimbine and pizotifen provided evidence for the existence of both postjunctional ₁- and ₂-adrenoceptors and for the existence of 5-HT receptors. The venoconstrictor effects of dihydroergotamine were unchanged by prazosin. Yohimbine antagonized both dihydroergotamine and 5-HT at about 60 times higher concentrations than required against noradrenaline whereas pizotifen inhibited responses to both dihydroergotamine and 5-HT at about 100 times lower concentrations than those to noradrenaline.These new results are in contrast to conclusions drawn from animal studies and do not support the suggestion that in man the venoconstrictor activity of dihydroergotamine is mediated through stimulation of -adrenoceptors. The present results strongly suggest that in human saphenous veins the constrictor activity of dihydroergotamine is mediated at least in part through stimulation of 5-HT receptors.     

Study of a new oral beta-adrenergic drug,clenbuterol, in patients with chronic bronchitis

Summary In a double-blind, placebo-controlled, incomplete cross-over study the bronchodilator, cardiovascular, respiratory and metabolic effects of 3 different oral doses of clenbuterol were studied in 12 patients suffering from partly reversible airways obstruction due to chronic bronchitis. The ventilatory response to oral clenbuterol or placebo was assessed by measurement of specific airway resistance (sRaw) to detect changes in central airways, and of flow at 85% of vital capacity ( _{85% VC}) to detect change in peripheral airways. Clenbuterol 20, 30 and 40 µg produced a significant decrease in sRaw between 15 and 480 min after administration. Its effect on the large airways was not related to the dose. Clenbuterol 30 and 40 µg caused a significant increase in _{85% VC} between 60 and 480 min after administration. After 20 µg a significant improvement in _{85% VC} was found between 120 and 240 min. The over-all effect of 30 µg on the small airways was significantly more pronounced than that of 20 µg and was more sustained than that of 40 µg 120 min after administration. No significant changes in heart rate, ECG or blood pressure were noted. Decreases in PaO₂ and O₂-saturation after clenbuterol were not related to dose. Slight falls in PaO₂ and O₂-saturation were also observed after placebo. These observations are briefly discussed. There was negligible lipid mobilization after either the placebo or bronchodilator. A slight but insignificant rise in blood glucose was observed after both 30 and 40 µg of clenbuterol.     

超声骨刀在椎管内肿瘤切除椎管成形术中的应用

目的探讨超声骨刀在椎管内肿瘤切除后椎管成形术中的实用性及安全性。方法回顾分析 2015 年 12 月—2017 年 4 月采用超声骨刀行椎管内肿瘤切除后椎管成形术治疗的 17 例胸腰椎椎管内肿瘤患者临床资料。患者均为男性；年龄 42～73 岁，平均 57.4 岁。病程 2～47 个月，平均 21.1 个月。其中胸椎管内肿瘤 4 例（T₁₀ 1 例、T₁₂ 3 例），腰椎管内肿瘤 13 例（L₁ 5 例、L₂ 4 例、L₃ 2 例、L₄ 2 例）。术后病理诊断为神经鞘瘤 8 例，脊膜瘤 4 例，神经纤维瘤 2 例，皮样囊肿 2 例，室管膜瘤 1 例。术前按 Frankel 分级标准评估脊神经功能，B 级 2 例，C 级 7 例，D 级 8 例。术中实时记录应用超声骨刀进行单个节段椎管后壁切开的时间、整体手术时间、术中出血量、术中有无硬脊膜损伤及脑脊液漏、有无脊髓及神经根损伤；术后 3～6 个月根据 MRI、CT 三维重建观察肿瘤情况及骨愈合情况，并采用 Frankel 分级评价脊神经功能。 结果应用超声骨刀进行单个节段椎管后壁切开的时间为 3.4～5.7 min，平均 4.1 min；整体手术时间 135～182 min，平均 157.3 min；术中出血量 300～500 mL，平均 342.6 mL。术中无意外性硬脊膜损伤及脑脊液漏发生，无神经根损伤和脊髓损伤发生。术后切口均Ⅰ期愈合。17 例患者均获随访，随访时间 9～18 个月，平均 12.7 个月。MRI 检查未见肿瘤复发，CT 三维重建示所有患者骨质愈合良好。随访期间无内固定物松动、断裂情况，未见脊髓再受压等情况。末次随访时 Frankel 分级为 B 级 1 例，C 级 5 例，D 级 7 例，E 级 4 级。结论应用超声骨刀系统进行肿瘤切除后椎管成形术，可保留脊柱后柱骨-韧带结构的完整性，保持椎管容积，操作安全性高、实用性强，术后效果好。     

Midterm Outcomes of the Dissected Aorta Repair Through Stent Implantation Trial

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腺病毒介导的靶向P85和Akt1短发夹RNA对人胃腺癌细胞生长抑制作用的研究

目的 构建靶向P85和蛋白激酶B1(PKB1/Akt1)的短发夹RNA(shRNA)腺病毒载体,研究其对人胃腺癌细胞SGC-7901生长的抑制效果.方法 构建腺病毒载体rAd5-P+A,体外转染SGC-7901细胞后,以实时定量PCR和Western blot分别检测P85和Akt1的mRNA和蛋白质的表达.以噻唑蓝比色分析法(MTT法)和流式细胞法评价转染后胃癌细胞的增殖活性.构建裸鼠皮下荷瘤模型进一步观察rAd5-P+A对SGC-7901细胞生长的抑制效果,并应用原位末端标记技术(TUNEL法)检测肿瘤细胞的凋亡情况.结果 成功构建的rAd5-P+A重组腺病毒载体转染SGC-7901细胞后可显著抑制p85和Akt1的mRNA表达,而P85和Aktl蛋白表达量在转染48 h、72 h后分别下调57.5%、63.7%和67.8%、75.6%,与空白对照组和通用腺病毒对照(rAd5-HK)组相比,差异具有统计学意义(P=0.005,P=0.003).与空白对照组和rAd5-HK组相比,SGC-7901细胞的增殖活性在rAd5-P+A转染后第2天明显下降(P<0.001),且rAd5-P+A转染组进入S期的细胞数减少了5.9%～7.1%,而进入G0/G1期的细胞增加了12.1%～13.7%.裸鼠皮下荷瘤模型治疗实验也显示,rAd5-P+A可抑制胃癌细胞的生长,诱导细胞的凋亡.结论 腺病毒介导的靶向P85和Akt1的shRNA可抑制人胃腺癌细胞的生长,这可能为胃腺癌靶向性联合基因治疗提供新的策略.