MUS81基因在喉癌中的突变和表达

目的 探讨MUS81基因突变和表达与喉癌发生发展的相关性.方法 应用聚合酶链反应-单链构象多态性分析技术结合DNA测序检测分析了42例喉癌患者MUS81基因第9、10外显子的突变;应用半定量逆转录-PCR和Western印迹方法分析MUS81基因在喉癌组织中的表达情况.结果 42例喉癌、癌旁组织标本中,癌旁正常组织均无突变,喉癌组织标本中19例发生突变,占45.2%(19/42),11例喉癌组织第9外显子发现有突变,占26.2%(11/42),8 例喉癌组织第10外显子有突变,占19%(8/42),分析表明具有统计学意义(P<0.01).逆转录-PCR结果表明,42例喉癌中有17例MUS81基因mRNA低表达,占40.48%(17/42).Western印迹方法分析结果表明,42例喉癌中有17例MUS81蛋白质低表达,占40.48%(17/42),经统计学分析肿瘤组与对照组差异有统计学意义(P<0.01).分析表明MUS81基因突变与mRNA和蛋白质低表达有显著相关性(P<0.01).统计结果显示喉癌MUS81基因突变与TNM分期、年龄和淋巴结转移无相关性(P>0.05).MUS81基因低表达与TNM分期、年龄和淋巴结转移无相关性(P>0.05).结论 发现MUS81基因在喉癌组织中有突变发生及表达异常,提示MU81基因突变和表达异常可能是喉癌发生及发展的重要因素之一.     

Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs

Background: Histamine N-methyltransferase (HMT) modulates histamine- and antigen-induced bronchoconstriction. However, it is unclear whether vascular permeability evoked by an allergic reaction can be exaggerated by inhibition of HMT activity. Methods: We studied the effects of intravenously injected SKF 91488, a specific HMT inhibitor, on increases in plasma extravasation induced by intravenously injected histamine in unsensitized guinea pigs and by intravenously injected ovalbumin antigen in guinea pigs sensitized to ovalbumin in vivo with Evans blue dye as a marker. Results: Pretreatment with SKF 91488 shifted, in a dose-dependent fashion, the dose-response curves of the leakage of dye to histamine to lower concentrations in the trachea, main bronchi, and nasal mucosa. Likewise, pretreatment with SKF 91488 (20 mg/kg intravenously) significantly increased the leakage of dye induced by ovalbumin antigen (200 μg/kg intravenously) in three parts of the airway (p < 0.05). In contrast to SKF 91488, intravenously injected aminoguanidine, a specific inhibitor of diamine oxidase (16 mg/kg intravenously), did not alter the leakage of dye induced by histamine (from 0.001 μg/kg to 10 μg/kg intravenously) (p > 0.20). HMT activities were observed in the nasal mucosa, as well as in the trachea and main bronchi, as shown in a previous study. Conclusion: These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine induced by antigen challenge on plasma extravasation in the airway in guinea pigs in vivo. (J ALLERGY CLIN IMMUNOL 1995;96:910-6.)     

Effect of irradiation on the formation of hemodynamic pulmonary edema

Experiments on 233 albino rats showed that large doses of ionizing radiation, causing marked leukopenia, increased the resistance of animals to pulmonary edema under the influence of adrenalin. This effect was particularly marked on the fourth day after irradiation. Relatively small doses (under 100R) and also irradiation separately of the head, thorax, or abdomen, on the other hand facilitated the development of pulmonary edema.Department of Pathological Physiology, Yaroslavl' Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Fedorov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 9, pp. 280–282, September, 1978.     

喉癌细胞中S100A8新的相互作用蛋白质的鉴定

目的探索S100A8相互作用蛋白在喉癌发生、发展中的可能机制。方法应用抗S100A8抗体通过免疫沉淀的方法从喉癌细胞系Hep-2中分离与S100A8相互作用的蛋白质。用基质辅助激光解析电离飞行时间质谱仪分析目的蛋白条带。根据这些目的蛋白条带的肽指纹谱,用Mascot软件预测其相应的蛋白质。用P-Match软件预测这些蛋白质的NF-kappa B结合位点。用免疫共沉淀方法证实其中一个蛋白质与S100A8相互结合的能力。结果获得了4种与S100A8相互作用的新的蛋白质,它们分别是假想蛋白质LOC80154（hypothetical protein LOC80154）、MHCclass Ⅰ HLA-B、T-box1异构体C相似蛋白质（similar to T-box1 isoformC）和肌纤维膜相关蛋白1（sarcolemmal associated protein 1）。这4种蛋白质均具有NF-kappa B的结合位点,其中MHCclass Ⅰ HLA-B是NF-kappa B通路中的一个成员,我们首次证实该蛋白质具有结合S100A8的能力。结论本研究获得的S100A8新的伴侣可能是NF-kappa B通路的成员。MHCclass Ⅰ HLA-B与S100A8的结合提示S100A8可能作为新成员与包括HLA-B在内的其他蛋白质在NF-kappa B通路中发挥作用。这些发现为进一步研究S100A8在喉癌发生中的分子机制提供了新线索。     

Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome

The human pulmonary edema fluid concentrations of LTC₄ and of LTD₄ and LTE₄, derived peptidolytically from LTC₄, were assessed by radioimmunoassays of the mediators resolved by reverse-phase high-performance liquid chromatography. The mean pulmonary edema fluid concentration (± SD) of LTD₄ of 19.2±25.6 nM for 12 patients with the adult respiratory distress syndrome and of LTE₄ of 192±309 nM for 10 of the patients were significantly higher (P<0.005 andP<0.05) than those of 2.2±2.4 and 11.0±18.2 nM, respectively, for 10 patients with cardiogenic pulmonary edema, whereas the lower mean concentrations of LTC₄ were not significantly different for the two groups. Pulmonary edema fluid from five patients with adult respiratory distress syndrome, one with cardiogenic pulmonary edema, and one with an indeterminate syndrome contained similar concentrations of peptidoleukotriene peptidases. The LTC₄ and LTD₄ peptidolytic activities in ARDS fluids were 81 and 142 kD, respectively, by gel filtration. The extents of peptidolysis of [³]LTC₄ and [³]LTD₄ by 100 µl of pulmonary edema fluid attained respective mean maximum levels of 74.5±2.9% (N=5) and 37.7±10.2% (N=4) after 30 min at 37°C and were inhibited by serine-borate and by cysteine, respectively. The predominance of LTD₄ and LTE₄ over LTC₄ in states of altered pulmonary vascular pressure and permeability thus is attributable to two distinct peptidases.     

以HPLC法测定马来酸氯苯那敏含量的方法中马来酸峰及氯苯那敏峰定位的问题

目的：探讨在《国家药品标准化学药品地方标准上升国家标准》收载品种中采用HPLC方法测定马来酸氯苯那敏的含量时，所采集的HPLC图谱中，出现的马来酸峰与氯苯那敏峰保留位置如何确定的问题。方法：采用高效液相色谱法，色谱柱：Waters C18（4．6mm×150mm，5μm），江苏淮阴C18（4．6mm×250mm，5μm）；流动相：庚烷磺酸钠溶液（冰醋酸调pH值至3．3）-甲醇-乙腈（25：30：18）；检测波长262nm。结果：在本文收集的试验条件下所采集的色谱图中，马来酸氯苯那敏对照品均出现了前后两个峰，马来酸峰与氯苯那敏峰保留位置可能在不同的色谱条件下有明显变化。结论：色谱图中马来酸峰与氯苯那敏峰保留位置应加以确定，以防止对马来酸氯苯那敏对照品纯度产生疑虑。     

喉的应用解剖与临床意义

目的：为功能性喉手术提供解剖形态学数据。方法：对50例结构完整的喉标本进行解剖观察和测量。结果：提供了喉重建术相关的甲状软骨、环状软骨、甲状舌骨膜、环甲韧带、弹性圆锥和方形膜等共75项按性别分组的测量数据。结论：为临床功能性喉手术以及喉功能重建提供了形态学参考数据。     

丹酚酸B对缺血小鼠脑能量代谢和脑水肿的影响

目的： 通过探讨丹酚酸B（SalB）对缺血小鼠脑能量代谢的影响，研究其对脑水肿的作用。方法：将NIH小鼠分为假手术组、缺血组、SalB治疗组和尼莫地平（Nim）治疗组，测定缺血30 min时脑组织能荷（EC）、磷酸肌酸（PCr）、ATP酶活性、兴奋性氨基酸（EAA）含量以及脑含水量。结果：SalB治疗组EC（0.520±0.034）和PCr［（98.344±13.249）μmol/g］的含量、Na⁺-K⁺-ATPase［（0.593±0.013）×10³ U/g］和Ca²⁺-ATPase［（0.484±0.053）×10³ U/g］的活性明显高于缺血组EC（0.465±0.037）、PCr［（81.614±9.919）μmol/g］的含量、Na+-K+-ATPase［（0.244±0.065）×10³ U/g］和Ca²⁺-ATPase［（0.321±0.086）×10³ U/g］ 的活性，2者相比显著差异（P<0.01）；而SalB治疗组Glu［（0.405±0.110）μmol/g］和Asp［（0.141±0.020）μmol/g］的含量和脑含水量［（38.1±0.1）%］ 则明显低于缺血组Glu［（0.550±0.140）μmol/g］、Asp［（0.287±0.050）μmol/g］的含量和脑含水量［（44.1±0.1）%］，2者比较亦有显著差异（P<0.05,P<0.01）。结论：增强脑组织能量代谢和ATP酶活性，并降低脑组织中兴奋性氨基酸的含量，可能是SalB减轻小鼠缺血性脑水肿的作用机制。     

Criteria for grading in the Ljubljana classification of epithelial hyperplastic laryngeal lesions. A study by members of the Working Group on Epithelial Hyperplastic Laryngeal Lesions of the European Society of Pathology

AIMS: To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly-used model of intraepithelial neoplasia in the cervix. METHODS AND RESULTS: Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion). CONCLUSIONS: Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semiobjective methods of quantitative morphometry and immunohistochemistry.     

Primary polypeptide hormones and mucin-producing malignant carcinoid of the larynx

A case of primary malignant laryngeal carcinoid with dual endocrine and mucous differentiation i s reported. Histologically the tumor showed a characteristic organoid pattern and exhibited Alcian-blue, periodic acidschiff, and Grimelius silver positivity. By the immunoperoxidase technique cal citoni n, ACTH, and or-hCG subunit were demonstrated in the tumor cells. ELectron microscopy revealed two different types of endocrinelike cells: mucous cells and occasional cells containing both endocrinelike granules and mucin droplets. Diagnostic morphologic criteria of this rare tumor entity are discussed and reference t o biologic behavior and possible h istogenesis is made.