Structure-activity studies with chiral isomers and with segments of the antimitotic marine peptide dolastatin 10

Eighteen configurational isomers of the antimitotic peptide dolastatin 10 (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990) derived from Dolabella auricularia, together with segments obtained as precursors in its synthesis (Pettit et al., J Am Chem Soc 111: 5463-5465, 1989), were examined as inhibitors of tubulin polymerization and as inhibitors of growth of L1210 murine leukemia cells in culture. Dolastatin 10 consists of four amino acids (in order from the amino terminus: dolavaline, valine, dolaisoleucine, and dolaproine), three unique to D. auricularia, linked to an unusual primary amine (dolaphenine, probably derived from phenylalanine) at what would otherwise be its carboxyl terminus. Dolastatin 10 has nine asymmetric carbon atoms, and available isomers included alternate configurations at five positions (positions 9 and 10 in the dolaproine moiety and positions 18, 19 and 19a in the dolaisoleucine moiety). For tubulin polymerization, only alterations at positions 18 and 19 resulted in loss of inhibitory activity of the isomer. In addition, a tripeptide containing dolavaline, valine and dolaisoleucine with all asymmetric carbons identical configurationally to those in dolastatin 10 was found to be about 30% as effective as dolastatin 10 in inhibiting tubulin polymerization. Cytotoxic effects were much more sensitive to alterations in the dolastatin 10 structure. The only modification which did not lead to reduced cytotoxicity was reversal of configuration at position 19a in the dolaisoleucine moiety. Both this isomer and dolastatin 10 had IC50 values of less than 1 nM. Several other isomers had IC50 values with the L1210 cells in the range of 30-90 nM, but these did not correlate well with their inhibitory effects on tubulin polymerization. The tripeptide effective as an inhibitor of tubulin polymerization had no activity against the L1210 cells.     

致倦库蚊（Culex pipiens quinquefasciatus）引诱产卵信息素的合成及其生物活性

致倦库蚊（Ｃｕｌｅｘｐｉｐｉｅｎｓｑｕｉｎｑｕｅｆａｓｃｉａｔｕｓ）产生的引诱产卵的信息素被鉴定为赤式－６－乙酰氧基－５－十六碳内酯。用环戊酮和十一碳醛经醇醛缩合产生２－（１－羟基十一烷基－１－）环戊酮，再通过拜尔－维利格反应和乙酰化作用合成了这种内酯的赤式和苏式异构体的混合物。合成产物由等比例的四种异构体组成，包括具有活性的赤式－（５Ｒ，６Ｓ）和它的对映异构体，以及另外两个苏式异构体。用合成的信息素对四种（亚种）蚊虫做了引诱产卵的生物测定，发现该产物对同种不同亚种的淡色库蚊（Ｃｘ．ｐｉｐｉｅｎｓｐａｌｌｅｎｓ）和致倦库蚊均有引诱雌蚊产卵的活性，且对前者的引诱力更强，并能保持至少１０天以上；而对同属不同种的三带喙库蚊（Ｃｘ．ｔｒｉｔａｅｎｉｏｒｈｙｎｃｈｕｓ）和另一个属的埃及伊蚊（Ａｅｄｅｓａｅｇｙｐｔｉ）则无活性，表明该信息素具有种的（而非属的）特异性。     

阴股沟皮瓣显微解剖学特征及其在组织修复功能重建中的应用

目的：明确阴股沟皮瓣的显微解剖基础，为临床应用此皮瓣提供解剖依据。资料来源：应用计算机检索Medline1991-01／2005-01的相关文章，检索词“pudendal-thigh flap，micranatomy”，并限定文章语言种类为English。并且手工检索《中文科技资料目录一医药卫生）1998-01／2005-01的相关文章，检索途径：分类途径。 资料选择：对资料进行初审，并查看每篇文献后的引文。纳入标准：①随机对照的基础及临床试验。②无论是否为单盲，双盲或非盲法。排除标准：重复性研究或综述性文章。 资料提炼：共检索到42篇相关文章，21篇文献符合纳入标准，排除的21篇文献为内容陈旧或重复。 资料综合：阴股沟区动脉血液供应充足，并且位置均比较恒定，尤以阴部外动脉最为恒定。静脉回流丰富，神经支配可靠。阴股沟皮瓣是位于股内侧上方与会阴部之间的无毛区域，上界平耻骨联合上缘水平，下界为两侧坐骨结节连线，内侧界为阴囊或大阴唇外侧缘，外侧界为股内侧皱襞，自阴囊（唇）外侧缘向大腿内上方延伸约5cm包括的范围。该区动脉血液供应丰富，计有阴部外动脉，闭孔动脉前皮支，阴囊（唇）后动脉的外侧支，旋股内侧动脉的皮支，股内侧的主要动脉支，以及来自阴部内动脉的肛动脉（直肠下动脉）等，并且位置均比较恒定，其中尤其以阴部外动脉最为恒定。在阴股沟区，阴囊（唇）后动脉与旋股内动脉、闭孔动脉前支及阴部外动脉的分支存在广泛的吻合并在内收肌内侧以上的深筋膜层形成血管网。进入阴股沟区的多支血管相互吻合成网。阴股沟区静脉回流丰富，神经支配可靠。 结论：阴股沟皮瓣血运丰富，解剖简便易行，切取方便，供区隐蔽，再造性器官外形及恢复神经感觉均取得较为理想的效果，是一种值得推广的方法。     

Pre-Implantation Multiple Cytokine mRNA Expression Analysis of Donor Lung Grafts Predicts Survival After Lung Transplantation in Humans

While current donor selection with clinical findings is generally effective, the imprecise nature of the assessment forces clinicians to remain on the conservative side. A reliable biological marker would assist donor selection and would improve donor organ utilization. We collected biopsies from 169 donor lungs before implantation. Expression levels of IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and IL-1beta were measured by quantitative real-time RT-PCR (qRT-PCR). Seventeen cases died within 30 days after transplantation. No donor factor was significantly associated with 30-day mortality. Univariate analysis of the 84 cases for development of the prediction model showed that IL-6, IL-8, TNF-alpha and IL-1beta were risk factors for mortality and IL-10 and IFN-gamma were protective factors. We analyzed the cytokine expression ratios of risk to protective cytokines. A stepwise logistic regression for 30-day mortality demonstrated that a model containing the ratio of IL-6/IL-10 was the most predictive (p = 0.0013). When applied to the remaining 85 cases for validation, the test of model fit was significant (p = 0.039). Using the cytokine ratio, we were able to define three risk groups with striking differences in survival (p = 0.0003). Multi-cytokine analysis of the donor lung graft with qRT-PCR shows significant promise as a strategy to biologically evaluate the donor lung prior to implantation.     

应用吊带方法经皮膀胱颈悬吊治疗女性压力性尿失禁

目的：介绍吊带方法经皮膀胱颈悬吊术治疗女性压力性尿失禁的经验。方法：在近膀胱颈水平，阴道前壁与尿道之间隧道状切口内预置两端带有尼龙线的网状聚丙烯片，术中窥镜监视下，应用Vesica穿刺针经皮穿刺行膀胱颈悬吊治疗女性压力性尿失禁19例。结果：随访3－45个月，平均17个月，除1例逼尿肌反射低下排尿稍费力外，18例患者无尿失禁及排尿困难。结论：吊带方法经皮膀胱颈悬吊术治疗女性压力性尿失禁，操作简便，创伤小，恢复快，临床效果满意。     

更年期妇女生理心理健康状况探讨

目的探讨更年期妇女生理、心理健康状况及相互关系 ,为进一步缓解更年期妇女的症状提供医疗和护理上的依据。方法对北京大学第一临床医院更年期门诊病人进行问卷调查 ,数据结果应用SPSS 8 0数据分析软件包进行处理。结果更年期妇女Kupperman总体平均分为 2 0 12± 9 97分 ,SCL 90评分量表总体平均分为 4 6 6 2±36 2 8分 ,并且以潮热出汗、失眠等躯体症状 ,以及强迫症状、人际关系敏感、抑郁、焦虑等心理症状表现突出。应用激素替代疗法后 ,能有效缓解更年期妇女潮热出汗、抑郁心烦、疲乏、骨关节痛、敌对的症状 ,与未用激素替代疗法者有显著差异。对更年期妇女的生理、心理进行分析显示 ,更年期妇女生理心理症状呈中等程度相关性 (r=0 6 17,P <0 0 0 1)。结论医护人员应加强对更年期妇女生理心理双方面的关注。     

哺乳期营养对室间隔心肌细胞发育的影响——游离心肌细胞的形态测量

在心肌细胞分化性生长时期,改变新生鼠的哺乳期营养条件对这些鼠的空间隔心肌细胞将会产生暂时性作用和持久性影响。哺乳期高营养的暂时性作用是增加空间隔心肌细胞的大小和数量;而低营养的暂时性作用则是减慢室间隔心肌细胞的生长。哺乳期高营养的持久性作用是限制室间隔心肌细胞的过度肥大;而低营养则促进成熟鼠的室间隔心肌细胞的过度肥大。     

下颌骨骨折致颞下颌关节紊乱综征相关因素的临床分析

为分析下颌骨骨折后颞下颌关节发生紊乱综合征的相关因素.按照Helkimo指数对45例下颌骨骨折患者的临床资料进行了回顾性分析.结果显示Helkimo指数的严重程度与下颌骨骨折术后的恢复时间以及下颌骨骨折部位有关.表明下颌骨骨折患者在一定时期内易出现颞下颌关节紊乱综合征.     

细菌素产生菌的筛选及其细菌素的分离纯化

从香肠中分离得到一株产细菌素的乳酸片球菌，其发酵液经硫酸铵沉淀，CM—Sephadex C50阳离子交换柱层析后，得到的细菌素样品通过SDS—PAGE证明是一条带，分子量约20．83ku，该细菌素对热及酸碱稳定，易被酶降解而失去活性，对许多革兰氏阳性茵有较强的抑制作用，而对革兰氏阴性茵、酵母和霉没有作用。