13例肝结核临床分析

我院于1998年1月-2005年5月共收治13例肝结核病患者，现分析如下。     

烧伤后早期应用中/长链甘油三酯对患者免疫功能的影响

目的　探讨烧伤后早期肠内喂养中链甘油三酯 (MCT) /长链甘油三酯 (LCT)对机体免疫功能的影响及其可能机制。　方法　选取 30例烧伤面积 >30 %TBSA的患者 ,随机分为两组 (每组 15例 )。F组 ,饲以含MCT/LCT的肠内营养制剂Fresubin 75 0MCT ;N组 ,饲以只含LCT的肠内营养制剂Nutrison。于伤后 2 4h内进行完全肠内营养支持 ,共持续 10d。于伤后 1、4、7、10d检测两组患者血浆白细胞介素 (IL) 2、IL 4、前列腺素 (PG)E2 及外周血T淋巴细胞转化率的改变。　结果　伤后各时相点F组患者血浆IL 2水平与N组相比 ,无明显差异 (P >0 .0 5 ) ;伤后 4dF组PGE2 水平较N组明显降低 (P <0 .0 1) ;伤后 4、7、10dF组IL 4水平及外周血T淋巴细胞转化率均明显高于N组 (P <0 .0 5～ 0 .0 1)。　结论　在改善烧伤后机体的免疫功能方面 ,含MCT/LCT的肠内营养制剂较单纯LCT制剂更具优势。     

喉癌染色体6q25区域的杂合性丢失和微卫星不稳定性分析

目的：在6q25区域内筛查喉癌相关的基因，探计胰岛素样生长因子受体Ⅱ(IGF2R)基因及脆性住点FRA6E在喉癌发生中的作用。方法：在6q25区域选择3个微卫星多态标记，其中D6S980位于IGF2R的5′端且与FRA6E紧密连锁。应用聚合酶链式反应-聚丙烯酰胺尿素凝胶电泳-DNA银染方法对70例喉癌进行杂合性丢失(LOH)和微卫星不稳定性(MI)分析。结果：在这3个座位上，喉癌LOH频率以D6s980处最高，达41．4％，MI频率为26．8％。总的异常频率为68．2％。LOH和MI与喉癌临床分期无关。结论：提示IGF2R可能是喉癌相关的抑癌基因。脆性位点FRA6E所在的染色体区段可能存在与喉癌相关的肿瘤抑制基因。     

复方胰岛素凝胶剂促进大鼠皮肤溃疡愈合的初步研究

目的:研究复方胰岛素凝胶剂对大鼠皮肤溃疡的促愈合作用,并探讨其可能的作用机制。方法:18只Wistar大鼠背部各制备4个皮肤溃疡模型,共复制溃疡72个,随机将溃疡分为复方胰岛素凝胶治疗组(A组)、凝胶基质对照组(B组)、空白对照组(C组)。以治疗后不同时间点各组溃疡面积、溃疡愈合速度及组织病理学检查评价修复效果。结果:在伤后头10天内,A组溃疡缩小最明显,愈合速度明显快于B组、C组。伤后14天,A组溃疡基本愈合,皮肤结构完整、上皮化较厚;而B、C组溃疡仍未完全愈合,皮肤结构不完整、上皮化较薄。结论:局部应用复方胰岛素凝胶剂对大鼠皮肤溃疡有促愈合作用。     

MDR1特异性核酶逆转肝癌多药耐药的实验研究

目的探讨MDR1核酶（N2A＋tRNAi^met-iMDRl-sRz，sRz）在裸鼠体内逆转人肝癌组织多药耐药（MDR）的可行性。方法将原发性MDR人肝癌组织裸鼠原位移植模型第2代随机分为A组（空白对照组：生理盐水40μl＋Lipofect AMINE^TM2000 10μ1）、B组（阴性对照组：N2A＋tRNAi^met 10μg／40μl＋Lipofect AMINE^TM2000 10μl）和C组（核酶组：sRz 10μg／40μl＋LipofectAMINE^TM2000 10μl），均开腹瘤内注射。瘤内注药1周后用表阿霉素15mg／kg腹腔注射，每周1次，连续4周。彩色B超测量肿瘤体积。化疗结束后1周处死裸鼠，RT-PCR、Western blot法检测肿瘤中MDR1 mRNA及其蛋白P-gp的表达。结果C组每次化疗后肿瘤体积均较前缩小（F=659．99，P〈0．05）。除第1次化疗外，其余各次化疗后C组的抑制率均高于A、B组（F=35．36，12．77，97．60，P〈0．05）。化疗结束后，C组与瘤源以及A、B组相比，肿瘤组织中MDR1 mRNA和P-gp的表达明显降低（F=45．36，3590．40，P〈0．05）。结论sRz可有效降低肝癌细胞表达MDR1 mRNA和P-gp，一定程度上逆转MDR，提高E-ADM的化疗效果。单纯E-ADM化疗可使肝癌组织MDR1 mRNA和P-gp表达升高，诱导MDR的产生。     

多粘菌素B琼脂糖层析柱清除体液中内毒素

用多粘菌素B琼脂糖亲和层析法清除内毒素,结果表明:5ml多粘菌素B层析柱的总吸附内毒素能力为450 μg,用此法可完全清除体液或各种液体中的内毒素,对血清及腹水中的内毒素也有明显的吸附作用,而其他各种主要成分(除内毒素外)经过处理后无明显改变。去氧胆酸是一种强有力的去污剂,可使已饱和的柱子复活,复活率达85％左右。该方法有简便,可靠,吸附能力大,柱子的复活率高等优点。本方法的建立为内毒素血症的治疗展示了新的前景。     

Synthesis and biological activities of novel 5-(2-acylethynyl)uracils

5-(2-Acylethynyl)-2,4-dimethoxypyrimidines (3-6) were synthesized in excellent yields from 2,4-dimethoxy-5-[2-(trimethylsilyl)ethynyl]pyrimidine (2) by treatment with acid chlorides in the presence of anhydrous aluminum chloride. Compounds 3-6 were deblocked with chlorotrimethylsilane and sodium iodide in acetonitrile to the corresponding 5-[(2-acyl-1-iodo)vinyl]uracils (7-10), which on treatment with potassium hydroxide in dioxane yielded the corresponding 5-(2-acylethynyl)uracils (11-14). The 5-(2-acylethynyl)uracils were found to be active against Ehrlich ascites carcinoma (EAC) cells in vivo, the most active compounds being 5-(2-benzoylethynyl)uracil (11) and 5-(2-p-toluoylethynyl)uracil (12). The T/C values of 281 and 300 were obtained for compounds 11 and 12, respectively, in the case of mice bearing EAC cells. The 5-(2-acylethynyl)uracils have also shown in vitro activity against CCRF-CEM and L1210/0 tumor cell lines. The lead compound 5-(2-p-toluoylethynyl)uracil effectively inhibited thymidylate synthetase.     

Quantitative structure-activity relationships in MAO-inhibitory 2-phenylcyclopropylamines: Insights into the topography of MAO-A and MAO-B

Ten (E)-and (Z)-isomers of 2-phenylcyclopropylamine (PCA), 1-Me-PCA, 2-Me-PCA, N-Me-PCA, and N, N-diMe-PCA and fifteeno ⁻, m⁻, p⁻ isomers of (E)-PCA with substituents of Me, Cl, F, OMe, OH were synthesized in this laboratory and tested for the inhibition of rat brain mitochondrial MAO-A and MAO-B. The effects of substituents, their positions, and stereochemistry on the inhibition were assessed for the compounds with substituents at cyclopropyl and amino groups and QSAR analyses were performed using the potency data of ring-substituted compounds. The best correlated QSAR equations are as follows: pI₅₀=0.804 Π² Blo−1.069 Blm+0.334 Lp−1.709 HDp+7.897 (r=0.945, s=0.211, F=16.691, p=0.000) for the inhibition of MAO-A; pI₅₀=1.815 π-0.825 Π² R+0.900 Es²+0.869 Es³+0.796 Es⁴−0.992 HDp+0.562 HAo+3.893 (r=0.982, s=0.178, F=23.351, p=0.000) for the inhibition of MAO-B. Based on the potency difference between stereoisomers of cyclopropylamine-modified compounds and on QSAR results, it is proposed that the active sites of MAO-A are composed of one deep hydrophobic cavity near para position, two hydrophobic cavities interacting with Me group, a hydrophobic area accomodating phenyl and cyclopropyl backbone, steric boundaries, a hydrogen-acceptor site near para position, and an amino group binding site and that in addition to the same two hydrophobic cavities, hydrophobic area, steric boundaries, hydrogen-acceptor site, and amino group binding site, another steric boundary near para position and a hydrogen donating site near ortho position constitute active sites of MAO-B.     

Characterization of a progesterone-binding, three-domain antibody fragment (VH/K) expressed in Escherichia coli.

The heavy chain variable region (VH) and the kappa light chain of the anti-progesterone monoclonal antibody (mAb) DB3, have been expressed as a single-chain three-domain polypeptide, designated VH/K, and secreted into the periplasmic space of Escherichia coli (E. coli). The linker sequence was derived from the VH-CH1 elbow region. The C kappa domain provides a sensitive detection tail for Western blotting and enzyme-linked immunosorbent assay (ELISA). Periplasmic extracts of transformed E. coli contained material that bound progesterone and related steroids with similar specificity and affinity to DB3, and displayed the DB3 idiotype and kappa chain epitopes. Reference to the crystal structure of DB3 suggests that all the characteristics of the combining site interaction with steroids are retained in the bacterially expressed material. Western blotting demonstrated material with a molecular weight equivalent to three domains after reduction, but six domains in the unreduced state, suggesting that the VH/K polypeptide is assembled in the periplasm as a disulphide-bridged dimer. The VH/K construct provides a novel route to expression of antibody combining sites in E. coli for antibody engineering.     

Changes of Intestinal Caicitonin Gene-related Peptide in Acute Intestinal Radiation Sickness in Rats

The characteristic distribution of calcitonin gone-related peptide(CGRP)inthe small intestine of rats and its changes in acute intestinal radiation sickness(AIRS)were studied with immunocytochemistry(whole mount stretch preparations of the smallintestine and cryostat sections)and radio-immunoassay.It was found that in all the lay-ers of the intestinal walls,there were large amounts of CGRP immunoreactive(CGRP-I)nerve fibers which existed in especiaUy high density in the myenteric,submucosal andmucosal plexuses.There was also a rather high density of the nerves around the smallvessels of the small intestine and the intestinal crypts.Some CGRP-I neurons were seenin the myenteric and submucosal plexuses.In AIRS,the intestinal CGRP showed a dip-hasic change,in a lower level in the 24th h and a higher level in the 48th and 72nd h af-ter irradiation.The results indicate that CGRP may be related to the regulation of the motility,se-cretion,absorption,sensation,and regional blood flow of the gastrointestinal tract.Pro-bably,CGRP is released under the stress of AIRS and participates in the mechanism ofinjury through many ways especially through the influence on the regional blood flowand the increase of the permeability of blood vessels.