Epithelium-derived inhibition of [3H]acetylcholine release from the isolated guinea-pig trachea

Summary To investigate presynaptic, regulatory mechanisms on parasympathetic nerve fibres innervating the airways, the release of newly-synthesized [³H]acetylcholine from the isolated trachea was studied. Reverse phase HPLC followed by liquid scintillation spectrometry was used to separate and quantify the radioactive compounds choline, phosphorylcholine and acetylcholine in the incubation medium and the tissue.During the incubation of the tracheae with [³H]choline a significant synthesis of [³H]acetylcholine (35,000 dpm/preparation) and [³H]phosphorylcholine (500,000 dpm/preparation) occurred. In epithelium-deficient tracheae the formation of [³H]phosphorylcholine was enhanced, whereas the content of [³H]acetylcholine remained unchanged. The spontaneous outflow of tritium consisted mainly of [³H]phosphorylcholine (900 dpm/3 min) and [³H]choline (800 dpm/3 min); [³H]acetylcholine was only a minor fraction (50 dpm/3 min). Electrical stimulation of tracheae with intact epithelium caused only a small release of [³H]acetylcholine (460 dpm in the sample obtained during stimulation), but a considerable outflow of [³H]phosphorylcholine (1,900 dpm) without affecting the outflow of [³H]choline. Electrical stimulation of epithelium-deficient tracheae, however, induced a substantial release of [³H]acetylcholine (2,400 dpm), but only a small outflow of [³H]phosphorylcholine. Chemical stimulation (30 mol/1 veratridine) also caused a large release of [³H]acetylcholine (1,700 dpm) without affecting the outflow of [³H]phosphorylcholine or [³H]choline. Indomethacin (3 mol/1) enhanced the electrically-evoked release of [³H]acetylcholine from tracheae with intact epithelium by 89%.The present experiments demonstrate a strong inhibition by the epithelium of the electrically-evoked release of [³H]acetylcholine from the isolated guinea-pig trachea. Cyclooxygenase products of arachidonic acid do not appear as the main mediators of the epithelium-derived inhibition of acetylcholine release. Send offprint requests to I. Wessler at the above address     

Schedule dependent potentiation of antitumor drug effects by α-difluoromethylornithine in human gastric carcinoma cells in vitro

A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with -difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.     

幽门螺杆菌感染与肝硬化关系的研究

目的：研究肝硬化患者的幽门螺杆菌（HP）感染状况及其对肝性脑病和上消化道出血的影响。方法：用尿素酶快速染色和瑞一姬染色确定HP的感染,分析肝硬化与十二指肠疾病患者HP感染率的差异;HP感染对肝硬化患者血氨浓度的影响;随访HP阳性与阴性肝硬化患者肝性脑病的发生率;观察肝硬化并上消化道出血与非出血患者间HP感染的差异。结果：肝硬化与胃十二指肠疾病患者HP感染无明显差异;HP感染能使肝硬化患者血氨浓度增加,从而使肝性脑病发生率增高;肝硬化并出血与非出血组HP感染无明显差异。结论：肝硬化患者的HP感染无特异性;HP感染能促使肝性脑病的发生;HP感染在肝硬化并上消化道出血中未起主要作用。     

杂多化合物九钨三钛硅酸盐致畸毒性研究

目的 :观察九钨三钛硅酸盐 ( α- K8H2 〔Si W9Ti3 O4 0 〕· 1 5H2 O,简称 α- Ti3 )孕期给药对大鼠胎仔的毒性影响。方法 :大鼠孕期以 57.0 9,1 71 .2 8和 51 3.83mg/ kg剂量经口给予α- Ti3 ,并以Vit A为阳性对照及蒸馏水为阴性对照 ,产前剖腹检测胎鼠生长发育指标、外观内脏骨骼形态等。结果 :三个剂量组均未见胎鼠外观、内脏及骨骼畸形。低剂量组与高剂量组的活胎率升高 ,吸收胎数下降 ,与阴性对照组比较有显著性差异 (均为 P<0 .0 5)。低、中、高剂量组的胎鼠体重和身长高于阴性对照组 (分别为 P<0 .0 5,P<0 .0 1 ,P<0 .0 1 ) ,且增长程度与剂量呈正相关 ( r=0 .840 8,0 .72 2 8,P<0 .0 0 5,0 .0 5)。低、中、高三个剂量组的上枕骨骨化程度及胸骨块数高于阴性对照组和阳性对照组 ( P<0 .0 5,0 .0 1 ,0 .0 1 ,0 .0 5和 P<0 .0 5,0 .0 1 ,0 .0 1 )。各剂量组的母鼠肝脏重量及肝体比值不同程度下降。其中 ,中、高剂量组及阳性对照组的肝重及肝体比值与阴性对照组比较差异显著 (肝重比较分别为 P<0 .0 5,P<0 .0 5和 P<0 .0 1 ,肝体比值比较均为 P<0 .0 5)。结论 :α- Ti3 致畸试验未见胎鼠畸形 ,但可提高胎鼠生长发育指标和骨骼骨化程度。     

nm23-H1基因在人贲门癌中的表达

目的 :检测转移抑制基因 nm2 3- H1在贲门癌中的表达 ,探讨其与贲门癌生物学特性和其他病理学指标的关系。方法 :应用免疫组化染色技术对 2 8例贲门癌组织中的 nm2 3- H1进行检测并与正常组织对照。结果 :贲门癌及其相应的正常组织中 nm2 3- H1蛋白表达率分别为 67.9%和71 .4% ,两者间无显著性差异 ( P<0 .0 5)。 nm2 3- H1蛋白在贲门癌中的表达 ,随肿瘤浸润程度的增加而表达下降 ( P>0 .0 5) ;在淋巴结转移阳性组贲门癌中 ,表达阳性率为 46.2 % ,而淋巴结转移阴性组为 92 .8% ,两者差异显著 ( P<0 .0 5)。结论 :nm2 3- H1蛋白表达在肿瘤分化程度高组与低组之间 ,无显著性差异。     

显脉香茶菜化学成分的研究

在继续对显脉香茶菜Ｒａｂｄｏｓｉａ ｎｅｒｖｏｓａ （Ｈｅｍｓｌ）Ｃ．Ｙ．Ｗｕ ｅｔ Ｈ．Ｗ．Ｌｉ茎叶有效成分的研究中,又分得一种新的对映－甲壳杉烷型二萜,经理化常数和波谱分析,确定其结构为１α、１５β－二羟基－６β－乙氧基－６,７－Ｂ－断裂－对映－贝壳杉－１６－烯－６,２０－环氧－７,２０－内酯,命名为显脉香茶菜丙素（ｒａｂｄｏｎｅｒｖｏｓｉｎＣ）。     

乙烯直接氧化制乙酸的研究

采用固定床流动装置考察了乙烯直接氧化制乙酸的新工艺,并对该过程的催化剂进行研究开发。结果表明,以硅胶为载体、铬氧化物为助剂、Ｐｄ和Ｈ３ＰＯ４的质量分数分别为０．０１５和０．３０时（以载体的质量计）,催化剂具有最佳活性,此时乙烯的转化率和乙酸的选择性分别可达４．４％和６８．９％,乙酸的单程时空收６率达１３４ｇ／（Ｌ．ｈ）。     

羊红膻根中羊红膻素H等的分离与鉴定

从草药羊红膻Ｐｉｍｐｉｎｅｌｌａ ｔｈｅｌｌｕｎｇｉａｎａ Ｗｏｌｆｆ。根降压有效部位中首次分得５个化合物,经光谱（ＵＶ,ＩＲ,ＭＳ,＾１ＨＮＭＲ,＾１３ＣＮＭＲ,＾１Ｈ－＾１ＨＣＯＳＹ,＾１Ｈ－＾１３ＣＣＯＳＹ,ＤＥＰＴ）解析,鉴定为５－甲氧基－２－甲基苯骈呋喃（Ｉ）,甘油二乙酸酯（Ⅱ）,异香草醛（Ⅲ）,棕榈酸（Ⅳ）,油酸（Ⅴ）,其中化合物Ｉ为具有降压活性的新化合物,命名为羊红膻素Ｈ;化合物Ⅱ～     

心室成纤维细胞条件培养液促进成纤维细胞增殖

目的：探讨心室成纤维细胞条件培养液成纤维细胞自身增殖作用。方法：利用成纤维细胞培养、同位素掺入率测定和RT－PCR方法。结果：心室成纤维细胞条件培养液能显增加细胞自身的[^3H]-胸腺嘧啶核苷的掺入率,并具有剂量依赖性,促进细胞自身的c-fos基因的表达,刺激后1h达高峰。ETA受体拮抗剂BQ123能部分阻断条件培养液增加成纤维细胞增殖的作用,而AT1受体拮抗剂CV11974和（α-肾上腺素受体拮抗剂regitin无此效果。结论：心室成纤维细胞能自分泌内皮素等生物活性物质,促进成纤维细胞增殖。     

Immunization with excretory-secretory molecules of intestinal nematodes induces antigen-specific protective memory Th2 cell responses

Parasitic nematodes infect more than 1 billion people in the global south. The development of effective antihelminthic vaccines is a crucial tool for their future elimination. Protective immune responses to nematodes depend on Gata3⁺ Th2 cells, which can also be induced by nematode-released products. Whether these nematode products induce antigen-specific long-lived memory T cells and thereby confer protection against a challenge infection is not known yet. Hence, we set out to characterize the formation of memory Th2 cells induced by immunization with Heligmosomoides polygyrus excretory-secretory (HES) products, infection-induced versus immunization-induced recall responses to a challenge infection, and whether HES-induced memory T cells show protective properties following adoptive transfer. Our results show that 8 weeks postimmunization, HES induces long-lived functional memory Th2 cells at the site of immunization in the peritoneal cavity. Following a H. polygyrus challenge infection, HES-immunized mice display MHC-II-dependent antigen-specific Th2 cytokine responses in the gut-draining lymph nodes, comparable to those induced by a prior natural infection. Moreover, adoptive transfer of sorted memory CD4⁺ T cells from HES-immunized donors reduces female worm fecundity following a challenge H. polygyrus infection in recipient mice, highlighting a protective role for immunization-induced memory T cells.