家兔十二指肠粘膜碳酸氢盐分泌机理的研究

本实验旨在探讨ＨＣＯ３－分泌的调节及其转运的离子通道。取大白兔近端十二指肠，置于尤氏小室间（ＵｓｓｉｎｇＣｈａｍｂｅｒ），测定血管活血肠肽（ＶＩＰ）、前列腺素Ｅ２（ＰＧＥ２），二丁酰环磷腺甙（ｄｂ－ｃＡＭＰ）及电刺激（ＥＦＳ）对碳酸氢盐（ＨＣＯ３－）分泌量、电流（Ｉｓｃ）和电位差（ＰＤ）的影响，以及缺氧、缺氯、缺钠和加入ＤＩＤＳ（４，４－ｄｉｉｓｏｔｈｉｏｃｙａｎｏｓｔｉｌｂｅｎｅ－２，２’－ｄｉｓｕｌｆｏｎｉｃａｃｉｄ）、哇巴因（Ｏｕａｂａｉｎ）和神经毒素（Ｔｅｔｒｏｄｏｔｏｘｉｎ，ＴＴｘ）后对上述指标的影响。结果示，ＶＩＰ、ＰＧＥ２、ｄｂ－ｃＡＭＰ和ＥＦＳ均刺激ＨＣＯ３－分泌和Ｉｓｃ、ＰＤ的升高，而缺氧、缺钠和哇巴因呈抑制作用。ＤＩＤＳ和缺氯则完全抑制由ＰＧＥ２引起的刺激作用，部分抑制（５０％）由ＶＩＰ的刺激作用，而对ｄｂ－ｃＡＭＰ则无抑制作用。ＴＴＸ抑制由ＥＦＳ引起的作用。ＨＣＯ３－分泌与ＶＩＰ、ＰＧＥ２及ｄｂ－ｃＡＭＰ引起的细胞内ｃＡＭＰ水平不成正相关。     

CGRP对高血压病患者动脉VSMC的NOS活性和NO合成的影响

目的:为探讨降钙素基因相关肽（ＣＧＲＰ）对高血压病（ＥＨ）患者动脉血管平滑肌细胞（ＶＳＭＣ）的一氧化氮合酶（ＮＯＳ）和一氧化氮（ＮＯ）产生的作用。方法:对ＥＨ患者和血压正常者（ＮＴ）的动脉ＶＳＭＣ进行培养,分别测定ＥＨ组和ＮＴ组ＶＳＭＣ的ＮＯ含量和ＮＯＳ活性,观察ＥＨ患者ＶＳＭＣＮＯ的产生以及ＣＧＲＰ对其的影响。结果:①基础状态下,ＥＨ组ＶＳＭＣ的ＮＯ含量和ＮＯＳ活性分别为４２．７３±６．７６μｍｏｌ／（２．５×１０６ｃｅｌｓ）和０．２４±０．０５ｎｍｏｌ／（２．５×１０６ｃｅｌｓ）,均显著低于ＮＴ组的７４．５２±４．３７μｍｏｌ／（２．５×１０６ｃｅｌｓ）和０．５５±０．１０ｎｍｏｌ／（２．５×１０６ｃｅｌｓ）（Ｐ＜０．０５）;②在ＣＧＲＰ作用下,ＥＨ组的ＮＯ含量和ＮＯＳ活性分别为８８．６３±４．１２μｍｏｌ／（２．５×１０６ｃｅｌｓ）和１０．５５±１．２８ｎｍｏｌ／（２．５×１０６ｃｅｌｓ）,均显著低于ＮＴ组的１００．４９±９．６９μｍｏｌ／（２．５×１０６ｃｅｌｓ）和１２．４５±１．６１ｎｍｏｌ／（２．５×１０６ｃｅｌｓ）（Ｐ＜０．０５）;③基础状态和ＣＧＲＰ作用下两组ＶＳＭＣ的ＮＯ含量和ＮＯＳ活性随?     

不同龄SHR心肌细胞内Ca~（2＋）及心肌组织NE含量的变化

采用荧光探针结合计算机图像处理技术测定幼年、成年、老年ＳＨＲ心肌单细胞内游离Ｃａ~（２＋）浓度，采用高压液相色谱法测定幼年、成年、老年ＳＨＫ心肌去甲肾上腺素（ＮＥ）含量。结果显示随着年龄增加，ＳＨＲ心肌细胞内游离Ｃａ~（２＋）增加，而心肌组织ＮＥ含量下降。与老年ＷＫＹ大鼠比较，老年ＳＨＲ心肌细胞内Ｃａ（２＋）含量较高（Ｐ＜０．０１），而其心肌组织ＮＥ含量却较少（Ｐ＜０．０５）。本研究提示心肌组织ＮＥ与ＳＨＲ的血压升高及心肌细胞内游离Ｃａ~（２＋）增多无直接关系。＊Ｐ＜０．０１，ａ．ｖｓ．ＳＨＲ２ｍ，ｂ．ｖｓＳＨＲ６ｍ，ｃ．ｖｓ．ＳＨＲ１２ｍ３不同年龄阶段ＳＨＲ心肌组织ＮＥ含量ＳＨＲ的年龄越大，其心肌组织ＮＥ的含量越少，各年龄组之间均有显著差异（Ｐ＜０．０１）。与老年ＷＫＹ大鼠比较．老年ＳＨＲ是心肌组织ＮＥ含量明显降低（Ｐ＜０．０５）（Ｆｉｇ３）。Ｆｉｇ３ＮＥｃｏｎｔｅｎｔｓｉｎｃａｒｄｉａｃｔｉｓｓｕｅｓＩｎＳＨＲｓｏｆｖａｒｉｏｕｓａｇｅｓａｎｄｅｌｄｅｒＷＫＹｒａｔｓ：Ｐ＜０．０５．＊：Ｐ＜０．０１，ａ．ｖｓ．ＳＨＲ２ｍ，ｂ．ｖｓＳＨＲ６ｍ．ｃ．ｖｓＳＨＲ１２ｍ．ＤＩＳＣＵＳＳＩＯＮＦｕｒａ－２能选择性地     

组胺H2受体拮抗剂促进人胃粘膜上皮细胞的增殖和迁移

目的评价二盐酸组胺和组胺Ｈ２受体拮抗剂西咪替丁对人胃粘膜上皮细胞ＧＥＳ１增殖和迁移的影响．方法细胞增殖检测采用酸性磷酸酶细胞原位计数法．细胞迁移用细胞损伤检测法．同时，用Ｆｌｕｏ３ＡＭ为荧光标记物在粘附式细胞仪上进行了细胞内游离钙测定．结果西咪替丁浓度为１０５，１０６，１０７，１０８和１０９ｍｏｌ／Ｌ时，细胞数分别比对照组增加５８２％、６００％、７３７％和７４５％（Ｐ＜００１），细胞迁移数（１０６ｍｏｌ／Ｌ）为对照组的５９２％（Ｐ＜００５）；而组胺对细胞的增殖和迁移无明显影响．西咪替丁刺激可使ＧＥＳ１细胞内（Ｃａ２＋）ｉ浓度呈双向改变．结论西咪替丁可促进体外人胃粘膜上皮细胞的增殖和迁移，这可能是Ｈ２受体拮抗剂抗溃疡的机制之一，其途径可能部分是通过钙离子信号系统介导的．     

奥曲肽预防ERCP术后高淀粉酶血症及胰腺炎的疗效

目的探讨奥曲肽对内镜逆行胰胆管造影（ＥＲＣＰ）术后高淀粉酶血症及胰腺炎的预防作用．方法行ＥＲＣＰ患者２７６例，随机分为两组：预防组１６７例，分别于术前３０ｍｉｎ及术后４ｈ内ｓｃ奥曲肽０１ｍｇ；对照组１０９例，ＥＲＣＰ术前后分别予生理盐水１ｍＬｓｃ．两组患者术前后均不用其他任何抑制胰腺分泌及预防胰腺炎药物．并分别于术前、术后２ｈ，２４ｈ作血清淀粉酶测定，同时观察胰腺炎的发生情况．结果预防组ＥＲＣＰ术后２ｈ，２４ｈ血淀粉酶（Ｕ／Ｌ）分别为２４６±２２４和２５２±２９１；明显低于对照组（４９９±５９７和４６６±５５９，Ｐ＜００１）；预防组发生胰腺炎７例（４２％），对照组发生９例（８３％，Ｐ＜００１）．结论小剂量奥曲肽能有效地预防ＥＲＣＰ术后的高淀粉酶血症及胰腺炎     

老年慢性阻塞性肺疾病患者血浆内皮素－1含量与PaO_2、PaCO_2及肺动脉压的关系

目的探讨血浆内皮素－１（ｅｎｄｏｔｈｅｌｉｎ－１，ＥＴ－１）在慢性阻塞性肺疾病（ｃｈｒｏｎｉｃｏｂｓｔｒｕｃｔｉｖｅｐｕｌｍｏｎａｒｙｄｉｓｅａｓｅ，ＣＯＰＤ）中的作用。方法应用放射免疫法测定４３例老年ＣＯＰＤ急性发作期患者和１５名健康对照者血浆ＥＴ－１水平，其中８例肺心病患者行右心微导管检测肺动脉压。结果ＣＯＰＤ患者和肺心病患者的血浆ＥＴ－１含量分别为５．２４±０．５０、５．８０±０．６６ｐｇ／ｍｌ，较健康对照组血浆ＥＴ－１含量（４．６５±０．６５ｐｇ／ｍｌ）明显升高（Ｐ值＜０．０１及０．００１）；血浆ＥＴ－１含量与ＰａＯ２呈显著性负相关（ＣＯＰＤ组：ｒ值＝－０．５８３，Ｐ值＜０．０１；肺心病组：ｒ值＝－０．６２７，Ｐ值＜０．００１），与ＰａＣＯ２呈显著性正相关（ＣＯＰＤ组：ｒ值＝－０．５１４，Ｐ值＜０．０５；肺心病组：ｒ值＝０．５９３，Ｐ值＜０．００１）；ＥＴ－１含量与肺动脉收缩压及平均压均存在正相关（ｒ值＝０．７２７及０．６８１，Ｐ值均＜０．０５）。结论血浆ＥＴ－１参与肺心病肺动脉高压的形成，缺氧和二氧化碳潴留是刺激ＥＴ－１释放的重要原因之一     

糖尿病患者血清生长激素与肌酐清除率

测定了１６例胰岛素依赖型糖尿病（ＩＤＤＭ）患者，１９例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者和２３例对照者的血清生长激素（ＧＨ）水平。在ＩＤＤＭ组，无论是肌酐清除率（Ｃｃｒ）正常或减低，其ＧＨ值均为２．５３±１．７３μｇ／Ｌ，均高于对照组的０．７１±０．５３μｇ／Ｌ（Ｐ＜０．０５），ＧＨ与Ｃｃｒ呈负相关（ｒ＝０．６３，Ｐ＜０．０１），ＮＩＤＤＭ组Ｃｃｒ＜５０ｍｌ／ｍｉｎ者ＧＨ值为１．８３±０．４７μｇ／Ｌ显著高于对照组（Ｐ＜０．０５）和Ｃｃｒ＞８０ｍｌ／ｍｉｎ组（ＧＨ０．８３±０．４９μｇ／Ｌ，Ｐ＜０．０５）。糖尿病（ＤＭ）伴微血管并发症者，ＧＨ值为２．９２±１．７０μｇ／Ｌ，高于无此并发症者ＧＨ１．２４±０．９７μｇ／Ｌ，（Ｐ＜０．０１），认为ＧＨ与ＤＭ微血管并发症有关。     

胃十二指肠疾病患者骨矿物质含量的变化意义

目的研究慢性胃炎、胃十二指肠溃疡和胃癌患者骨矿物质含量变化的意义．方法用单光子吸收法，以桡骨长度中下１／３处为测定点，测定慢性胃炎（ｎ＝３１）、消化性溃疡（ｎ＝２６）、胃癌（ｎ＝９）及正常对照组（ｎ＝４３）的骨矿物质含量，并以骨矿含量（ＢＭＣ，ｇ／ｃｍ）及骨面密度（ＢＭＣ／ＢＷ，ｇ／ｃｍ２）表示，并进行比较．结果慢性萎缩性胃炎（ｎ＝１４），ＢＭＣ＝１００８±０２２８ｇ／ｃｍ）和十二指肠球部溃疡（ｎ＝１６），ＢＭＣ＝０９０４ｇ／ｃｍ±０２０５ｇ／ｃｍ，ＢＭＣ／ＢＷ＝０６５２ｇ／ｃｍ２±００８６ｇ／ｃｍ２）骨矿含量显著低于正常对照组（ｎ＝４３，ＢＭＣ＝１１７６ｇ／ｃｍ±０３４１ｇ／ｃｍ，ＢＭＣ／ＢＷ＝０７８２ｇ／ｃｍ２±０１３４ｇ／ｃｍ２，Ｐ＜００５）．结论萎缩性胃炎及十二指肠溃疡患者ＢＭＣ明显下降，需纠正．     

缺氧及外源一氧化碳对肺动脉内皮细胞PDGF—A链和—B链基因表达…

目的 观察肺动脉内皮细胞血小板源性生长因子（ＰＤＧＦ）旁分泌及其调节在缺氧性肺动脉高压中所起的作用。方法 采用核酸分子杂交技术，分析缺氧时小牛肺动脉内皮细胞（ＰＡＥＣ）表达ＰＤＧＦ－Ａ链、－Ｂ链ｍＲＮ的变化及外源一氧化氮（ＮＯ）对其表达的调节作用。结果缺氧（２．５％Ｏ２和０％Ｏ２）早期（１．５，３ｈ）能寺增加肺动脉 细胞ＰＤＧＦ－Ａ，ＰＤＧＦ－Ｂ锭ｍＲＮＡ的表达的，缺氧６－４８ｈ与常氧级相比ＰＤＧ     

应用ONE－TOUCHⅡ型血糖监测仪测定毛细血管全血糖

应用ＯＮＥ－ＴＯＵＣＨⅡ型血糖仪测定毛细血管全血糖（ＣＢＧ）１２６４例次，并与ＢｅｃｋｎｉａｎＣｘ４自动生比分折仪测定静脉血浆糖（ＶＰＧ）比较。结果表明，ＶＰＧ较ＣＢＧ高１０．２±０．４％，且两者明显相关。当ＶＰＧ在４．４ｍｍｏｌ／Ｌ以上时，ＶＰＧ＞ＣＢＧ，血糖愈高，差别愈大；而在４．４ｍｍｏｌ／Ｌ以下时，ＶＰＧ＜ＣＢＧ。进餐（或葡萄糖）后３０分钟、６０分钟，ＶＰＧ与ＣＢＧ相对差最小，至１２０分钟、１８０分钟时恢复到空腹水平。误差表格分析显示，所有测定值的９０．２％，７．５％处于Ａ、Ｂ区，仅２．３％处于↑Ｄ区。贫血时ＣＢＧ测值偏高。说明ＯＮＥ－ＴＯＵＣＨⅡ血糖仪测ＣＢＧ快速、简便、准确，故不仅用于糖尿病患者血糖自我监测，且可用于糖尿病的筛选、普查。     

Classification and characterization of hereditary types 2A, 2B, 2C, 2D, 2E, 2M, 2N, and 2U (unclassifiable) von Willebrand disease.

All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with increased triplet structure of each visuable band (not present in types 2M and 2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. VWD 2B differs from 2A by normal VWF in platelets, and increased ristocetine-induced platelet aggregation (RIPA). RIPA, which very likely reflects the VWF content of platelets, is normal in mild, decreased in moderate, and absent in severe type 2A VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically featured by low VWF:RCo and RIPA with the relative lack of high large VWF multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern with a lack of high molecular weight multimers, the presence of one single-banded multimers instead of triplets caused by homozygosity or double hereozygosity for a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is rare and characterized by the lack of high molecular weight multimers and the presence of a characteristic intervening subband between individual oligimers due to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large VWF multimers are missing and the pattern of the individual multimers shows only one clearly identifiable band, and there is no intervening band and no marked increase in the smallest oligomer. 2E appears to be less well defined, is usually autosomal dominant, and accounts for about one third of patients with 2A in a large cohort of VWD patients.     

Structure-function of Hb Marseille-Long Island [alpha 2 beta 2 N-methionyl-2(NA2) His----Pro

Suspensions of red cells containing Hb Marseille-Long Island showed decreased oxygen affinity and low interaction with 2,3-diphosphoglycerate. Oxygen equilibrium studies of the purified component confirmed these abnormalities. Oxidation rate measurements of carbonmonoxy-Hb Marseille and carbonmonoxy-Hb A by ferricyanide showed an increased rate for the former, suggesting an increased dissociation constant for carbon monoxide. Nuclear Magnetic Resonance spectra in the high field region revealed small changes in the proximal region of the heme pocket. These results indicated that the mutation causes a perturbation at a distance from the mutation site.     

Different RBC aggregating properties of the Aalpha2Bbeta2gammaA2 and Aalpha2Bbeta2gammaAgamma' subpopulations of human fibrinogen

Human fibrinogen (TF) has been separated into two fractions: F1 - homodimers with respect to the gamma chain, and F2 - heterodimers composed of gammaA and gamma' polypeptides. Their rouleaux-inducing properties were as follows: (1) both, at the same concentration of 0.8%, were less effective than TF; (2) F1 produced larger rouleaux even under static conditions of a hemocytometer where F2 was silent; (3) F2 induced the process when a suspension was gently sheared between microscopic slides. Since the synthetic peptide gamma'(414-427) inhibited the rouleau formation in a mixture with F2, the C-terminal amino acids of the gamma' polypeptide probably bind the molecule to the cell. The inhibition was feebly visible in the native ratio of F1/F2, implicating a compensatory effect of F1.     

Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling

The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain conserved dimerization (DD), pleckstrin homology, and SH2 domains. The DD domain mediates the formation of homo- and heterodimers between members of the SH2B family. The SH2 domain of SH2B1 (previously named SH2-B) or SH2B2 (previously named APS) binds to phosphorylated tyrosines in a variety of tyrosine kinases, including Janus kinase-2 (JAK2) and the insulin receptor, thereby promoting the activation of JAK2 or the insulin receptor, respectively. JAK2 binds to various members of the cytokine receptor family, including receptors for GH and leptin, to mediate cytokine responses. In mice, SH2B1 regulates energy and glucose homeostasis by enhancing leptin and insulin sensitivity. In this work, we identify SH2B2beta as a new isoform of SH2B2 (designated as SH2B2alpha) derived from the SH2B2 gene by alternative mRNA splicing. SH2B2beta has a DD and pleckstrin homology domain but lacks a SH2 domain. SH2B2beta bound to both SH2B1 and SH2B2alpha, as demonstrated by both the interaction of glutathione S-transferase-SH2B2beta fusion protein with SH2B1 or SH2B2alpha in vitro and coimmunoprecipitation of SH2B2beta with SH2B1 or SH2B2alpha in intact cells. SH2B2beta markedly attenuated the ability of SH2B1 to promote JAK2 activation and subsequent tyrosine phosphorylation of insulin receptor substrate-1 by JAK2. SH2B2beta also significantly inhibited SH2B1- or SH2B2alpha-promoted insulin signaling, including insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1. These data suggest that SH2B2beta is an endogenous inhibitor of SH2B1 and/or SH2B2alpha, negatively regulating insulin signaling and/or JAK2-mediated cellular responses.