Modification of DiFrancesco-Noble equations to simulate the effects of vagal stimulation onin vivo mammalian sinoatrial node electrical activity

We present a new mathematical model for vagal control of rabbit sinoatrial (SA) node electrical activity based on the DiFrancesco-Noble equations. The original equations were found to be unstable, resulting in progressive cycle by cycle depletion or accumulation of ions in intra- and extracellular compartments. This problem was overcome by modifying the maximum Na−K pump current and the time constant for uptake of intracellular calcium. We also included a formulation for the acetylcholine (ACh)-activated potassium current which was consistent with experimental data. This formulation was based on kinetics first proposed by Osterrieder and later modified by Yanagihara. The resulting model exhibits cycle-cycle ionic stability, and includes an ACh-activated potassium current which accurately reproduces experimentally observed effects of vagal stimulation on both the membrane potential and its timederivative. Simulations were performed for both brief-burst and prolonged vagal stimulation using simplified square wave profiles for the concentration of ACh in the synaptic cleft space. This protocol permits the isolation of cardiac period dynamics caused by changes in membrane potential and intra- and extracellular ionic concentrations from those caused by other mechanisms including the dynamics of ACh release, diffusion, hydrolysis and washout. Simulation results for the effects of brief-burst single cycle stimulation on the cardiac period agree closely with experimental data reported in the literature, accurately reproducing changes in membrane potential and the phasic dependency of the response to the position of vagal stimulus bursts within the cycle. Simulation of the effects of prolonged vagal stimulation accurately reproduced the steady-state characteristics of heart period response, but did not yield the complex multimodal dynamics of the recovery phase, or the pronounced post vagal tachycardia observed experimentally at the termination of the stimulus. Our results show that the major chronotropic effects of vagal stimulation on the SA cell membrane can be explained in terms of the ACh-activated potassium current. The effects of this membrane current however are generally fast acting and cannot contribute to any long lasting dynamics of the cardiac period response. The modified DiFrancesco-Noble model presented in this article provides a valuable theoretical tool for further analysis of the dynamics of vagal control of the cardiac pacemaker.     

The instability of membrane markers expressed by human monocytes and macrophages in culture

Surface markers were tested on freshly isolated human monocytes and following their in vitro maturation to macrophages. The markers tested were HLA-DR antigens, receptors for the Fc of IgG and complement as well as membrane markers defined by monoclonal antibodies. The results revealed a dynamic expression of some of the markers on monocytes which was influenced by several variables. The expression of the markers was modulated by the presence of different sera, by treatment with lymphokines and interferon and following the in vitro maturation of monocytes to macrophages. The most unstable marker was found to be the HLA-DR, which was modulated by all these variables. The 63D3 was affected by different sera and culture supernatant, as well as following the maturation of monocytes to macrophages, but not by lymphokines and interferon. One of the markers, the Mac 120, was found to be relatively stable and did not change significantly following the maturation of monocytes to macrophages. The Fc and complement receptors were also stable in their expression under these conditions, but were probably partially blocked in the presence of human serum. These results indicated that at least some of the heterogeneity related to the monocyte population was probably not due to the occurrence of stable subsets of cells, but rather to reversible changes in marker expression.     

Specific and non-specific components in the triggering of proliferative and cytotoxic responses of T lymphocytes with different cell density

We hve analyzed the functional behavior of lymphocyte subsets separated on the basis of cell density. Low and high density subpopulations were cultured in FCS, alone or with allogeneic irradiated PBL, and then examined for proliferation and cytotoxic activity against autologous (responder) and allogeneic (stimulator) PHA-induced blasts, K562 and Daudi. In the high density subset proliferation and generation of anti-K562 and anti-Daudi effects were induced by FCS and to higher extent by allospecific stimulation. Exposure to alloantigens induced allospecific cytotoxicity. Autologous PHA blasts were not affected. The results with the low density subset differed. Independently of the type of stimulus imposed, the low density fraction showed little if any proliferation, but its cytotoxic activity was stronger against all targets tested. In some of the experiments, anti-alloblast cytotoxicity was generated in the control cultures. Thus, polyclonal activation induced by FCS triggered in this fraction allospecific cytotoxicity. In this subset, the effect against allogeneic PHA blasts comprised a specific and a non-specific component because autologous PHA blasts were also lysed. Limiting dilution analysis involving allostimulation showed higher frequency of cytotoxic precursors in the low density subset. Split minicultures were tested for lysis of auto- and allogeneic blasts. Alloreactive cultures that did not lyse the autologous target were more frequent in the cultures initiated with the high density cells. There was no conclusive evidence for the existence of autoreactive cultures that did not lyse the allogeneic blasts.     

流行性乙型脑炎病毒活疫苗株SA14-14-2基因稳定性研究

目的 通过研究流行性乙型脑炎活疫苗减毒株基因稳定性，从分子水平证实流行性乙型脑炎活疫苗的遗传稳定性。方法分析流行性乙型脑炎活疫苗主种子、工作种子及其相应的疫苗病毒E蛋白基因核苷酸和氨基酸序列，并与其强毒株和基因库中乙脑病毒减毒株(AF15119)比较。结果乙脑活疫苗主种子、工作种子及其相应的疫苗病毒的E蛋白基因核苷酸序列完全相同。这些病毒E蛋白的氨基酸序列与基因库中乙脑病毒弱毒株(AF315119)比较显示第E447位点氨基酸有差异。结论乙脑病毒活疫苗减毒株遗传学特性稳定。     

Association study of a SNAP‐25 microsatellite and attention deficit hyperactivity disorder

Several lines of evidence implicate synaptosomal‐associated protein of 25 kDa (SNAP‐25) in the etiology of attention deficit hyperactivity disorder (ADHD). Most notably, the coloboma mouse mutant, considered to be a good animal model of hyperactivity, has a deletion spanning this gene. Introducing a SNAP‐25 transgene into these animals alleviates hyperlocomotion. We have identified a novel microsatellite repeat in SNAP‐25 located between the 5′UTR and the first coding exon, and tested for association with ADHD. Case‐control analyses suggest there may be a role of this polymorphism in ADHD, with one allele over‐represented in controls and another over‐represented in probands. Within‐family tests of linkage and association confirmed these findings. Further work is needed to ascertain the role of SNAP‐25 in ADHD and assess the functional significance of this polymorphism. © 2002 Wiley‐Liss, Inc.     

Cytotoxic effector cells against HLA antigens in strong linkage disequilibrium: identification of a strong,new, CML determinant

Three sets of cytotoxic effector cells were generated against the A1, B8, DR3 haplotype using haptoidentical individuals in three different families. The three sets of effector cells generated against this haplotype showed excellent reproducibility testing, strong cytotoxicity against their specific targets, low autologous kill, and segregation with the sensitizing haplotype within the family. When tested against a panel of cells bearing all combinations the A1, B8. DR3 antigens, a hierarchy of contribution of the individual HLA antigens as CML target determinants was seen. A new strong target cell determinant was identified by cytotoxicity with one of the effector cells not explicable in terms of the A1, B8, DR3 antigens or known HLA cross-reactivity. A family study demonstrated that this determinant clearly segregates with HLA. The success of this approach in defining new CML determinants may result from the generation of effector cells across a single haplotype in strong linkage disequilibrium or from the presentation of CML determinants in the context of self.     

胃癌患者8种肿瘤标志物测定的临床价值

对 30 2例胃癌术前检测CA5 0、CA199、CA12 5、CA72 4、CEA、β2 -MG、SA、Fer等 8种肿瘤标志物 ,并按年龄、胃癌病期及病理分类分组分析。结果 :(1) 30 2例胃癌血清中 8种肿瘤标志物总的阳性率依次为 β2 -MG6 5 .9%、CA19932 .1%、CA72 42 9.5 %、SA2 4.5 %、CA12 5 16 .9%、CEA13 .2 %、CA5 0 11.6 %、Fer(- )。 (2 ) 8种肿瘤标志物阳性率与年龄大小均无关。 (3) β2 -MG、CA72 4、CA12 5、CA199、SA、CEA、在Ⅲ、Ⅳ期病例中均较敏感 ,且随病期增加 ,阳性率增高。 (4 )CA199和CA72 4对腺癌、β2 -MG和SA对低分化腺癌、β2 -MG和CA72 4对粘液癌、混合型癌阳性率较高。提示血清测β2 -MG、CA199、CA72 4、SA、CA12 5对胃癌的辅助诊断有一定应用价值     

流行性乙型脑炎减毒活疫苗大面积接种后安全性和流行病学效果的5年观察

目的 考核乙脑减毒活疫苗大面积接种后的安全性和降低乙脑发病率,在乙脑高发区安徽省蒙城和涡阳县进行为期５年（１９９２￣１９９６年）的人群观察。方法 观察对象１￣６岁儿童。１岁初免１针,２岁加强１针。结果 通过５年连续观察共接种乙脑活疫苗３３５９４１人。 表明：①疫苗对小龄儿童接种后近期和５年内均未出现不良反应,表明疫苗是安全的。②当地乙脑平均总发病率有显著性下降,从接种观察前１９８７￣１９９１年的１     

食管癌患者手术切除前后SA、CEA和SCP检测的临床意义

目的　探讨食管癌患者手术切除前后血清 SA、CEA、SCP水平的变化。方法　应用放免法测定 4 3例食管癌患者血清 CEA含量 ,化学法测定 SA和 SCP含量 ,并以 35名正常健康人作对照。结果　食管癌患者在手术切除前血清 SA、CEA、SCP水平非常显著地高于正常人组 (P<0 .0 1) ,手术切除后 6个月转移者血清 SA、CEA、SCP水平持续异常 ,未转移者血清 SA、CEA、SCP在正常水平。结论　血清 SA、CEA、SCP含量测定的变化与食管癌患者的病情和预后密切相关 ,有一定的临床应用价值     

血清SA,Cu／Zn比值联合检测诊断肺癌患者的临床意义

对１７８例原发性肺癌患者血清唾液酸（ＳＡ）含量、铜／锌（Ｃｕ／Ｚｎ）比值进行了测定分析，并与８０例正常人作对照。结果表明：原发性肺癌患者血清ＳＡ含量（１２２．２０±３６．３０）、Ｃｕ／Ｚｎ比值显著高于对照组，（Ｐ＜０．０１）。单项检测：两项指标对肺癌的诊断敏感性分别为７６．４％和６１．２％，特异性为９７．５％和７６．３％；联合检测：以两项之一阳性为诊断依据时，特异性可达９８．７％。表明ＳＡ和Ｃｕ／Ｚｎ比值联合检测较单项检测对肺癌的诊断更有临床应用价值。