基于LabVIEW构架的多道心电生理记录仪开发及临床应用

迄今多道生理记录仪已成为心脏介入术及医学基础研究不可缺少的重要设备。本研究首创用美国国家仪器 (NI)公司的 L ab VIEW开发系统为软件基本构架 ,自制低噪声多道前置放大器 ,配合 DAQ数据采集模块和通用计算机为开发硬件平台 ,研制了临床实用型多道心电生理记录仪。产品具有心电生理实时显示 ,数字高通、低通、5 0 Hz陷波和增益调节 ,即时存贮、任意回放和打印 ,基本程控刺激等功能。仪器小型化、经济实用、使用灵活 ,有利于心脏介入诊疗技术在医院推广和应用。     

A 38-kilobase pathogenicity island specific for Mycobacterium avium subsp. paratuberculosis encodes cell surface proteins expressed in the host

We have used representational difference analysis to identify a novel Mycobacterium avium subsp. paratuberculosis-specific ABC transporter operon (mpt), which comprises six open reading frames designated mptA to -F and is immediately preceded by two putative Fur boxes. Functional genomics revealed that the mpt operon is flanked on one end by a fep cluster encoding proteins involved in the uptake of Fe(3+) and on the other end by a sid cluster encoding non-ribosome-dependent heterocyclic siderophore synthases. Together these genes form a 38-kb M. avium subsp. paratuberculosis-specific locus flanked by an insertion sequence similar to IS1110. Expression studies using Western blot analyses showed that MptC is present in the envelope fraction of M. avium subsp. paratuberculosis. The MptD protein was shown to be surface exposed, using a specific phage (fMptD) isolated from a phage-peptide library, by differential screening of Mycobacterium smegmatis transformants. The phage fMptD-derived peptide could be used in a peptide-mediated capture PCR with milk from infected dairy herds, thereby showing surface-exposed expression of the MptD protein in the host. Together, these data suggest that the 38-kb locus constitutes an M. avium subsp. paratuberculosis pathogenicity island.     

女性毒品犯人格的基本特征及其相关因素的研究

目的 探讨在押女性毒品犯人格的基本特征、类型特征及其影响因素。方法 以252名在押女性毒品犯为被试，对CPI的测验数据进行t检验、Z检验和F检验。结果 ①女性毒品犯不仅与常模团体相比较具有显著特征．而且与男性毒品犯相比较也存在特殊性；②女性毒品犯在4种人格类型上的分布不平衡．较多地在Delta型；③民族、地域、年龄及关押时间对女性毒品犯的人格特征的变异均有一定影响．但减刑次数未见反映出被试人格积极改变的效果。结论 女性毒品犯广泛而明显的消极性人格特征，并与民族、地域、年龄及关押时间有关。     

Contrasting Roles of Mannan-Specific Monoclonal Immunoglobulin M Antibodies in the Activation of Classical and Alternative Pathways by Candida albicans

Polyclonal antimannan immunoglobulin G (IgG) activates the classical complement pathway and accelerates initiation of the alternative pathway by Canidida albicans. This dual role was assessed for two antimannan IgM monoclonal antibodies (MAbs). MAb B6.1 is specific for an epitope on the acid-labile portion of C. albicans phosphomannan; MAb B6 is specific for an epitope on the acid-stable region. Both MAbs were potent activators of the classical pathway but poor facilitators of alternative pathway initiation.Candida albicans activates the human complement system via both the classical and the alternative pathways, leading to deposition of opsonic complement fragments on the yeast cell surface (8, 10, 18). In previous studies, we described a critical role for naturally occurring antimannan immunoglobulin G (IgG) in complement activation by C. albicans. Those studies used a kinetic assay for C3 deposition on the yeast and immunofluorescence evaluation of the sites of C3 binding (10, 17, 18). Deposition of C3 onto C. albicans cells incubated in normal human serum (NHS) occurs rapidly via the classical pathway and can be detected within the first 2 min of incubation. If the classical pathway is blocked by chelation of Ca²⁺ with EGTA, C3 deposition occurs via the alternative pathway, but C3 deposition is delayed and a 6-min incubation is required before bound C3 is readily detectable on the yeast surface. Removal of naturally occurring antimannan IgG from the serum by mannan absorption profoundly delays accumulation of C3 on the yeast cell surface, with 12 min or more of incubation being required before appreciable amounts of bound C3 are detected. However, this 12-min delay can be overcome by supplementation of the mannan-absorbed serum with affinity-purified human antimannan IgG in the absence of EGTA to mediate classical pathway initiation or shortened to 6 min in the presence of EGTA to allow antibody-facilitated activation of the alternative pathway. These observations demonstrate a dual role for antimannan IgG in serum from healthy adults in complement activation by C. albicans. Antimannan IgG mediates activation of the classical pathway and facilitates initiation of the alternative pathway (17, 18).In studies described above, we used polyclonal antimannan IgG purified from pooled human plasma. Since C. albicans cells express a number of immunodominant mannan components recognized by rabbits (15, 16), the human polyclonal antimannan IgG likely contains a range of specificities for distinct mannan determinants. It has been shown that rabbit antibodies that are reactive with three different cell wall determinants of group A streptococci display differential abilities to activate the classical or alternative pathway (2). Although the antibodies specific for three different cell wall epitopes all activated the classical pathway, only antibody specific for the N-acetyl-d-glucosamine epitope activated the alternative pathway (2). In a separate study, capsular as well as noncapsular antibodies were found to direct classical-pathway-mediated killing of Haemophilus influenzae type b, whereas only the capsular antibodies promoted killing by the alternative pathway (12). These studies provide evidence that epitope specificity may influence the ability of an antibody to activate the alternative pathway and prompted us to examine whether antibodies that recognize different mannan determinants are able to mediate activation of the classical and alternative pathways by C. albicans.Two IgM monoclonal antibodies (MAbs) that recognize distinct mannan determinants were compared for their abilities to activate the classical or alternative pathway. MAb B6.1 is specific for an acid-labile component of the Candida phosphomannan complex, and MAb B6 is specific for an acid-stable component (5). The MAbs were produced commercially (Montana ImmunoTech, Inc., Bozeman, Mont.).C. albicans CA-1 was grown as yeast forms to stationary phase in glucose (2%)-yeast extract (0.3%)-peptone (1%) broth for 24 h at 37°C as described elsewhere (4, 6, 10). The mannan of CA-1 yeast was purified as described previously (7, 18) and coupled to CNBr-Sepahrose 4B (Pharmacia Biotech, Uppsala, Sweden) (18).Pooled NHS was prepared from peripheral blood from at least 10 healthy adult donors and stored at −80°C. C3 was isolated from frozen human plasma (9, 13) and stored at −80°C until used. C3 was labeled with ¹²⁵I as described previously (3) by use of IODO-GEN reagent (Pierce, Rockford, Ill.). NHS was absorbed with mannan-Sepharose 4B to remove antimannan antibodies (18).Kinetics of C3 binding were assayed by the method of Kozel et al. (10). To determine whether MAb B6 or B6.1 activates the classical pathway, 2 × 10⁶ yeast cells were incubated at 37°C in 1 ml of a complement binding medium that contained (i) 40% NHS, mannan-absorbed serum, or mannan-absorbed serum supplemented with MAb B6 or B6.1, (ii) sodium Veronal (5 mM)-buffered saline (142 mM, pH 7.3) containing 0.1% gelatin, 1.5 mM CaCl₂, and 1 mM MgCl₂, and (iii) ¹²⁵I-labeled C3. To study whether MAb B6 or B6.1 plays a role in alternative pathway initiation, yeast cells were incubated in the manner described above except that the binding medium was not supplemented with Ca²⁺ and contained 5 mM EGTA and 5 mM MgCl₂. At various time intervals from 2 to 16 min, 50-μl samples were withdrawn in duplicate and added to 200 μl of phosphate-buffered saline–0.1% sodium dodecyl sulfate–20 mM EDTA in Millipore MABX-N12 filter plates fitted with BV 1.2-μm-pore-size filter membranes (Millipore, Bedford, Mass.). The cells were washed with phosphate-buffered saline–0.1% sodium dodecyl sulfate, and filter-bound radioactivity was determined with a gamma counter. Nonspecific binding was estimated from cells incubated in NHS containing EDTA and was subtracted from the total counts.Mannan absorption of serum profoundly delayed C3 accumulation on yeast from 2 min to approximately 10 min (Fig. ​(Fig.11 and ​and2).2). However, addition of either MAb B6 or MAb B6.1 at 50 μg per ml of reaction mixture to the absorbed serum generated rapid activation kinetics characteristic of C3 deposition via the classical pathway (Fig. ​(Fig.1)1) (10, 17, 18). This observation was not unexpected, as polyvalent IgM is known to be a potent activator of the classical pathway. Open in a separate windowFIG. 1Effect of MAb B6 or B6.1 on the kinetics of C3 deposition on C. albicans cells via the classical pathway. Yeast cells were incubated in a C3 binding medium containing (i) 40% NHS (•), (ii) 40% mannan-absorbed NHS (○), (iii) 40% mannan-absorbed NHS supplemented with MAb B6 (▴), or (iv) 40% mannan-absorbed NHS supplemented with MAb B6.1 (▿) at 50 μg per ml of reaction mixture. C3 deposition patterns from three independent assays were similar; results from one representative assay are shown.Open in a separate windowFIG. 2Effect of MAb B6 or B6.1 on the kinetics of C3 deposition on C. albicans cells via the alternative pathway. Yeast cells were incubated in a C3 binding medium containing (i) 40% NHS (•), (ii) 40% NHS–EGTA (■), (iii) 40% mannan-absorbed NHS containing EGTA (○), (vi) 40% mannan-absorbed NHS containing EGTA supplemented with MAb B6 (▴), or (iv) 40% mannan-absorbed NHS supplemented with MAb B6.1 (▿) at 50 μg per ml of reaction mixture. C3 deposition patterns from four independent assays were similar; results from one representative assay are shown.The effects of MAbs B6 and B6.1 on activation of the alternative pathway were assessed by addition of the antibodies to mannan-absorbed serum in the presence of EGTA. The results (Fig. ​(Fig.2)2) showed that neither MAb B6 nor MAb B6.1 at 50 μg per ml of reaction mixture altered the alternative pathway activity of the mannan-absorbed serum. To determine whether the inability of MAb B6 or B6.1 to facilitate initiation of the alternative pathway was influenced by antibody concentration, the experiment represented in Fig. ​Fig.22 was repeated with mannan-absorbed serum that was supplemented with 10 to 160 μg of MAb B6 or B6.1 per ml. These antibody concentrations were chosen because in our previous studies we found that affinity-purified human antimannan IgG activates both the classical and alternative pathways (17). However, at 10, 40, or 160 μg per ml of reaction mixture, both antibodies failed to enhance alternative pathway activity of mannan-absorbed serum but promoted classical pathway activity (data not shown).The observation that both MAbs were unable to enhance alternative pathway activity was unexpected. Our previous studies showed that addition of polyclonal antimannan IgG to mannan-absorbed NHS containing EGTA produced C3 binding kinetics that were indistinguishable from the kinetics observed with nonabsorbed NHS containing EGTA (17). We further demonstrated IgG-dependent initiation of the alternative pathway by C. albicans using the six purified alternative pathway proteins (17).There are at least three possible explanations for the failure of MAbs B6 and B6.1 to facilitate activation of the alternative pathway. First, it is possible that antimannan antibodies of the IgM class are unable to enhance C3 deposition via the alternative pathway. However, there is evidence that polyclonal IgM is able to enhance alternative pathway-mediated lysis of rabbit erythrocytes by NHS (11, 14). Second, the ability of an antibody to facilitate deposition of C3 via the alternative pathway could be epitope specific; MAbs B6 and B6.1 could have the wrong epitope specificity. As noted above, Eisenberg and Schwab (2) found that polyclonal antibodies specific for one antigen found on group A streptococcal cell walls were able to facilitate initiation of the alternative pathway, whereas antibodies specific for two other antigens were not. If antibody-facilitated activation of the alternative pathway is dependent on epitope specificity, such a finding might influence strategies for induction of protective immunity to Candida. Optimal immunization may require an immunogen that induces antibodies with epitope specificities needed to facilitate activation of the alternative pathway. Finally, we cannot exclude the possibility that human antimannan antibodies are able to facilitate activation of the alternative pathway, whereas mouse antibodies lack this capability.In studies involving a murine model of disseminated candidiasis, MAb B6.1 was shown to be protective, whereas MAb B6 was not (4). However, the protection mechanisms remain to be elucidated. In an in vitro assay, MAb B6.1 but not MAb B6 was found to enhance candidacidal activity of polymorphonuclear leukocytes in the presence of fresh mouse serum, suggesting the involvement of mouse complement in the killing (1). Although assessing the role of complement in MAb B6.1-mediated protection was beyond the scope of this study, our observation that the two antibodies mediate similar kinetics of C3 deposition for C. albicans does not preclude the possibility that the composition and/or accessibility of opsonic complement fragments bound to the yeast cells might differ following complement activation by these two antibodies. Alternatively, the concerted action of several protective functions, including activation of the complement system, may be required for MAb B6.1-mediated protection.     

郃郎喘必消冲剂的药理研究

本文通过对小鼠急性毒性实验,抗炎实验,对胸腺脾脏的影响及对豚鼠在体、离体气管平滑肌作用实验,观察了郃郎喘必消冲剂的药理学效应。结果表明,该制剂无明显毒性,最大耐受量为1000g/kg/d。它有明显的对抗二甲苯致小鼠耳炎及延长组胺诱发哮喘发作潜伏期的作用,对豚鼠离体气管平滑肌无松驰作用,对小鼠胸腺和脾脏有使其重量减小的趋势,但与对照组比较无显著性差异。     

正常新生儿脐血血流变学的研究

本文总结报道了我院于1992-1993年对35例正常新生儿脐血进行血液流变学检测,结果提示正常新生儿早期全血粘度、血浆粘度、血小板聚集率,均较正常成人对照组显著增高;而红细胞沉降率显著降低.证明新生儿血液里高粘滞状态,这是新生儿疾病如新生儿硬肿症、肺出血、DIC等的病理生理基础,也为这些新生儿疾病的诊断和治疗提供了理论依据.     

Retinoic acid receptor beta variant‐related colonic hypoganglionosis

Retinoic acid receptor beta (RARB) variants are heavily linked to pathologies of neural crest cell migration. The purpose of this report is to present a 23‐month‐old male with the previously described R387C RARB gain‐of‐function variant whose gastrointestinal issues and long‐term constipation lead to the discovery of colonic hypoganglionosis. This case further delineates the pattern of malformation associated with RARB variants. The findings are also consistent with the known etiology of aganglionic colon due to failed neural crest cell migration.     

川芎嗪对内毒素脂多糖诱导的体外血脑屏障模型通透性增高的保护作用及其机制

目的:探讨川芎嗪对内毒素脂多糖(LPS)诱导的体外血脑屏障模型通透性增高的保护作用及其调控机制。方法:利用脑微血管内皮细胞与星型胶质细胞共培养建立体外大鼠血脑屏障模型,随机分为正常对照组、川芎嗪对照组、LPS干预组和川芎嗪治疗组。采用γ计数仪检测~(125)I-BSA通透量观察体外血脑屏障模型通透性的改变,Western印迹法检测紧密连接蛋白(zonula occludens-1,ZO-1)表达量的变化。结果:LPS使体外血脑屏障模型对~(125)I-BSA的通透量明显增加,脑微血管内皮细胞ZO-1蛋白表达下降,川芎嗪治疗组能明显拮抗LPS的上述作用。结论:川芎嗪对LPS诱导的体外血脑屏障通透性增高具有保护作用,其机制与它能影响血脑屏障紧密连接蛋白ZO-1表达有关。     

Selenium improves cardiac function by attenuating the activation of NF-kappaB due to ischemia-reperfusion injury

Although selenium, an essential trace element and a component of glutathione peroxidase, is known to protect the heart from ischemia-reperfusion (I/R)-induced injury, the mechanisms of this protection are not fully understood. For this purpose, isolated rat hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion; sodium selenite (25-1,000 nM) was added in the perfusion medium 10 min prior to ischemia, as well as during reperfusion. Selenium caused a dose-dependent improvement in cardiac performance and attenuated the decrease in the ratio of reduced glutathione to oxidized glutathione, as well as the increased level of malondialdehyde in I/R heart. Elevated ratios of nuclear factor-kappaB (NF-kappaB) in particulate and cytosolic fraction and of phosphorylated NF-kappaB and total NF-kappaB in I/R hearts were reduced by selenium. Cardiac dysfunction in hearts perfused with xanthine plus xanthine oxidase mixture, as well as hydrogen peroxide, or subjected to Ca2+ paradox was also attenuated by selenium. These data suggest that selenium protects the heart against I/R injury due to its action on the redox state and deactivation of NF-kappaB in I/R hearts.     

蝎蜂毒肽对大鼠纤溶系统作用初探

本研究采用大鼠肢体血管灌流和整体给药两种模型，观察蝎蜂毒（ＳＢＰ）对血管理灌流液内纤溶酶原激活物（ＰＡ）活性、血浆优球蛋白纤溶性（ＥＦＡ）和纤溶酶（ＰＬ）活性的影响。结果说明，ＳＢＰ有明显激活纤溶系统作用；其机制可能涉及血管内皮细胞释放ＰＡ活性增加，进一步促使纤溶酶原活化为ＰＬ增多的途径。