扩张型心肌病抗心肌抗体的临床观察及其针对性治疗

目的:探讨扩张型心肌病(DCM)的发病机制,观察针对抗心肌抗体进行免疫学治疗的临床疗效和预后.方法:对2001年1月-2007年12月入院治疗的DCM患者(747例)的病史、诊治过程、随访情况进行回顾性分析.结果:747例中抗心肌抗体阳性者527例(70.55%),随访时间为0.9-7.2年,抗心肌线粒体ADP/ATP载体抗体阳性患者(A组)治疗后平均左室舒张末期内径(LVEDd)为(62.53±9.17)mm,左室射血分数(LVEF)为(37.65±11.15)%;抗β1-肾上腺素能受体抗体(抗β1-受体抗体)阳性患者(B组)治疗后LVEDd (61.35±5.68)mm, LVEF (40.65±12.78)%;抗ADP/ATP载体抗体和抗β1-受体抗体均阳性患者(C组)治疗后LVEDd(61.28±7.72)mm, LVEF(38.35±7.05)%.3组与治疗前比较LVEDd差异均有统计学意义(P<0.05)、NYHA心功能分级均改善Ⅰ～Ⅱ级.结论:自身免疫是DCM的常见致病因素,针对抗ADP/ATP载体抗体使用地尔硫和针对抗β1-受体抗体使用美托洛尔治疗DCM均可明显改善患者心脏功能及心室重构,改善预后.     

系列抗心肌多肽自身抗体对扩张型心肌病的诊断价值

目的 :探讨抗人工合成多肽自身抗体在扩张型心肌病 ( DCM)诊断中的价值。方法 :根据计算机预测心肌 ADP/ ATP载体 ( ANT)、β1 受体、M2 受体和肌球蛋白重链 ( MHC)抗原决定簇的氨基酸序列并合成多肽片段 ,以此片段作为抗原 ,同时用天然抗原对比 ,以酶联免疫吸附方法检测 48例 DCM患者 ( DCM组 )和 48例健康献血员 (对照组 )血清中抗心肌多肽自身抗体。结果 :DCM组中抗 ANT抗体、抗 β1 受体抗体、抗 M2 受体抗体和抗MHC抗体阳性分别有 31、2 6、2 0和 2 3例 ,与对照组比较有显著性差异 ( P <0 .0 0 5 ) ,且与天然心肌抗原检测结果高度一致 ( P <0 .0 1)。结论 :人工合成多肽可代替天然心肌抗原用于检测抗心肌自身抗体 ,抗心肌多肽抗体检测可以作为 DCM免疫学诊断方法     

抗心肌抗体消长与病毒性心脏病转化关系探讨

目的:探讨抗心肌抗体消长与病毒性心脏病(VHD)病程的关系及在病毒性心肌炎(VMC)向扩张型心肌病(DCM)转化过程中所起的作用。方法:通过计算机预测ADP/ATP载体(ANT)、β1-受体、M2-胆碱能受体及肌球蛋白重链(MHC)抗原决定簇的氨基酸序列,用人工多肽合成仪合成的多肽作为抗原,应用ELISA方法,对不同病程的VHD患者进行抗心肌抗体的检测,同时对慢性VMC(CVMC)患者进行追踪观察及干预,并评价疗效。结果:随着VHD患者病程的延长,4种抗心肌抗体的检出率呈先升高后降低的趋势,CVMC和早期DCM患者抗心肌抗体阳性率最高;22例抗体阳性的CVMC患者经过3.1年随访,其中8例演变成为DCM,经给予相应药物干预治疗后6例恢复正常;而6例抗体阴性的患者随访期间均未出现DCM表现。结论:监测患者血清中抗心肌抗体有助于防止VMC向DCM转化,对DCM的早期诊断和干预及VHD的疗效判断和预后都可以提供重要的线索。     

肠病毒RNA和抗ANT抗体在健康献血员中检出的意义

目的 :探讨肠病毒 RNA和抗 ANT抗体在健康献血员中检出的临床意义。方法 :应用酶联免疫吸附实验 (EL ISA)和逆转录 -聚合酶链式反应 (RT- PCR)方法对健康献血员和扩张型心肌病 (DCM)患者进行抗心肌多肽自身抗体 (抗 ANT抗体 )和肠病毒 (RNA)的检测。结果 :48例健康献血员中有 4例抗 ANT抗体阳性 (阳性率为 8.3% ) ,3例肠病毒 RNA阳性 (阳性率为 6 .3% ) ,而 48例 DCM患者中有 31例抗 ANT抗体阳性 (阳性率为6 4.6 % ) ,2 9例肠病毒 RNA阳性 (阳性率为 6 0 .4% ) ,两组比较差异有显著性意义 (P <0 .0 5 )。在 DCM组中 ,自身抗体和肠病毒 RNA的检出具有一致性 (r =0 .5 6 ) ,而健康献血员中 ,二者则没有相关性 (r =0 .0 8)。结论 :健康人可能存在肠病毒隐性感染 ,但不一定能激活自身免疫系统引起自身免疫损伤而导致 DCM;而肠病毒持续感染与肠病毒感染后激活自身免疫系统引起自身免疫损伤则可能是 DCM的主要发病机制。     

病毒与抗心肌抗体在围生期心肌病发病中的作用

目的:通过研究围生期心肌病(PPCM)患者的病因,探讨病毒与抗心肌抗体(AHA)在PPCM发病中的作用。方法:收集2010-03-2016-03在我院住院确诊为PPCM的女性患者32例,平均年龄(27.6±4.4)岁;其中NYHA心功能分级Ⅲ级者12例(37.5%)、Ⅳ级15例(46.8%)。采用逆转录聚合酶链式反应法(RT-PCR)检测以下病毒:柯萨奇病毒(CoxB-IgM)、埃可肠病毒(EVs-RNA)、巨细胞病毒(CMV-IgM);以酶联免疫吸附测定(ELISA)法检测血清AHA:抗心肌线粒体腺嘌呤核苷酸异位酶(ANT)抗体,抗β1-肾上腺素受体(β1-AR)抗体,抗M2-胆碱能受体(M2R)抗体,抗肌球蛋白重链(MHC)抗体;同时对患者病史、诊治过程、随访结果进行回顾性分析。结果:病毒检测为阳性者共22例(68.7%),其中CoxB-IgM阳性21例(65.6%)、EVs-RNA阳性19例(59.4%)、CMV-IgM阳性12例(37.5%)。AHA为阳性者共17例(53.1%),其中抗ANT抗体阳性15例(46.8%)、抗β1-AR阳性15例(46.8%)、抗M2R抗体阳性13例(40.6%)、抗MHC抗体阳性13例(40.6%)。病毒与AHA均阳性17例(53.1%)。32例患者中有高龄产妇9例(28.1%),经产妇13例(40.6%);经抗心力衰竭等治疗后28例(87.5%)患者获好转,NYHA分级改善Ⅰ~Ⅱ级。平均随访(26.7±12.4)个月,2例患者死亡。结论:病毒与AHA可能在PPCM的发病中起重要作用。     

一种抗心肌抗体检测试剂盒的验证评价

目的:开发和验证一种高灵敏度和高特异度的抗心肌抗体(AHA)检测试剂盒。方法:合成具有抗原决定簇的心肌线粒体腺苷酸转运酶(ANT)、β1肾上腺素受体(β1-AR)、肌球蛋白重链(MHC)、L-型钙通道(LCC)的多肽,制成相应的AHA检测试剂盒,用ELISA法检测急性病毒性心肌炎(AVMC)患者(176例)、扩张型心肌病(DCM)患者(226例)、其他心脏病患者及健康体检者(共210例)血清中4种AHA,计算检验的灵敏度、特异度,并行kappa一致性检验。结果:抗ANT抗体、抗β1-AR抗体、抗MHC抗体、抗L-CC抗体在AVMC/DCM患者中检测的灵敏度分别为91.5%/90.3%、98.9%/97.3%、88.6%/94.7%、98.9%/98.7%,特异度分别为87.6%、74.3%、81.9%、63.3%;与临床诊断比较,kappa值分别为0.79/0.78、0.71/0.72、0.70/0.77、0.60/0.63,均P0.01。若同一份血清4种AHA均阳性诊断AVMC/DCM的灵敏度、特异度分别为80.1%/86.7%、91.9%/91.9%;与临床诊断比较,kappa值为0.73/0.79,P0.01。结论:此自主研发的AHA试剂盒检测AVMC/DCM结果与临床诊断具有高度一致性,可作为AVMC/DCM的辅助诊断指标。     

大剂量丙种球蛋白对扩张型心肌病心衰患者心肌肌凝蛋白重链自身IgG抗体滴度的影响

目的:探究大剂量丙种球蛋白对扩张型心肌病(DCM)心力衰竭患者心肌肌凝蛋白重链(CMHC)自身免疫球蛋白G(IgG)抗体滴度和临床疗效的影响。方法:选择2011年3月~2014年5月我院心内科收治的DCM心力衰竭患者160例。按照随机数字表法,患者被随机均分分为常规治疗组(80例)和丙种球蛋白组(80例,在常规治疗组基础上接受大剂量丙种球蛋白治疗)。观察比较两组患者治疗前后的心功能指标,IgG抗体滴度以及血清心肌肌钙蛋白T(cTnT)和cTnI水平。结果:与治疗前比较,治疗6个月后丙种球蛋白组左室舒张末期内径[LVEDd,(67.50±5.50)mm比(56.50±2.50)mm]和左室收缩末期内径[LVESd,(55.50±6.80)mm比(43.50±2.30)mm]显著降低,左室射血分数[LVEF,(33.50±3.50)%比(53.50±8.50)%]显著升高,而常规治疗组仅LVEF[(32.80±4.20)%比(41.50±5.50)%]显著升高,P均0.05;与常规治疗组比较,治疗6个月后丙种球蛋白组的LVEDd[(63.50±2.50)mm比(56.50±2.50)mm]和LVESd[(51.60±4.80)mm比(43.50±2.30)mm]显著降低,LVEF显著升高,P均0.05。治疗1、3、5和6个月后,丙种球蛋白组IgG抗体滴度显著降低,且均显著低于同期常规治疗组的(P均0.05)。治疗6个月后两组cTnT和cTnI水平均较治疗前显著减低(P均0.05),且与常规治疗组比较,丙种球蛋白组cTnT[(0.55±0.10)μg/L比(0.26±0.02)μg/L]和cTnI水平[(1.20±0.40)μg/L比(0.60±0.10)μg/L]下降更显著(P均0.05)。结论:大剂量丙种球蛋白治疗扩张型心肌病心力衰竭患者,能够显著改善患者的心肌功能,明显降低心肌肌凝蛋白重链自身IgG抗体水平,显著降低血清肌钙蛋白T和I的含量,值得在临床上推广。     

地尔硫卓对老年扩张型心肌病患者血清microRNA表达的调控

目的:探讨盐酸地尔硫卓缓释片对老年扩张型心肌病(DCM)患者血清microRNA表达的影响。方法:选择120例老年DCM患者为DCM组,60例身体健康的老年人为正常对照组。DCM组被进一步随机均分为常规治疗组(60例,接受常规治疗)和地尔硫卓组(60例,在常规治疗基础上加用盐酸地尔硫卓缓释片)。观察比较常规治疗组和地尔硫卓组治疗前后左室舒张末期内径(LVEDd)、左室后壁厚度(LVPWT)和左室射血分数(LVEF),以及治疗后两组心功能改善情况,比较三组治疗前,治疗后6周和12周时血清miR-1,-133,-499和-208表达量的变化。结果:与治疗前比较,常规治疗组治疗后LVEDd、LVPWT和LVEF无显著变化(P均0.05);地尔硫卓组LVEDd[(69.41±6.42)mm比(61.32±5.31)mm]和LVPWT[(20.98±1.98)mm比(12.05±2.42)mm]均显著降低,且显著低于常规治疗组[LVEDd:(67.25±4.21)mm,LVPWT:(18.49±2.86)mm],LVEF[(32.81±4.71)%比(50.52±6.88)%]显著升高,且显著高于常规治疗组[(47.77±3.92)%],P均0.05。心功能改善:地尔硫卓组的显效率(71.7%比56.7%)和总有效率(98.3%比85.0%)显著高于常规治疗组,P均0.05。DCM常规治疗组的4种miR表达量较正常对照组显著下降,而地尔硫卓组的miR表达量较常规治疗组有显著上升(P均0.01),但与治疗6周时比较,治疗12周时有下降趋势以miR-208最显著(P0.01)结论:地尔硫卓可有效调控老年扩张型心肌病患者血清中microRNA的表达,为研究地尔硫卓的作用机制提供了分子生物学依据。     

扩张型心肌病新型抗钙通道抗体的发现

目的:观察扩张型心肌病(DCM)患者血清中是否独立存在抗心肌细胞L型钙离子通道(Human Cav1.2)自身抗体(简称:抗钙通道抗体)。方法:以合成多肽片段作为抗原,用ELISA法检测DCM患者(DCM组)及正常人(正常对照组)(各60例)血清中的抗钙通道抗体和抗心肌细胞线粒体内膜ADP/ATP载体蛋白(ANT)抗体。用亲合层析法提纯DCM患者(DCM组)血清中的抗钙通道抗体,以制备的大鼠抗Human Cav1.2α1亚单位多克隆抗体作为阳性对照,用免疫印记技术,免疫荧光组织化学技术检测DCM患者血清中抗钙通道抗体。结果:ELISA检测60例DCM患者中29例抗钙通道抗体阳性(29/60,阳性率48.33%),明显高于正常对照组(4/60,6.67%,P<0.01)。抗钙通道抗体和抗ANT抗体检出结果无一致性(P>0.05)。免疫印记中亲合层析法提纯的DCM患者抗钙通道抗体可特异地识别240000的多肽(Human Cav1.2α1c亚单位),结果与阳性对照相符。抗钙通道抗体经抗原充分吸附后特异性识别被阻断。免疫荧光实验显示,抗钙通道抗体能特异性地结合在大鼠心室肌细胞膜上。结论:DCM患者血清中存在新型的抗钙通道抗体。     

抗人心肌线粒体抗体在病毒性心肌炎和扩张型心肌病中的检测及其意义

目的检测病毒性心肌炎(VMC)和扩张型心肌病(DCM)患者血清中是否有抗人心肌线粒体抗体存在及其意义。 方法以人心肌线粒体作抗原,应用免疫点印迹在29例VMC(VMC组)、24例DCM(DCM组)、33例其它心脏病(OCD组)及20例健康献血者(HBD组)进行抗人心肌线粒体抗体检测,用免疫印迹方法检测其抗原分子量。 结果VMC组(12例,41.4%)DCM组(10例,41.7%)抗人心肌线粒体抗体阳性明显高于OCD组(2例,6.1%)及HBD(0%);②抗体阳性的VMC和DCM患者中有43.8%的心肌肌钙蛋白T升高,抗体阴性者为12.0%(P＜0.05)有显著性差异;③人心肌线粒体特异性抗原的分子量为30KD。 结论①在VMC和DCM患者血清中存在抗人心肌线粒体抗体,说明部分VMC及DCM与自身免疫有关,该抗体是引起心肌损伤的因素之一,对该抗体的检测可作为VMC和DCM的辅助诊断手段之一;②该抗体的特异性抗原可能为人心肌线粒体腺苷酸转位酶。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.