CD146在血管炎患者外周血白细胞表达的意义初探

目的探讨血管炎患者外周血白细胞CD146表达与临床活动性间的关系。方法流式细胞术检测39例活动期系统性血管炎患者[显微镜下多血管炎（MPA）13例,韦格纳肉芽肿（WG）9例,变应性肉芽肿性血管炎（CSS）2例,大动脉炎（TA）9例,白塞病（BD）4例,结节性多动脉炎（PAN）2例]及24例系统性红斑狼疮（SLE）患者外周血白细胞CD146表达,其中18例（MPA5例,WG4例,CSS2例,SLE4例,PAN2例,TA1例）患者经糖皮质激素和环磷酰胺治疗后于病情好转时再次检测。结果（1）与健康者相比,血管炎患者活动期中性粒细胞、淋巴细胞CD146表达增多,尤以中性粒细胞最多,差异均有统计学意义（P〈0．05）。（2）中性粒细胞CD146表达与淋巴细胞、单核细胞CD146表达相关（r值分别为0．66、0．853,P=0．000）,与病程、年龄、血沉、C反应蛋白、抗中性粒细胞胞浆抗体（ANCA）、PR3-ANCA、MPO-ANCA、血肌酐、伯明翰血管炎活动指数（BVAS）、系统性红斑狼疮疾病活动指数（SLEDAI）等无明显相关（r值分别为-0．108、-0．059、-0．073、-0．103、0．012、-0．5、-0．232、0．001、-0．08、0．089,P〉0．5）。（3）18例患者经治疗后好转期中性粒细胞、淋巴细胞CD146表达多数呈逐渐减少的趋势（P〈0．05）。结论CD 146在血管炎患者活动期外周血白细胞尤其是中性粒细胞中表达明显升高,随着糖皮质激素和免疫抑制剂治疗病情好转后呈下降或转阴趋势,其在血管炎发病机制中的意义有待深入研究。     

重组人内皮细胞抗原成分α烯醇化酶的表达及其在弥漫性结缔组织疾病中的意义

目的 对蛋白质组学分离和鉴定的抗内皮细胞抗体(AECA)相关抗原-α烯醇化酶进行基因重组和表达,榆测其特异性抗体在血管炎和其他自身免疫性疾病患者血清中的阳性率.方法 聚合酶链反应(PCR)扩增人enol基冈CDS片段并与表达载体重组,在大肠杆菌中表达和纯化重组人α烯醇化酶.用质谱鉴定后的重组蛋白作为抗原,用点印迹法和酶联免疫吸附试验(ELISA)法分别检测健康人和不同结缔组织病患者血清中抗人α烯醇化酶抗体水平.结果 克隆了人enol基因cDNA片段.将重组的人α烯醇化酶在大肠杆菌中进行原核表达和纯化.用重组蛋白作为抗原,点印迹法检测健康对照和不同结缔组织病患者血清中抗人α烯醇化酶抗体,证实:①系统性血管炎(SV)、系统性红斑狼疮(SLE)、干燥综合征(SS)和类风湿关节炎(RA)患者血清中抗α烯醇化酶抗体的阳性率分别为76.7%、78.3%、63.6%和78.9%,均明显高于多发性肌炎/皮肌炎(PM/DM)组和健康对照组(P<0.01).②系统性血管炎中自塞病(BD)、多发性大动脉炎(TA)、韦格纳肉芽肿病(WG)、显微镜下多动脉炎(MPA)和Churg-Strauss综合征(CSS)患者血清中抗α烯醇化酶抗体阳性率各为74.0%、81.5%、62.5%、92.3%和80.0%.③SV和SLE患者血清中抗α烯醇化酶抗体的阳性率与SS和RA患者血清中该抗体的阳性率差异无统计学意义(P>0.05).④不同患者血清中抗α烯醇化酶抗体强阳性者所占比例分别为:SV 51.7%,SLE 33.3%,SS42.9%,RA 20.0%.RA组与SV组差异有统计学意义(P<0.05).结论 SV和SLE、SS、RA患者血清中均存在不同水平的抗α烯醇化酶抗体,α烯醇化酶是AECA识别的自身抗体之一.     

抗内皮细胞抗体检测对老年ANCA相关性小血管炎病情活动程度的影响

目的探讨抗内皮细胞抗体(AECA)检测对老年抗中性粒细胞胞质抗体(ANCA)相关性小血管炎病情活动程度的预测价值。方法选取56例老年抗中性粒细胞胞浆抗体相关性小血管炎(AASV)患者作为观察组,60例健康献血者作为对照组,全部研究对象采集固定的人脐静脉内皮细胞(HUVEC)为抗原,细胞酶联免疫吸附试验(ELISA)法检测血清AECA,比较两组患者AECA阳性率的差异,分析AASV患者AECA与临床病情活动性指标的相关性。结果观察组血清AECA阳性率明显高于对照组(P0.05),不同类型AASV患者中的血清AECA阳性率比较发现,变应性肉芽肿性血管炎血清AECA阳性率明显高于显微镜下多血管炎和肉芽肿性多血管炎,肉芽肿性多血管炎血清AECA阳性率明显高于显微镜下多血管炎(P0.05),AASV病情活动期血清AECA阳性率、血清AECA和血沉(ESR)水平均明显高于病情缓解期(P0.05),且AECA阳性组BVAS分值和ESR水平明显高于AECA阴性组患者(P0.05)。结论抗内皮细胞抗体在AASV诊断和鉴别诊断、病情活动程度预测中具有重要的价值。     

白塞病患者中抗内皮细胞抗体的研究

目的研究白塞病患者抗内皮细胞抗体(AECA)的阳性率,并分析其临床意义。方法以固定的人脐静脉内皮细胞为抗原,细胞ELISA法检测59例白塞病患者中AECA的阳性率,分析其AECA与临床生化指标的相关性。同时检测70例其他原发性系统性血管炎(包括大动脉炎28例,韦格纳肉芽肿20例,结节性多动脉炎8例,显微镜下多血管炎9例,变应性肉芽肿血管炎5例)、57例系统性红斑狼疮(SLE)、25例类风湿关节炎和85例正常对照者中AECA阳性率。结果以人脐静脉内皮细胞为底物,细胞ELISA法检测的白塞病患者的AECA阳性率为47.5%(28/59),与类风湿关节炎患者(4.0%)和正常人组(1.2%)相比,白塞病、其他系统性血管炎(68.6%)和SLE(45.7%)患者AECA阳性率明显增高(P<0.01)。白塞病患者中,AECA阳性病人具有皮肤针刺反应阳性率明显增多(P<0.05)。随诊的6例白塞病患者治疗前后AECA滴度和血沉的变化,差异均有统计学意义(P<0.05)。结论白塞病患者有较高的AECA阳性率,且此抗体与白塞病的临床活动度明显相关,可作为观察其病情活动的指标之一。但其他原发性系统性血管炎和SLE患者亦有一定的AECA阳性率。     

间接免疫荧光法检测抗内皮细胞抗体在白塞病诊断中的意义

目的 探讨抗内皮细胞抗体(AECA)在白塞病(BD)诊断和鉴别诊断中的意义,并分析该抗体与BD患者临床特点及与其他免疫学指标的相关性.方法 采用间接免疫荧光法(IIF),以人脐静脉内皮细胞为底物抗原,检测73例白塞病患者、60例系统性红斑狼疮(SLE)患者、35例系统性硬化症(SSc)患者、30例类风湿关节炎(RA)患者、62例系统性血管炎患者和40名健康献血员血清中的AECA,并评价其与BD患者临床指标的关系.结果 ①AECA在BD患者中的敏感性为54.8%,特异性为87.2%.与SLE患者(8%)、SSc患者(9%)、RA患者(10%)、系统性血管炎患者(27%)及正常对照(2%)相比,BD患者血清AECA的阳性率(54.8%)明显增高(均P<0.01).②在BD患者中,ANA及其他常见自身抗体、低补体血症、蛋白尿等发生率分别为(5.5%、1.4%、11.O%、6.8%),明显低于疾病对照组(p<0.01). ③AECA阳性BD患者红细胞沉降率明显高于AECA阴性患者(P<0.01).结论 AECA在BD中有较高的敏感性和特异性,可作为诊断该病的血清学指标之一.     

系统性小血管炎的分类

过去的150年间,随着对肾、肺等活体器官病理研究及抗中性粒细胞胞浆抗体（anti-neutrophil cytoplasmic autoantibodies, ANCA）的发现,人们对血管炎发病机制研究的深入,小血管炎的分类发生了很大的变化.根据目前的分类方法,寡免疫性小血管炎包括Wegner肉芽肿（Wegner＇s granulomatosis, WG）、微型多血管炎（microscopic polyangitis, MPA）、Churg-strauss综合征（Churg-strauss syndrome,CSS）[1].这是一类与ANCA相关,临床又难以区分的系统性小血管炎,因而统称为ANCA相关性小血管炎（简称ANCA小血管炎）.本文介绍血管炎分类的历史演变、ANCA致病机制,并对现行的血管炎分类进行评价.     

抗中性粒细胞胞质抗体相关性小血管炎的神经系统损害

目的 总结显微镜下多血管炎(MPA)、韦格纳肉芽肿病(WG)和Churg-Strauss综合征(CSS)患者的神经系统损害特点.方法 同顾性分析1991-2006年住院治疗的104例抗中性粒细胞胞质抗体(ANCA)相关性血管炎患者,其中MPA 58例,WG 31例,CSS 15例.总结患者的临床特征和神经系统损害特点.结果 患者诊断时平均年龄:MPA为50.7岁,WG为47.5岁,CSS为41.7岁.MPA组和WG组男女比例相似,但CSS组男性多见.MPA、WG和CSS组中分别有25例(43%),16例(52%)和13例(87%)出现周围或中枢神经损害,三组均以周围神经损害多见,但WG的颅神经受累明显高于其他两组.合并神经损害和无神经损害的患者血管炎活动指数(BVAC)在三组差异均无统计学意义.所有患者均进行了ANCA检测,MPA组中44例(76%)阳性,WG组中24例(77%)阳性,CSS组中4例(27%)阳性.结论 神经系统损害是ANCA相关性血管炎最常见的临床表现之一,风湿病医生应重视神经损害的诊断和及时治疗.     

自身免疫性肺部疾病应引起我们的重视

临床上常见的自身免疫性疾病,包括类风湿性关节炎（RA）、系统性红斑狼疮（SLE）、混合性结缔组织病（MCTD）、干燥综合征（SS）、多发性肌炎／皮肌炎（PM／DM）、韦格纳肉芽肿病（WG）、白塞病（BD）、大动脉炎（TA）、     

25例肺部受累的原发性小血管炎的HRCT表现及临床分析

目的研究肺部受累的原发性小血管炎的HRCT表现等临床特点。方法对本院2004年1月~2010年1月收治的肺部受累的19例显微镜下多血管炎（MPA）患者及6例变应性肉芽肿性血管炎（CSS）患者的临床资料进行回顾性分析。结果 19例MPA的肺部HRCT表现有：（1）两肺弥漫浸润性阴影、类似肺间质性改变12例;（2）肺内多发斑片影7例。6例CSS的肺部HRCT均表现为多发斑片影。19例MPA中抗中性粒细胞胞浆抗体（ANCA）阳性18例,阳性率高达94.74%。6例CSS中ANCA阳性1例。结论肺部受累的原发性小血管炎HRCT影像学表现无明显特异性,结合临床及实验室检查,可以提高认识,早期诊治。     

抗中性粒细胞胞浆抗体相关性小血管炎伴肾脏损害的治疗进展

韦格纳肉芽肿 (Wegener’sgranulomatosis,WG)、变应性肉芽肿性血管炎 (Churg Strausssyndrome,CSS)、微型多血管炎(microscopicpolyangitis,MPA)、局限于肾脏的血管炎 (renallimitedvasculitis,RLV)等患者血液中抗中性粒细胞胞浆抗体 (ANCA)阳性率高达 80 %以上 ,临床也将这些疾病称之为ANCA相关性小血管炎 (AAV) [13 ] 。过去的几十年中系统性小血管炎伴肾脏损害的治疗无很大突破 ,基本延用常规的免疫抑制剂如糖皮质激素、环磷酰胺 (CTX)及硫唑嘌呤 (Aza)等。这类免疫抑制剂作用广泛 ,无选择性 ,副作用大 ,因此 ,长期治疗过程…     

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.