狼疮肾炎肾小球微血栓形成及其与抗凝血相关因子抗体抗磷脂抗体的相关性研究

目的 评估肾小球微血栓(GMT)在狼疮肾炎(LN)中的发生率,并探讨针对某些凝血相关因子的抗体和抗磷脂抗体在LN患者GMT形成中的临床意义.方法 连续收集124例LN患者肾活检组织标本和血浆,观察组织标本中GMT的发生率.并分成LN-GMT组和LN-non-GMT组;比较两组患者的疾病活动度、相关实验室检查指标和肾组织活动,慢性指数;测定患者的狼疮抗凝物(LA)、抗心磷脂抗体(ACL)、抗β2糖蛋白I(抗β2GP I)抗体、抗凝血酶抗体、抗纤溶酶抗体、抗组织型纤溶酶原激活物(t-PA)抗体和抗膜联蛋白AⅡ(Annexin A II)抗体.结果 GMT在LN中的发生率约为20.2%;LN-GMT组系统性红斑狼疮疾病活动指数(SLEDAI)、肾组织病变活动指数、肾组织病变慢性指数、尿蛋白定量(24 h)、血清肌酐、血清尿素氮的水平和高血压的发生率都较LN-non-GMT组高(P＜0.01);LN-GMT组LA、IgG型抗B2GP I抗体和抗凝血酶抗体阳性率均显著高于LN-non-GMT组(P＜0.05);两组IgG型ACL抗体、抗纤溶酶抗体、抗t-PA抗体和抗Annexin A II抗体阳性率差异均无统计学意义(P＞0.05);两组各抗体IgM型差异无统计学意义(P＞0.05).结论 LN中伴有GMT形成的患者肾脏病变重于无GMT者;LA、IgG型抗β2GP I抗体和抗凝血酶抗体与LN患者GMT形成相关.     

抗β2糖蛋白I抗体在系统性红斑狼疮合并自身免疫性溶血性贫血中的意义

目的检测抗β2糖蛋白I抗体(β2 glycoprotein I,aβ2GPI)等多种自身抗体在系统性红斑狼疮(systemic lupus erythematous,SLE)并发自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)患者的阳性率,评估aβ2GPI在并发AIHA的SLE患者中的意义。方法收集2008年12月至2013年4月福建医科大学附属第一医院风湿科门诊和病房SLE患者资料,根据有无发生AIHA分为SLE-AIHA组和SLE-non-AIHA组。选取AIHA患者为AIHA组。检测IgM和IgG类的aβ2GPI、抗心磷脂抗体(anticardiolipin,ACL),以及抗Sm抗体、核小体抗体、组蛋白抗体、核糖体P蛋白抗体等多种自身抗体,采用SPSS11.5软件统计分析。结果共纳入SLE患者104例,SLE-AIHA组22例,SLE-non-AIHA组82例;AIHA组20例。SLE-AIHA组和SLE-non-AIHA组在年龄、性别、病程、受累器官等方面均无统计学差异;而SLE-AIHA组的IgG类aβ2GPI阳性率达45.5%,显著高于SLE-non-AIHA组的15.9%,差异有统计学意义(P0.01);两组患者的IgM类aβ2GPI、IgM和IgG类ACL、抗Sm抗体、核小体抗体、组蛋白抗体、核糖体P蛋白抗体阳性率比较差异均无统计学意义(均P0.05);SLE-AIHA组和AIHA组患者aβ2GPI和ACL阳性率比较差异均无统计学意义(均P0.05);SLE-AIHA组IgG类aβ2GPI阳性患者肾损害发生率高于该抗体阴性者,差异有统计学意义(P0.05)。结论 IgG类aβ2GPI在并发AIHA SLE患者和原发性AIHA患者中均表现较高阳性率,可能是SLE并发AIHA的重要血清学特征;同时该抗体可能是继溶血事件后加重狼疮患者肾损害的重要因素之一。     

抗心磷脂抗体与系统性红斑狼疮高血压的相关性

目的 探讨抗心磷脂抗体在系统性红斑狼疮(SLE)高血压患者中的临床意义.方法 应用酶联免疫吸附法(ELISA)检测110例SLE患者和50名健康者血清中抗心磷脂抗体IgG(IgG-ACA)、抗心磷脂抗体IgM(IgM-ACA)、抗β2糖蛋白I(β2-GP1)抗体的浓度水平.结果 SLE高血压组IgG-ACA、IgM-ACA、抗β2-GP1抗体浓度水平高于SLE正常血压组、健康对照组(P＜0.05),而SLE正常血压组与健康对照组比较差异无统计学意义(P＞0.05).结论 SLE患者合并高血压时IgG-ACA、IgM-ACA、抗β2-GP1抗体浓度水平升高,提示ACA升高与狼疮性高血压的发生有关,抗心磷脂抗体检测对预测狼疮性高血压有一定参考价值.     

抗心磷脂抗体与系统性红斑狼疮高血压的相关性

目的探讨抗心磷脂抗体在系统性红斑狼疮(SLE)高血压患者中的临床意义。方法应用酶联免疫吸附法(ELISA)检测110例 SLE 患者和50名健康者血清中抗心磷脂抗体 IgG(IgG-ACA)、抗心磷脂抗体 IgM(IgM-ACA)、抗β_2糖蛋白Ⅰ(β_2-GP1)抗体的浓度水平。结果 SLE 高血压组 IgG-ACA、IgM-ACA、抗β_2-GP1抗体浓度水平高于 SLE 正常血压组、健康对照组(P<0.05),而 SLE 正常血压组与健康对照组比较差异无统计学意义(P>0.05)。结论 SLE 患者合并高血压时 IgG-ACA、IgM-ACA、抗β_2- GP1抗体浓度水平升高,提示 ACA 升高与狼疮性高血压的发生有关,抗心磷脂抗体检测对预测狼疮性高血压有一定参考价值。     

抗β2-糖蛋白I抗体在RSA患者血清中的表达及意义

采用ELISA法对40例反复自然流产患者（RSA组）和20例正常妇女（对照组）的血清抗β2-糖蛋白Ⅰ抗体（anti-β2-GPI）进行检测。结果RSA组anti-β2-GPI总阳性率明显高于对照组（P〈0.01）,其中IgG型阳性率明显高于对照组（P〈0.05）,而IgM型阳性率无显著差异;早期与中晚期流产、流产2次与≥3次者阳性率均无显著差异。提示RSA与anti-β2-GPI密切相关。     

系统性红斑狼疮合并肺动脉高压23例临床分析

目的分析系统性红斑狼疮（SLE）合并肺动脉高压（PAH）的发生率、临床特点及诊断方法，以便早期诊断PAH并进行治疗。方法选取我院102例诊断明确、资料完整的SLE患者，按照PAH诊断标准，对其进行回顾性分析。结果102例SLE患者中23例出现PAH，发生率为22．5％，其中女性19例，男性4例；年龄21-67岁，平均年龄（45±13）岁。进一步分析各项临床指标并进行两组间比较（t检验X^2检验、秩和检验）。单因素分析结果显示：PAH组与无PAH组在病程、栓塞史、浆膜腔积液、抗Sm抗体、抗核糖体抗体、血尿酸、右房横径、右房长径、肺动脉内径、右室横径等指标上差异有统计学意义（P〈0．05）；对以上因素进行Logistic回归分析显示SLE合并PAH与病程长短、栓塞史、抗sm抗体、右房横径明显相关（P〈0．05）。结论本组SLE患者PAH的发生率为22．5％，其中60％为轻度PAH。病程长、抗Sm抗体阳性、合并血栓形成的SLE患者易出现PAH。     

抗磷脂抗体各亚型在1021例原发性肾小球疾病中的表达研究

目的探讨原发性肾小球疾病中抗磷脂抗体(APA)及各亚型表达情况。方法选取2015年6月至2017年7月,在浙江大学医学院附属第一医院肾脏病中心行肾穿刺活检,并确诊为原发性肾小球疾病的患者1021例(包括膜性肾病303例,IgA肾病483例,系膜增生性肾小球肾炎76例,微小病变肾病119例,局灶性节段性肾小球硬化40例),检测抗心磷脂抗体(ACL)不同亚型(IgG、IgM和IgA型)和抗β2糖蛋白1(β2GP1)抗体不同亚型(IgG、IgM和IgA型),并进行比较。结果膜性肾病组APA阳性率最高为17.5%,微小病变型肾病组最低为11.8%,组间比较差异无统计学意义。IgA肾病和系膜增生性肾小球肾炎ACL阳性率分别为11.4%和14.5%,均显著高于抗β2GP1抗体阳性率(P0.001,P=0.009);膜性肾病组抗β2GP1抗体阳性率为11.2%,与ACL阳性比差异无统计学意义,但显著高于其余4组患者。系膜增生性肾小球肾炎组ACL-IgM阳性率为13.2%,明显高于其余4组(P0.05)。IgA肾病组ACL-IgA阳性率为5.8%,明显高于其余4组,差异有统计学意义(P0.05)。结论原发性肾小球疾病患者中存在抗磷脂抗体阳性,其亚型在不同病理类型肾炎患者中阳性率差异有统计学意义,可有助于疾病鉴别诊断以及治疗。     

系统性硬化症相关性肺动脉高压的临床特点

目的 探讨系统性硬化症（SSc）合并肺动脉高压（PAH）的发病率、临床特点及评估指标.方法 分析本院确诊的18例系统性硬化症合并肺动脉高压的患者临床资料和诊治过程,并以同期确诊的系统性硬化症（未合并肺动脉高压）患者作为对照.结果 两组患者在性别比和年龄上并无统计学差异.但SSc合并PAH组（SSc-PAH）患者在肺动脉收缩压（sPAP）、雷诺现象发生率、肺间质性改变发生率等方面明显高于SSc组.此外,SSc-PAH组患者的RNP抗体阳性率、IgG水平显著高于对照组.结论 雷诺现象、肺间质性改变、RNP抗体、血清IgG水平与SSc患者合并PAH密切相关.这类患者应及早行心超检查,以求早期诊治,改善预后.     

抗磷脂抗体在原发性胆汁性肝硬化患者的临床意义

目的检测原发性胆汁性肝硬化（PBC）患者血清抗磷脂抗体（APA）,探讨其在PBC中的阳性状况和临床意义。方法采用ELISA检测209例PBC患者、44例自身免疫性肝炎（AIH）患者、56例肝病对照（LDC）患者血清抗心磷脂抗体（ACL）-IgG和抗β2糖蛋白1（β2GP1）-IgG抗体。结果 PBC患者抗ACL-IgG、抗β2GP1-IgG、抗ACL或抗β2GP1-IgG抗体的阳性率分别为11.5%、19.1%、26.8%;与AIH、LDC组间的阳性率比较,差异均无统计学意义（χ12分别为0.662、0.776、0.959;χ22分别为0.327、1.34、0.073,P均〉0.05）;PBC患者中抗ACL-IgG、抗β2GP1-IgG抗体在抗线粒体抗体（AMA）、抗核膜糖蛋白210（GP210）抗体、抗酸性磷酸化核蛋白100（SP100）抗体的阳性组与阴性组间阳性率差异均无统计学意义（χ12分别为0.692、0.625、1.082;χ22分别为0.033、0.062、1.692;χ32分别为0.059、0.358、0.118,P均〉0.05）;抗β2GP1-IgG抗体阳性PBC患者的血清总胆红素（TBIL）、直接胆红素（DBIL）、天门冬氨酸氨基转移酶（AST）、总胆汁酸（TBA）、腺苷脱氨酶（ADA）、免疫球蛋白M（IgM）、红细胞沉降率（ESR）高于抗β2GP1-IgG抗体阴性PBC患者（U值分别为1407、1482、1433、1258.5、1353、716、432.5,P均〈0.05或0.01）,而血清白蛋白（ALB）、白蛋白/球蛋白比例（A/G）、胆碱脂酶（CHE）和前白蛋白（PA）低于抗β2GP1-IgG抗体阴性PBC患者（U值分别为1531.5、1565.5、1318.5、1357,P均〈0.05或0.01）。抗ACL-IgG抗体阳性PBC患者与阴性患者肝功能损伤指标和免疫学指标差异均无统计学意义（P均〉0.05）。结论 APA是PBC患者体内普遍存在的自身抗体,在PBC患者有较高的阳性率,且以抗β2GP1-IgG抗体为主。抗β2GP1-IgG抗体与PBC患者肝功能损伤指标和免疫活动指标改变有关,而抗ACL-IgG抗体与PBC患者肝功能损伤指标和免疫活动指标改变无关。     

抗心磷脂抗体与神经精神性狼疮

用酶联免疫吸咐试验检测神经精神性狼疮(NPLE)、非NPLE狼疮患者,非SLE脑血管疾病患者及正常对照者血清及脑脊液中抗心磷脂抗体(ACL抗体)。结果显示NPLE组ACL抗体阳性率在血清为90％,脑脊液为33％,非NPLE狼疮组ACL阳性率在血清为44％,脑脊液为8.3％,非SLE脑血管疾病组ACL阳性率在血清为50％,脑脊液为40％,无神经精神症状的非SLE手术患者,阳性率在血清及脑脊液均为0。ACL抗体在NPLE组与其它组之间(除非SLE脑血管疾病组脑脊液中ACL抗体)有显著差别,它的检测将有助于NPLE的临床诊断。     

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.     

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.     

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.     

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.