HLA-DR抗原β链的共同表位与类风湿关节炎相关性研究

目的　探讨人类白细胞抗原 (HLA) DR基因编码的共同表位 (SE)与武汉籍汉族类风湿关节炎 (RA)的相关性。方法　采用聚合酶链反应 序列特异性引物技术 (PCR SSP) ,对武汉籍汉族人群 78例RA患者和 12 6例健康者的HLA DRB1 0 1、 0 4基因型进行检测。结果　RA患者中具有编码QKRAA或QRRAA的共同表位阳性率为 43 6 % ,明显高于正常对照组 (15 1% ,P <0 0 1) ;SE阳性的RA患者的关节压痛数、侵蚀性病变以及关节外表现明显高于SE阴性的RA患者(P <0 0 1)。结论　HLA DR基因编码的SE与武汉籍汉族RA易感性及疾病严重性相关 ,共同表位的检测可作为一项病情及预后判断的指标     

内蒙古地区汉族类风湿关节炎与HLA-DRB1基因共同表位的相关性研究

目的探讨内蒙古地区汉族人群类风湿关节炎(RA)与HLA-DRB1基因共同表位(SE)的关联性。方法采用特异性引物聚合酶链反应(PCR-SSP)方法对内蒙古地区汉族人群80例RA患者及110名正常健康者的HLA-DRB1*01、*04、*10的17个等位基因进行检测。结果内蒙古地区RA患者中携带有SE的基因频率显著高于正常对照组(48．8％：20％,P＜0．01),HLA-DR4亚型*0405是主要的易感基因(28．8％：12％,P＜0．01),其他亚型包括DRB1*0101(2．5％：0．9％),*0102(2．5％：0),*0103(1．25％：0．9％),*0104(2．5％：0％),*0401(6．25％：1．8％),*0402(3．75％：0．9％),*0403(1．25％：1．8％),*0404(2．5％：1．8％),*0406(2．5％：2．7％),*0407(1．25％：0．9％),*0408(3．75％：0．9％),*0409(1．25％：0),*0410(2．5％：0．9％),*0411(0：0)和*001(8．75％：4．5％)的差异均无统计学意义。Logistic回归分析表明：SE纯合子对RA的危害性要比杂合子大(P＜0．01)。在RA患者中。SE纯合子和SE杂合子的病程、关节肿痛数、关节压痛数、血沉(ESR),C反应蛋白(CRP)、类风湿因子(RF)、X线(Ⅲ期 Ⅳ期)与SE阴性组比较,差异有统计学意义。SE纯合子与SE杂合子相比较,各观察指标差异均无统计学意义。结论SE与内蒙古地区汉族RA易感性及疾病严重性有关。     

HLA-DR-DQ单倍型与类风湿关节炎的关系

目的　探讨HLA -DR -DQ单倍型与我国汉族类风湿关节炎 (RA)的相关性。方法　以 10 0名健康人为对照 ,采用PCR -RFLP法对汉族人群中 35例RA患者的DRBl、DRB3、DRB5、DQAl和DQBl基因位点多态性进行分析。结果　DRBl 0 4 0 5 -DQAl 0 30 1-DQBl 0 4 0 1单倍型频率在RA患者明显高于正常人 (分别为14 0 %和 4 5 % ,P <0 0 1) ,该单倍型阳性RA患者的病情重于其它RA患者 ,包括关节肿胀数、晨僵时间、RF滴度和病情严重例数在阳性组明显高于阴性组 (P均 <0 0 5 ) ;而DRBl 15 0 1-DRB5 0 10 1-DQAl 0 10 2 -DQBl 0 6 0 2单倍型频率在正常人明显高于RA患者 (分别为 12 %和 4 3% ,P <0 0 1)。结论　DRBl 0 4 0 5 -DQAl 0 30 1-DQBl 0 4 0 1单倍型与RA发病及病情严重程度相关 ;而DRB1 15 0 1-DRB5 0 10 1-DQA1 0 10 2 -DQBl 0 6 0 2单倍型则可能对易患RA起保护作用     

中国大陆汉族人群类风湿关节炎与HLA-DRB1*0401基因的相关性分析

目的 探讨中国大陆汉族人群类风湿关节炎(RA)与人类白细胞抗原(HLA)-DRB1*0401基因的关联情况。方法 检索已发表的有关中国大陆汉族人群RA患者和HLA-DRB1*0401的文献，进行Meta分析。结果 国内7项研究共578例RA患者和743例正常对照，DRB1*0401基因亚型是中国大陆汉族人群RA的关联基因(OR=2．66，P=0．004)。结论 Meta分析证实DRB1*0401与中国大陆汉族人群RA有相关性，样本大小对基因关联分析有重要影响。     

中国内地人群类风湿关节炎与HLA-DRB1共同表位基因关联性的Meta分析

目的探讨中国内地人群类风湿关节炎(RA)与人类白细胞抗原(HLA)-DRB1共同表位(SE)基因的关联情况。方法检索已发表的有关中国内地人群RA和HLA-DRB1的文献,进行汇总分析分析。结果14项研究共纳入1118例RA患者和1301名正常对照,中国内地人群RA的关联基因有HLA-DR4[比值比(OR)=4.05,P<0.0001)]、DRB1*0401(OR=2.66,P=0.004)、DRB1*0404(OR=2.10,P=0.02)、DRB1*0405(OR=3.98,P<0.0001)、DRB1*0410(OR=3.36,P=0.008)、SE(OR=2.75,P<0.00001)。其中DRB1*0405是主要基因亚型。结论汇总分析分析不仅证实了DRB1*0405与中国内地人群RA的关联,而且发现了相对少见基因亚型DRB1*0401、DRB1*0404、DRB1*0410与RA的关联,样本大小对基因关联分析的结论有重要影响。     

利用新型分类体系评价人类白细胞抗原-DRB1基因与中国北方汉族人群类风湿关节炎的易感性

目的 从等位基因及基因型2个层次探讨人类白细胞抗原(HLA)-DRB1基因与中国北方汉族人群类风湿关节炎(RA)的相关性.方法 选取RA患者281例及健康对照202名,以直接测序法(SBT)对HLA-DRB1的亚型进行检测,并用UTYPE软件进行分析.HLA-DRB1的分类采用经典的共同表位(SE)分类及2005年Tezenas du Montcel等提出的新分类:即根据DRB 1的72～74位氨基酸序列是否具有精氨酸-丙氨酸-丙氨酸(RAA)序列特点,将DR分子分为S及X,再根据70及71位氨基酸的特点进一步将S分成S1～S3.采用直接计数法计算等位基因频率.统计学方法采用x2检验.结果 在281例中国北方RA患者中,共检出41种DRB1亚型,含SE的患者占44.8％.其中70～74位编码QRRAA序列的亚型占33.8％(95/281),显著高于健康人(P＜0.05),是RA的易感亚型.在汉族人中这些亚型包括*0101,*0102,*0404,*0405及*0410.编码DRRAA以及DERAA序列者为RA的保护亚型,分别占22.5％(91/562)和3.7％(15/562),显著低于健康对照(P＜0.05).利用2005年Tezenas du Montcel等提出的新分类体系,对HLA-DRB1基因型进行分析,携带SE及Tezenas du Montcel新分类中S3P的基因型为RA的易感基因型,而新分类中的S3D及S1E为RA的保护基因型.结论 中国汉族人群的HLA-DRB1的易感亚型特点皆为QRRAA序列,保护亚型为DRRAA与DERAA,具体分型及分布与白种人不同,需要建立更完善的中国人群HLA分型数据库.     

蒙汉族儿童过敏性紫癜临床特点与HLA-DRB1基因关联性对比分析

目的　探索内蒙古地区蒙、汉族儿童过敏性紫癜 (AP)临床特点的不同与HLA DRB1等位基因的关联性。方法　选择祖籍三代居住内蒙古地区 ,无血缘关系、与异族通婚史及其他风湿性疾病史和家族史的蒙、汉族儿童AP 5 7例和 74例。比较临床特点 ,引入PCR SSP技术 ,分析HLA DRB1等位基因的型别 ,结合检索查新分析讨论。结果　①汉族病例组肾、心、多器官损害、肾病综合征、肾病综合征伴肾炎综合征损害率分别为 5 4 %、30 %、73%、12 %和 15 % ;比蒙古族相应损害率为 35 %、5 %、4 2 %、0和 0增高 (χ2 值分别是 4 6 6 6、12 4 82、12 736、—和— ,P分别为 0 0 31、0、0、0 0 0 5和 0 0 0 2 )。蒙古族平均住院 (18± 7)d ,比汉族 (2 7± 18)d短 ,(t′ =2 4 5 0 ,P =0 0 2 1)。②蒙古族病例组DRB1 110x基因频率为 13 2 % ,高于对照组 6 1% (χ2 =4 378,P =0 0 36 ) ,OR =2 386 ,95 %可信区间为 1 0 4 5～ 5 4 4 7。汉族病例组DRB1 0 10x基因频率为 14 6 % ,高于对照组4 8% (χ2 =10 0 7,P =0 0 0 2 ) ,OR =3 4 36 ,95 %可信区间为 1 5 4 3～ 7 6 5 2 ;而DRB1 0 80x基因频率为 2 7% ,低于对照组 8 7% (χ2 =5 2 4 ,P =0 0 2 2 )。并得出OR =0 337,95 %可信区间为 0 12 0～0 94 7。③汉族病     

山东地区汉族骨髓捐献者HLA-DRB1基因分型及多态性分析

目的观察山东地区汉族人群人白细胞抗原(HLA)-DRB1基因多态性及其分布特点。方法采用聚合酶链反应—测序为基础的分型方法(PCR-SBT)对随机抽取的909例中华骨髓库山东分库内山东汉族骨髓供者血样进行HLA-DRB1基因分型和多态性分析。结果共检测出42种HLA-DRB1等位基因,其中HLA-DRB1*0901等位基因频率最高(16.28%),其次为HLA-DRB1*1501(15.13%)和HLA-DRB1*0701(14.04%),基因频率最低的是DRB1*0408、DRB1*0809、DRB1*1103、DRB1*1303、DRB1*1412、DRB1*1425、DRB1*1601,各占0.06%。山东汉族骨髓供者HLA-DRB1等位基因的分布与江苏、湖北、新疆、广东、韩国、日本和德国人群存在明显差异(P均<0.05)。结论掌握了山东地区汉族人群HLA-DRB1基因多态性及其分布特征。     

HLA-DQB1-HLA-DRB1单倍型与中国南方汉族肺结核的相关性分析

目的　探讨HLA DQB1 HLA DRB1单倍型在中国南方汉族肺结核发病机制中的可能作用。方法 采用病例 对照的研究方法 ,应用PCR SSP技术对110例中国南方汉族肺结核患者和 10 1例中国南方汉族健康对照者的 2 0个HLA DRB1和 8个HLA DQB1等位基因进行分型 ,比较两组间DQ2,3(8) DRB1、DQ3(7) DRB1、DQ3(8,9) DRB1、DQ2 ,3(7,9) DRB1、DQ2 DRB1、DQ4 DRB1、DQ5DRB1和DQ6 DRB1单倍型频率 (HF)并计算其相对危险性 (RR)。结果 DQ2 ,3(8) DR14 .1、DQ3(7)DR16单倍型的频率肺结核病例组显著高于对照组 (6 .10vs .0 .5 0、4 .18vs .0 .99) ,其RR分别为 13.4 0和 4 .41;DQ2 DR1、DQ2 DR12、DQ2 DR13.3、DQ3(7) DR1、DQ3(7) DR13.3、DQ3(8,9) DR13.3、DQ2,3(7,9) DR1、DQ2 ,3(7,9) DR13.3、DQ2 ,3(7,9) DR13.4、DQ4 DR4单倍型的频率肺结核病例组显著低于对照组(分别为 1.84vs .5 .6 0、1.37vs .5 .6 0、4 .18vs .11.0 0、2 .30vs .9.89、12 .6 2vs .2 2.2 8、5 .6 1vs .11.5 6、3.70vs .14 .4 0、16 .88vs .2 8.94、5 .13vs .12 .12、2 .30vs.6 .13) ,其RR分别为 0 .31、0 .2 3、0 .34、0 .2 1、0 .4 7、0 .4 4、0 .4 6、0 .38和 0.35。结论 DQ2 ,3(8) DR14 .1、DQ2 DR12、DQ2 ,3(7,9 )-DR13.4、DQ4-DR4单倍型的存在可能与中国南方汉族肺结核的发病有着关联,而其他单倍型差异的显著性则可能是因其组成基因的基因频率差异所致。     

HLA-DR基因与中国南方汉族部分人群肺结核易感基因的研究

目的　探讨人类白细胞抗原 (HLA) DR基因与中国南方汉族部分人群肺结核发病的关联性 ,并寻找与肺结核发病可能相关的HLA易感基因。方法　采用病例 对照的研究方法 ,应用聚合酶链反应 序列特异性引物 (PCR SSP)技术对 110例中国南方汉族肺结核患者 (肺结核病例组 )和 10 1例中国南方汉族健康对照者 (健康对照组 )的 2 3个HLA DR等位基因进行分型 ,比较其等位基因频率(GF)并计算其比值比 (OR)。结果　HLA DR基因PCR SSP分型显示 :(1)肺结核病例组中的DR16等位基因的基因频率显著高于健康对照组 ,两组的GF值分别为 12 6 2 %、5 6 0 % ,两者之间差异具有显著性 (χ2 =5 915 ,PC<0 0 5 ,OR值为 2 5 3)。 (2 )肺结核病例组中的DR1、DR13 3等位基因的基因频率分别为 8 0 8%、2 3 5 7% ,显著低于健康对照组的 2 9 2 9%、5 0 2 4 % ,两组比较 ,差异具有显著性 (χ2值分别为 17 84 7和 14 2 5 8,PC 值均 <0 0 1;OR值分别为 0 2 6、0 33)。结论　 (1)DR16等位基因与南方汉族部分人群的肺结核发病可能密切相关 ,或与真正起作用的易感基因连锁。 (2 )中国南方汉族部分人群DR1、DR13 3等位基因的表达对结核分枝杆菌感染者的发病可能具有拮抗作用。     

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.     

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.     

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.