肺结核患者肿瘤坏死因子-α基因多态性的研究

目的通过病例-对照研究,探讨肿瘤坏死因子-α(TNF-α)基因启动子区-238A/G、-308A/G位点单核苷酸多态性(SNP)与肺结核病的关系。方法采用序列特异性引物PCR(PCR-SSP)及测序技术检测深圳地区汉族人群肺结核患者200例及健康对照者197例TNF-α启动子区-238A/G、-308A/G位点基因多态性。采用直接计数法计算各组基因型频率及等位基因频率,并进行χ2检验;采用SHEsis软件进行单倍型分析。以P值0.05为具有统计学意义。结果2组人群TNF-α启动子区-238A/G、-308A/G位点基因型及等位基因分布频率差异无统计学意义(P0.05);两位点各种单倍型在2组间分布差异无统计学意义(P0.05)。结论TNF-α启动子区-238、-308位点基因多态性与中国汉族人群肺结核病易感性未见关联。     

溃疡性结肠炎易感性与肿瘤坏死因子基因多态性的相关性研究

目的探究溃疡性结肠炎(IBD)易感性和肿瘤坏死因子(TNF)基因多态性的临床关系。方法选取2012年6月至2015年6月期间收治的102例IBD患者(观察组)和同期体检的94名健康志愿者(对照组)为研究对象,提取DNA,采用特定引物的聚合酶链反应方法检测TNF基因的多态性,比较两组的差异。结果两组的TNF-308构成中AA差异无统计学意义(P0.05),其余差异均有统计学意义(P0.05),观察组TNF-308 G等位基因频率显著低于对照组(P0.05),TNF-308 A等位基因频率显著高于对照组(P0.05),两者分别与IBD易感性存在负相关性和正相关性(r=-0.574,P=0.018;r=0.341,P=0.035);两组TNF-857构成中TT差异无统计学意义(P0.05),其余差异均有统计学意义(P0.05),观察组TNF-857 C等位基因频率显著高于对照组(P0.05),TNF-857 T等位基因频率显著低于对照组(P0.05),两者分别与IBD易感性存在正相关性和负相关性(r=0.415,P=0.027;r=-0.327,P=0.031)。结论IBD易感性与TNF-308 G等位基因频率呈负相关,与TNF-857 C等位基因频率呈正相关。     

肿瘤坏死因子-α-863-857基因多态性与强直性脊柱炎的相关性研究

目的：在中国湖南籍汉族强直性脊柱炎（AS）患者中,探讨肿瘤坏死因子（TNF）-α基因多态性与AS的相关性,及其致病的分子生物学机制。方法：在164例AS患者和121名健康志愿者对照中,用等位基因特异性扩增的方法,对TNF-α基因启动子的2个单核苷酸多态性（SNPs）-863C/A、-857C/T进行基因分型,分析单个位点的等位基因和基因型频率是否与AS相关。结果：在AS患者中,TNF-α-857T的等位基因频率（P=0.002）和基因型频率（P=0.000002）均显著超过正常对照组,经Bonferroni校正后仍为阳性;TNF-α-863的等位基因频率及基因型频率与正常对照组差异无统计学意义。结论：本研究显示TNF-α-857基因多态性与AS存在显著的相关性,TNF-α-857T可能增加AS的易感性。     

TNF-α、TGF-β1和IL-10基因多态性与乙型肝炎后肝硬化的关系

目的:探讨上海人群中TNF-α、TGF-β1及IL-10单核苷酸多态性与乙型肝炎后肝硬化的关联.方法:运用PCR-RFLP结合测序的方法,测定119例健康对照者与169例肝硬化患者TNF-α基因-308G/A、TGF-β1基因-509T/C、IL-10基因-592A/C的多态性,并确定其基因型与等位基因频率的分布.结果:乙型肝炎后肝硬化患者TNF-α的GG基因型和G等位基因出现的频率明显高于健康对照者(P<0.001,OR>3);TGF-β1-509位点的3种基因型整体间没有差异,但T等位基因出现的频率明显高于健康对照者(P<0.05);IL-10-592A/C的多态性在乙型肝炎后肝硬化患者与健康对照者之间差异没有统计学意义.结论:TNF-α-308G/A与TGF-β1-509T/C的多态性可能与乙型肝炎后肝硬化的遗传易感性有关.     

黑龙江地区慢性阻塞性肺疾病与肿瘤坏死因子基因多态性的相关性研究

肿瘤坏死因子（TNF）在慢性阻塞性肺疾病（COPD）的气道炎症和肺功能损害中起重要作用。已知肿瘤坏死因子α（TNF-α）和TNF-β存在单核苷酸多态性（SNP）TNF-α-308G/A和TNF-β＋252G/A，影响TNF在气道内的表达，因而可能是COPD发病的分子机制之一。我们的研究采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和等位基因特异性聚合酶链反应（AS-PCR）方法，分析黑龙江地区汉族COPD患者及健康人群的TNF基因多态性分布情况，探讨其多态性在COPD发病中的作用。     

细胞毒T淋巴细胞相关抗原4基因多态性与溃疡性结肠炎

目的炎症性肠病的发病与T细胞过度活化有关,细胞毒T淋巴细胞相关抗原4（CTLA-4）是重要的T细胞活化负性调节因子.本课题研究CTLA-4基因启动子区-1722位点（T/C）及-1661位点（A/G）多态性与中国汉族人群中溃疡性结肠炎（UC）的相关性.方法采用PCR-限制性片段长度多态性方法,对87例中国汉族UC患者和116例正常对照者进行CTLA-4基因-1722位点和-1661位点多态性检测.结果UC患者CTLA-4基因-1661位点A/G＋G/G基因型频率,-1661位点G等位基因频率显著高于正常对照组（34.5%比15.5%,P=0.002,OR=2.865,95%CI=1.467～5.596;19.0%比8.2%,P=0.002,OR=2.624,95%CI=1.435～4.796）;而在-1722位点的基因型频率、等位基因频率与对照组比较差异无统计学意义（P＞0.05）.结论CTLA-4基因启动子区-1661位点G等位基因与中国汉族UC存在显著相关性.     

胃癌患者肿瘤坏死因子基因型与其血清水平的关系

目的 研究胃癌患者肿瘤坏死因子(TNF)-α308和TNF-β252基因型与血清TNF-α、β水平的关系.方法 收集病理诊断证实的57例胃癌患者,49例来白武汉大学中南医院,8例来自湖北省肿瘤医院.同时选取年龄与性别相匹配的18名健康体检者作为对照.采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)方法检测患者外周静脉血.采用ELISA方法检测57例胃癌患者及18名对照者的血清TNF-α、β水平,比较胃癌患者各TNF基因型之间血清TNF水平的差异及其与对照者血清TNF水平的差异.分析胃癌患者TNF水平与临床病理特征的关系.结果 胃癌患者总体血清TNF-α水平较对照组明显增高(中位数445×10-3 μg/L比5×10-3 μg/L,P＜0.05),而且TNF-α308和TNF-β252各基因型(TNF α308 GA基因型6例、GG基因型51例,TNF-β252 GG基因型17例,GA和AA基因型各20例)的血清TNF-α水平较对照组也明显增高(P＜0.05),但血清总体TNF-β水平与对照组比较差异无统计学意义(P＞0.05).此外,TNF α308G/TNF-β252G和TNF-α308G/TNF-β252A单倍型胃癌患者血清TNF-α水平较对照组也明显增高(P＜0.05),其增高与血清总体TNF-α水平一样,与患者年龄、淋巴结转移显著相关(P＜0.05).TNF-α308A和TNF-β252G的高危等位基因携带者的TNF β水平与吸烟史显著相关(P＜0.05).结论 胃癌患者血清TNF-α水平增高与TNF-α308和TNF-β252基因型无显著相关性.TNF- α308G/TNF-β252G和TNF-d308G/TNF- β252A单倍型胃癌患者的血清TNF-α水平增高与年龄、淋巴结转移显著相关,提示TNF基因单倍型对胃癌TNF的表达及临床类型可能具有一定的影响.     

自然杀伤细胞2D基因多态性与中国人群溃疡性结肠炎的相关性

目的自然杀伤细胞2D（NKG2D）是一种重要的激活性受体,参与全身炎症反应及免疫应答。NKG2D蛋白功能及其基因的特定位置均提示NKG2D基因可能是溃疡性结肠炎（UC）的一个理想候选基因,本研究旨在检测NKG2D基因多态性与中国浙江地区汉族UC患者遗传易感的相关性。方法血样来自浙江地区110例UC患者及292例健康对照者。通过PCR一单链多态性方法直接检测野生型及NKG2D基因的2个多态性（NKG2D 10676G／,908A／）。结果在UC患者中908A的等位基因频率为19．1％,在健康对照者中为16．3％,两者差异无统计学意义（P〉0．05）。而无论是UC患者或健康者均未能发现10676G的杂合子或纯合子。结论我们没有发现NKG2D基因多态性与汉族UC患者遗传易感性相关。更大样本的队列研究、分层分析、全基因测序有助于明确NKG2D基因在UC发病过程中的作用。     

TNF-α-308基因多态性与甘肃地区乙肝病毒感染的相关性研究

目的研究TNF—α-308基因多态性与甘肃地区乙肝病毒（HBV）感染的关系。方法选择汉族慢性乙型肝炎患者156例,其中男118例,女38例及80例正常对照,将病人分组后采用等位基因特异引物聚合酶链反应（ASPCR）方法．分析甘肃地区TNF-α-308启动子基因多态性。结果TNF-α-308位各基因型频率在HBV感染者中和在健康对照者中的基因型差异有显著性。TNF-1和TNF-2等位基因频率两组之间相比差异亦有显著性,且C等位基因与HBV感染有一定关联性。HBV感染者中G／G基因型明显升高。在ALT〉50u／L、ALT〈40u／L及正常对照组之间,基因型频率差异均有显著性。且A等位基因与ALT的升高有一定的相关性。在对等化基因频率的比较中,应答组与对照组,无应答组与对照组相比差异均有显著性。应答组与无应答组等位基因频率相比差异无显著性。对抗病毒治疗的反应与A等他基因有一定的相关性。HBV DNA定量中高载量组与低载量组TNF—α-308位基因型频率相比差异无显著性,而两组与对照组相比差异均有显著性。结论甘肃地区HBV感染者TNF-α-308位基因多态性与慢性HBV感染有关。     

肿瘤坏死因子基因多态性与多发性肌炎/皮肌炎的相关性分析

目的探讨我国汉族人群中多发性肌炎/皮肌炎(PM/DM)与肿瘤坏死因子(TNF)基因多态性之间的相关性。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法对正常对照人群与PM/DM患者的TNF-α-308和TNF-β-252基因的等位基因多态性进行了检测。结果譹整体水平上,PM/DM患者TNF-α的等位基因TNF2频率与正常相比显著升高,差异有统计学意义[22.9%(16/70)vs9.5%(29/304),χ2=9.534,P<0.01],PM和DM患者分别与正常对照相比TNF2基因频率亦显著升高,差异有统计学意义[PM:23.1%(6/26),DM:22.7%(10/44),χ2=4.630,P<0.05和χ2=6.718,P=0.01];譺整体水平上,PM/DM患者的TNF-β-252的两个等位基因频率与正常人群相似[TNF-β*1的基因频率在PM/DM患者和正常对照间分别为48.6%(34/70)和40.5%(123/304),TNF-β*2分别为51.4%(36/70)和59.5%(181/304),差异均无统计学意义(P均>0.05)]。PM和DM患者分别与正常对照相比,TNF-β的两个基因频率与正常对照相比差异无统计学意义(P均>0.05)。结论TNF-α-308的等位基因多态性与中国汉族PM/DM的易感性相关,TNF-β-252的等位基因多态性与中国汉族PM/DM的易感性无关。     

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.