慢性丙型肝炎免疫调节机制的研究

丙型肝炎病毒（HCV）主要通过血液和血制品传播,引起人类丙型病毒性肝炎。丙型病毒性肝炎的转归有两种,一是机体免疫系统清除HCV,二是机体免疫系统与HCV之间发生一系列复杂反应,导致HCV慢性持续感染,即为慢性丙型病毒性肝炎。流行病学调查显示,全球3％左右的人VI感染HCV,其中54％～86％感染者6个月内HCV感染慢性化,形成持续性感染。后者是发展为慢性肝病、肝硬化和原发性肝癌的主要原因之一。     

慢性HBV感染的天然免疫与获得性免疫应答

HBV感染人体后,宿主的抗病毒免疫应答是决定感染结局的关键因素。目前普遍认为,在慢性HBV感染过程中宿主的天然免疫及获得性免疫功能受损,从而导致病毒持续无法清除。要实现对HBV感染持久免疫控制,需要更加全面地理解HBV感染慢性化引起的机体天然免疫和特异性免疫应答功能障碍的机制。总结了国内外研究团队在HBV感染慢性化免疫应答参与机制中取得的进展。     

肝炎病毒基因工程抗体的研究

0引言乙型病毒性肝炎?丙型病毒性肝炎分别是由乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染引起的世界性传染病[1-10].HBV?HCV感染不仅引起急性?慢性病毒性肝炎,而且与肝硬化和肝细胞癌的发生和发展密切相关[11-20].流行病学调查表明,HB V感染的阳性率为10%,抗-HCV的阳性率为3.2%,对我国人民健康危害极大.因此,急需研究有效的针对乙型?丙型病毒性肝炎的防治措施.其中肝炎病毒人源化基因工程抗体及其应用是目前的主要研究方向之一.1乙型肝炎病毒?丙型肝炎病毒基因工程抗体的研究背景目前在我国引起慢性病毒性肝炎的肝炎病毒类型主要是H…     

丙型肝炎病毒受体研究进展

丙型肝炎病毒(HCV)是丙型肝炎的主要致病因子,目前全球至少有1.7亿人感染HCV.HCV感染具有高度慢性化特点,高达50％～80％的感染者由于不能有效清除体内病毒而发展为慢性感染,以及肝硬化和肝细胞癌,对人类的生活质量构成严重威胁.HCV属黄病毒科单股正链RNA病毒,基因组全长9.6 Kb,共编码包括包膜糖蛋白E1、E2在内的十种蛋白.     

丙型肝炎的肝外表现与抗病毒治疗进展

全球约有1.7～2.0亿人感染丙肝病毒(HCV),流行率平均为3%～5%,每年新感染者300～400万例,死亡25万例.丙型肝炎易呈慢性化,约75%～85%甚至90%急性丙型肝炎可发展为慢性丙型肝炎(CHC).感染HCV 10～20年后,肝硬化的年发生率为10%～20%,一旦发展为肝硬化,每年肝癌的发生率为1%～7%.我国一般自然人群的丙型肝炎抗体流行率为3.2%,约有4 000万HCV感染者.     

HBV天然免疫的研究进展

HBV入侵人体时,天然免疫首先发挥重要的作用。成人感染HBV后,常常会被自发清除,然而在出生或者年幼时期感染HBV时,病情更容易慢性化并且迁延终生。在HBV感染初期,天然免疫应答对病毒复制的抑制发挥了重要作用,HBV感染的转归取决于宿主和病毒共同作用。简述了近年来有关HBV与宿主天然免疫中发挥重要作用的细胞类型、细胞因子、信号通路及其作用机制的研究进展,并指出了其在临床治疗方面的潜在价值。     

HCV感染过程中相关细胞因子研究进展

丙型病毒性肝炎(丙肝)是一种世界范围内的疾病,目前全世界大约有2亿丙肝病毒(HCV)感染者。HCV感染后有80%以上的急性病例转变为慢性持续感染,且易发展至肝硬化,甚至肝癌[1]。细胞免疫,包括固有免疫和特异性细胞免疫,在抗HCV感     

HCV基因6型流行病学研究进展

正HCV是慢性肝病和肝癌的主要原因之一。目前全球约有1.7亿人感染HCV病毒。HCV基因多样性程度高,分为至少6种基因型和至少83种基因亚型,这是HCV感染慢性化的一个重要因素。了解HCV各基因型的流行病学特点将有助于临床诊断、治疗和疾病预防。HCV基因6型有多种亚型,同时特殊的传播途径又加快了这种基因型病毒的传播速度,因此了解HCV基因6型的流行病学特点显得越来越重要。现将相关研究进展总结如下。     

丙型肝炎疫苗研究进展

HCV是引起慢性肝炎的主要病原之一,严重危害人类健康.据统计,在世界范围内约有1.7亿感染者[1].75%左右的HCV急性感染者转为慢性,其中10%～20%的慢性丙型肝炎患者发展至肝硬化,1%～5%发展为肝细胞癌[2].我国约有3800万人感染HCV,超过60%的HCV感染者可发展为慢性感染,而慢性HCV感染与肝硬化和肝细胞癌直接相关.在美国、澳大利亚等西方国家,慢性HCV感染已成为终末期肝病的首位病因.世界卫生组织评估东部地中海国家约有2.13亿HCV携带者,这个数字相当于美国和欧洲的总人数.有证据显示,基因型不同可影响抗病毒治疗的效果[3].目前首选的治疗方法仅40%～50%的感染者应答良好,彻底清除病毒者更为鲜见.因此丙型肝炎疫苗的研制已成为国际研究热点之一.     

HIV／HCV共感染国内外研究进展

由于艾滋病病毒（HIv）的感染可导致丙型肝炎病毒（HCV）感染的慢性化率增高,丙型肝炎进程加快,病毒载量升高,肝硬化及肝癌概率升高等问题,逐渐成为人们关注的公共卫生问题。因此该文对HIV／HCV共感染的流行病学特征、HIV／HCV共感染中HIV和HCV各自的基因分型、HIv与HCV两种病毒的相互作用、HIV／HCV共感染的检测、治疗以及预防等方面的国内外的研究进展进行了综述。     

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.