Toll样受体4、Myd88在溃疡性结肠炎结肠组织中的表达及相关性研究

Toll样受体(Toll-like receptor,TLR)是与果蝇Toll蛋白具有同源性的表达于细胞膜上与免疫系统识别微生物有关的一类受体家族[1].TLR4是其中一种跨膜受体,髓样分化分子88 (myeloid differentiation factor,Myd88)为TLR4信号转导途径中的主要接头蛋白,TLR4和Myd88相互作用最终介导炎性因子的释放.本实验通过检测TLR4、Myd88在溃疡性结肠炎(ulcerative colitis,UC)大鼠结肠组织中的表达水平及相互关系,探讨TLR4信号转导通路在UC发病过程中的作用机制,同时为UC的严重程度及预后判定提供可靠的参考指标.     

TLR4、TLR9与结直肠癌关系的研究进展

Toll样受体(Toll-like receptors,TLRs)是一组蛋白识别受体,能够识别微生物的成分并引起对抗微生物入侵的免疫应答。TLRs诱导的信号转导通路在肿瘤形成过程中起重要作用,TLR4和TLR9蛋白可能通过不同的信号转导途径促进肿瘤细胞增殖、抑制肿瘤细胞凋亡及免疫逃逸,它们是目前发现与肿瘤发病关系最密切的TLRs家族成员。TLR4与TLR9在大肠癌组织中的表达与结直肠癌细胞的分化程度、淋巴结转移及Dukes分期密切相关。本文就TLR4和TLR9蛋白参与结直肠癌发生、发展的相关机制及其在结直肠癌中的表达情况和临床意义作一概述。     

Toll样受体2与缺血性脑白质损害

Toll样受体2(Toll-like receptor 2,TLR2)是Toll样受体家族中表达范围最广的受体,也是固有免疫系统对病原微生物的重要模式识别受体.另外,TLR2还可识别内源性危险信号,参与缺血性损伤等非病原微生物性炎性反应.有关TLR2及其信号转导在缺血性脑白质损害中的作用日益受到关注,文章对TLR2与缺血性脑白质病变的关系进行了综述.     

Toll样受体4与缺血性脑损伤

Toll样受体是天然免疫系统识别病原微生物的主要受体,在天然免疫反应中具有重要作用。Toll样受体4(TLR4)不仅是介导脂多糖信号跨膜转导的主要受体,而且也参与了缺血性损伤等非病原微生物性炎症反应。有关TLR4及其介导的信号转导在脑血管病中的作用日益引起人们的关注。深入研究TLR4在脑血管病中的作用,有可能为进一步揭示脑血管病的发病机制并为寻求有效的防治措施提供重要的理论基础。     

Toll样受体4与脓毒症性急性肾损伤

脓毒症性急性肾损伤(AKI)发病机制复杂且缺乏有效的药物治疗.Toll样受体4(TLR4)是固有免疫系统中的病原模式识别受体之一,通过识别并结合革兰阴性杆菌细胞壁成分脂多糖,激活信号转导通路.TLR4信号通路激活后释放多种炎症介质如肿瘤坏死因子α、白细胞介素(IL-1)、IL-6介导脓毒症性AKI发生.因此,TLR4信号通路可成为脓毒症性AKI治疗的新靶点;目前TLR4信号通路阻断剂已问世并进入Ⅲ期临床研究阶段,以期为脓毒症性急性肾损伤患者的救治提供全新的思路.     

髓样分化蛋白2对重症急性胰腺炎的影响

脂多糖（LPS）是革兰氏阴性菌（G-）细胞壁的主要成分,它能被Toll样受体4（TLR4）所识别,并且TLR4是LPS跨膜信号转导的主要受体。已有研究表明,TLR4的表达在发生胰腺炎的胰腺中存在上调趋势,且急性坏死性胰腺炎时,肝、肺等组织中TLR4 mRNA的表达明显增强。所以,在SIRS和早期MODS,TLR4受体的激动即可被认为是诱导炎症反应失控的最初因素之一。本文主要就髓样分化蛋白2（MD2）在TLR4信号转导过程中的重要作用,及在其诱导下产生的炎症反应对重症急性胰腺炎（SAP）的影响和临床意义加以阐述。     

Toll样受体4致乙型肝炎病毒免疫损伤的研究进展

乙型肝炎病毒(HBV)不具严格嗜肝特点,因此,其不但可致肝脏病变,而且还可引起其他组织损害。尽管HBV诱导组织细胞损伤的具体机制尚不明确,但Toll样受体4(TLR4)是人们最早发现、能够直接介导机体与病原体反应的Toll样受体,分布于各组织细胞表面,其信号分子是连接先天和后天免疫的重要桥梁。近年来TLR4在抗病毒免疫中的作用日益受到关注,其能识别多种病毒,启动细胞内信号转导通路,诱导特异性免疫反应,分泌细胞因子/趋化因子,发挥抗病毒作用,同时造成免疫损伤。本文综述Toll受体4在HBV免疫损伤中的作用。     

Toll样受体4表达在冠状动脉粥样硬化中的意义

Toll样受体(TLR)是一类表达于细胞膜上能够抵抗外源性微生物侵袭而产生免疫识别的受体家族,TLR4是TLR家族中表达最有活力的蛋白质分子,其主要在人体内皮细胞、心肌细胞、脂肪细胞、中性粒细胞等细胞上表达。TLR4与冠状动脉粥样硬化(CAS)存在相关性,因此本文通过查阅国内外相关文献,重点阐述TLR4表达在CAS中的意义。     

Toll样受体在免疫紊乱中的作用

Toll样受体(Toll-like receptor,TLR)对先天性免疫有重要作用。个别的Toll样受体能识别积聚在病原体中的微生物成分。这种识别能促发必需的炎症免疫反应并诱发获得性免疫的活化。研究人编码TLR信号分子基因多态性,可以解释TLR与感染性疾病、动脉粥样硬化和免疫缺陷等人类疾病之     

Toll样受体4信号转导通路及其在缺血性卒中中的作用

缺血性卒中常伴有炎症反应.研究表明,Toll样受体4(Toll-like receptor 4,TLR4)介导了缺血性卒中的发生、发展和继发性脑损伤.文章综述了TLR4信号转导通路及其在缺血性卒中中的作用,以期为开发以TLR4为靶点的治疗药物提供一定依据.     

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.