转录调节因子Foxn1与胸腺的关系及研究现状

转录调节因子Foxn1主要表达于胸腺上皮细胞,在胸腺发育以及T细胞的增殖、分化、成熟等方面发挥重要作用,其表达异常可引起机体免疫功能紊乱,导致相关自身免疫性疾病及肿瘤等的发生.本文拟就Foxn1基因的研究进展及其在胸腺相关疾病中的作用做一综述.     

大鼠胚胎垂体生长激素细胞的体外诱导研究

目的探讨地塞米松和生长激素释放激素(GHRH)对大鼠胚胎垂体生长激素(GH)细胞分化的作用,为将来选择性细胞移植治疗生长激素缺乏症(GHD)奠定基础。方法利用免疫组织化学方法和放射免疫分析方法,在大鼠胚胎垂体组织的原代培养中,对糖皮质激素诱导GH细胞分化的最佳浓度、诱导GH细胞发生分化所需要的最短时间以及GHRH在大鼠胚胎垂体细胞分化中的作用进行实验研究。结果地塞米松诱导GH细胞分化的最佳浓度为50nmol/L(P<0.01)。体外培养的胚胎垂体细胞经地塞米松诱导16h,GH细胞开始分化,诱导48h,分化更明显,上清液中GH水平也明显增加(P<0.01);当GHRH的浓度达到10-7mol/L时,可以增强地塞米松对GH细胞的诱导分化作用,明显提高GH细胞的百分比和GH的分泌量(P<0.01)。结论地塞米松可以诱导生长激素前体细胞最终分化为具有功能活性的GH细胞,GHRH与地塞米松发挥协同作用,调节GH细胞的分化与GH分泌。     

PIT-1及PROP-1与联合垂体激素缺乏症

垂体前叶特异性转录因子(PIT)-1及其祖先蛋白(PROP)-1异常可致联合垂体激素缺乏症(CPHD)。其中PIT-1与胚胎期垂体前叶的发育和促甲状腺激素(TSH)、催乳素(PRL)及生长激素(GH)基因的表达有关,其基因突变者典型表现为血TSH、PRL、GH完全缺乏,MRI示垂体萎缩。而PROP-1也是一种垂体特异转录因子,启动胚胎期PIT-1基因的起始表达及维持个体出生后的持续表达,并可直接促使PIT-1细胞系的前体分化为促性腺细胞系,其基因突变患者除GH、PRL、TSH缺乏外,尚有促黄体激素、促卵泡激素或促肾上腺皮质激素缺乏。     

PIT-1及PROP-1与联合垂体激素缺乏症

垂体前叶特异性转录因子(PIT)-1及其祖先蛋白(PROP)-1异常可致联合垂体激素缺乏症(CPHD)。其中PIT-1与胚胎期垂体前叶的发育和促甲状腺激素(TSH)、催乳素(PRL)及生长激素(GH)基因的表达有关，其基因突变者典型表现为血TSH、PRL、GH完全缺乏，MRI示垂体萎缩。而PROP-1也是一种垂体特异转录因子，启动胚胎期PIT-1基因的起始表达及维持个体出生后的持续表达，并可直接促使PIT-1细胞系的前体分化为促性腺细胞系，其基因突变患者除GH、PRL、TSH缺乏外，尚有促黄体激素、促卵泡激素或促肾上腺皮质激素缺乏。     

信号素的免疫调节作用及其与自身免疫病的关系

信号素是一大类分泌型和膜结合型糖蛋白分子。它们在免疫应答的各个阶段都具有重要的调节作用,参与胸腺皮质和髓质结构的形成,促进树突状细胞(DC)的成熟及迁移,调节T、B细胞的活化、增殖及分化等。当信号素发生异常时,可导致免疫调节功能紊乱,从而促使自身免疫病的发生发展。本文将信号素在免疫系统的作用以及与自身免疫病的关系综述如下。     

生长激素对免疫细胞功能调节的研究进展

目前研究表明 ,生长激素 (GH)在体内和体外能促进胸腺基质细胞 (TEC)分泌胸腺素 ,并且能增强细胞外基质介导的TEC与胸腺细胞的相互作用 ;在体外GH能促进植物血凝素刺激的正常人T淋巴细胞的增殖 ,GH能增加外周血分泌γ干扰素 (IFN γ)单个核细胞的数量及IFN γ分泌的量 ;GH可直接或间接影响B细胞的发育和功能 ;GH缺乏的儿童和成人的自然杀伤 (NK)细胞数量正常 ,但活性降低 ,而补充GH后NK细胞活性增加 ;GH能增强佛波酯刺激单核细胞的一氧化氮产生。     

生长激素与儿童骨发育

生长激素 (GH)通过双重作用机制增加成骨、破骨细胞的增殖 :GH促进前体细胞的分化 ,而胰岛素样生长因子 (IGF) 1促进已分化细胞的增殖。并且IGF 1、2和胰岛素样生长因子结合蛋白 (IGFBP)分别通过抑制和增加生长激素受体 (GHR)的活性来调节GH的作用。GH缺乏 (GHD)儿童的骨形成指标降低 ,但却不影响骨吸收指标。GH治疗促进儿童骨形成和骨吸收指标的上升 ,增加骨密度 ,减少GHD儿童成年后骨折的发生率。对GHD儿童用GH治疗的指标不仅要看其身高而且要看峰骨量是否形成。     

胰岛素样生长因子-Ⅰ与肝硬化

胰岛素样生长因子-Ⅰ(insulin-like growth factor-Ⅰ,IGF-Ⅰ)是机体组织细胞增殖、分化和成熟过程中重要的细胞因子。IGF-Ⅰ生物学作用广泛,它不仅能模拟生长激素(growth hormone,GH)的某些生物学效应,同时也具有类似胰岛素的代谢活性,对多个器官组织有生物学功能。研究发现,IGF-Ⅰ与肝硬化患者或肝硬化鼠的肝功能、肾功能和营养状况等均有关。本文就IGF-Ⅰ及其与肝硬化的关系作一综述。     

生长介素对肢端肥大症患者垂体瘤生长激素分泌影响的体外研究

作者在8例肢端肥大症体外培养的垂体GH瘤细胞上探讨IGF-1对GH分泌的反馈调节作用。10~(-7)mol IGF-1使3例垂体GH瘤细胞GH基础分泌抑制到对照的44.6％～52.4％(P<0.05),1例GH分泌增加134.9％(P<0.05),4例GH基础分泌没有明显改变,表明体外培养的垂体GH瘤有一半以上对IGF-1 3小的·的急性作用失去正常的GH分泌抑制反应。3例对IGF-1失去GH分泌抑制反应的垂体GH瘤细胞同时伴有GH对GHRH_(1-44)及(或)生长抑素激动剂SMS_(201-995)反应消失,提示部分垂体GH瘤细胞的IGF-1和某些下丘脑激素受体或受体后有异常。     

胸腺免疫制剂临床应用回顾

胸腺免疫制剂为新型的免疫调节剂。有胸腺肽(TP)、胸腺素(TS)、胸腺因子(TF)、胸腺因子_D(TF_D)、胸腺原、胸腺免疫抑制提取物(TISH)等药物。是从人、猪、牛等胸腺组织中提取的多种能调节免疫细胞功能的重要的多肽类生物活性物质。动物实验,25～100μg·ml~(-1)的TP对小鼠T细胞增殖和mIL-2R的表达均有促进作用;TS能刺激骨髓产生的干细胞转化为T淋巴细胞,增强机体的细胞免疫功能;调节T-B细胞的平衡作用,抑制B细胞相对功能亢盛所致中种脏器组织损伤。随着医药学研究不断发展,胸腺免疫制剂对各种疾病的治疗及     

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.     

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.     

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.     

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.