炎症性肠病中低氧诱导因子-1α表达的研究

目的 观察低氧诱导因子-1α(HIF-1α)在炎症性肠病的炎症组织中的表达,探讨HIF-1α在炎症性肠病发病机制中的调控作用。方法 取经过临床表现、内镜、病理、影像学等方法共同确诊的炎症性肠病活检的石蜡标本和肠癌手术切除标本残端的正常组织的石蜡标本,用枸橼酸-微波-SP-免疫组织化学方法检测HIF—1的表达情况,并分析HIF-1α表达状况与患者年龄、性别的关系。结果 溃疡性结肠炎中HIF-1α表达阳性率(73.39％±1.32)显著高于正常肠组织(2.44％±1.69％)(P<0.01),克隆氏病中HIF-1α表达阳性率(68.54％±1.39％)也显著高于正常肠组织(2.44％±1.69％)(P<0.01),溃疡性结肠炎和克隆氏病中HIF-1α的表达与患者的年龄、性别无显著的相关性(P>0.05)。结论 HIF-1α作为一种转录因子可能在炎症性肠病发病机制中充当重要角色。     

脆性组氨酸三联体蛋白在炎症性肠病中表达丢失的研究

目的 探讨炎症性肠病中脆性组氨酸三联体(FHIT)基因蛋白表达状况及其与临床病理指标的可能关系。方法 采用兔抗人FHIT蛋白抗体和拘橼酸-微波-SP-免疫组织化学方法检测60例甲醛固定、石蜡包埋的炎症性肠病活检蜡块标本中FHIT表达状况并分析其与年龄、性别的天系。结果 溃疡性结肠炎中FHIT基因表达阳性率(31.88％±20.33％)显著低于正常的结肠组织(57.05％±8.86％)(P<0 01);克隆氏病中FHIT基因表达阳性率(29.99％±19.82％)显著低于正常的结肠组织(57.05％±8.86％)(P<0.01);而溃疡性结肠炎和克隆氏病中FHIT基因表达阳性率无显著差别(P>0.05);溃疡性结肠炎和克隆氏病中FHIT基因表达水平降低与炎症性肠病患者的年龄、性别无显著相关性(P>0.05)。结论 FHIT基因的表达下降或缺失与炎症性肠病的发生发展过程密切相关,可能是炎症性肠病中从炎症过渡到癌变的一个早期事件之一。     

低氧诱导因子-1α和炎症诱导酶在炎症性肠病中的表达及意义

目的探讨低氧诱导因子-1α(HIF-1α)、参与炎症的重要诱导酶-环氧合酶-2(COX-2)和诱导型一氧化氮合酶(iNOS)蛋白在炎症性肠病中的表达及作用.方法采用免疫组织化学方法检测60例甲醛固定、石蜡包埋的炎症性肠病活检蜡块标本以及10例正常结肠黏膜组织中HIF-1α、COX-2、iNOS蛋白表达情况.结果 HIF-1α、COX-2、iNOS蛋白在炎症性肠病中表达均明显增加,分别与正常组比较有显著性差异(P＜0.01);COX-2(溃疡性结肠炎:r=0.690,克罗恩病:r=0.723,P＜0.05)和iNOS蛋白水平(溃疡性结肠炎:r=0.625,克罗恩病:r=0.782,P＜0.05)分别与HIF-1α蛋白水平呈正相关.结论 HIF-1α、COX-2、iNOS蛋白均参与了炎症性肠病的发生和发展,HIF-1α可能是COX-2、iNOS基因表达中的一个重要调节者.     

HIF-1α、COX-2在溃疡性结肠炎中的表达及与疾病活动性的关系

目的 探讨低氧诱导因子-1α(HIF-1α)、环氧合酶-2(COX-2)在溃疡性结肠炎组织中的表达及与疾病活动性的关系.方法 采用免疫组织化学方法检测51例UC患者(活动期38例,缓解期13例)和20例正常对照组中的HIF-1α、COX-2表达.结果 溃疡性结肠炎患者活动期HIF-1α表达显著高于正常人,差异有显著性(153.29±15.26vs.193.28±16.65)(P<0.01),缓解期HIF-1α表达与正常人差异无显著性(185.45±12.08 vs.193.28±16.65)(P>0.05).溃疡性结肠炎中HIF-1α的表达与Walmsley评分标准有相关性,且呈正相关;COX-2在溃疡性结肠炎患者的活动期的表达显著高于正常人,差异有显著性(156.45±18.25 vs.199.28±15.43)(P<0.01),缓解期的表达与正常人差异无显著性(190.93±13.78 vs.199.28±15.43)(P>0.05).溃疡性结肠炎中COX-2的表达与Walmsley评分标准也呈正相关;溃疡性结肠炎中HIF-1α和COX-2蛋白表达水平呈正相关(r=0.690)(P<0.5).结论 HIF-1α和COX-2均参与了溃疡性结肠炎的发病且与疾病的活动性有关,HIF-1α作为一种转录因子可能是COX-2均参与了溃疡性结肠炎的发病且与疾病的活动性有关,HIF-1α作为一种转录因子可能是COX-2基因表达中的一个重要调节者.     

炎症性肠病患者可溶性髓系细胞表达触发受体-1与环氧化酶-2的表达及其意义

目的研究炎症性肠病(IBD)患者肠黏膜可溶性髓系细胞表达触发受体(sTREM)-1与环氧化酶(COX)-2的表达,以及两者与溃疡性结肠炎患者病情严重程度和内镜分级程度的关系。方法分别采用流式细胞技术和免疫组化方法对50例IBD患者和20例对照组肠黏膜中sTREM-1和COX-2的表达进行测定。结果 50例IBD患者中,包括42例溃疡性结肠炎(UC)和8例克罗恩病(CD)患者。UC患者结肠黏膜中sTREM-1和COX-2的表达较对照组显著增高(P<0.05),且sTREM-1和COX-2在UC不同的病情分级及不同内镜分级中表达中有显著差异(F=19.055,P<0.05;F=34.119,P<0.05.F=54.617,P<0.05;F=58.608,P<0.05)。IBD患者结肠黏膜中sTREM-1和COX-2的表达呈正相关(r=0.642,P<0.05);UC患者结肠黏膜中sTREM-1的表达水平与患者病情程度及内镜分级呈正相关(r=0.945,P<0.05;r=0.944,P<0.05),COX-2的表达水平与患者病情程度及内镜分级亦呈正相关(r=0.944,P<0.05;r=0.944,P<0.05)。IBD患者肠黏膜中sTREM-1和COX-2的表达与对照组比较差异有统计学意义(P<0.05)。结论 sTREM-1和COX-2参与了IBD的发病过程,并且可以反映UC的炎症活动情况。     

炎症性肠病患者肠黏膜炎症和非炎症组织CD27的激活表达

目的比较炎症性肠病患者肠黏膜炎症组织、非炎症组织及正常对照者肠黏膜CD27激活表达的差异,探讨CD27激活表达在炎症性肠病发病中的意义。方法共纳入32例克罗恩病患者、41例溃疡性结肠炎患者及40例正常对照者。分别应用West-ern blot试验和SYBR-green real time PCR方法分析炎症性肠病患者肠黏膜炎症组织、非炎症组织及正常对照者肠黏膜CD27蛋白及其mRNA的表达。数据处理使用GraphPad Prism 5软件。结果克罗恩病和溃疡性结肠炎患者肠黏膜炎症组织CD27蛋白及其mRNA表达均显著高于非炎症组织及正常对照组织(P均0.01);克罗恩病患者肠黏膜非炎症组织CD27蛋白及其mRNA表达显著高于正常对照组织(P=0.000);溃疡性结肠炎患者肠黏膜非炎症组织CD27蛋白表达显著高于正常对照组织(P=0.000)。结论炎症性肠病患者肠黏膜组织中存在CD27的激活表达,这种激活效应不仅出现在内镜表现为炎症性肠病的炎症组织中,甚至出现在炎症性肠病患者内镜表现为正常的肠黏膜中,CD27的激活表达是炎症性肠病发病的早期事件。     

炎症性肠病患者肠黏膜白细胞分化抗原-14的表达及意义

目的: 探讨炎症性肠病患者肠黏膜CD14的表达及与该病的关系.方法: 收集活动性溃疡性结肠炎(ulcerative colitis, UC)患者25例及克罗恩病(Crohn's disease, CD)患者15例;20例对照来自于非炎症性肠病患者手术切除的正常结肠组织(肠镜及肠黏膜病理组织学检查结果均正常).炎症性肠病的临床诊断均依据于常规影像学、内镜学及组织学标准.采用免疫组织化学方法检测肠黏膜组织中CD14表达量.结果: 肠黏膜固有层单个核细胞表达CD14.UC患者CD14阳性细胞百分数高于CD患者,但二者差异无统计学意义(P>0.05);UC患者较正常对照有显著性差异(t=4.404, P<0.01),CD患者较正常对照亦见显著性差异(t=3.324,P<0.01).CD14的表达与疾病活动度(diseaseactivity index, DAI)相关, UC组轻、中、重度比较有显著性差异(F=56.709, P<0.01);CD组轻、中、重度比较亦有显著性差异(F=12.880, P<0.01).结论: CD14参与了炎症性肠病的发病过程, 其表达强度反映了该病的程度.     

缺氧诱导因子-1α、环氧化酶-2和C反应蛋白联合检查用于溃疡性结肠炎诊断的研究

目的 探讨检测缺氧诱导因子-1α(HIF-1α)、环氧化酶-2(COX-2)和C反应蛋白(CRP)用于诊断溃疡性结肠炎的价值.方法 98例溃疡性结肠炎按照病情轻重分为A组(轻度)31例、B组(中度)34例和C组(重度)33例,25例未患溃疡性结肠炎志愿者作为对照组D.采用RT-PCR方法分析各组检查对象结肠组织处HIF-1α、COX-2和C反应蛋白mRNA转录水平.采用ELISA方法检测各组检查对象血清中HIF-1α、COX-2和C反应蛋白水平.结果 HIF-1α mRNA转录水平随着溃疡性结肠炎病情加重而逐渐增加;COX4 mRNA转录水平A组显著高于D组(P＜0.05),B组显著高于A组(P＜0.05),C组与B组差异无统计学意义(P＞0.05);CRP mRNA转录水平,B组显著高于A组(P＜0.05),C组显著高于B组(P＜0.05),A组与D组差异无统计学意义(P＞0.05).A组、B组和C组血清中HIF-1α、COX-2和C反应蛋白平均水平显著高于对照组D组(P均＜0.05),且随着溃疡性结肠炎病情加重水平逐渐升高.结论 病灶细胞中HIF-1α、COX-2和C反应蛋白mRNA转录水平和血清蛋白表达水平与溃疡性结肠炎病情进展呈正相关性,联合检测HIF-1α、COX-2和C反应蛋白有助于判断溃疡性结肠炎病情严重程度.     

环氧合酶2和前列腺素在溃疡性结肠炎中的作用

环氧合酶 (COX)是花生四烯酸代谢过程中的限速酶 ,可催化花生四烯酸生成一系列前列腺素 (PGs) ,包括PGE2和血栓素 (TXs)。COX有 2种同工酶 :COX 1和COX 2。我们通过研究COX 2在活动性溃疡性结肠炎 (UC)肠黏膜中的表达 ,并测定PGE2 和TXB2 的水平 ,探讨其在UC中的作用。一、对象和方法1 对象 :( 1)UC组 :2 2例 ,男 8例 ,女 14例 ;年龄 15～6 6岁 ,平均 4 5岁 ;诊断符合“2 0 0 0年全国炎症性肠病学术会议”制定的标准。病程 1周～ 14年 ;轻度 6例 ,中度 9例 ,重度 7例。 ( 2 )对照组 :2 0例 ,男 9例 ,女 11例 ;年龄 19～ 6 4岁…     

结肠克隆氏病和溃疡性结肠炎的早期诊断

近年来应用钡剂灌肠双重对比造影X线检查,对结肠克隆氏病和溃疡性结肠炎(溃结)的鉴别诊断是一项可靠的方法,且能发现一般钡剂灌肠检查尚属“正常”的早期病变。方法:用适当高密度的钡液灌注深达结肠的脾曲。待部分钡液由肛管流出后,从另一管灌注空气。在检查前患者必须作彻底清洁灌肠。除中毒性巨结肠症及十分严重的结肠炎为禁忌症外,本检查对炎症性肠病是一种较安全的方法,尚未遇到任何副反应。克隆氏病:早期肠粘膜形态改变是口疮样或散在     

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.