胰腺癌组织中MMP-2、MMP-9的表达

目的 检测胰腺癌组织基质金属蛋白酶( MMP-2,MMP-9)的表达,分析其与临床病理特征的关系.方法 应用免疫组化SP法检测30例胰腺癌及配对癌旁胰腺组织以及11例慢性胰腺炎、6例正常胰腺组织中MMP-2、MMP-9的表达,运用统计软件SPSS 12.0分析其与临床病理特征的相关性.结果 正常胰腺组织均无MMP-2及MMP-9的表达.慢性胰腺炎组织MMP-2、MMP-9的阳性表达率均为18.2％ (2/11).胰腺癌组织MMP-2、MMP-9的阳性表达率分别为63.3％ (19/30)和56.7％ (17/30);配对癌旁组织的阳性表达率分别为23.3％ (7/30)和40.0％( 12/30).胰腺癌组织的MMP-2及MMP-9阳性表达率均显著高于配对癌旁组织(P＜0.05);胰腺癌组织及癌旁组织中MMP-2及MMP-9的表达均显著高于慢性胰腺炎组织和正常胰腺组织(P值均＜0.05).MMP-2、MMP-9的表达与胰腺癌临床分期、肿瘤大小、分化程度及淋巴结转移相关.结论 胰腺癌组织中MMP-2、MMP-9呈高表达,其高表达与肿瘤的恶性程度相关.     

Plk1在胰腺癌中的表达及临床意义

目的 研究胰腺癌组织标本及细胞系中Plk1的表达及临床意义.方法 应用免疫组化EnVision两步法检测33例胰腺癌及其癌旁组织、3例胰腺浆液性囊腺瘤、3例黏液性囊腺瘤、5例慢性胰腺炎的石蜡标本中Plk1的表达.用半定量RT-PCR检测5例新鲜胰腺癌组织及其癌旁组织中Plk1 mRNA的表达.用Western blot检测两株胰腺癌细胞PANC1和CFPAC1中Plk1表达.结果 胰腺癌组织中Plk1的阳性表达率为72.7%(24/33),其表达与胰腺癌患者的年龄、性别、临床分期、组织学分级、淋巴结转移、肿瘤的部位无显著相关(P ＞ 0.05).癌旁组织、慢性胰腺炎和良性胰腺肿瘤组织中Plk1的表达均为阴性.5例新鲜胰腺癌组织中都有Plk1 mRNA的高表达,两株胰腺癌细胞中也有Plk1蛋白的表达.结论 Plk1在胰腺癌中的表达具有一定肿瘤特异性,有可能成为胰腺癌诊治的理想靶标.     

Mucin4在胰腺癌组织中的表达及其临床意义

目的研究胰腺癌组织中Mucin 4(MUC4)的表达及其与临床病理参数间的关系.方法 (1)采用ABC免疫组织化学方法检测35例胰腺癌、12例胰腺良性肿瘤及5例慢性胰腺炎组织MUC4的表达.(2)通过RT-PCR方法检测12例胰腺癌组织、癌旁胰腺组织以及2株胰腺癌细胞株MUC4 mRNA的表达.结果 (1)35例胰腺癌组织中MUC4蛋白阳性表达24例,12例胰腺良性肿瘤中MUC4蛋白阳性表达2例,5例慢性胰腺炎组织中MUC4蛋白均为阴性.MUC4蛋白胰腺癌组织中阳性表达率显著高于胰腺良性肿瘤及慢性胰腺炎组织(P ＜ 0.05).MUC 4在胰腺癌组织中阳性表达率与肿瘤的部位、淋巴结转移、临床分期无关(P ＞ 0.05).(2)12例胰腺癌组织中MUC4 mRNA表达阳性有6例,癌旁组织中无阳性表达,2株胰腺癌细胞株均呈阳性表达.MUC4 mRNA在胰腺癌组织中阳性表达率显著高于癌旁组织(P ＜ 0.05).结论 MUC4在胰腺癌中有较高的表达率,检测其表达可能有助于胰腺癌的诊断,并可作为鉴别胰腺癌和慢性胰腺炎一个重要参考指标.     

Toll样受体9和低氧诱导因子1α在胰腺癌中的表达及其意义

目的 研究Toll样受体9(TLR9)和低氧诱导因子1α(HIF-1 α)在胰腺癌组织中的表达,探讨其临床意义.方法 采用实时定量PCR法、蛋白质印迹法及免疫组织化学法检测30例胰腺癌组织及其相邻癌旁组织、10例正常胰腺组织中TLR9和HIF-1α的表达,分析两者表达的相关性、与肿瘤临床病理特征的关系以及对患者生存时间的影响.结果 胰腺癌TLR9 mRNA及HIF-1αmRNA表达量分别为正常胰腺组织的2.32(1.41～3.22)倍和2.26(1.62～2.89)倍,癌旁组织表达量分别为正常胰腺组织的1.23(1.18 ～1.28)倍和1.36(1.17～1.55)倍,胰腺癌的表达量显著高于癌旁组织(t=2.642,P=0.023;t=4.076,P=0.001).胰腺癌组织TLR9和HIF-1α蛋白阳性表达率分别为73.3％(22/30)和70.0％(21/30),癌旁组织分别为33.3％ (10/30)和36.7％ (11/30),正常胰腺组织分别为20％(2/10)和10％(1/10),呈递减趋势(x2=13.99,P=0.001;x2=13.15,P=0.001).胰腺癌组织TLR9 mRNA与HIF-1 αmRNA表达呈正相关(r=0.537,P=0.003),TLR9和HIF-1α蛋白阳性表达率亦呈正相关(r =0.511,P=0.001).胰腺癌组织TLR9和HIF-1α表达与肿瘤分化程度、TNM分期、淋巴结转移呈正相关,与患者的生存时间呈负相关.结论 胰腺癌组织TLR9和HIF-1α基因均高表达,且与肿瘤细胞的恶性生物学行为及患者预后差有关.     

胰腺癌组织中转化生长因子β1及其Ⅰ型受体的表达及意义

目的 研究人正常胰腺、慢性胰腺炎、胰腺癌及癌旁组织中转化生长因子(TGF)β1及其Ⅰ型受体(TβR1)的表达,及其与肿瘤TNM分期、病理类型等临床特征的相关性.方法 取胰腺癌及癌旁组织(30例)、慢性胰腺炎组织(10例)和正常胰腺组织(10名),用免疫组化法检测组织中TGFβ1及TβR1表达.采用分层方法对年龄、性别、肿瘤大小、分化类型、TNM分期进行统计学分析.结果 30例胰腺癌患者中25例TGFβ1表达阳性,阳性率为83.3%(其中强阳性9例,占36%);10例慢性胰腺炎中5例TGFβ1表达阳性;10例正常胰腺组织中仅3例TGFβ1表达阳性,且都为弱阳性;三组间阳性率差异有统计学意义(P＜0.01).TGFβ1表达与患者年龄、性别、肿瘤大小、组织分化均无相关性,但与肿瘤TNM分期有关.TβR1在正常胰腺及癌旁组织中均有较高表达,阳性率分别为9/10和83.3%,在慢性胰腺炎中则有减弱趋势(阳性率8/10),而在胰腺肿瘤组织中的表达则明显下降(40%),组间差异有统计学意义(P＜0.05).结果 TGFβ1过表达及其表达量与肿瘤TNM分期有关,提示 TGFβ1表达上调是胰腺癌发生、发展中的重要事件.TβR1在胰腺癌中表达明显减少,提示其下调是肿瘤逃逸TGFβ1负性生长调控的机制之一.     

TMPRSS4在胰腺癌组织中的表达及其临床意义

目的 检测Ⅱ型跨膜丝氨酸蛋白酶4( TMPRSS4)在胰腺癌组织中的表达及其与临床病理特征的关系.方法 采用实时PCR法和蛋白质印迹法检测16例胰腺癌和配对癌旁组织TMPRSS4 mRNA和蛋白表达;采用免疫组织化学法检测61例胰腺癌标本、26例配对癌旁组织、4例正常胰腺组织TMPRSS4蛋白的表达,分析其与临床病理特征的相关性.结果 胰腺癌组织TMPRSS4mRNA和蛋白表达明显高于配对癌旁组织(9.09±7.01比1.27±0.72;1.223±0.125比0.667 ±0.106,P值均＜0.01),胰腺癌组织TMPRSS4蛋白阳性表达率为67.2％ (41/61),显著高于癌旁组织3.8％ (1/26)的阳性表达率(P＜0.01).正常胰腺组织未见TMPRSS4蛋白表达.胰腺癌TMPRSS4表达与患者年龄、性别及肿瘤部位、肿瘤大小无关,而与肿瘤分化程度、淋巴结转移、临床分期密切相关(P值均＜0.05).结论 胰腺癌组织高表达TMPRSS4,其表达与肿瘤的恶性程度相关.     

Plk1在胰腺癌中的表达及临床意义

目的 研究胰腺癌组织标本及细胞系中Plk1的表达及临床意义。方法 应用免疫组化EnVision两步法检测33例胰腺癌及其癌旁组织、3例胰腺浆液性囊腺瘤、3例黏液性囊腺瘤、5例慢性胰腺炎的石蜡标本中Plk1的表达。用半定量RT—PCR检测5例新鲜胰腺癌组织及其癌旁组织中Plk1 mRNA的表达。用Westernblot检测两株胰腺癌细胞PANC1和CFPAC1中Plk1表达。结果 胰腺癌组织中Plk1的阳性表达率为72、7％（24／33），其表达与胰腺癌患者的年龄、性别、临床分期、组织学分级、淋巴结转移、肿瘤的部位无显著相关（P〉0.05）。癌旁组织、慢性胰腺炎和良性胰腺肿瘤组织中Plk1的表达均为阴性。5例新鲜胰腺癌组织中都有Plk1mRNA的高表达，两株胰腺癌细胞中也有Plk1蛋白的表达。结论 Plk1在胰腺癌中的表达具有一定肿瘤特异性，有可能成为胰腺癌诊治的理想靶标。     

Midkine在胰腺癌组织中的表达及临床意义

目的 探讨人胰腺癌组织中Midkine(MK)的表达及其与肿瘤细胞增殖的关系和意义.方法 免疫组织化学SP法检测49例胰腺癌、13例慢性胰腺炎及15例正常胰腺组织中MK和Ki67蛋白的表达.结果 胰腺癌组织中MK和Ki67均高表达,阳性率分别为77.1 %(35/49)、81.6%(40/49),二者的表达都与肿瘤组织学分级、临床分期和淋巴结转移有关(P ＜0.05).胰腺癌组织中Ki67表达显著高于慢性胰腺炎(3/13,P ＜0.01)和正常胰腺组织(0/15,P ＜0.01).慢性胰腺炎和正常胰腺组织中未见MK阳性表达.胰腺癌组织中MK蛋白的表达与Ki67的表达呈正相关(r ＝ 0.4,P ＜0.05).结论 检测MK蛋白对于胰腺癌的诊断及与慢性胰腺炎的鉴别诊断具有参考价值.MK在胰腺癌中高表达可能与肿瘤的发生发展及细胞增殖密切相关.     

胰腺癌组织中COX-2、VEGF-C表达和淋巴管密度

目的 检测胰腺癌及癌旁组织中COX-2、VEGF-C的表达与淋巴管密度(LVD),探讨它们之间的关系.方法 应用组织芯片技术和免疫组化方法检测40例胰腺癌及相应癌旁组织和12例远处正常胰腺组织中COX-2、VEGF-C的表达及LVD,分析它们之间的关系,以及与临床病理指标的关系.结果 胰腺癌组织COX-2、VEGF-C表达阳性率分别为70.0%(28/40)和67.5%(27/40),显著高于癌旁组织的42.5%(17/40)和35.O%(14/40,P＜0.01),也显著高于正常胰腺的8.3%(1/12)和25.0%(3/12).癌、癌旁及正常胰腺的LVD分别为4.75±2.77、15.20±4.70和1.67±1.15,以癌旁组织最高(P＜0.01).癌组织COX-2表达与肿瘤分化程度、淋巴结转移相关;VEGF-C的表达与淋巴结转移相关.癌旁组织LVD与肿瘤分化程度、淋巴结转移有关,并与癌组织COX-2、VEGF-C表达存在一定相关性.结论 胰腺癌新生淋巴管主要存在于癌旁,淋巴管的形成可能有COX-2及VEGF-C的参与.     

Mucin4在胰腺癌组织中的表达及其临床意义

目的研究胰腺癌组织中Mucin 4(MUC4)的表达及其与临床病理参数间的关系。方法(1)采用ABC免疫组织化学方法检测35例胰腺癌、12例胰腺良性肿瘤及5例慢性胰腺炎组织MUC4的表达。(2)通过RT-PCR方法检测12例胰腺癌组织、癌旁胰腺组织以及2株胰腺癌细胞株MUC4 mRNA的表达。结果 (1)35例胰腺癌组织中MUC4蛋白阳性表达24例,12例胰腺良性肿瘤中MUC4蛋白阳性表达2例,5例慢性胰腺炎组织中MUC4蛋白均为阴性。MUC4蛋白胰腺癌组织中阳性表达率显著高于胰腺良性肿瘤及慢性胰腺炎组织(P<0．05)。MUC4在胰腺癌组织中阳性表达率与肿瘤的部位、淋巴结转移、临床分期无关(P>0．05)。(2)12例胰腺癌组织中MUC4 mRNA表达阳性有6例,癌旁组织中无阳性表达,2株胰腺癌细胞株均呈阳性表达。MUC4 mRNA在胰腺癌组织中阳性表达率显著高于癌旁组织(P<0．05)。结论 MUC4在胰腺癌中有较高的表达率,检测其表达可能有助于胰腺癌的诊断,并可作为鉴别胰腺癌和慢性胰腺炎一个重要参考指标。     

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.