一氧化氮合酶和微血管生成与胃癌发展的关系

目的　研究诱导型一氧化氮合酶 (iNOS)在人胃癌组织中的表达及其与胃癌微血管形成、淋巴结转移及临床分期的关系。方法　采用免疫组化S P法检测 50例原发性胃癌组织、癌周组织及 2 0例正常胃黏膜组织中iNOS的表达 ,同时检测微血管密度 (MVD) ,以抗CD3 4标记血管内皮细胞 ,并分析其与肿瘤行为之间的关系。结果　 50例胃癌组织中iNOS阳性表达率为 70 .0 % ,MVD均值为 2 2 .0± 9 .8,显著高于癌周组织 (16.2 % ,6.1± 3 .4)和正常胃组织 (15.0 % ,5.5± 2 .6;P <0 .0 1)。按TNM分期 ,Ⅳ期胃癌组织iNOS阳性表达率为 93 .8% ,MVD为 42 .3± 3 .7,两者显著高于Ⅰ、Ⅱ、Ⅲ期 ,差异有显著性 (P <0 .0 1)。有淋巴结转移组iNOS的阳性表达率为 84.6% ,MVD均值为 2 7.4± 6.5;无淋巴结转移组iNOS阳性表达率为 54.2 % ,MVD均值为 15.3± 4.7,两组差异有显著性 (P <0 .0 5)。iNOS阳性表达组及高MVD值 (≥ 2 2 .0 )组的 3年生存率均显著低于iNOS阴性表达组及低MVD值 (<2 2 .0 )组 ,差异有显著性 (P <0 .0 5)。结论　胃癌组织中iNOS高阳性表达 ,随着iNOS阳性表达的增强 ,MVD值也增加 ,两者呈正相关。iNOS的表达及MVD与胃癌TNM分期、淋巴结转移及预后有密切关系。iNOS的表达及MVD值可作为判断胃癌预后的重要指标     

胃癌组织中Survivin、PTEN、P53基因的表达及意义

目的　探讨凋亡抑制基因 Survivin和抑癌基因 PTEN、P53在胃癌组织中的表达及其与胃癌发生发展、临床病理特征之间的关系。方法　应用免疫组织化学链霉亲和素方法 (SABC) ,检测 Survivin、PTEN和 P53基因在 6 5例胃癌、2 6例不典型增生胃黏膜、10例浅表性胃炎和 30例正常胃黏膜组织中的表达。结果　胃癌组织中Survivin、PTEN、突变型 P53基因的阳性表达率分别为 70 %、4 8%、6 5 % ,不典型增生胃黏膜中分别为 4 2 %、85 %、31% ,Survivin和突变型 P53基因在正常胃黏膜和浅表性胃炎组织中不表达 ,PTEN基因在正常胃黏膜和浅表性胃炎组织中全部呈阳性表达。胃癌组织中 PTEN基因的表达与正常胃黏膜组织中的表达差异有显著性 (P<0 .0 5 ) ,胃癌组织、不典型增生胃黏膜以及正常胃黏膜中 Survivin和突变型 P53基因的表达差异均有显著性 (P<0 .0 5 )。随临床分期增加、胃癌分化程度降低、浸润深度加深、淋巴结的转移 ,突变型 P53基因的阳性表达率逐渐上升 (P<0 .0 5 ) ,PTEN基因的阳性表达率逐渐降低 (P<0 .0 5 )。在胃癌组织中 Survivin与突变型 P53基因的表达呈正相关 (P<0 .0 5 ) ,与 PTEN基因的表达呈负相关 (P<0 .0 5 ) ,PTEN基因与突变型 P53基因的表达呈负相关 (P<0 .0 5 )。结论　 Survivin、PTEN和 P53     

凋亡抑制基因生存素在胃癌中的表达及其意义

目的　探讨生存素 (survivin)在胃癌中的表达及其生物学意义。方法　收集 3 2例胃癌组织标本及相应的癌旁组织 ,以半定量RT PCR法检测生存素mRNA表达 ;利用免疫组织化学法检测生存素蛋白表达 ;用流式细胞仪检测胃癌细胞的凋亡指数。结果　 62 .5 %( 2 0例 )的胃癌组织表达生存素蛋白和mRNA ,而癌旁正常组织内无 1例阳性表达。生存素表达与胃癌组织的大小、分化程度、临床分期及淋巴结转移无明显相关关系。所有胃癌组织中都能检测到凋亡细胞 ,但生存素表达阳性组的凋亡指数AI值 ( 3 %± 0 .5 %)显著低于生存素表达阴性组 ( 11%± 0 .9%)。结论　生存素在胃癌组织中表达上调 ,提示该基因对胃癌的发生发展起重要的作用 ,生存素基因有望成为胃癌基因治疗的新靶点     

Ki-67核抗原在良、恶性胃粘膜病变中的表达及临床意义

目的　研究Ki 6 7核抗原在良、恶性胃粘膜病变中的表达及与胃癌生物学行为的关系。方法　采用免疫组化技术检测 36例正常胃粘膜和 6 4例胃癌Ki 6 7核抗原的蛋白表达。结果　正常胃粘膜中Ki 6 7核抗原的表达率为 5 6 %,胃癌中Ki 6 7核抗原的表达率为 43 8%,二者相比具有显著性差异 (P <0 0 1) ;侵犯肌层或浆膜层胃癌的Ki 6 7核抗原表达率 ( 5 4 5 %)显著高于局限于粘膜层和粘膜下层者 ( 2 0 0 %) (P <0 0 5 ) ;低分化胃癌的Ki 6 7核抗原表达率 ( 5 6 8%)显著高于高、中分化胃癌 ( 2 5 0 %) (P <0 0 5 ) ;淋巴结转移阳性组胃癌Ki 6 7核抗原表达率 ( 6 7 7%)显著高于淋巴结转移阴性组 ( 2 1 2 %) (P <0 0 5 )。结论　Ki 6 7核抗原的表达与胃癌的侵袭、低分化、淋巴结转移显著相关 ,是判断胃癌患者预后的一项有价值的参考指标。     

不同胃组织中bcl-2蛋白的亚细胞定位及意义

目的　探讨 bcl- 2蛋白在胃癌、癌旁组织中的不同亚细胞定位及其意义。方法　采用 SP免疫组化法检测 4 6例胃癌和 2 5例癌旁组织中 bcl- 2的表达。结果　胃癌、癌旁组织中 bcl- 2表达率分别为 6 0 .87% (2 8/4 6 )、4 8.0 0 % (12 / 2 5 ) ,两者比较无显著差异 (P >0 .0 5 )。癌旁组 bcl- 2在胞浆定位 2例 (8.0 0 % ) ,核膜及混合定位10例 (40 .0 0 % )。胃癌组在胞浆定位 16例 (34.78% ) ,核膜和混合定位 12例 (2 6 .0 9% ) ,两组比较差异有显著性 (P <0 .0 5 )。bcl- 2蛋白在胃癌不同分化程度、病理分期及淋巴结转移中的阳性表达和定位均无统计学意义 (P >0 .0 5 )。结论　 bcl- 2蛋白超表达定位于核膜或混合定位是胃良性病变的标志 ,而单一胞浆定位是引起细胞恶变的一个可能机制     

胃癌中胸苷磷酸化酶和基质金属蛋白酶2的表达及意义

目的探讨胃癌中胸苷磷酸化酶（TP）和基质金属蛋白酶2（MMP-2）表达的意义及其与肿瘤浸润转移的关系。方法免疫组化SP法检测69例不同胃黏膜组织（正常胃黏膜组10例、慢性胃炎组10例、胃癌组39例、胃癌转移的淋巴结组10例）中TP和MMP-2的表达情况。结果胃癌组织及淋巴结胃癌转移灶中TP与MMP-2的表达较正常组及慢性胃炎组显著增高（P〈0．05）。TP与MMP-2表达与胃癌患者的性别、年龄及肿瘤的分化程度无关。肿瘤≥5cm组及T3-4组TP阳性率湿著高于〈5cm组及T1-2组,有远处转移的胃癌组TP阳性率高于无远处转移组,差具有显著性（P〈0．05）;临床Ⅰ-Ⅱ期和Ⅲ-Ⅳ期之间TP阳性率的差异也具有显著性（P〈0．001）。MMP-2在T1-2组与T3-4组的阳性率分别为60．87％和93．75％,有显著性差异（P〈0．05）。在有淋巴结转移的胃癌组MMP-2阳性率显著高于无淋巴结转移组（P〈0．05）;临床Ⅰ-Ⅱ期阳性表达59．09％,Ⅲ-Ⅳ期阳性表达为94．12％,两组有显著性差异（P〈0．05）。而MMP-2表达却与肿瘤大小及远处转移无关。TP表达阳性的胃癌中MMP-2阳性率88．00％高于TP阴性组的50．00％。结论胃癌中TP与MMP-2表达增高与肿瘤进展的病理临床参数有关;TP的表达与MMP-2的表达有关,提示TP在影响肿瘤进展的过程中可能通过MMP-2促进肿瘤浸润转移。     

MMP-2、MMP-7与胃癌的侵袭转移关系探讨

目的　观察基质金属蛋白酶 (MMP)系列中的 型胶原酶 (MMP- 2 )和基质溶解素 (MMP- 7)在胃癌和癌旁组织中的表达 ,探讨其与胃癌侵袭转移的关系。方法　采用逆转录 - PCR(RT- PCR)方法分别检测 4 0例胃癌及癌旁组织 MMP- 2和 MMP- 7m RNA的阳性表达及含量。结果　 4 0例胃癌组织中 MMP- 2和 MMP- 7的阳性表达率分别为 82 .5 %、72 .5 % ,明显高于癌旁组织的 72 .5 %、17.5 % ,二者比较差异有显著性 (P<0 .0 0 1)。MMP-2和 MMP- 7表达量高于其癌旁组织 (t=3.6 7,t=7.894 ) ,差异有显著性 (P均≤ 0 .0 0 1)。MMP- 2和 MMP- 7的表达量与胃癌患者的性别、年龄、肿瘤的大小均无相关性 (P>0 .0 5 )。 MMP- 2的表达量在晚期、低分化及伴有淋巴结转移的胃癌患者中明显高于早期、高分化及无淋巴结转移的胃癌患者 (P<0 .0 5、P<0 .0 1)。 MMP- 7在各期胃癌中的表达无差异 (P>0 .0 5 ) ,但在中低分化及合并有淋巴结转移的胃癌患者中其表达量明显高于高分化及不伴有淋巴结转移的胃癌患者 (P<0 .0 5 )。结论　 MMP- 2和 MMP- 7的表达与胃癌侵袭转移性有关     

生存素转录变异体在胃癌中的表达及其与细胞增殖、凋亡的关系

目的　研究生存素各转录变异体表达及其与胃癌细胞增殖和凋亡的关系。方法　采用实时荧光定量RT PCR技术 ,对 77例胃恶性肿瘤患者的肿瘤组织和正常胃黏膜的成对冰冻标本进行mRNA定量检测。对相同病例的石蜡标本 ,采用DNA缺口原位末端标记 (TUNEL)技术检测肿瘤细胞凋亡 ,免疫组化 (Ki 6 7)检测细胞增殖。结果　与患者正常胃黏膜比较 ,肿瘤组中 3个转录变异体表达水平显著上调 (P <0 .0 0 0 1)。野生型生存素在胃癌中的表达率为 10 0 .0 % (77/77) ,生存素 2B表达率是 79.2 % (6 1/77) ,并且高表达组为早期胃癌 (P =0 .0 0 1)、分化型胃癌 (P =0 .0 0 7)以及浸润浅的胃癌组织 (P =0 .0 31) ;生存素△Ex3在胃癌中的表达率为 6 4 .9% (5 0 /77) ,并且高表达组的凋亡指数显著降低(P =0 .0 19,r =0 .2 6 7)。本实验未发现生存素的 3个转录变异体表达水平与肿瘤细胞增殖指数相关。结论　生存素 2B的表达与肿瘤的分期、分化和肿瘤浸润深度相关 ,表明生存素 2B可能是野生型生存素和生存素 △Ex3的天然拮抗物 ;同时还发现生存素 △Ex3在胃癌组织中的表达与凋亡指数负相关。     

胃癌中CD44S和CD44V6的表达及意义

目的　研究胃癌中CD44的表达 ,旨在探讨CD44在胃癌发生发展中的作用及临床意义。方法　采用免疫组化S-P方法检测CD44S及CD44变异体V6在 5 4例胃良性病变 (BGD)及 6 3例胃癌 (GC)中的表达 ,并比较了阳性表达与肿瘤组织分型、淋巴转移等的关系。结果　CD44S在浅表性胃炎 (CSG)、萎缩性胃炎伴肠上皮化生 (CAG/IM)及GC中表达阳性率分别为 46 5 %、5 7 1%、5 2 4%。CD44V6在CSG中无表达 ,在CAG/IM及GC中表达阳性率为 :19 1%和5 3 7%。在有淋巴转移组CD44V6表达率 6 8 6 % ,明显高于无转移组 3 5 7%。在肠型胃癌中 ,CD44V6表达率 73 7% ,明显高于弥漫型胃癌 2 4%。CD44S阳性表达与有否淋巴转移及组织分型无关。结论　CD44S、CD44V6在胃癌中均有表达 ,CD44V6表达率与胃癌淋巴转移及组织来源有关。     

COX-2与MMP-2蛋白在胃癌组织中的表达及意义

目的　探讨COX 2和MMP 2蛋白在胃癌组织中的表达、相互关系及意义。方法　应用免疫组化S P法检测 45例胃癌及 2 0例正常胃组织MMP 2、COX 2蛋白的表达情况。结果　 45例胃癌组织COX 2的表达阳性率为 60 % ( 2 7/ 45 ) ,2 0例正常胃组织COX 2的表达阳性率为 15 %O( 3 / 2 0 ) ,COX 2在胃癌组织中的表达阳性率显著高于正常胃组织中的表达阳性率 (P <0 0 1) ;45例胃癌组织中MMP 2的表达阳性率为 64 4% ( 2 9/ 45 ) ,2 0例正常胃组织MMP 2表达阳性率为 2 5 % ( 5 / 2 0 ) ,MMP 2在胃癌组织中的表达阳性率显著高于在正常胃组织中的表达阳性率 (P <0 0 1) ;在胃癌组织中MMP 2、COX 2蛋白的表达之间存在显著正相关 (rs=0 5 69,P <0 0 1)。结论　胃癌组织中存在COX 2、MMP 2的高表达 ,且两者之间的表达强度具有等级相关性。COX 2蛋白可通过诱导MMP 2蛋白的表达上调 ,增加胃癌细胞的侵袭力 ,从而成为其促进胃癌浸润、转移的途径之一     

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.