凋亡相关基因在非小细胞肺癌组织中表达的研究

目的　探讨ｂｃｌ２ 、ｂａｘ、Ｆａｓ、ＦａｓＬ凋亡相关基因在非小细胞肺癌中表达及与肿瘤临床病理学的关系。方法　采用免疫组织化学方法检测４５ 例非小细胞肺癌中ｂｃｌ２、ｂａｘ、Ｆａｓ 和ＦａｓＬ的表达。结果　２３ 例（５１ ％）ｂｃｌ２ 阳性,３８ 例（８４％ ）ｂａｘ 阳性（ Ｐ＜ ０－０１） ,二者之间表达无明显关系,但Ｆａｓ 与ＦａｓＬ之间表达呈正相关（Ｐ＜０－０１） 。ｂｃｌ２ 蛋白表达率随肿瘤期别进展而降低（ Ｐ＜ ０－０５） ,ｂａｘ 蛋白在低分化癌中表达减少（Ｐ＜０－０５） ,ＦａｓＬ在肺腺癌细胞中表达较高（Ｐ＜ ０－０１） 。ｂｃｌ２ 和ｂａｘ 蛋白同时表达阳性与肺癌ＴＮＭ 分期显著相关（Ｐ＜０－０５） ,ｂｃｌ２ 蛋白单一表达与细胞分化有关（ Ｐ＝０－０３３）。结论ｂｃｌ２、ｂａｘ、Ｆａｓ 和ＦａｓＬ可能通过不同途径参与了非小细胞肺癌组织中细胞凋亡的调节,并在肿瘤的发生与发展中发挥重要作用。     

胃癌及癌旁组织中bcl—2蛋白表达及其与细胞凋亡的关系

目的：研究胃癌及癌旁组织中ｂｃｌ－２蛋白的表达状态及其与细胞凋亡之间的关系。方法：采用免疫组织化学方法及脱氧核糖核酸末端转移酶介导的缺口末端标记（ＴＵＮＥＬ）技术对５０例胃癌及３３例癌旁组织中ｂｃｌ－２蛋白表达状态及凋亡细胞的密度和分布进行原位观察和比较。结果：胃癌组织中ｂｃｌ２蛋白的表达率、表达强度明显高于癌旁组织（Ｐ＜００５）。ｂｃｌ２蛋白在胃癌组织中的表达与患者性别、年龄、肿瘤大小、浸润深度、淋巴结转移及临床分期无明显关系（Ｐ＞００５），与胃癌形态学分型及分化程度有关（Ｐ＜００５及Ｐ＜００１）。癌旁组织中的凋亡细胞指数高于胃癌组织（Ｐ＜００１）。ｂｃｌ２蛋白表达阴性胃癌及癌旁组织中凋亡细胞指数明显高于ｂｃｌ２阳性组（Ｐ＜００１）。结论：ｂｃｌ２蛋白对胃癌及癌旁组织中的细胞凋亡具有抑制性调控作用。在胃粘膜细胞恶性转化过程中可能存在细胞凋亡受抑制，ｂｃｌ２蛋白表达异常增加可能是细胞凋亡受抑的机制之一。细胞凋亡调控异常在胃癌发病中可能起重要作用     

胰腺癌Bcl-2,P53蛋白表达和细胞凋亡

目的　探讨ｂｃｌ２ ,ｐ５３ 基因和细胞凋亡在胰腺癌发病机制中的作用以及它们之间相互关系．方法　应用ＡＢＣ 免疫组化技术检测５０ 例胰腺癌中Ｂｃｌ２ 和Ｐ５３ 蛋白表达,运用原位末端标记法观察肿瘤中细胞凋亡数量．结果　Ｐ５３ 蛋白表达阳性率为５４ ％ ,临床Ⅰ期阳性率（２６－７ ％ ）却显著低于Ⅱ期（６１－１ ％ ） 和Ⅲ＋ Ⅳ期（７０－６ ％ ,Ｐ＜ ０－０５） ;Ｂｃｌ２蛋白表达阳性率为６４ ％ ,临床Ⅰ期阳性率（９３－３ ％ ） ,显著高于Ⅱ期（５５－６ ％ ） 和Ⅲ＋ Ⅳ期（４７－１ ％ ,Ｐ＜ ０－０５） ;组织学Ⅲ级癌细胞中凋亡指数明显高于Ⅰ,Ⅱ级（ Ｐ＜ ０－０５） ,Ｂｃｌ２ 蛋白阴性病例中凋亡指数明显高于Ｂｃｌ２ 阳性者（ Ｐ＜ ０－０１） ．结论　Ｂｃｌ２ 是通过抑制细胞凋亡参与肿瘤的生长过程,Ｂｃｌ２和Ｐ５３ 蛋白表达之间 存在密切负相关（τ＝ － ０－１７４７ ,Ｐ＜ ０－０５） ．     

胆囊肿瘤组织中细胞凋亡及bcl-2基因的研究

目的探讨细胞凋亡及其调控基因ｂｃｌ２在胆囊癌发生发展中的作用．方法用原位末端标记法（ＩＳＥＬ）和免疫组化ＡＢＣ法对２４例胆囊癌和１６例胆囊腺瘤中的凋亡细胞及其调控基因ｂｃｌ２的表达产物进行了检测．同时观察胆囊癌中的调亡细胞与胆囊癌病理类型、分化程度和浸润转移的关系，分析ｂｃｌ２基因对细胞凋亡的调控作用．结果胆囊癌、胆囊腺瘤中的细胞凋亡发生率分别为１００％和５６％；胆囊癌中的凋亡细胞数明显高于胆囊腺瘤（χ２＝３６１１１，Ｐ＜００１）；低分化腺癌及Ｎｅｖｉｎ分期Ｓ１～Ｓ３胆囊癌中的凋亡细胞数明显高于高分化及Ｎｅｖｉｎ分期Ｓ４，Ｓ５者（χ２＝１９０５１，Ｐ＜００１）．高分化腺癌中的凋亡细胞多呈点状分布，低分化腺癌及转移性胆囊癌中的凋亡细胞呈片状或块状分布．ｂｃｌ２基因在胆囊癌和胆囊腺瘤中的表达无显著差异（χ２＝１１１１，Ｐ＞００５）．在胆囊癌中，ｂｃｌ２产物阳性表达与细胞凋亡密切相关（χ２＝１１８２，Ｐ＜００１）．结论细胞凋亡ｂｃｌ２基因在胆囊癌发生发展中起重要作用     

肝细胞癌细胞凋亡相关蛋白bcl-2和bax的表达及意义

Ｂｃ１－２基因家族对细胞凋亡具有广泛的调控作用。其中，ｂｃｌ－２和ｂａｘ分别是最主要的抑制凋亡和促凋亡基因。多数肿瘤的ｂｃｌ－２蛋白表达升高，ｂａｘ蛋白表达下降。我们检测ｂｃｌ－２和ｂａｘ蛋白在肝癌组织及其细胞系的表达，并以正常肝组织及其细胞系作对照，探讨它们在肝癌细胞凋亡调控中的作用。 １．标本和细胞来源：第四军医大学西京医院手术切除的６６例人肝癌组织，其中肿瘤细胞分化程度高的Ⅰ级１９例、肿瘤细胞分化程度中等的Ⅱ级３０例、肿瘤细胞分化程度低的Ⅲ级３０例。２４例人正常肝组织取自尸检。人肝癌细胞系…     

bcl-2基因在阻塞性黄疸大鼠肝组织细胞凋亡中作用的研究

目的　探讨阻塞性黄疸大鼠肝组织损害的机制．方法　用末端脱氧核苷酸转移酶（ＴｄＴ） 介导的ｄＵＴＰ 缺口末端标记技术（ＴＵＮＥＬ） 和免疫组织化学方法检测阻塞性黄疸大鼠肝脏组织细胞凋亡状态及凋亡相关基因ｂｃｌ２ 的表达．结果　胆总管结扎后,随结扎时间的延长细胞凋亡增加,结扎１４ ｄ 后细胞凋亡达高峰,凋亡指数（ＡＩ） 达５８－２３ ±１－５８ ,各组ＡＩ差异有显著性意义（ Ｐ＜ ０－０５） ． 在阻塞性黄疸过程中,ｂｃｌ２ 蛋白表达越强,ＡＩ就越少．结论　ｂｃｌ２ 蛋白参与了阻塞性黄疸肝组织中细胞凋亡的调节,并在阻塞性黄疸肝损害的发生和发展中起重要作用．     

C-myc,Bcl-2与胃癌生物学行为和细胞凋亡

目的探讨癌基因Ｂｃｌ２，Ｃｍｙｃ的表达变化与胃癌生物学行为和细胞凋亡的关系．方法采用免疫组化ＬＳＡＢ法，检测６０例原发性胃癌组织（男３８例，女２２例，年龄３７岁～７５岁）癌基因Ｂｃｌ２，Ｃｍｙｃ蛋白的表达变化；在普通光学显微镜下对受检组织的ＨＥ片进行形态学测量和凋亡细胞计数．结果受检组织６０例中，Ｃｍｙｃ阳性表达３７例（６２％），其表达与分化程度和临床分期呈显著性相关，且Ｃｍｙｃ阳性组织细胞凋亡指数（０７±０３）明显高于阴性组织（０３±０２）；所检标本中，Ｂｃｌ２阳性表达率为６８％（４１／６０），其中高分化胃癌的阳性表达率明显高于低分化胃癌（３２％ｖｓ９％）（Ｐ＜００５），阳性Ｂｃｌ２组织与阴性Ｂｃｌ２组织比较，前者凋亡指数明显低于后者（０４±０３ｖｓ０９±０５）（Ｐ＜００５）．结论Ｃｍｙｃ与Ｂｃｌ２基因的异常表达是胃癌生物学行为的重要影响因素，二者在胃癌形成过程中均起着一定的作用，并对细胞增生与凋亡有重要调节作用．     

胃癌癌旁组织中p53、p16和bcl-2蛋白表达及其关系的探讨

目的：研究胃癌癌旁组织中抑癌基因和抗凋亡基因蛋白的表达及其内在关系。方法：胃镜及外科手术中取４０例 胃癌患者的癌组织和癌旁组织各两块,石蜡包埋,切片ＨＥ染色作病理及免疫组织化学检查ｐ５３、ｐ１６和ｂｃｌ－２基因蛋 白表达。结果：ｐ５３在胃癌组织中阳性表达率４２．５％,癌旁组织１２．５％,有显著性差异（Ｐ＜０．０１）,其表达强度也有显著 性差异（Ｐ＜０．０１）;ｐ１６在癌旁组织阳性表达率为６０％,显著高于胃癌组织３７．５％（Ｐ＜０．０５）,其表达强度也有显著性差 异（Ｐ＜０．０５）;ｂｃｌ－２在胃癌组织和癌旁组织阳性表达率无显著性差异（６７．５％比４７．５％,Ｐ＞０．０５）,其表达强度也无显 著性差异（ｐ＞０．０５）。ｐ５３与ｐ１６、ｐ１６与ｂｃｌ－２表达之间均无显著相关性（Ｐ＞０．０５）,而ｐ５３与ｂｃｌ－２表达之间存在显著相 关性（Ｐ＜０．０５）。结论：在胃癌发生发展过程中,抑癌基因（ｐ５３、ｐ１６）４抗凋亡基因（ｂｃｌ－２）之间存在既独立又协同的作 用。     

高血压对靶器官细胞凋亡影响的实验研究

本研究采用自发性高血压大鼠（ Ｓ Ｈ Ｒ）、服用依那普利的 Ｓ Ｈ Ｒ大鼠（ Ｓ Ｈ Ｒ ｄ）及正常血压大鼠（ Ｗ Ｋ Ｙ）三组作对照研究,应用原位标记检测技术观察高血压左室肥厚及心脏左室逆转后心肌平滑肌细胞凋亡现象。并检测凋亡相关基因ｂｃｌ ２,ｃ ｍ ｙｃ 的表达。结果显示: Ｓ Ｈ Ｒ ｄ 左室肥厚逆转,其左室壁细胞凋亡数比 Ｓ Ｈ Ｒ 组明显增多（ Ｐ＜ ０．０１）。 Ｓ Ｈ Ｒ 组左心室肥厚,其左室壁细胞凋亡数则比 Ｗ Ｋ Ｙ,即无高血压及左室肥厚组明显增多（ Ｐ＜ ０．０１）。各组ｂｃｌ ２,ｃ ｍ ｙｃ 均有表达,依据辉度检测表达强度,则ｂｃｌ ２ 表达的强度为 Ｓ Ｈ Ｒ明显高于 Ｓ Ｈ Ｒ ｄ 及 Ｗ Ｋ Ｙ（ Ｐ＜ ０．０１）; Ｓ Ｈ Ｒ ｄ 和 Ｗ Ｋ Ｙ 辉度接近（ Ｐ＞ ０．０５）;ｃ ｍ ｙｃ 表达的强度为 Ｓ Ｈ Ｒ ｄ＞ Ｓ Ｈ Ｒ＞ Ｗ Ｋ Ｙ,各组比较,差别有非常显著意义（ Ｐ＜ ０．０１）或显著意义（ Ｐ＜ ０．０５）。     

Bcl—2及相关蛋白bax在慢性乙型肝炎肝组织中的表达

目的：探讨原癌基因ｂｃｌ－２及相关蛋白ｂａｘ在慢性乙型肝炎发病中的作用。方法：采用免疫组化技术研究１４例慢性迁延性肝炎和１９例慢性活动性肝炎组织中原癌基因ｂｃｌ－２及相关蛋白ｂａｘ的表达。结果：慢迁肝，慢活肝和正常肝组织中ｂｃｌ－２表达均较低，三组间差异不明显（Ｐ值〉０．０５）；慢迁肝和慢活肝中肝细胞ｂａｘ表达较正常肝细胞增加，而又以慢活肝中有更多ｂａｘ蛋白表达，结论：乙肝病毒ｂａｘ蛋白可能有诱导     

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.