C－sis、C－myc癌基因反义寡脱氧核苷酸抑制动脉平滑肌细胞增殖

用合成Ｃ－ｓｉｓ、Ｃ－ｍｙｃ癌基因反义寡脱氧核苷酸（ＡＯＤＮ）与兔动脉平滑肌细胞（ＡＳＭＣｓ）共同培养，旨在通过ＡＯＤＮ对癌基因的封闭，动态观察ＡＯＤＮ对ＡＳＭＣｓ增殖的影响，探讨ＡＯＤＮ对动脉粥样硬化（ＡＳ）尤其是冠脉成形术后再狭窄（ＲＡＣＡ）的防治作用。结果表明：①Ｃ－ｓｉｓＡＯＤＮ、Ｃ－ｍｙｃＡＯＤＮ具有明显抑制ＡＳＭＣｓ增殖作用，其抑制作用随浓度增加而加强；②Ｃ－ｓｉｓＡＯＤＮ＋Ｃ－ｍｙｃＡＯＤＮ具有协同抑制ＡＳＭＣｓ增殖作用；③Ｃ－ｓｉｓＡＯＤＮ、Ｃ－ｍｙｃＡＯＤＮ明显抑制ＤＮＡ合成，二者联合应用，具有加强抑制ＤＮＡ合成作用。研究结果提示：Ｃ－ｓｉｓ、Ｃ－ｍｙｃ癌基因ＡＯＤＮ抑制ＡＳＭＣｓ增殖，尤其是二者联合应用，有可能为ＡＳ，特别是ＲＡＣＡ防治提供一个新的途径。     

单纯疱疹病毒Ⅱ型感染极早期对离体人动脉平滑肌细胞原癌基因c-sis及c-myc表达的影响

目的：观察单纯疱疹病毒Ⅱ型（ＨＳＶ－２）感染极早期对离体人动脉平滑肌细胞（ｈＡＳＭＣ）原癌基因ｃ－ｓｉｓ及ｃ－ｍｙｃ表达的影响。方法：采用不同感染剂量的ＨＳＶ－２吸附单层ｈＡＳＭＣ１小时作为病毒感染细胞模型,应用Ｎｏｒｔｈｅｒｎ杂交方法观察上述原癌基因表达。结果：病毒吸附细胞后０分钟、３０分钟、６０分钟,病毒感染组［５感染复数（ＭＯＩ）和１０ＭＯＩ;ＭＯＩ＝空斑形成单位／细胞数（ＰＦＵ／细胞数）］均比对照组的原癌基因ｃ－ｓｉｓ、ｃ－ｍｙｃ表达增加,且基因表达与感染时间也有关。结论：ＨＳＶ－２感染可以诱导ｈＡＳＭＣ原癌基因ｃ－ｓｉｓ、ｃ－ｍｙｃ表达增加,该作用可能是病毒促进ｈＡＳＭＣ异常增殖进而参与动脉粥样硬化或血管成形术后再狭窄形成的分子机制之一。     

C-sis反义寡脱氧核苷酸抑制兔主动脉平滑肌细胞增殖的时效关系

为观察局部处理Ｃ－ｓｉｓ反义寡脱氧核苷酸对平滑肌细胞增殖及新生内膜肥厚的抑制作用，球囊导管损伤６０只新西兰白兔胸主动脉后，经导管局部处理每只兔１ｍｇ（２ｍＬ）Ｃ－ｓｉｓ反义或正义寡脱氧核苷酸或２ｍＬ生理盐水，于损伤后第３、７、１４天和第２８天，用免疫组织化学方法结合图象分析，评价损伤动脉内膜平滑肌细胞增殖及新生内膜改变。结果发现，Ｃ－ｓｉｓ反义寡脱氧核苷酸明显抑制内膜平滑肌细胞增殖，最高抑制作用出     

DDPH对实验性腹主动脉狭窄高血压大鼠血管平滑肌细胞增殖及癌基因表达的影响

观察１－（２，６－二甲基苯氧基）－２－（３，４－二甲氧基苯乙胺基）丙烷盐酸盐（ＤＤＰＨ）对实验性腹主动脉狭窄高血压大鼠血管平滑肌细胞（ＶＳＭＣ）增殖的作用及对原癌基因及抑癌基因的影响。方法氚－胸腺嘧啶核苷（３Ｈ－ＴｄＲ）掺入，电镜，原位杂交及Ｎｏｒｔｈｅｒｎｂｌｏｔ杂交。结果ＤＤＰＨ在降低血压同时，能减少血管平滑肌细胞（ＶＳＭＣ）的线粒体，粗面内质网及３Ｈ－ＴｄＲ掺入量（Ｐ＜０．０１），并能逆转ｃ－ｆｏｓ，ｃ－ｍｙｃ，ｃ－ｓｉｓ原癌基因ｍＲＮＡ表达增强（Ｐ＜０．０５～０．０１），Ｐ５３抑癌基因ｍＲＮＡ表达减弱（Ｐ＜０．０５）。结论ＤＤＰＨ能抑制实验性高血压大鼠的ＶＳＭＣ增殖，与癌基因调控的分子生物学机制有关。     

c-myc反义寡核苷酸对缺氧内皮细胞条件培养液刺激的肺血管平滑肌细胞增殖的影响

目的探讨ｃ－ｍｙｃ反义寡核苷酸（ＯＤＮｓ）对缺氧内皮细胞条件培养液（ＨＥＣＣＭ）刺激的肺血管平滑肌细胞（ＳＭＣ）增殖的影响。方法制备ＨＥＣＣＭ，用其刺激肺动脉ＳＭＣ后，Ｎｏｒｔｈｅｒｎ杂交分析ｃ－ｍｙｃ基因表达，３Ｈ－胸腺嘧啶核苷（３Ｈ－ＴｄＲ）掺入试验及细胞生长计数分析ＳＭＣ增殖情况。结果ＨＥＣＣＭ显著刺激ＳＭＣ增殖及ｃ－ｍｙｃ基因表达增强，反义ＯＤＮｓ显著下调ＨＥＣＣＭ刺激的ｃ－ｍｙｃ表达，显著抑制ＨＥＣＣＭ刺激的ＳＭＣ增殖。同义ＯＤＮｓ无上述作用。结论ＨＥＣＣＭ可能通过刺激ＳＭＣ之ｃ－ｍｙｃ表达而使ＳＭＣ增殖，反义ＯＤＮｓ通过下调ｃ－ｍｙｃｍＲＮＡ表达而抑制ＨＥＣ－ＣＭ刺激的ＳＭＣ增殖。     

HCV5‘NCR调控抑制活性的反义寡核苷酸的筛选

目的 寻找高效特异的新型抗ＨＣＶ药物,探讨针对ＨＣＶ基因的硫代修饰反义寡核苷酸（Ｓ－ＡＳＯＤＮｓ）最佳作用靶序列。方法 参考ＨＣＶ５’ＮＣＲ计算机预测的二级结构图,设计合成了１５条Ｓ－ＡＳＯＤＮ、３条正义寡核苷酸及１条随机序列,采用ＨＣＶ５’ＮＣＲ调控荧光素酶基因的瞬时表达系统,将Ｓ－ＡＳＯＤＮ与ｐＨＣＶ－ｎｅｏ４共转染,通过荧光素激活性表达高低,反映Ｓ－ＡＳＯＤＮ对ＨＣＶ调控基因的抑制活性。结果     

一氧化氮和自由基对大鼠急性肝损伤的作用

目的用硫代乙酰胺（ＴＡＡ）诱发大鼠急性肝损伤,观察肝损伤过程中一氧化氮与自由基的变化．方法实验Ⅰ：大鼠２４只分为４组,一组为正常组,其余３组为损伤组．ＴＡＡ６００ｍｇ／ｋｇｓｃ２４,４８,７２ｈ测定内毒素及ＮＯ３－／ＮＯ２－,ＡＬＴ,ＡＳＴ含量．取肝组织匀浆,测定蛋白含量．脂质过氧化物歧化酶（ＳＯＤ）及谷胱甘肽过氧化物酶（ＧＳＨＰＸ）活性,并观察肝组织学变化．实验Ⅱ：大鼠３２只分为４组,Ａ组为正常组,Ｂ,Ｃ,Ｄ组ＴＡＡ６００ｍｇ／ｋｇｓｃ;同时给予Ｂ组生理盐水０４ｍＬ／ｋｇ,Ｃ组７５％ＬＡｒｇ３００ｍｇ／ｋｇ,Ｄ组２５％ＬＮＮＡ１０ｍｇ／ｋｇ．２４ｈ后重复注射１次．２４ｈ后按实验Ⅰ取血、肝组织,测定有关指标．结果大鼠注射ＬＡｒｇ后,ＮＯ的合成增多,转氨酶及肝组织损伤程度明显降低,注射ＬＮＮＡ组大鼠肝损伤程度加重,肝组织自由基的测定表明,抑制肝损伤大鼠ＮＯ合成,肝组织ＬＰＯ含量增高而ＳＯＤ,ＧＳＰＨＸ活性降低,ＳＯＤ,ＧＳＨＰＸ协同作用可清除体内自由基．结论抑制ＮＯ的生物合成,自由基水平增高,从而加重了肝损伤     

家兔心肌缺血再灌注时中性粒细胞胞浆游离钙、MDA、SOD变化规律比较

目的通过对比观察青、老年家兔心肌缺血再灌注时外周血中性粒细胞（ＰＭＮｓ）胞浆游离钙（［Ｃａ~（２＋）］ｉ）、丙二醛（ＭＤＡ）及超氧化物歧化酶（ＳＯＤ）的变化规律，探索上述变化对老年兔心肌缺血再灌注损伤的影响特征，并寻找一种可替代心肌组织标本作为判断再灌注损伤的检测指标。方法５年龄及６月龄家兔实验性心肌缺血３０分钟、再灌注３０、９０、３６０分钟，分别取外周血ＰＭＮｓ及心肌组织测定ＭＤＡ、ＳＯＤ、ＰＭＮ［Ｃａ~（２＋）］ｉ和心肌组织钙。结果青、老年组ＰＭＮ［Ｃａ~（２＋）］ｉ、ＭＤＡ于缺血期均明显升高，至再灌注时更显著，而ＳＯＤ活性则明显降低（Ｐ值均＜０．０１）；上述改变在老年组更明显（Ｐ值＜０．０５及０．０１）。ＰＭＮ［Ｃａ~（２＋）］ｉ、ＭＤＡ、ＳＯＤ的变化分别与心肌钙、ＭＤＡ、ＳＯＤ的变化呈正相关（ｒ值分别为０．９２９２、０．９４３６和０．９８６７）。结论钙超载、氧自由基不但共同参与心肌缺血再灌注损伤，且老年期对致损因子更敏感。ＰＭＮｓ指标测定可作为判断心肌缺血再灌注损伤程度的可靠方法。     

NATIONAL PROGRAM OF MALARIA CONTROL OF PEOPLE'S REPUBLIC OF CHINA

ＮＡＴＩＯＮＡＬＰＲＯＧＲＡＭＯＦＭＡＬＡＲＩＡＣＯＮＴＲＯＬＯＦＰＥＯＰＬＥ’ＳＲＥＰＵＢＬＩＣＯＦＣＨＩＮＡＸｕＳｈｕ—ＨｕｉＤｅｐａｒｔｍｅｎｔｏｆｐａｒａｓｉｔｉｃＤｉｓｅａｓｅｓ，ＭｉｎｉｓｔｒｙｏｆＰｕｂｌｉｃＨｅａｌｔｈｏｆＣｈｉｎａ（...     

Wegener肉芽肿病CD4＋CD28－T细胞的免疫表型及功能的研究

目的　研究Ｗｅｇｅｎｅｒ 肉芽肿病（ Ｗｅｇｅｎｅｒ′ｓ ｇｒａｎｕｌｏｍａｔｏｓｉｓ,ＷＧ） 协同刺激分子（ｃｏｓｔｉｍｕｌａｔｏｒｙ ｍｏｌｅｃｕｌｅｓ,ＣｏｓＭ）ＣＤ２８／ＣＴＬＡ４ＣＤ８０／ＣＤ８６ 的表达以及ＣＤ４ ＋ ＣＤ２８ － Ｔ 细胞的免疫表型特征和功能。方法　ＣｏｓＭ 的表达用ＦＡＣＳ多参数分析测定。ＣＤ４ ＋ ＣＤ２８－ Ｔ细胞与不同刺激剂共同培养后测定其增生反应的程度及细胞因子的分泌。结果　ＷＧ 外周血中ＣＤ４ ＋ ＣＤ２８ － Ｔ 细胞明显增多。它们表达ＣＤ２５、ＣＤ３８ 、ＣＤ４５ＲＯ、ＨＬＡＤＲ 以及ＣＤ８６ 显著增加,且对自身抗原蛋白酶３ 的刺激呈明显增生反应。在抗原提呈细胞（ａｎｔｉｇｅｎ ｐｒｅｓｅｎｔｉｎｇ ｃｅｌｌ,ＡＰＣ） 及抗ＣＤ３ 共同作用下,ＣＤ４＋ＣＤ２８－ Ｔ 细胞的增生活跃,但这种增生反应不能被ＣＴＬＡ４ Ｉｇ、抗ＣＤ８０ 及抗ＣＤ８６ 所抑制。ＣＤ４＋ＣＤ２８－ Ｔ细胞分泌ＩＦＮγ的量明显高于ＣＤ４ ＋ ＣＤ２８ － Ｔ 细胞。另外,ＣＤ４ ＋ ＣＤ２８ － Ｔ 细胞还能诱导正常ＣＤ４ ＋ Ｔ 细胞的活化和增生。结论　ＷＧＣＤ４ ＋ ＣＤ２８－ Ｔ 细胞明显增多,它们可能是一类已被活化的自身     

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.