胆固醇酯转运蛋白基因373 Ala→Pro和451 Arg→Gln的突变频率及其对脂质代谢的影响

为了进一步探讨胆固醇酯转运蛋白基因突变３７３ Ａｌａ → Ｐｒｏ 和４５１ Ａｒｇ → Ｇｌｎ 的频率及其对血脂代谢的影响,采用致突变分离聚合酶链反应技术,检测了９１ 例健康德国大学生和４０９ 例冠心病患者在胆固醇酯转运蛋白基因第３７３ 和第４５１ 位密码子的基因型,并对照测定其血脂参数。结果表明,３７３ Ａｌａ → Ｐｒｏ 和４５１ Ａｒｇ → Ｇｌｎ 等位基因频率为３ ％ ～５ ％ ,在绝大多数受检者中联合出现,但尚存二者的不完全连锁性;在健康志愿者和冠心病患者中两个突变的杂合子与野生型比较均呈现血清高密度脂蛋白胆固醇水平的降低（ Ｐ＜ ０ ．０５） ,健康志愿者的杂合子还显示出甘油三酯的升高（ Ｐ＜ ０ ．０５） 。从而提示３７３ Ａｌａ → Ｐｒｏ 和４５１ Ａｒｇ→ Ｇｌｎ 为频发误义突变,其在健康志愿者和冠心病患者中的携带者可表现为血清高密度脂蛋白胆固醇水平的降低和甘油三酯水平的升高。     

p53基因突变及p53、APC基因缺失与胃癌关系的研究

为明确ｐ５３基因突变、缺失，ＡＰＣ基因缺失在胃癌发病机制中的作用，应用ＰＣＲ－ＳＳＣＰ方法对抑癌基因ｐ５３第４、５、６、７、８外显子、第６内含子在８７例胃癌及癌前病变中的突变规律以及ＰＣＲ－ＲＦＬＰ方法对ｐ５３基因第４外显子、第６内含子、ＡＰＣ基因在２５对胃癌及癌旁组织中的杂合缺失规律进行了探讨。结果发现，ｐ５３突变率在肠化、不典型增生、胃癌分别为３７．５％ （３／８），４２．１％（８／１９），５３．３％（１６／３０）。正常组织、浅表胃炎未发现ｐ５３突变。肠化、不典型增生、胃癌与正常对照组、浅表胃炎组相比均存在显著差异（Ｐ＜０．０５，Ｐ＜０．０１，Ｐ＜０．０１）。在肠化、不典型增生病变中未发现Ｅｘｏｎ８的突变，而在胃癌组Ｅｘｏｎ８的突变为４例（４／３０），提示Ｅｘｏｎ８的突变主要发生在晚期。在各病变组未发现Ｅｘｏｎ４、Ｉｎｔｒｏｎ６的突变。对Ｅｘｏｎ４、Ｉｎｔｒｏｎ６、ＡＰＣ基因的杂合缺失研究表明，２５对胃癌标本中有１９对Ｅｘｏｎ４杂合子，杂合率为７６．０％，９对有杂合缺失，ＬＯＨ为４７．４％，２３对Ｉｎｔｒｏｎ６杂合子，杂合率为９２．０％，其中２对为杂合缺失，ＬＯＨ为８．７％，１８对ＡＰＣ杂合子（１８／２５     

胆固醇酯转运蛋白在动脉粥样硬化中的作用

胆固醇酯转运蛋白介导血浆高密度脂蛋白、低密度脂蛋白和极低密度脂蛋白之间胆固醇酯、磷脂和甘油三酯的转运,直接关联各种脂蛋白分子的组成、大小和浓度,在胆固醇的逆向转运中起关键作用,与动脉粥样硬化的发生发展密切相关。胆固醇酯转运蛋白基因有多种突变,基因突变者胆固醇酯转运蛋白浓度和活性发生改变,并伴有高密度脂蛋白胆固醇水平升高等显著的脂代谢异常。雌激素对胆固醇酯转运蛋白水平也有调节作用。胆固醇酯转运蛋白在小颗粒致密的B型低密度脂蛋白形成中起重要作用,大而轻的A型低密度脂蛋白在高甘油三酯的条件下,经胆固醇酯转运蛋白介导极低密度脂蛋白中甘油三酯与低密度脂蛋白中胆固醇酯交换,导致典型的A型低密度脂蛋白变成强致病性的B型低密度脂蛋白。     

血浆k-ras基因突变检测对胆道系统癌的诊断意义

探讨胆道系统癌患者外周血中是存在ｋ－ｒａｓ基因突变及其诊断价值。方法 提取血浆ＤＮＡ,通过ｍｕｔａｎｔａｌｌｅｌｅｓｐｅｃｉｆｉｃ ａｍｐｌｉｆｉｃａｔｉｏｎ（ＭＡＳＡ）方法检测ｋ－ｒａｓ基因ｃｏｄｏｎ１２突变。结果 ７例胆囊癌中５例－ｒａｓ基因突变阳性（１７．４％）,６便肝内胆管细胞癌和３例总胆管癌中分别有２例（３３．３％）及１例（３３．３％）ｋ－ｒａｓ基因突变检测阳 性。ｋ－ｒａｓ基因突变检测     

胃粘膜p53抑癌基因异常与癌变的研究

目的系统研究各种胃粘膜病变中ｐ５３抑癌基因的变异和意义．方法内镜活检组织１５４例，其中浅表性胃炎３０例，萎缩性胃炎３３例，萎缩性胃炎伴肠上皮化生３１例，萎缩性胃炎伴异型增生３０例，胃腺癌３０例．用免疫组化法检测Ｐ５３蛋白表达；用单链构象多态性分析及ＤＮＡ测序检测ｐ５３第５～８外显子点突变．结果胃良性病变粘膜未见Ｐ５３蛋白表达．胃癌中Ｐ５３蛋白阳性表达率为３３３％（１０／３０例）．单链构象多态性分析ｐ５３点突变的检出率，在胃癌为５４５％（６／１１例），异型增生为２０％（３／１５例），肠化生为６７％（１／１５例），测序证实１例胃癌在第５外显子存在点错义突变和碱基缺失，２例异型增生在第６外显子存在点错义突变．结论ｐ５３抑癌基因变异与胃粘膜癌变有关．     

中国汉、蒙古、回、东乡、维吾尔、傣族六个民族居民胆固醇酯转运蛋白D442G和I14A基因突变调查

研究中国不同民族健康人群胆固醇酯转运蛋白两种主要基因突变D442G和I14A的发生率，血清胆固醇酯转运蛋白水平及其与其他血脂的关系，应用聚合酶链反应－限制片长多态性分析方法检测胆固醇酯转运蛋白基因两种主要突变的发生率，采用ELISA法测定蒙古族，维族，回族，东乡族，傣族和汉族6个民族共600例健康成人血清胆固醇酯转运蛋白水平，同时测定血清总胆固醇，甘油三酯，高密度脂蛋白胆固醇，低密度脂蛋白固醇，载脂蛋白AI和载脂蛋白B水平。结果发现，蒙古族，回族，东乡族，傣族和维吾尔族居民血清胆固醇酯转运蛋白水平与汉族居民无显著差异，胆固醇酯转运蛋白基因D442G和I14A两种主要突变频率也无明显差异；与汉族居民相比，其它5个民族居民总胆固醇水平均显著降低（P＜0．05），回族居民甘油三酯水平显著高于汉族居民（P＜0．05）；蒙古族，回族和东乡族居民高密度脂蛋白胆固醇水平明显低于汉族居民（P＜0．05），维吾尔族，回族和东乡族居民低密度脂蛋白胆固醇水平显著低于汉族居民（P＜0．05）。结果提示，胆固醇酯转运蛋白基因两种主要突变的频率在不同民族之间无明显差异，6个民族居民中地理和膳食等环境因素对胆固醇酯转运蛋白水平影响较小。     

雌激素对绝经后妇女冠心病治疗作用的观察

目的探索雌激素对绝经后妇女冠心病的防治机制及疗效。方法将１０８例绝经１年以上的女性冠心病患者随机分为三组（各３６例），甲组口服结合雌激素（倍美力）０．６２５ｍｇ１／ｄ，乙组口服７甲基异炔诺酮（利维爱）２．５ｍｇ１／ｄ，丙组口服安慰剂１片１／ｄ，于服药前及服药后第３、６个月末检测血脂谱及ＥＣＧ，并记录心绞痛发作情况。结果倍美力治疗后可使胆固醇（ＴＣ）降低１２．８％，甘油三酯（ＴＧ）降低１７．０％，低密度脂蛋白胆固醇（ＬＤＬＣ）降低２９．０％，高密度脂蛋白胆固醇（ＨＤＬＣ）上升１４６％。利维爱治疗后ＴＣ降低８．７％，ＴＧ降低１５．６～３３．８％、ＨＤＬＣ降低１９．７～２８．３％（Ｐ值均＜００１），ＬＤＬＣ无显著变化。倍美力及利维爱治疗第３、６个月后对心绞痛症状的总有效率分别为９０９％、９３５％和８３．３％和９３．１％，对ＥＣＧ缺血性改变的总有效率分别为７６．７％、８２．１％和７８．６％、８１４％，两种药物对妇女冠心病的心肌缺血疗效差异无显著性（Ｐ＞０．０５）。结论雌激素替代治疗可显著改善绝经后妇女冠心病患者的异常血脂及心肌缺血     

儿童肝豆状核变性基因突变初步研究

报告８例儿童肝豆状核变性（ＨＬＤ）患者Ｐ型ＡＴＰ７Ｂ酶基因突变情况。应用ＰＣＲ－ＳＳＣＰ方法检测第１４外显子,运用限制性内切酶酶切和ＤＮＡ直接序列分析技术检测第８外显子。结果８例患儿均未发现第１４外显子泳动变位,４例发生第８外显子Ａｒｇ７７８Ｌｅｕ纯合子突变,１例存在Ａｒｇ７７８Ｌｅｕ杂合子突变。所有上述Ａｒｇ７７８Ｌｅｕ突变均伴有第７７０位Ｃ→Ｃ多态。在８例患儿中受累染色体频率：纯合子（８／１６     

p53基因突变及p53,APC基因缺失与胃癌关系的研究

为明确ｐ５３基因突变，缺失，ＡＰＣ基因缺失在胃癌发病机制中的作用，应用ＰＣＲ－ＳＳＣＰ方法对抑癌基因ｐ５３第４，５，６，７，８外显子，第６内含子在８７例胃癌及癌前病变中的突变规律以及ＰＣＲ－ＲＦＬＰ方法对ｐ５３基因第４外显子，第６内含子，ＡＰＣ基因在２５对胃癌及癌旁组织的杂合缺失规律进行了探讨，结果发同，ｐ５３突变率在肠化，不典型增生，胃癌分别为３７．５％（３／８），４２．１％（８／１９），５３．     

胆固醇酯转运蛋白基因373 Ala→Pro和451 Arg→Gln的突变频率及其对脂质代谢的影响

为了进一步探讨胆固醇酯转运蛋白基因突变３７３Ａｌａ→Ｐｒｏ和４５１Ａｒｇ→Ｇｌｎ的及其对血脂代谢的影响，采用致突变分离聚合酶链反应技术，检测了９１例健康德国大学生和４０９例冠心病患者在胆固醇酯转运蛋白基因第３７３和第４５１位密码子的基因型，并对照测定其血脂参数。     

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.