家族性糖尿病人群中线粒体ND-1基因点突变的分析研究

目的了解线粒体ND-1基因mt3316G→A、mt3394T→C变异在中国家族性糖尿病人群中的发生率及其临床特点。方法应用PCR-RFLP结合直接测序方法对随机抽取的无亲缘关系的770个糖尿病家系的先证者及309例非糖尿病对照者进行线粒体基因mt3316G→A、mt3394T→C变异的筛查。结果在糖尿病先证者组中发现17例（2.21%）mt3316G→A变异,18例（2.34%）mt3394T→C变异;在正常对照组中分别发现5例（1.62%）和6例（1.94%）变异携带者,变异的发生率在两组间差异无统计学意义。在糖尿病先证者组见到2例同时携带上述两种变异者。伴mt3316G→A或mt3394T→C突变的糖尿病组与无该变异的糖尿病组之间的临床特点（年龄、体质指数、胰岛素抵抗指数）比较差异无统计学意义。结论线粒体ND-1基因mt3316G→A,mt3394T→C变异可能不是中国人线粒体糖尿病发病的致病原因,而是中国人线粒体的基因多态。     

线粒体DNA ND-1基因点突变与2型糖尿病的关系

2型糖尿病患者中线粒体DNA（mtDNA)3316G→A，3316G→A，3394T→C突变频率分别为3.9%(6/152)和5.3%(8/152)，显著高于正常对照者及冠心病患者，提示mtDNA3316G→A，3394T→G突变与2型糖尿病相关。     

浙江地区汉族人线粒体DNA ND1基因T3394C突变与老年2型糖尿病

目的 探讨线粒体DNA ND1基因T3394C突变与老年2型糖尿病的关系. 方法 采用聚合酶链反应(PCR)产物直接测序法对340例无血缘关系的2型糖尿病患者(其中老年糖尿病组90例,非老年糖尿病组250例)和265例健康对照者(老年健康对照组130例,非老年健康对照组135例)的血细胞线粒体DNA进行突变位点检测,并用DNASTAR和Antheprot 5.0软件分析突变位点. 结果 老年糖尿病组、老年健康对照组和非老年糖尿病组分别检出5例、1例和2例T3394C突变.T3394C突变在老年糖尿病组和老年健康对照组之间分布差异有统计学意义(P＜0.05),在老年糖尿病组和非老年糖尿病组之间分布差异也有统计学意义(P＜0.05).蛋白质结构预测显示T3394C突变引起ND1蛋白二级结构改变. 结论 线粒体DNA ND1基因T3394C突变可能与老年2型糖尿病的发生有关.     

线粒体DNA变异与老年2型糖尿病患者易感性的相关性

目的 研究湖北地区老年2型糖尿病(T2DM)患者中线粒体基因突变的发生率及其相关性.方法 采用PCR-RFLP、基因测序技术,对175例老年T2DM患者和200例糖耐量正常的健康老年对照组进行检测.结果 MIND1 3316(G→A)、MTTL1 3243(A→G)、MIND13394( T→C)、MIND14216(T→C) MIND14164(A→G)和MIND2 5178( T→C)变异率分别为3.26％、2.72％、1.71％、4％、34.9％;对照组检出3316(G→A)突变2例(0.99％)、4164 5例(0.99％)、5718(T→C)变异64例(32.3％),未检出3394、4216的点突变;两组间3394(T→C)变异率差别有统计学意义(P＜0.05);且T2DM组5178A基因型血清TC水平低于5178C基因型(P＜0.05),但TG、LDL-C、HDL-C、apoA、apoB、Lp(a)水平两组无统计学意义.结论 3394( T→C)与老年T2DM患者的易感性有一定关联,5178(T→C)变异与湖北地区老年汉族人T2DM的脂代谢相关.     

线粒体DNA ND1基因nt3394 T→C突变与老年人2型糖尿病

目的：了解线粒体烟酰胺腺嘌呤脱氧核苷酸（NADH）脱氢酶第一亚单位（ND1）基因中339位点T→C突变与我国老年人2型糖尿病的关系。方法：收集无血缘关系的208例老年2型糖尿病患者，同时以180例无糖尿病家族史的老年糖耐量正常者作为对照，用聚合酶链反应扩增。限糖尿病患者，同时以180例无糖尿病家族史的老年糖耐量正常者作为对照，用聚合酶链反应扩增、限制性内切酶HaeⅢ消化进行点突变筛选。结果：发现9例患者存在线粒体DNA ND1基因3394位点T→C突变（4．3％），非糖尿病者中仅有1例突变（0．6％），两组比较差异有显著性（P＜0．05）。结论：线粒体DNA ND1基因中3394位点T→C突变可能与我国老年人2型糖尿病的发病有关。     

175例2型糖尿病患者线粒体基因变异分析

本文采用PCR-RFLP及DNA测序方法对湖北省汉族人群无血缘关系的175例2型糖尿病患者及200例正常对照个体的线粒体DNA进行突变分析。两组间仅3394T→C突变发生率的差异有统计学意义。推测该位点变异与汉族人群中的线粒体糖尿病的发生发展有关。     

2型糖尿病中线粒体DNA的3316G→A和3394T→C点突变

目的　了解天津地区线粒体DNA点突变 (3 2 43A→G、3 3 16G→A、3 3 94T→C和 3 42 6A→G)与 2型糖尿病的关系。方法　对无血缘关系的 478例 2型糖尿病患者进行研究 ,同时选择 43 0例无糖尿病家族史的糖耐量正常者作为对照 ,用PCR RFLP筛选点突变。结果　 2型糖尿病组 3 3 16点突变发生率为2 .72 % (13 / 478) ,3 3 94点突变发生率为 2 .5 1% (12 / 478) ;两种点突变在对照组发生率分别为 0和 0 .47%(2 / 43 0 ) ,两组比较差异均有显著性 (P <0 .0 1或P <0 .0 5 )。 2型糖尿病组 3 42 6点突变发生率为 0 .42 %(2 / 478) ;对照组未见该突变 ,两组间差异无显著性。两组中皆未发现 3 2 43A→G突变。结论　线粒体DNA 3 3 16G→A和 3 3 94T→C突变与天津地区人群糖尿病的发病有关。     

母系遗传糖尿病线粒体基因突变的观察

采用PCR-RFLP、DNA直接测序技术对14个有明确母系遗传史的糖尿病家系进行线粒体基因筛查。结果14例先证者及对照组均未检出A3243G等3个线粒体基因突变位点。家系成员发现携带G3316A突变，T3394C突变，三例均为健康携带者。结论G3316A突变、T3394C突变不是糖尿病的独立致病因素。     

2型糖尿病相关线粒体ND1基因的荟萃分析

目的利用荟萃分析评价线粒体NDI基因点突变与2型糖尿病发病的相关性。方法通过文献检索收集1999年1月至2008年9月在中英文公共数据库检索或已经发表的线粒体NDl基因点突变与2型糖尿病相关的病例对照研究。按照本研究纳入和排除标准,筛选线粒体NDl基因G3316A、T3394C 2个点突变作为研究对象。应用STATA 9.0 SE软件对各研究进行综合分析。结果在病例对照研究中,线粒体G3316A、T3394C相对危险度合并OR值和95%CI分别为:2.70(1.39～5.24)、3.44(1.41～8.40)。结论线粒体G3316A、T3394C点突变可能与中国人2型糖尿病遗传易感性相关。     

线粒体DNA3161-3610片断基因突变与糖尿病的关系

104例糖尿病（DM）患者和50名正常无DM家族史对照者的基因测序研究显示，线粒体DNA3316G→A伴随3290 T→C、3421G→A点突变；3497C→T和3571C→T同时基因突变可能与DM发生有关。     

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.