• 【田纳西州东部怀孕少女的生殖道沙眼衣原体感染:一项为期7年的病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1016/s1083-3188(97)70060-3 复制DOI
    作者列表:Chokephaibulkit K,Patamasucon P,List M,Moore B,Rodriguez H
    BACKGROUND & AIMS: STUDY OBJECTIVE:To examine the prevalence, symptomatology, risk factors, and other infections associated with urogenital chlamydial infection in pregnant teenagers. DESIGN:Retrospective case-control study by medical record review. SETTING:Prenatal care clinic for adolescents at University of Tennessee Medical Center, Knoxville, Tennessee. PARTICIPANTS:Pregnant adolescents younger than 19 years of age who were diagnosed with chlamydial infection on the first prenatal visit from 1988 to 1994 were studied. Pregnant adolescents of similar age and socioeconomic background who came in the same day for the first prenatal visit, but were not infected, made up the control group. INTERVENTION:Routine prenatal questionnaires regarding personal and medical histories, and routine prenatal screening, including pelvic examination with Papanicolaou (PAP) smear and laboratory investigations for common genital infections and sexual transmitted disease (STDs), were obtained. MAIN OUTCOME MEASURES:Analyzed the prevalence of chlamydial infection and compared the infected group to the control group with regard to race, behavioral factors, symptoms, prenatal screening results, other concurrent genital infections, and histories of STDs. RESULTS:Of a total population of 596 pregnant teenagers, 67 (11.24%) were infected with Chlamydia trachomatis. In multivariate analysis, black race (odds ratio [OR] = 4.01; 95% confidence interval [CI] = 1.74-9.23; p = 0.001) and greater gestational age at first prenatal visit (OR = 1.11; 95% CI = 1.04-1.18; p = 0.001) were independently associated with chlamydial infection. Age, marital status, number of pregnancies, smoking, alcohol abuse, drug abuse, age at first intercourse, and multiple sex partners were not associated with the infection. Likewise, the symptom of vaginal discharge (a complaint of > 70% in each group), other genital co-infections (found > 50% in each group, mainly candidiasis and bacterial vaginosis), abnormal PAP smears (found > 60% in each group) and histories of STDs or previous chlamydial infection were not significantly different between case and control groups. Human papillomavirus infection, trichomonal infection, and dysplasia or atypia were found more often in patients infected with chlamydia, but were not statistically significant. CONCLUSION:Pregnant adolescents in east Tennessee were at risk for chlamydial infection as well as for other genital infections and abnormal PAP smears. Routine prenatal chlamydial screening is warranted because of a lack of specific symptoms.
    背景与目标: 目的:研究孕妇青少年泌尿生殖道衣原体感染的患病率,症状,危险因素和其他感染情况。
    设计:回顾性病例对照研究,病历审查。
    地点:田纳西州诺克斯维尔市田纳西大学医学中心的青少年产前保健诊所。
    研究对象:1988年至1994年第一次产前检查时被诊断患有衣原体感染的19岁以下的青少年。年龄相同,社会经济背景相似的怀孕青少年在同一天进行第一次产前检查,但未感染,组成了对照组。
    干预措施:获得有关个人和医学史的常规产前问卷,以及常规的产前筛查,包括用帕潘尼古拉(PAP)涂片进行盆腔检查以及常见生殖器感染和性传播疾病(STD)的实验室检查。
    主要观察指标:分析衣原体感染的发生率,并比较种族,行为因素,症状,产前筛查结果,其他并发生殖器感染和性病史,比较感染者与对照组。
    结果:在596名怀孕的青少年总数中,有67名(11.24%)感染了沙眼衣原体。在多变量分析中,黑人种族(赔率[OR] = 4.01; 95%置信区间[CI] = 1.74-9.23; p = 0.001)和第一次产前检查时的胎龄较高(OR = 1.11; 95%CI = 1.04- 1.18; p = 0.001)与衣原体感染独立相关。年龄,婚姻状况,怀孕次数,吸烟,酗酒,药物滥用,初次性交年龄和多性伴侣均与感染无关。同样,白带的症状(每组的投诉> 70%),其他生殖器合并感染(每组的发现> 50%,主要是念珠菌病和细菌性阴道病),PAP涂片异常(每发的发现> 60%)病例组和对照组之间的性病史或以前的衣原体感染史无显着差异。感染衣原体的患者更常发现人乳头瘤病毒感染,滴虫感染和异型增生或异型性,但无统计学意义。
    结论:田纳西州东部的怀孕青少年有衣原体感染以及其他生殖器感染和PAP涂片异常的危险。由于缺乏特定症状,需要常规的产前衣原体筛查。
  • 【意大利北部某地区的综合废物管理:堆肥的生产和使用,以及堆肥,土壤和农作物的分析控制。】 复制标题 收藏 收藏
    DOI:10.1080/03601230600857031 复制DOI
    作者列表:Guerini G,Maffeis P,Allievi L,Gigliotti C
    BACKGROUND & AIMS: :Agricultural soils of two Italian maize farms were treated for five years with an industrially produced high-quality compost. Cattle manure and the usual mineral fertilizer were used for comparison purposes. The effects of the organic and mineral fertilizer treatments were studied by analyzing the compost and manure, cultured soils, and harvested material. The grain yield was also determined. Organic fertilization improved soil pH, CEC, content of organic matter and NPK. Soil respiration and N mineralization were found to be higher than in the purely mineral-treated soil. Plant K take-up was improved, whereas grain yield was not affected. It was confirmed that organic fertilization, particularly compost use, maintained and increased soil fertility. The study demonstrated the feasibility of using in loco analytical facilities to follow the entire recycling process-from waste to compost production-and the use of the final product in the field.
    背景与目标: :意大利的两个玉米农场的农业土壤用工业生产的高质量堆肥处理了五年。为了比较,使用了牛粪和通常的矿物肥料。通过分析堆肥和肥料,耕种的土壤和收获的物料,研究了有机肥料和矿物肥料的处理效果。还确定了谷物产量。有机肥改善了土壤的pH,CEC,有机质含量和NPK。发现土壤呼吸和氮矿化比纯矿物处理过的土壤要高。钾素吸收量得到改善,而谷物单产却没有受到影响。可以肯定的是,有机肥,特别是堆肥的使用,保持并增加了土壤肥力。该研究证明了在机车分析设施中使用该方法以跟踪整个回收过程的可行性(从废物到堆肥的生产)以及最终产品在野外的使用。
  • 【巴巴多斯黑人中严重的原发性HIV-1感染。】 复制标题 收藏 收藏
    DOI:10.1258/0956462971920325 复制DOI
    作者列表:Hudson CP,Levett PN,Edwards CN,Moosai R,Roach TC
    BACKGROUND & AIMS: :Descriptions of primary HIV-1 infection have so far been based on Caucasians living in industrialized nations. Due to studies of leptospirosis in the predominantly black population of Barbados, serum was available for patients admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By searching the medical records of 510 adult patients with known HIV-1 infection we identified 10 patients who had stored serum from an admission for an acute febrile illness that predated or coincided with their first HIV-1-positive test. Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in the 10th patient. The clinical features of these 10 patients were in keeping with previous descriptions of primary HIV-1 infection but differed from leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. The findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established. :A retrospective review was conducted of the medical records of 510 HIV-1-positive adult patients who had attended the Queen Elizabeth Hospital (QEH) to determine whether any had been admitted for an illness compatible with a diagnosis of primary HIV-1 infection. A serum bank, created from patients who had been admitted with acute febrile illnesses and investigated for leptospirosis, provided serological evidence for primary HIV-1 infection in 10 patients. Serological testing of the serum samples confirmed primary HIV-1 infection in nine patients and was suggestive in the tenth. The clinical features of the 10 patients fit the earlier descriptions of primary HIV-1 infection, but differed from the leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. These findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established.
    背景与目标: :到目前为止,主要针对HIV-1感染的描述都是基于生活在工业化国家中的高加索人。由于对巴巴多斯主要是黑人人群的钩端螺旋体病进行了研究,因此伊丽莎白女王医院(QEH)接受了急性发热性疾病的患者可获得血清。通过搜索510例已知HIV-1感染的成年患者的病历,我们确定了10例在首次发热HIV-1阳性测试之前或与其同时发生的急性发热疾病患者入院时就储存了血清的患者。血清学检查证实了9例原发性HIV-1感染,并提示第10例患者。这10例患者的临床特征与原发性HIV-1感染的先前描述相符,但与QEH所见的钩端螺旋体病病例有所不同。一名患者在血清转化疾病中死亡,另一名患者在血清转化后3个月死亡。研究结果表明,严重的原发性HIV-1感染可能是相对罕见的事件,该病可能被误诊,只有在AIDS流行之前,病例才可能发生。
    :回顾性分析了510例曾在伊丽莎白女王医院(QEH)住院的HIV-1阳性成年患者的病历,以确定是否有人因与原发性HIV-1感染诊断相符的疾病而入院。由被接纳患有急性发热性疾病的患者创建的血清库,并研究了钩端螺旋体病,为10例患者的原发性HIV-1感染提供了血清学证据。血清样本的血清学检测证实了9名患者的原发性HIV-1感染,而第十名患者则具有启发性。这10例患者的临床特征符合原发性HIV-1感染的早期描述,但与QEH所见的钩端螺旋体病病例有所不同。一名患者在血清转化疾病中死亡,另一名患者在血清转化后3个月死亡。这些发现表明,严重的原发性HIV-1感染可能是相对罕见的事件,可能会误诊该病,并且直到艾滋病流行才可能发生。
  • 【扎西他滨。在管理HIV感染方面其药效学和药代动力学特性以及临床功效的更新。】 复制标题 收藏 收藏
    DOI:10.2165/00003495-199753060-00009 复制DOI
    作者列表:Adkins JC,Peters DH,Faulds D
    BACKGROUND & AIMS: :Zalcitabine is a dideoxynucleoside antiretroviral agent that is phosphorylated to the active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) within both uninfected and HIV-infected cells. At therapeutic concentrations, ddCTP inhibits HIV replication by inhibiting the enzyme reverse transcriptase and terminating elongation of the proviral DNA chain. The results of 3 large pivotal trials comparing zidovudine monotherapy with combination therapy have now clearly established that zalcitabine plus zidovudine combination with an improvement in viral load and CD4+ cell count compared with zidovudine monotherapy. More recently, clinical end-point and surrogate marker data have established the efficacy of zalcitabine in combination with the protease inhibitor saquinavir in zidovudine-experienced patients. Other studies have demonstrated the utility of zalcitabine in combination with ritonavir and the nucleoside analogue lamivudine. Importantly, early use of zalcitabine in the treatment sequence does not appear to limit the therapeutic efficacy of subsequent therapy with other nucleoside analogues such as lamivudine. Peripheral neuropathy is the most frequent dose-limiting adverse effect associated with zalcitabine therapy and is generally reversible on discontinuation of treatment. Stomatitis and mouth ulcers may occur frequently with zalcitabine therapy but tend to resolve with continuing treatment. Haematological toxicity, which is a common adverse effect associated with zidovudine, is reported infrequently with zalcitabine. Overall, combination therapy with zalcitabine plus zidovudine or saquinavir has been shown to have a tolerability profile comparable to that of either agent alone, although treatment with zidovudine plus zalcitabine was associated with a significant increase in the incidence of haematological toxicity compared with zidovudine monotherapy in one study. Therefore, current data suggest that zalcitabine is a useful antiretroviral agent for inclusion as a component of initial double combination therapy with zidovudine or as part of triple combination therapy including zidovudine plus a protease inhibitor in the management of patients with HIV infection.
    背景与目标: 扎西他滨是一种双脱氧核苷抗逆转录病毒药,在未感染和感染HIV的细胞中均被磷酸化为活性代谢物2',3'-二脱氧胞苷5'-三磷酸(ddCTP)。在治疗浓度下,ddCTP通过抑制酶逆转录酶并终止原病毒DNA链的延伸来抑制HIV复制。齐多夫定单一疗法与联合疗法比较的3个大型关键试验的结果现已清楚地确定,与齐多夫定单一疗法相比,齐西他滨加齐多夫定联合疗法可改善病毒载量和CD4细胞计数。最近,临床终点和替代标记数据已经确定了扎西他滨与蛋白酶抑制剂沙奎那韦联合在齐多夫定患者中的疗效。其他研究表明扎西他滨与利托那韦和核苷类似物拉米夫定联合使用。重要的是,在治疗顺序中早期使用扎西他滨似乎没有限制后续用其他核苷类似物如拉米夫定进行治疗的疗效。周围神经病变是与扎西他滨治疗相关的最常见的剂量限制性不良反应,通常在停药后可逆。扎西他滨治疗可能会经常发生口腔炎和口腔溃疡,但继续治疗后往往会缓解。扎西他滨很少报道血液毒性,这是与齐多夫定有关的常见不良反应。总的来说,与齐多夫定单一疗法相比,齐多夫定+齐多夫定或沙奎那韦联合治疗的耐受性与单独使用任一种药物相当,尽管与齐多夫定单一疗法相比,齐多夫定+齐西他滨治疗的血液学毒性发生率显着增加。学习。因此,目前的数据表明,扎西他滨是一种有用的抗逆转录病毒药物,可作为包含齐多夫定的初始双重联合疗法的组成部分或包含齐多夫定加蛋白酶抑制剂在内的三重联合疗法的一部分用于治疗HIV感染患者。
  • 【在正常和脱水大鼠中,μ阿片受体是否参与了内皮素-1从垂体的释放控制?】 复制标题 收藏 收藏
    DOI:10.1016/s0167-0115(97)02134-4 复制DOI
    作者列表:Płonowski A,Szymańska-Debińska T,Radzikowska M,Baranowska B,Woźniewicz B
    BACKGROUND & AIMS: UNLABELLED:The objective of the present study was to investigate whether the endogenous opioids are involved in the control of endothelin-1 release from the pituitary gland. To test this hypothesis we have measured the peripheral plasma concentration of ET-1 as well as the content of immunoreactive ET-1 (irET-1) in the pituitary in response to opioid receptors blockade in euhydrated and 24 h water-deprived Wistar-Kyoto rats. Placebo or naltrexone (50 micrograms/kg body wt.) were given i.v. in both groups. Trunk blood was collected to determine hematocrit, plasma sodium and ET-1 levels (RIA). Immunostaining of ET-1 in the whole pituitary glands was performed by colloidal gold labeling. The quantitative analysis of irET-1 was carried out under a light microscope using a computerized image analyzer (MultiScan). RESULTS:(1) Twenty-four-hour dehydration resulted in marked increase of peripheral concentration of ET-1. Naltrexone injection induced a significant elevation of ET-1 plasma concentration in both, dehydrated and control animals. (2) The content of irET-1 in anterior and intermediate lobes of the pituitary in dehydrated rats was markedly higher than in control group. (3) Naltrexone injection caused a rapid and significant reduction irET-1 within the anterior, intermediate and posterior lobes in dehydrated and control animals. CONCLUSIONS:(1) An elevation of irET-1 in the pituitary gland and peripheral circulation in dehydrated animals may play a role in maintaining of water-electrolyte balance. (2) The mu-opioid system appears to control the ET-1 release from the pituitary in normal and dehydrated animals.
    背景与目标: 未标记:本研究的目的是调查内源性阿片类药物是否参与垂体中内皮素-1的释放。为了验证这一假设,我们测量了在无水和缺水24小时的Wistar-Kyoto中阿片受体阻滞后,垂体中ET-1的血浆浓度以及垂体中免疫反应性ET-1(irET-1)的含量。大鼠。静脉注射安慰剂或纳曲酮(50微克/千克体重)。在两组中。收集躯干血液以确定血细胞比容,血浆钠和ET-1水平(RIA)。 ET-1在整个垂体中的免疫染色是通过胶体金标记进行的。使用计算机图像分析仪(MultiScan)在光学显微镜下对irET-1进行定量分析。
    结果:(1)脱水24小时导致ET-1的外周血浓度明显升高。纳曲酮注射液在脱水和对照动物中均引起ET-1血浆浓度的显着升高。 (2)脱水大鼠垂体前叶和中间叶中irET-1的含量明显高于对照组。 (3)纳曲酮注射液导致脱水和对照动物的前叶,中叶和后叶内irET-1迅速大量降低。
    结论:(1)脱水动物垂体中irET-1的升高和外周循环可能在维持水电解质平衡中起着重要作用。 (2)在正常和脱水动物中,μ阿片样物质系统似乎可以控制ET-1从垂体的释放。
  • 【线粒体相关的己糖激酶在本氏烟草中对程序性细胞死亡的控制中发挥作用。】 复制标题 收藏 收藏
    DOI:10.1105/tpc.106.041509 复制DOI
    作者列表:Kim M,Lim JH,Ahn CS,Park K,Kim GT,Kim WT,Pai HS
    BACKGROUND & AIMS: :Recent findings suggest a pivotal role for mitochondria-associated hexokinase in the regulation of apoptosis in animal cells. In this study, virus-induced gene silencing (VIGS) of a hexokinase-encoding Hxk1 caused necrotic lesions on leaves, abnormal leaf morphology, and retarded plant growth in Nicotiana benthamiana. Hxk1 was associated with the mitochondria, and this association required the N-terminal membrane anchor. VIGS of Hxk1 reduced the cellular glucose-phosphorylating activity to approximately 31% of control levels without changing the fructose-phosphorylating activity and did not alter hexose phosphate content severely. The affected cells showed programmed cell death (PCD) morphological markers, including nuclear condensation and DNA fragmentation. Similar to animal cell apoptosis, cytochrome c was released into the cytosol and caspase-9- and caspase-3-like proteolytic activities were strongly induced. Furthermore, based on flow cytometry, Arabidopsis thaliana plants overexpressing Arabidopsis HXK1 and HXK2, both of which are predominantly associated with mitochondria, exhibited enhanced resistance to H(2)O(2)- and alpha-picolinic acid-induced PCD. Finally, the addition of recombinant Hxk1 to mitochondria-enriched fractions prevented H(2)O(2)/clotrimazole-induced cytochrome c release and loss of mitochondrial membrane potential. Together, these results show that hexokinase critically regulates the execution of PCD in plant cells, suggesting a link between glucose metabolism and apoptosis.
    背景与目标: :最近的发现表明线粒体相关的己糖激酶在调节动物细胞凋亡中起着关键作用。在这项研究中,编码己糖激酶的Hxk1的病毒诱导的基因沉默(VIGS)导致了本特烟草的叶片坏死性病变,异常的叶片形态并延缓了植物的生长。 Hxk1与线粒体相关联,这种关联需要N端膜锚。 Hxk1的VIGS可以将细胞的葡萄糖磷酸化活性降低至对照水平的约31%,而不会改变果糖磷酸化活性,并且不会严重改变磷酸己糖的含量。受影响的细胞显示出程序性细胞死亡(PCD)形态标志物,包括核浓缩和DNA片段化。与动物细胞凋亡相似,细胞色素c被释放到细胞质中,并强烈诱导了caspase-9-和caspase-3-like蛋白水解活性。此外,基于流式细胞仪,拟南芥植物过表达拟南芥HXK1和HXK2,这两个主要与线粒体相关联,表现出增强的抗H(2)O(2)-和α-吡啶甲酸诱导的PCD。最后,向线粒体富集的部分中添加重组Hxk1可以防止H(2)O(2)/克霉唑诱导的细胞色素c释放和线粒体膜电位的损失。总之,这些结果表明,己糖激酶严格调节植物细胞中PCD的执行,表明葡萄糖代谢与细胞凋亡之间存在联系。
  • 【血管紧张素转换酶抑制剂和主动脉破裂:基于人群的病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1016/S0140-6736(06)69250-7 复制DOI
    作者列表:Hackam DG,Thiruchelvam D,Redelmeier DA
    BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.
    背景与目标: 背景:血管紧张素转换酶(ACE)抑制剂可防止动物主动脉瘤的扩张和破裂。我们调查了腹主动脉瘤患者中ACE抑制剂与破裂之间的关系。
    方法:我们在加拿大安大略省的相关行政数据库中进行了基于人群的病例对照研究。该样本包括1992年4月1日至2002年4月1日之间入院的65岁以上的连续患者(n = 15,326),其主要诊断为腹主动脉瘤破裂或完整。
    结果:与未接受ACE抑制剂的患者相比,入院前接受ACE抑制剂的患者出现动脉瘤破裂的可能性显着降低(优势比[OR] 0.82,95%CI 0.74-0.90)。调整人口统计学特征,破裂危险因素,合并症,ACEI禁忌症,卫生保健措施和动脉瘤筛查得出相似的结果(0.83,0.73-0.95)。在高破裂风险的亚组(包括75岁以上和有高血压病史的患者)中发现了一致的发现。相反,对于β受体阻滞剂(1.02,0.89-1.17),钙通道阻滞剂(1.01,0.89-1.14),α受体阻滞剂(1.15,0.86-1.54),血管紧张素受体阻滞剂(1.24,0.71-2.18)未观察到这种保护性关联。 ,或噻嗪类利尿剂(0.91、0.78-1.07)。
    解释:与其他降压药不同,ACE抑制剂与降低腹主动脉瘤破裂的风险有关。 ACE抑制剂预防主动脉破裂的随机试验可能是必要的。
  • 【新型抗CD4单克隆抗体将人免疫缺陷病毒感染和CD4细胞融合与病毒结合分离开来。】 复制标题 收藏 收藏
    DOI:10.1084/jem.172.4.1233 复制DOI
    作者列表:Healey D,Dianda L,Moore JP,McDougal JS,Moore MJ,Estess P,Buck D,Kwong PD,Beverley PC,Sattentau QJ
    BACKGROUND & AIMS: :Human immunodeficiency virus (HIV) binds to cells via an interaction between CD4 and the virus envelope glycoprotein, gp120. Previous studies have localized the high affinity binding site for gp120 to the first domain of CD4, and monoclonal antibodies (mAbs) reactive with this region compete with gp120 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gp120 to CD4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of CD4 that inhibit steps subsequent to virus binding critical for HIV infectivity and cell fusion. Binding of recombinant gp120 or virus to CD4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of HIV isolates are blocked. These findings demonstrate that in addition to virus binding, CD4 may have an active role in membrane fusion.
    背景与目标: 人类免疫缺陷病毒(HIV)通过CD4和病毒包膜糖蛋白gp120之间的相互作用与细胞结合。先前的研究已经将gp120的高亲和力结合位点定位在CD4的第一个域,并且与该区域反应的单克隆抗体(mAb)与gp120结合竞争,从而阻断了病毒的感染性和合胞体的形成。尽管对gp120与CD4的结合有了详细的了解,但对导致膜融合和病毒进入的后续事件知之甚少。我们描述了与CD4的第三个域具有反应性的两个新的单克隆抗体,可抑制继病毒结合后对HIV感染性和细胞融合至关重要的步骤。重组gp120或病毒与CD4的结合不受这些抗体的抑制,而许多HIV分离株的感染和合胞体形成却被阻止。这些发现表明,除病毒结合外,CD4可能在膜融合中发挥积极作用。
  • 【雌二醇调节反应的遗传控制的证据。对正常和病理性激素依赖性表型变异的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Griffith JS,Jensen SM,Lunceford JK,Kahn MW,Zheng Y,Falase EA,Lyttle CR,Teuscher C
    BACKGROUND & AIMS: :The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.
    背景与目标: :卵巢类固醇激素雌激素(E2)在体内引起多种全身和子宫促反应。例如,将E2给予去卵巢(Ovx)和性不成熟的啮齿动物会导致子宫特异性炎症浸润。在这项研究中,我们量化了从成年Ovx对照和经E2处理的C57BL / 6J,C3H / HeJ和(C57BL / 6J x C3H / HeJ)(B6C3)获得的子宫中嗜酸性粒细胞和BM8,Ia和CD4细胞的数量F1杂种小鼠。在E2处理后,所有三个菌株均表现出子宫嗜酸性粒细胞和BM8巨噬细胞数量的显着增加。但是,与C3H / HeJ相比,C57BL / 6J和B6C3 F1杂种小鼠反应的浸润性嗜酸性粒细胞和巨噬细胞数量更多。对Ia和CD4细胞的类似分析显示,E2处理在所有三个菌株中均下调或不影响此类细胞的数量。使用(C57BL / 6J x C3H / HeJ)x C3H / HeJ回交群体定位的基因组排斥定位于Est1,Est1是控制E2处理后浸润子宫的嗜酸性粒细胞数量的主要基因座,并指向染色体4。检测到10号和16号染色体上的基因并提供了基因座相互作用的证据。我们的结果最终证明,E2调节/依赖性反应可以通过基因控制,这表明在E2的正常和病理效应中观察到的表型变异可能部分归因于遗传成分。
  • 【ColE1质粒复制的控制。 Rom蛋白与RNA I和RNA II形成的不稳定复合物的相互作用。】 复制标题 收藏 收藏
    DOI:10.1016/0022-2836(90)90231-a 复制DOI
    作者列表:Tomizawa J
    BACKGROUND & AIMS: :A transcript (RNA I) from ColE1 inhibits initiation of replication of the plasmid DNA by binding to the precursor of the primer RNA (RNA II). The ability of RNA I to inhibit replication is altered by the presence of a plasmid-specified small protein, Rom. In vitro, RNA I binds to RNA II to form a very unstable complex, C*. Binding of a single molecule of Rom converts C* to a more stable complex, Cm*. Each of these complexes, C* or Cm*, transforms to a more stable complex, C** or Cm**, respectively. While formation of complex C* or Cm* is inferred from the inhibition of binding caused by a second RNA I species, that of complex C** or Cm** is detected by alteration of RNase sensitivity. Complex C* converts to complex Cm* very rapidly upon addition of Rom to the medium and complex Cm* converts to complex C* very rapidly by removal of Rom from the medium. On the other hand, complexes C** and Cm** do not rapidly interconvert, but can eventually transform to the same stable final product. Thus, Rom affects binding of RNA I to RNA II through conversion of a very unstable early intermediate to a more stable complex, creating a second pathway for their stable binding.
    背景与目标: :来自ColE1的转录本(RNA I)通过与引物RNA(RNA II)的前体结合,抑制质粒DNA复制的开始。质粒指定的小蛋白质Rom的存在改变了RNA I抑制复制的能力。在体外,RNA I与RNA II结合形成非常不稳定的复合物C *。 Rom单个分子的结合将C *转化为更稳定的复合物Cm *。这些复合物C *或Cm *分别转换为更稳定的复合物C **或Cm **。虽然可以通过抑制第二种RNA I物种的结合来推断复合物C *或Cm *的形成,但可以通过改变RNA酶的敏感性来检测复合物C **或Cm **的形成。在向培养基中添加Rom时,复合物C *非常迅速地转化为复合物Cm *,并且通过从培养基中去除Rom,复合物Cm *非常迅速地转化为复合物C *。另一方面,复合物C **和Cm **不会快速相互转换,但最终可以转换为相同的稳定最终产物。因此,Rom通过将非常不稳定的早期中间体转化为更稳定的复合物,从而影响RNA I与RNA II的结合,从而为它们的稳定结合创造了第二条途径。
  • 【保护患者和环境-医院感染控制的新方面和新挑战。】 复制标题 收藏 收藏
    DOI:10.1016/s0195-6701(97)90086-4 复制DOI
    作者列表:Daschner FD,Dettenkofer M
    BACKGROUND & AIMS: Environmental pollution has become a major concern for the future of life on our planet; medical care, especially in hospitals, contributes significantly to this pollution. The increasing usage of highly-developed medical devices, drugs and disposable products are a drain on natural resources as well as financial ones. In this situation, it is a major task for hospital epidemiologists to maintain high standards of hygiene while reducing environmental pollution, reducing consumption of limited natural resources, and minimizing costs. The reduction of hospital waste, the control of polluting and toxic emissions, the avoidance of unnecessary disinfection procedures and disposables, the implementation of energy and water saving technologies are practicable measures in hospital ecology. To realize a sustainable development within hospitals, it is necessary that the need to maintain a balance between effective infection control and a good ecological environment is recognized and supported by health-care workers and the hospital management.

    背景与目标: 环境污染已成为我们星球上未来生活的主要关注点;医疗服务,尤其是医院的医疗服务,是造成这种污染的重要原因。高度发达的医疗设备,药物和一次性产品的使用日益增加,既浪费了自然资源,也浪费了金融资源。在这种情况下,医院流行病学家的主要任务是保持较高的卫生标准,同时减少环境污染,减少有限自然资源的消耗并最大程度地降低成本。减少医院浪费,控制污染和有毒物质排放,避免不必要的消毒程序和一次性用品,实施节能节水技术是医院生态学中的切实可行的措施。为了实现医院内部的可持续发展,必须在卫生保健工作者和医院管理人员的认识和支持下,在有效的感染控制和良好的生态环境之间保持平衡。

  • 【病毒感染期间增强的IL-7信号传导可促进效应T细胞的更大扩增,但不会增强记忆力。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.177.7.4458 复制DOI
    作者列表:Sun JC,Lehar SM,Bevan MJ
    BACKGROUND & AIMS: :IL-7 signals are crucial for the survival of naive and memory T cells, and the IL-7R is expressed on the surface of these cells. Following viral infection, the IL-7R is expressed on only a subset of effector CD8 T cells, and has been demonstrated to be important for the survival of these memory precursors. IL-7 message levels remain relatively constant during the T cell response to lymphocytic choriomeningitis virus, but a short-lived burst of GM-CSF is observed soon after infection. Retroviral expression of a chimeric GM-CSF/IL-7R, in which binding of GM-CSF by T cells leads to IL-7 signaling, allows for the delivery of an IL-7 signal in all effector T cells expressing the receptor. In mice infected with lymphocytic choriomeningitis virus, CD8 and CD4 T cells transduced with this chimeric receptor underwent an enhanced proliferative response compared with untransduced populations in the same host. Similarly, TCR transgenic CD8 cells expressing the chimeric receptor produced higher effector numbers during the peak of the T cell response to infection. Surprisingly, the enhanced proliferation did not lead to higher memory numbers, as the subsequent contraction phase was more pronounced in the transduced cell populations. These findings demonstrate that artificial IL-7 signaling during an infection leads to significantly increased Ag-specific effector T cell numbers, but does not result in increased numbers of memory progeny. The extent of contraction may be dictated by intrinsic factors related to the number of prior cell divisions.
    背景与目标: :IL-7信号对于幼稚和记忆性T细胞的存活至关重要,而IL-7R在这些细胞的表面表达。病毒感染后,IL-7R仅在效应CD8 T细胞的一部分上表达,并已证明对这些记忆前体的存活很重要。在对淋巴细胞性脉络膜脑膜炎病毒的T细胞反应过程中,IL-7信息水平保持相对恒定,但是感染后不久就观察到了短暂的GM-CSF爆发。嵌合GM-CSF / IL-7R的逆转录病毒表达(其中T细胞与GM-CSF结合导致IL-7信号传导)允许在表达该受体的所有效应T细胞中传递IL-7信号。在感染了淋巴细胞性脉络膜脑膜炎病毒的小鼠中,用该嵌合受体转导的CD8和CD4 T细胞与同一宿主中未转导的种群相比,具有增强的增殖反应。同样,表达嵌合受体的TCR转基因CD8细胞在感染的T细胞反应高峰期间产生更高的效应子数量。出人意料的是,增强的增殖并未导致更高的记忆数,因为随后的收缩期在转导的细胞群中更为明显。这些发现表明,感染期间的人工IL-7信号转导会导致Ag特异性效应T细胞数量显着增加,但不会导致记忆后代数量增加。收缩的程度可以由与先前细胞分裂数有关的内在因素决定。
  • 【皮肤生物学中的神经肽控制机制:生理和临床意义。】 复制标题 收藏 收藏
    DOI:10.1038/sj.jid.5700429 复制DOI
    作者列表:Peters EM,Ericson ME,Hosoi J,Seiffert K,Hordinsky MK,Ansel JC,Paus R,Scholzen TE
    BACKGROUND & AIMS: :The skin as a barrier and immune organ is exposed to omnipresent environmental challenges such as irradiation or chemical and biologic hazards. Neuropeptides released from cutaneous nerves or skin and immune cells in response to noxious stimuli are mandatory for a fine-tuned regulation of cutaneous immune responses and tissue maintenance and repair. They initialize host immune responses, but are equally important for counter regulation of proinflammatory events. Interaction of the nervous and immune systems occurs both locally - at the level of neurogenic inflammation and immunocyte activation - and centrally - by controlling inflammatory pathways such as mononuclear activation or lymphocyte cytokine secretion. Consequently, a deregulated neurogenic immune control results in disease manifestation and frequently accompanies chronic development of cutaneous disorders. The current understanding, therapeutic options, and open questions of the role that neuropeptides such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide, neuropeptide Y, or others play in these events are discussed. Progress in this field will likely result in novel therapies for the management of diseases characterized by deregulated inflammation, tissue remodeling, angiogenesis, and neoplasm.
    背景与目标: :作为屏障和免疫器官的皮肤暴露于无处不在的环境挑战中,例如辐射或化学和生物危害。皮肤神经或皮肤释放的神经肽以及对有害刺激作出反应的免疫细胞对于皮肤免疫反应以及组织维持和修复的微调调节是必不可少的。它们可以启动宿主的免疫反应,但对于调节促炎事件也同样重要。通过控制诸如单核激活或淋巴细胞细胞因子分泌之类的炎症途径,神经和免疫系统的相互作用既在局部发生(在神经源性炎症和免疫细胞激活的水平),也发生在中央。因此,神经源性免疫控制失调导致疾病表现,并经常伴随皮肤疾病的慢性发展。讨论了有关神经肽(例如P物质,降钙素基因相关肽,血管活性肠肽/垂体腺苷酸环化酶激活多肽,神经肽Y或其他物质)在这些事件中的作用的当前理解,治疗选择和开放性问题。该领域的进展可能会导致新的疗法来治疗以炎症失调,组织重塑,血管生成和肿瘤为特征的疾病。
  • 【肝移植受者巨细胞病毒感染危险因素的多因素分析。】 复制标题 收藏 收藏
    DOI:10.1016/0016-5085(90)90352-2 复制DOI
    作者列表:Gorensek MJ,Carey WD,Vogt D,Goormastic M
    BACKGROUND & AIMS: :Thirty-three consecutive liver-transplant recipients were prospectively studied over a 37-mo period for evidence of cytomegalovirus infection. Sixteen (48%) episodes of cytomegalovirus infection were identified; 9 were primary infections and 7 were recurrent infections. Beginning with patient 8, gamma-globulin prophylaxis was routinely administered to most patients. Twelve potential risk factors for cytomegalovirus infection were evaluated and included pretransplant cytomegalovirus serological status of donor and recipient; recipient's age, sex, race, and liver disease; number and type of blood products transfused; type and intensity of immunosuppression; and occurrence of rejection. The Cox proportional hazards model identified positive donor cytomegalovirus serology as the single most important risk factor for subsequent development of cytomegalovirus infection, regardless of recipient cytomegalovirus serological status. In addition, use of gamma-globulin prophylaxis seemed to be protective against the occurrence of disseminated cytomegalovirus disease.
    背景与目标: :在37个月内对33例连续肝移植接受者进行了前瞻性研究,以发现巨细胞病毒感染的迹象。鉴定出十六例(48%)巨细胞病毒感染; 9例是原发性感染,7例是复发性感染。从患者8开始,常规对大多数患者进行了γ-球蛋白的预防。评价了十二种巨细胞病毒感染的潜在危险因素,包括供体和受体移植前巨细胞病毒的血清学状况;接受者的年龄,性别,种族和肝脏疾病;输血产品的数量和类型;免疫抑制的类型和强度;和拒绝的发生。 Cox比例风险模型将阳性供体巨细胞病毒血清学确定为随后发展成巨细胞病毒感染的唯一最重要的危险因素,而与受体巨细胞病毒血清学状况无关。另外,使用γ-球蛋白预防似乎可以预防弥漫性巨细胞病毒病的发生。
  • 【I型糖尿病易感性候选基因的分析:2q31-35号染色体上基因的病例对照和家庭关联研究。】 复制标题 收藏 收藏
    DOI:10.2337/diab.46.6.1069 复制DOI
    作者列表:Owerbach D,Naya FJ,Tsai MJ,Allander SV,Powell DR,Gabbay KH
    BACKGROUND & AIMS: Recent genome searches suggest a putative linkage of many loci to susceptibility to type I diabetes. The chromosome 2q31-35 region is reported to be linked to susceptibility to type I diabetes and is thought to contain several diabetes susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2, CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families are required to confirm and/or identify the actual susceptibility loci. We hereby report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5, which we have used along with previously known polymorphisms of HOXD8 and CTLA4 to test whether these candidate loci are the susceptibility genes on chromosome 2q31-35. Using a case-control design with a subsequent family-association approach to confirm associations, we find no evidence that these candidate genes are associated with susceptibility to type I diabetes.

    背景与目标: 最近的基因组搜索表明,许多基因位点与I型糖尿病易感性的推测联系。据报道,染色体2q31-35与I型糖尿病易感性相关,并被认为含有几个糖尿病易感性基因座。这些候选基因包括HOXD基因簇,BETA2,CTLA4,CD28,IGFBP2和IGFBP5。需要在人群和家庭中进行协会研究,以确认和/或识别实际的易感基因座。我们在此报告HOXD8,BETA2和IGFBP5的几种先前未知的DNA多态性,并将其与HOXD8和CTLA4的先前已知多态性一起用于测试这些候选基因座是否为2q31-35染色体上的易感性基因。使用病例对照设计和随后的家庭关联方法来确认关联,我们没有发现这些候选基因与I型糖尿病易感性相关的证据。

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