• 【克罗恩病中的白细胞介素12和Th1免疫应答:病原学意义和治疗意义。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i35.5606 复制DOI
    作者列表:Peluso I,Pallone F,Monteleone G
    BACKGROUND & AIMS: :Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathological characteristics. The most accredited hypothesis is that both CD and UC result from a deregulated mucosal immune response to normal constituents of the gut microflora. Evidence, however, indicates that the main pathological processes in these two diseases are distinct. In CD, the tissue-damaging inflammatory reaction is driven by activated type 1 helper T-cell (Th1), whereas a humoral response predominates in UC. Consistently, a marked accumulation of macrophages making interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC mucosa. Preliminary studies also indicate that administration of a monoclonal antibody blocking the IL-12/p40 subunit can be useful to induce and maintain clinical remission in CD patients. Notably, the recently described IL-23 shares the p40 subunit with IL-12, raising the possibility that the clinical benefit of the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23 activity. This review summarizes the current information on the expression and functional role of IL-12 and IL-12-associated signaling pathways both in patients with CD and experimental models of colitis, thus emphasizing major differences between IL-12 and IL-23 activity on the development of intestinal inflammation.
    背景与目标: :克罗恩病(CD)和溃疡性结肠炎(UC)是胃肠道的慢性炎性疾病,具有临床和病理学特征。最公认的假设是CD和UC均来自对肠道菌群正常成分的粘膜免疫反应失控。然而,证据表明这两种疾病的主要病理过程是不同的。在CD中,组织破坏性炎症反应是由激活的1型辅助性T细胞(Th1)驱动的,而体液反应在UC中占主导地位。一致地,在CD中可见大量的巨噬细胞积聚,使白介素(IL)-12(主要的Th1诱导因子)在CD中可见,而在UC粘膜中则未见。初步研究还表明,给予阻断IL-12 / p40亚基的单克隆抗体可用于诱导和维持CD患者的临床缓解。值得注意的是,最近描述的IL-23与IL-12共有p40亚基,从而增加了抗IL-12 / p40抗体在CD中的临床益处也可能是由于IL-23活性的中和所引起的可能性。这篇综述总结了关于CD患者和结肠炎实验模型中IL-12和IL-12相关信号通路的表达和功能作用的最新信息,从而强调了IL-12和IL-23活性在结肠炎患者中的主要差异。肠道炎症的发展。
  • 【在阿尔茨海默氏病中,MRI指导的SPECT测量颞叶内侧血流。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Julin P,Lindqvist J,Svensson L,Slomka P,Wahlund LO
    BACKGROUND & AIMS: UNLABELLED:In this study, we assessed the accuracy and reliability of MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's disease (AD).

    METHODS:Interactively aligned three-dimensional MP-RAGE MRI and 99mTc-HMPAO SPECT images were used for MRI-guided measurement of medial temporal lobe CBF in eight control subjects and eight patients with probable AD. Intraoperator reliability was assessed by repeated alignment and measurement by one experienced operator. Accuracy was assessed by examining two subjects with fiducial markers.

    RESULTS:The alignment error was less than 1 SPECT pixel size (3.5 mm) and the coefficient of variation in repeated measures of medial temporal-to-cerebellar CBF ratios was 3.2%. The difference in mean medial temporal-to-cerebellar CBF ratios between eight control subjects and eight AD patients was 12%. Also by using three-dimensional seed-grow defined healthy brain reference regions, there were significant differences between control subjects and AD patients in medial temporal blood flow. Furthermore, the volumes of the MRI-defined medial temporal ROIs were smaller in the AD patients. The best separation between AD patients and control subjects was achieved by combining MRI measurements of atrophy and SPECT measurements of CBF.

    CONCLUSION:These data show that the accuracy and reliability of MRI-guided SPECT measurements of medial temporal CBF clearly allow the detection of changes in AD. Also, a direct comparison of structural and functional changes is possible by this methodology, which might improve the early diagnosis of AD.

    背景与目标: UNLABELLED :在这项研究中,我们评估了MRI指导的SPECT测量中度颞叶血流在阿尔茨海默病(AD)中的准确性和可靠性。

    方法 strong>:交互式对准的三维MP-RAGE MRI和99mTc-HMPAO SPECT图像用于MRI指导的八名对照受试者和八名可能患有AD的患者的内侧颞叶CBF的测量。一位经验丰富的操作员通过反复对准和测量来评估操作员的可靠性。通过检查两个带有基准标记的受试者来评估准确性。

    结果:对准误差小于1个SPECT像素大小(3.5毫米),并且重复内侧测量的变异系数颞小脑CBF率为3.2%。八名对照受试者和八名AD患者之间的平均内侧颞小脑CBF比率的差异为12%。同样,通过使用定义的三维种子生长的健康大脑参考区域,对照受试者和AD患者之间的颞内侧血流存在显着差异。此外,在AD患者中,MRI定义的内侧颞部ROI的体积较小。通过将萎缩的MRI测量值和CBF的SPECT测量值相结合,可以使AD患者与对照组之间达到最佳分离。

    结论:这些数据表明,MRI指导的准确性和可靠性内侧颞CBF的SPECT测量清楚地允许检测AD的变化。同样,通过这种方法可以直接比较结构和功能的变化,这可能会改善AD的早期诊断。

  • 【氯氮平在帕金森氏病中治疗左旋多巴引起的精神病的回顾性研究。】 复制标题 收藏 收藏
    DOI:10.1177/089198879701000205 复制DOI
    作者列表:Widman LP,Burke WJ,Pfeiffer RF,McArthur-Campbell D
    BACKGROUND & AIMS: Levodopa-induced psychosis can complicate the treatment of Parkinson's disease (PD). In this retrospective, uncontrolled report, we describe our experience treating PD-related psychosis with clozapine, emphasizing those patients treated for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1 year. Most patients showed a rapid improvement from baseline within 1 month using the Clinical Global Impression and Global Psychosis Rating Scores. Five patients discontinued the drug due to side effects, but only two patients reported side effects after 6 months of treatment. Clozapine appears to be effective in treating PD related psychotic symptoms while not interfering with motor function.

    背景与目标: 左旋多巴引起的精神病会使帕金森氏病(PD)的治疗复杂化。在这份回顾性的,不受控制的报告中,我们描述了用氯氮平治疗PD相关性精神病的经验,强调那些接受治疗超过1年的患者。治疗了27例患者,其中14例的病程超过1年。使用临床总体印象和总体精神病评分分数,大多数患者在1个月内显示出从基线开始的快速改善。有5名患者由于副作用而停药,但只有2名患者在治疗6个月后报告了副作用。氯氮平似乎可以有效治疗PD相关的精神病症状,同时又不影响运动功能。

  • 【在其他健康的分枝杆菌病患者中发现了新的STAT1等位基因。】 复制标题 收藏 收藏
    DOI:10.1371/journal.pgen.0020131 复制DOI
    作者列表:
    BACKGROUND & AIMS: :The transcription factor signal transducer and activator of transcription-1 (STAT1) plays a key role in immunity against mycobacterial and viral infections. Here, we characterize three human STAT1 germline alleles from otherwise healthy patients with mycobacterial disease. The previously reported L706S, like the novel Q463H and E320Q alleles, are intrinsically deleterious for both interferon gamma (IFNG)-induced gamma-activating factor-mediated immunity and interferon alpha (IFNA)-induced interferon-stimulated genes factor 3-mediated immunity, as shown in STAT1-deficient cells transfected with the corresponding alleles. Their phenotypic effects are however mediated by different molecular mechanisms, L706S affecting STAT1 phosphorylation and Q463H and E320Q affecting STAT1 DNA-binding activity. Heterozygous patients display specifically impaired IFNG-induced gamma-activating factor-mediated immunity, resulting in susceptibility to mycobacteria. Indeed, IFNA-induced interferon-stimulated genes factor 3-mediated immunity is not affected, and these patients are not particularly susceptible to viral disease, unlike patients homozygous for other, equally deleterious STAT1 mutations recessive for both phenotypes. The three STAT1 alleles are therefore dominant for IFNG-mediated antimycobacterial immunity but recessive for IFNA-mediated antiviral immunity at the cellular and clinical levels. These STAT1 alleles define two forms of dominant STAT1 deficiency, depending on whether the mutations impair STAT1 phosphorylation or DNA binding.
    背景与目标: 转录因子信号转导子和转录激活因子1(STAT1)在抵抗分枝杆菌和病毒感染的免疫中起着关键作用。在这里,我们表征了来自其他健康的分枝杆菌病患者的三个人STAT1种系等位基因。像新的Q463H和E320Q等位基因一样,先前报道的L706S对干扰素γ(IFNG)诱导的γ激活因子介导的免疫和干扰素α(IFNA)诱导的干扰素刺激的基因因子3介导的免疫都具有内在的危害,如用相应等位基因转染的STAT1缺陷细胞所示。然而,它们的表型作用是由不同的分子机制介导的,L706S影响STAT1磷酸化,Q463H和E320Q影响STAT1 DNA结合活性。杂合子患者表现出特别受损的IFNG诱导的γ活化因子介导的免疫力,导致对分枝杆菌的易感性。确实,IFNA诱导的干扰素刺激基因因子3介导的免疫性没有受到影响,并且这些患者对病毒性疾病特别不敏感,这与两种表型均隐性的其他同样有害的STAT1突变的患者不同。因此,在细胞和临床水平上,这三个STAT1等位基因在IFNG介导的抗分枝杆菌免疫中占主导地位,而在IFNA介导的抗病毒免疫中却处于隐性地位。这些STAT1等位基因定义了两种主要形式的STAT1缺陷,具体取决于突变是否损害STAT1磷酸化或DNA结合。
  • 【疾病机制:2型糖尿病的肝脂肪变性-发病机理和临床意义。】 复制标题 收藏 收藏
    DOI:10.1038/ncpendmet0190 复制DOI
    作者列表:Roden M
    BACKGROUND & AIMS: :Hepatic steatosis is defined by an increased content of hepatocellular lipids (HCLs) and is frequently observed in insulin-resistant states including type 2 diabetes mellitus. A dietary excess of saturated fat contributes significantly to HCL accumulation. Elevated HCL levels mainly account for hepatic insulin resistance, which is probably mediated by partitioning of free fatty acids to the liver (fat overflow) and by an imbalance of adipocytokines (decreased adiponectin and/or increased proinflammatory cytokines). Both free fatty acids and adipocytokines activate inflammatory pathways that include protein kinase C, the transcription factor nuclear factor kappaB, and c-Jun N-terminal kinase 1 and can thereby accelerate the progression of hepatic steatosis to nonalcoholic steatohepatitis and cirrhosis. Proton magnetic resonance spectroscopy has made it possible to quantify HCL concentrations and to detect even small changes in these concentrations in clinical settings. Moderately hypocaloric, fat-reduced diets can decrease HCL levels by approximately 40-80% in parallel with loss of up to 8% of body weight. Treatment with thiazolidinediones (e.g. pioglitazone and rosiglitazone) reduces HCL levels by 30-50% by modulating insulin sensitivity and endocrine function of adipose tissue in type 2 diabetes. Metformin improves hepatic insulin action without affecting HCL levels, whereas insulin infusion for 67 h increases HCL levels by approximately 18%; furthermore, HCL levels positively correlate with the insulin dosage in insulin-treated type 2 diabetes. In conclusion, liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.
    背景与目标: 肝脂肪变性是由肝细胞脂质(HCL)含量增加所定义的,并且经常在包括2型糖尿病在内的胰岛素抵抗状态中观察到。饮食中饱和脂肪过多会大大增加HCL的积累。 HCL水平升高主要是肝脏胰岛素抵抗的原因,这可能是由于游离脂肪酸在肝脏中的分配(脂肪溢出)和脂肪细胞因子的失衡(脂联素减少和/或促炎性细胞因子增加)引起的。游离脂肪酸和脂肪细胞因子均激活包括蛋白激酶C,转录因子核因子kappaB和c-Jun N端激酶1在内的炎症途径,从而可以加速肝脂肪变性发展为非酒精性脂肪性肝炎和肝硬化。质子磁共振波谱使量化HCL浓度和检测临床环境中这些浓度的微小变化成为可能。适度低热量,低脂肪饮食可将HCL水平降低约40-80%,同时最多可减少8%的体重。噻唑烷二酮类药物(例如吡格列酮和罗格列酮)治疗可通过调节2型糖尿病的胰岛素敏感性和脂肪组织的内分泌功能将HCL水平降低30-50%。二甲双胍在不影响HCL水平的情况下改善了肝胰岛素的作用,而胰岛素输注67 h使HCL水平增加了约18%。此外,在用胰岛素治疗的2型糖尿病中,HCL水平与胰岛素剂量呈正相关。总之,肝脏脂肪是代谢通量和炎症过程的关键决定因素,因此代表了胰岛素抵抗和2型糖尿病的重要治疗靶标。
  • 【通过微孔过滤测量的外周血中性粒细胞流变学很好地反映了贝塞特的疾病活动。】 复制标题 收藏 收藏
    DOI:10.1016/s0923-1811(97)00599-9 复制DOI
    作者列表:Iijima S,Otsuka F
    BACKGROUND & AIMS: Activated neutrophils take a long time to pass through a narrow lumen like a micropore, and are supposed to play a deteriorating effect on microcirculation. Although the activation of neutrophils has been demonstrated in Behçet's disease, nobody analyzes the clinical activity of the disease by means of the rheological measure of neutrophils activity. Using a micropore (pore diameter 5 microns) filtration technique, we measured the filtration time of peripheral blood neutrophils, as a rheological measure of their activity, in order to determine the clinical activity of Behçet's disease. Twenty-one patients with Behçet's disease and 14 healthy control individuals were enrolled in the study. Symptoms and signs exhibited in the patients led us to distinguish the Behçet's disease into inactive and active cases. The latter were further differentiated into cases with absent symptoms and with present symptoms. Neutrophil filtration times were 11.5 +/- 4.8 s in the active cases with present symptoms, which were significantly (P < 0.05) larger than those (7.4 +/- 1.9 s) in the active cases with absent symptoms. The latter filtration times were further significantly (P < 0.001) larger than values (3.7 +/- 1.3 s) in the inactive cases and also those (4.8 +/- 1.2 s) in control subjects. Furthermore, increases in the filtration time obtained immediately after the exposure of cells to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP10 nM) were significantly (P < 0.01) larger in the active cases with present symptoms than those in the active cases with absent symptoms. The latter were also larger, but not significantly, than those in the inactive cases, and were significantly (P < 0.01) larger than those in control subjects. The present results demonstrate that the micropore filtration method reflects well the rheological activity of neutrophils as well as the clinical status of Behçet's disease. This method is much better than the measurement of O2 production to differentiate between active cases with absent symptoms and inactive patients or even control individuals. Furthermore, it is more sensitive and useful than laboratory data like the CRP value or the number of peripheral blood neutrophils.

    背景与目标: 活化的嗜中性粒细胞需要很长时间才能通过像微孔一样的狭窄内腔,因此应该对微循环起恶化作用。尽管在白塞氏病中已证明嗜中性粒细胞的活化,但没有人通过流变学方法测量嗜中性粒细胞的活性来分析该疾病的临床活性。我们使用微孔(孔径为5微米)过滤技术,测量外周血中性粒细胞的过滤时间,作为其活性的流变学指标,以确定贝塞特氏病的临床活性。本研究招募了21名Behçet病患者和14名健康对照者。患者表现出的症状和体征使我们将Behçet病区分为非活跃和活跃病例。后者被进一步区分为无症状和有当前症状的病例。在有症状的活跃病例中,中性粒细胞过滤时间为11.5 /-4.8 s,比没有症状的活跃病例中的中性粒细胞过滤时间显着(P <0.05)大(P <0.05)。后者的过滤时间比不活动的情况下的值(3.7 /-1.3 s)大得多(P <0.001),也比对照对象的值(4.8 /-1.2 s)大得多(P <0.001)。此外,在有症状的活动病例中,将细胞暴露于趋化肽甲酰基-甲硫酰基-亮氨酰-苯丙氨酸(FMLP10 nM)后立即获得的过滤时间增加明显大于活动病例(P <0.01)。没有症状。后者也比不活动者大,但不显着,并且比对照组大(P <0.01)。目前的结果表明,微孔过滤方法很好地反映了中性粒细胞的流变活性以及白塞氏病的临床状况。这种方法比测量氧气的产生要好得多,以区分没有症状的活动患者和无活动的患者,甚至是对照个体。此外,它比实验室数据(如CRP值或外周血中性粒细胞的数量)更为敏感和有用。

  • 【过敏性眼病的结膜上皮结构蛋白减少。】 复制标题 收藏 收藏
    DOI:10.1111/j.1398-9995.2006.01207.x 复制DOI
    作者列表:Hughes JL,Lackie PM,Wilson SJ,Church MK,McGill JI
    BACKGROUND & AIMS: AIMS:Allergic eye disease affects up to 20% of the population with varying severity. The conjunctival epithelium plays a key role in allergic eye disease. The purpose of this study was to determine whether the conjunctival epithelium is abnormal in allergic eye disease. METHODS:Conjunctival biopsy samples were taken from patients with seasonal allergic conjunctivitis (SAC) 'in' and 'out of season' and nonatopic control subjects. Specimens were fixed in glycol methacrylate, 2 microm serial sections cut and Image-J used to assess the sites and areas of immuno-staining. RESULTS:E-cadherin, CD44, keratins K5/6, K8, K13, K14, K18 and pan-keratin immuno-staining were all significantly lower in patients 'out of season' compared with normal controls. No structural differences in the epithelium were observed between the two groups. The epithelium of patients 'in season' was thicker and immuno-staining of the above markers similar to controls. CONCLUSIONS:The expression of a wide spectrum of epithelial cell adhesion proteins and cytoskeletal elements is downregulated in the conjunctiva of SAC patients 'out of season' compared with normal controls. We suggest that this could have an important impact on the ability of the epithelium to protect itself against allergen penetration, potentially influencing the development and course of allergic eye disease and offering a novel area for therapeutic control.
    背景与目标: 目的:过敏性眼病可影响多达20%的人口,其严重程度各不相同。结膜上皮在过敏性眼病中起关键作用。这项研究的目的是确定在过敏性眼病中结膜上皮是否异常。
    方法:结膜活检样本取自“季节内”和“季节外”的季节性过敏性结膜炎(SAC)患者以及非特应性对照者。将样品固定在甲基丙烯酸乙二醇酯中,切成2微米的连续切片,用Image-J评估免疫染色的部位和面积。
    结果:与正常对照组相比,“非季节性”患者的E-钙粘蛋白,CD44,角蛋白K5 / 6,K8,K13,K14,K18和泛角蛋白免疫染色均显着降低。两组之间未观察到上皮的结构差异。 “季节”患者的上皮较厚,上述标记物的免疫染色与对照相似。
    结论:与正常对照组相比,SAC患者结膜中的各种上皮细胞粘附蛋白和细胞骨架成分的表达被“下调”。我们建议这可能对上皮保护自身免受过敏原渗透的能力产生重要影响,从而可能影响过敏性眼病的发展和进程,并为治疗控制提供一个新领域。
  • 【荷兰用英夫利昔单抗治疗克罗恩病的指南。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Vermeire S
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【腹腔疾病患者的小麦淀粉不耐症。】 复制标题 收藏 收藏
    DOI:10.1016/S0002-8223(97)00156-9 复制DOI
    作者列表:Chartrand LJ,Russo PA,Duhaime AG,Seidman EG
    BACKGROUND & AIMS: OBJECTIVE:Evaluate in patients with celiac disease the tolerance of prolonged consumption of small amounts of gliadin contained in products containing wheat starch.

    DESIGN:Open 1-year trial of the addition of wheat starch to a gluten-free diet in a cohort of adult patients with biopsy-proven celiac disease who had never consumed wheat starch. The control group consisted of patients with celiac disease who tolerated wheat starch.

    SUBJECTS:Seventeen patients with celiac disease and 14 control patients, all diagnosed according to criteria of the European Society of Pediatric Gastroenterology and Nutrition, were recruited from the Canadian Celiac Association and the Quebec Celiac Foundation.

    SETTING:The study was conducted in the outpatient clinic of the Gastroenterology and Nutrition Service of Ste Justine Hospital, Montreal, Quebec, Canada.

    INTERVENTIONS:Patients were asked to consume four to six portions daily of a wheat starch-containing product, mainly bread, for up to 1 year.

    MAIN OUTCOME MEASURES:The gliadin content of the wheat starch product used in this trial was quantified by enzyme-linked immunosorbent assay. Patient outcome measures included symptoms, nutritional parameters (anthropometric data, complete blood count, serum folate and iron levels), and immunologic parameters (antigliadin antibody and antiendomysium antibody titers).

    RESULTS:A quantifiable amount of immunoreactive gliadin (0.75 mg/100 g) was found in the wheat starch. The majority of the patients with celiac disease (11 of 17) who had never consumed wheat starch previously developed symptoms, which resolved within weeks of discontinuing the product. Relapse of skin lesions was seen in two of three patients with coexisting dermatitis herpetiformis. No weight loss or biochemical changes were observed. Despite the presence of symptoms, antigliadin antibody and antiendomysium antibody determinations were not useful to detect the clinical intolerance.

    APPLICATIONS:The innocuousness of the long-term ingestion of "gluten-free" products containing wheat starch is still unproven, and prolonged use of such products by patients with celiac disease cannot be recommended.

    背景与目标: 目标:评估患有乳糜泻的患者长期食用含小麦淀粉的产品中所含少量麦醇溶蛋白的耐受性。

    设计:打开1-在一群经活检证实为乳糜泻但从未食用过小麦淀粉的成年患者中,在无麸质饮食中添加小麦淀粉的一项年度试验。对照组包括耐受小麦淀粉的腹腔疾病患者。

    受试者:17例腹腔疾病患者和14例对照患者,均根据欧洲儿科学会的标准诊断胃肠病学和营养学是从加拿大乳糜泻协会和魁北克乳糜泻基金会招募的。

    设置:这项研究是在Ste Justine医院胃肠病学和营养服务的门诊进行的。 ,加拿大魁北克省蒙特利尔。

    干预措施:患者被要求每天食用四到六份含小麦淀粉的产品(主要是面包),最多1年。 br>
    主要观察指标:该试验中使用的小麦淀粉产品的麦醇溶蛋白含量通过酶联免疫吸附法进行了定量。患者的预后指标包括症状,营养参数(人体测量数据,全血细胞计数,血清叶酸和铁水平)和免疫学参数(抗麦胶蛋白抗体和抗内胚层抗体滴度)。

    结果:在小麦淀粉中发现了定量的免疫反应性麦醇溶蛋白(0.75 mg / 100 g)。从未食用小麦淀粉的大多数乳糜泻患者(17例中的11例)以前都出现了症状,在停产该产品后数周内症状消失了。在三例并存的疱疹样皮炎患者中,有两例发现皮肤病变复发。没有观察到体重减轻或生化变化。尽管存在症状,但抗麦醇溶蛋白抗体和抗肌内膜抗体的测定仍不能用于检测临床耐受性。

    应用:长期摄入“不含麸质”的食物是无害的含有小麦淀粉的产品尚未得到证实,因此不建议乳糜泻患者长时间使用此类产品。

  • 【美国,1993-1995年,围产期B组链球菌疾病的发病率下降。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Centers for Disease Control and Prevention (CDC).
    BACKGROUND & AIMS: :Group B streptococcal (GBS) infections are the leading cause of bacterial disease and death among newborns in the United States and an important cause of morbidity among peripartum women and nonpregnant adults with chronic medical conditions. Disease in infants usually presents as sepsis, pneumonia or meningitis but also may include cellulitis or osteomyelitis. In 1990, GBS infections caused an estimated 7600 serious illnesses and 310 deaths among U.S. infants aged < or = 90 days; infections among infants aged < 7 days (i.e., early-onset disease) accounted for approximately 80% of these illnesses. To determine the incidence of GBS disease during 1993-1995, CDC conducted surveillance for this disease in an aggregate population of 12.5 million persons with 190,000 annual live-born infants. This report summarizes the findings of surveillance in this population, which indicate that a statistically significant decline in the incidence of early-onset GBS disease occurred in some surveillance areas.
    背景与目标: B组链球菌(GBS)感染是美国新生儿细菌性疾病和死亡的主要原因,也是围产期妇女和患有慢性病的未怀孕成年人中发病的重要原因。婴儿的疾病通常表现为败血症,肺炎或脑膜炎,但也可能包括蜂窝织炎或骨髓炎。 1990年,GBS感染在年龄小于或等于90天的美国婴儿中估计造成7600例严重疾病,并有310例死亡。小于7天的婴儿感染(即早发疾病)约占这些疾病的80%。为了确定1993-1995年间GBS疾病的发病率,疾病预防控制中心对1250万总人口和19万例活产婴儿进行了这种疾病的监测。该报告总结了该人群的监测结果,这表明在某些监测区域发生的早发性GBS疾病的发生率在统计学上显着下降。
  • 【Darier病影响牙龈和口腔粘膜表面。】 复制标题 收藏 收藏
    DOI:10.1016/j.tripleo.2005.10.040 复制DOI
    作者列表:Frezzini C,Cedro M,Leao JC,Porter S
    BACKGROUND & AIMS: :Darier disease is an uncommon genodermatosis reflecting defective desmosomal structure and function. The present report details the oral features of a patient with well-characterized Darier disease and reviews current knowledge of the genetic basis of this genodermatosis that can often affect the craniofacial tissues.
    背景与目标: :Darier病是一种罕见的遗传性皮肤病,反映了桥粒结构和功能的缺陷。本报告详细介绍了特征明确的Darier病患者的口腔特征,并回顾了这种遗传皮肤病的遗传基础的当前知识,这种遗传皮肤病经常会影响颅面组织。
  • 【JTE-607是一种多种细胞因子产生抑制剂,可改善SCID小鼠异种移植急性髓细胞白血病模型中的疾病。】 复制标题 收藏 收藏
    DOI:10.1016/j.exphem.2006.05.016 复制DOI
    作者列表:Uesato N,Fukui K,Maruhashi J,Tojo A,Tajima N
    BACKGROUND & AIMS: OBJECTIVE:Accumulating findings suggest that in acute myeloid leukemia (AML) patients, proinflammatory cytokines and growth factors play important roles in the proliferation and survival of AML cells in an autocrine and paracrine manner, leading to deterioration of AML. JTE-607 is a multiple cytokine inhibitor that potently suppresses production of proinflammatory cytokines. In the present study, we investigated the potency of JTE-607 as an antileukemic agent by exploiting a SCID mouse acute leukemia model. METHODS:SCID mice injected with anti-asialo-GM1 antibody were exposed to sublethal total-body irradiation at a dose of 3 Gy and then inoculated intravenously with AML cells. JTE-607 was administered using osmotic minipumps. The effects of JTE-607 on mouse survival time, human interleukin (IL)-8 levels in mouse plasma, and proportion of human CD45(+) cells in the bone marrow were studied. RESULTS:The survival time of the mice was strictly dependent on the number of U-937 cells proliferating in vivo. Administration of JTE-607 during the initial 7 days significantly prolonged survival of the mice, suggesting killing activity of JTE-607 against AML cells in vivo. Delayed administration of JTE-607 also prolonged the survival of mice bearing established leukemia with an effect comparable to the maximum tolerable dose of cytarabine. Flow cytometer analysis of bone marrow cells revealed decreased number of human CD45(+) cells. Human IL-8 level was also reduced by JTE-607. CONCLUSION:Our results indicate that JTE-607 has potential to be a new class of antileukemic drug that exerts inhibitory activities against both the proliferation and proinflammatory cytokine production of AML cells.
    背景与目标: 目的:大量研究结果表明,在急性髓细胞性白血病(AML)患者中,促炎性细胞因子和生长因子以自分泌和旁分泌方式在AML细胞的增殖和存活中起重要作用,从而导致AML恶化。 JTE-607是一种多细胞因子抑制剂,可有效抑制促炎细胞因子的产生。在本研究中,我们通过利用SCID小鼠急性白血病模型研究了JTE-607作为抗白血病药物的效力。
    方法:将注射了抗亚洲人GM1抗体的SCID小鼠暴露于3 Gy剂量的亚致死性全身照射下,然后静脉注射AML细胞。 JTE-607使用渗透微型泵进行管理。研究了JTE-607对小鼠存活时间,小鼠血浆中人白介素(IL)-8水平以及骨髓中人CD45()细胞比例的影响。
    结果:小鼠的存活时间严格取决于体内增殖的U-937细胞数量。在最初的7天中施用JTE-607可以显着延长小鼠的存活期,表明JTE-607在体内对AML细胞具有杀伤活性。 JTE-607的延迟给药也延长了已确诊白血病的小鼠的存活,其作用与阿糖胞苷的最大耐受剂量相当。骨髓细胞的流式细胞仪分析显示人类CD45()细胞数量减少。 JTE-607也降低了人IL-8水平。
    结论:我们的结果表明,JTE-607有潜力成为一类新型的抗白血病药物,对AML细胞的增殖和促炎性细胞因子产生均具有抑制作用。
  • 【雄激素依赖性病理显示在小鼠敲入模型中肌病对肯尼迪病表型的贡献。】 复制标题 收藏 收藏
    DOI:10.1172/JCI28773 复制DOI
    作者列表:Yu Z,Dadgar N,Albertelli M,Gruis K,Jordan C,Robins DM,Lieberman AP
    BACKGROUND & AIMS: :Kennedy disease, a degenerative disorder characterized by androgen-dependent neuromuscular weakness, is caused by a CAG/glutamine tract expansion in the androgen receptor (Ar) gene. We developed a mouse model of Kennedy disease, using gene targeting to convert mouse androgen receptor (AR) to human sequence while introducing 113 glutamines. AR113Q mice developed hormone and glutamine length-dependent neuromuscular weakness characterized by the early occurrence of myopathic and neurogenic skeletal muscle pathology and by the late development of neuronal intranuclear inclusions in spinal neurons. AR113Q males unexpectedly died at 2-4 months. We show that this androgen-dependent death reflects decreased expression of skeletal muscle chloride channel 1 (CLCN1) and the skeletal muscle sodium channel alpha-subunit, resulting in myotonic discharges in skeletal muscle of the lower urinary tract. AR113Q limb muscles show similar myopathic features and express decreased levels of mRNAs encoding neurotrophin-4 and glial cell line-derived neurotrophic factor. These data define an important myopathic contribution to the Kennedy disease phenotype and suggest a role for muscle in non-cell autonomous toxicity of lower motor neurons.
    背景与目标: :肯尼迪病是一种以雄激素依赖性神经肌肉无力为特征的变性疾病,是由雄激素受体(Ar)基因中的CAG /谷氨酰胺束扩张引起的。我们开发了肯尼迪病的小鼠模型,使用基因靶向技术将小鼠雄激素受体(AR)转化为人类序列,同时引入113种谷氨酰胺。 AR113Q小鼠发展出激素和谷氨酰胺长度依赖性神经肌肉无力,其特征是肌病性和神经源性骨骼肌病理的早期发生以及脊髓神经元中神经元核内包涵体的发育较晚。 AR113Q男性意外死于2-4个月。我们表明,这种雄激素依赖性死亡反映了骨骼肌氯化物通道1(CLCN1)和骨骼肌钠通道α亚基的表达下降,导致下尿路骨骼肌的肌强直放电。 AR113Q肢体肌肉表现出相似的肌病特征,并表达编码Neurotrophin-4和神经胶质细胞源性神经营养因子的mRNA水平下降。这些数据定义了对肯尼迪病表型的重要肌病性贡献,并暗示了肌肉在下运动神经元的非细胞自主毒性中的作用。
  • 【接触含汞美白霜后出现的最小变化病。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tang HL,Chu KH,Mak YF,Lee W,Cheuk A,Yim KF,Fung KS,Chan HW,Tong KL
    BACKGROUND & AIMS: :A 34-year-old woman developed nephrotic syndrome after using a skin lightening cream that contained an extremely high level of mercury. Blood and urine mercury levels were elevated and a renal biopsy revealed minimal change disease. Membranous nephropathy was excluded using immunofluorescence and electron microscopy. Her proteinuria remitted 9 months after she stopped using the cosmetic cream. This is the first reported case in the English literature of proven minimal change disease secondary to mercury exposure. It is important that mercury poisoning due to cosmetic cream is considered in the differential diagnoses for any woman who presents with nephrotic syndrome.
    背景与目标: :一名34岁的女性在使用含有极高汞含量的亮肤霜后患上了肾病综合症。血液和尿液中的汞含量升高,肾脏活检显示病变最小。使用免疫荧光和电子显微镜排除了膜性肾病。停止使用美容霜后9个月,她的蛋白尿症状得到缓解。这是英国文献中首次报道的继汞暴露后引起的最小变化疾病的病例。对于所有患有肾病综合征的女性,在鉴别诊断中都应考虑到由于美容霜引起的汞中毒。
  • 【成人先天性心脏病患者的亚临床甲状腺功能减退症。】 复制标题 收藏 收藏
    DOI:10.1007/s00246-012-0571-6 复制DOI
    作者列表:Martínez-Quintana E,Rodríguez-González F,Nieto-Lago V
    BACKGROUND & AIMS: :Subclinical hypothyroidism usually is asymptomatic, but it can be associated with various adverse cardiologic outcomes. With the objective of gaining insight into the role of thyroid-stimulating hormone (TSH) in congenital heart abnormalities, this study measured serum TSH concentrations in different subtypes of grown-up congenital heart disease (GUCHD) patients. Serum TSH (reference range, 0.34-5.6 mIU/L), creatinine, cholesterol, C-reactive protein (CRP), N-terminal proB-type natriuretic peptide (NT-pro-BNP), and 24-h proteinuria were measured in 249 GUCHD patients. Of 24 GUCHD patients (9.6 %) with a TSH level higher than 5.6 mUI/L, nine were cyanotic (37.5 %) and seven (29.1 %) had Down syndrome. The GUCHD patients with serum TSH exceeding 5.6 mIU/L had a significantly higher level of serum NT-pro-BNP (195.1 [0.28; 5,280.3] vs 57.6 [0.00; 929.8]; p = 0.001) and CRP (0.30 [0.06; 1.87] vs 0.16 [0.00; 1.40]; p = 0.011] than those with a TSH level of 5.6 mIU/L or lower. No significant differences were found in serum creatinine, lipids, or 24-h proteinuria between the two groups. The T4 concentrations in the GUCHD patients with TSH exceeding 5.6 mIU/L were within the normal range (0.89 ± 0.23 ng/dL). In the multivariate analysis, cyanosis (odds ratio [OR], 6,399; 95 % confidence interval [CI] 2,296-17,830; p < 0.001), Down syndrome (OR, 6,208; 95 % CI, 1,963-19,636; p = 0.002), and NT-pro-BNP concentrations (OR, 1,001; 95 % CI, 1,000-1,002; p < 0.026) proved to be risk factors for TSH levels higher than 5.6 mIU/L. Because subclinical hypothyroidism entails a cardiovascular risk, the authors postulate that TSH screening should be included in the routine follow-up evaluation of GUCHD patients with cyanosis or Down syndrome.
    背景与目标: 亚临床甲状腺功能减退症通常无症状,但可能与各种不良心脏预后相关。为了深入了解甲状腺刺激激素(TSH)在先天性心脏病中的作用,本研究测量了不同类型的成年先天性心脏病(GUCHD)患者的血清TSH浓度。测量血清TSH(参考范围0.34-5.6 mIU / L),肌酐,胆固醇,C反应蛋白(CRP),N端proB型利钠肽(NT-pro-BNP)和24小时蛋白尿。 249位GUCHD患者。 TSH水平高于5.6 mUI / L的24名GUCHD患者(9.6%)中,有9名发(37.5%)和7名(29.1%)患有唐氏综合症。血清TSH超过5.6 mIU / L的GUCHD患者的血清NT-pro-BNP显着更高(195.1 [0.28; 5,280.3] vs 57.6 [0.00; 929.8]; p = 0.001)和CRP(0.30 [0.06; 1.87) [] vs. 0.16 [0.00; 1.40]; p = 0.011],TSH水平为5.6 mIU / L或更低;两组之间的血清肌酐,脂质或24小时蛋白尿无显着差异。 TSH超过5.6 mIU / L的GUCHD患者的血药浓度在正常范围内(0.89±0.23 ng / dL)。在多变量分析中,紫((比值[OR]为6,399; 95%置信区间[CI]为2,296- 17,830; p <0.001),唐氏综合症(OR,6,208; 95%CI,1,963-19,636; p = 0.002)和NT-pro-BNP浓度(OR,1,001; 95%CI,1,000-1,002; p <0.026) )被证明是TSH水平高于5.6 mIU / L的危险因素。由于亚临床甲状腺功能减退症会引起心血管疾病风险,因此作者推测TSH筛查应包括在GUCHD的常规随访评估中紫osis或唐氏综合症患者。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录