• 【单纯性前脑畸形和单纯性低毛丝菌病的连续基因综合征: 与18p11.3缺失有关。】 复制标题 收藏 收藏
    DOI:10.1002/ajmg.a.31386 复制DOI
    作者列表:Kantaputra PN,Limwongse C,Tochareontanaphol C,Mutirangura A,Mevatee U,Praphanphoj V
    BACKGROUND & AIMS: :We report a patient with a unique combination of features, including microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic pituitary gland; hypothyroidism; alopecia universalis; single maxillary central incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10). The constellation of anomalies appears to represent a contiguous gene syndrome caused, at least in part, by deletion of TGIF and the gene responsible for hereditary hypotrichosis simplex. The phenotype of our patient differs other reported patients with del(18p). Possible explanations include (1) the effects of a different deleted region, (2) a positional effect caused by a gene close by, or (3) by interruption of a different gene resulting from chromosomal translocation.
    背景与目标: : 我们报告了一名具有独特特征组合的患者,包括小头畸形; 智力低下; 额叶发育不良; 垂体发育不良; 甲状腺功能减退; 普遍脱发; 单个上颌中切牙; 牛角牙症; 正中腭嵴; 纵向开槽的指甲; 和脊柱侧弯。发现他的不平衡核型为45,XY,der(15;18)(q10;q10)。异常星座似乎代表了一个连续的基因综合征,至少部分是由TGIF和负责遗传性低毛丝菌病的基因缺失引起的。我们患者的表型不同于其他报告的del患者 (18p)。可能的解释包括 (1) 不同缺失区域的影响,(2) 由接近的基因引起的位置效应,或 (3) 由染色体易位引起的不同基因的中断。
  • 【静脉血栓栓塞后血栓后综合征的频率和决定因素。】 复制标题 收藏 收藏
    DOI:10.1097/01.mcp.0000239543.40078.17 复制DOI
    作者列表:Kahn SR
    BACKGROUND & AIMS: PURPOSE OF REVIEW:Postthrombotic syndrome (PTS) is the most common complication of deep venous thrombosis (DVT). Identifying which patients are at high risk of developing PTS would help improve the management of patients with DVT and allow physicians to provide patients with individualized information on their expected prognosis. This review discusses the knowledge gained from key studies over the last decade on the incidence and determinants of PTS, with special emphasis on published studies from the last 2 years. RECENT FINDINGS:About a third to half of DVT patients will develop PTS, in most cases within 1-2 years of acute DVT. Important risk factors for PTS appear to be ipsilateral recurrence of DVT, poor quality of initial anticoagulation for the treatment of DVT and increased body mass index. SUMMARY:Preventing DVT recurrence by providing adequate intensity and duration of anticoagulation for the initial DVT and using effective thromboprophylaxis in high-risk settings is likely to reduce the frequency of PTS. Despite some advances in identifying risk factors for PTS, however, it is still not possible to reliably predict an individual patient's risk of developing PTS after an episode of DVT. Further studies of clinical determinants and biological markers of increased risk of PTS are needed to ultimately improve long-term prognosis after DVT.
    背景与目标:
  • 【美国风疹和先天性风疹综合征的流行病学概况,1998-2004: 缺乏地方性传播的证据。】 复制标题 收藏 收藏
    DOI:10.1086/505944 复制DOI
    作者列表:Reef SE,Redd SB,Abernathy E,Zimmerman L,Icenogle JP
    BACKGROUND & AIMS: :In 1969, the United States established its national rubella vaccination program. With the success of the program, 32 years later, reports of rubella reached record low numbers. To assess the achievement of elimination of rubella and congenital rubella syndrome (CRS) in the United States, 7 epidemiological criteria were used. Rubella cases reported to the National Notifiable Diseases Surveillance System from 1998 through 2004 and CRS cases reported to the National Congenital Rubella Syndrome Registry from 1998 through 2004 were analyzed. During 1998-2000, the median number of reported rubella cases was 272, whereas, during 2001-2004, the median number reported was 13. The incidence of rubella decreased significantly, from 0.1/100,000 population in 1998 to 0.005/100,000 population in 2004. Since 2001, 5 infants with CRS have been reported--3 were born in 2001, 1 was born in 2003, and 1 was born in 2004. The epidemiological evidence strongly supports the claim that rubella is no longer endemic in the United States. To prevent future rubella outbreaks and CRS cases, current strategies must be maintained.
    背景与目标: : 1969年,美国建立了国家风疹疫苗接种计划。随着该计划的成功,32年后,风疹的报道达到了历史新低。为了评估在美国消除风疹和先天性风疹综合征 (CRS) 的成就,使用了7个流行病学标准。分析了向国家法定疾病监测系统报告的风疹病例1998年2004年和向国家先天性风疹综合征登记1998年2004年报告的CRS病例。在1998-2000年期间,报告的风疹病例的中位数为272,而在2001-2004年期间,报告的中位数为13。风疹的发病率从0.1/100,000人口1998年下降到0.005/100,000人口2004年。自2001年以来,已报告5例CRS婴儿-3例2001年出生,1例2003年出生,1例2004年出生。流行病学证据强烈支持风疹在美国不再流行的说法。为了防止未来的风疹暴发和CRS病例,必须维持当前的策略。
  • 【Beckwith-Wiedemann综合征和半增生的肿瘤监测: 对证据的严格审查和当地实践的建议指南。】 复制标题 收藏 收藏
    DOI:10.1111/j.1440-1754.2006.00908.x 复制DOI
    作者列表:Tan TY,Amor DJ
    BACKGROUND & AIMS: :There is strong evidence for an association between overgrowth disorders such as Beckwith-Wiedemann syndrome and the development of neoplasia. An increased cancer risk has also been observed in individuals with isolated hemihyperplasia. We critically review the evidence for tumour surveillance in Beckwith-Wiedemann syndrome and isolated hemihyperplasia and suggest local practice guidelines.
    背景与目标: : 有强有力的证据表明,Beckwith-Wiedemann综合征等过度生长性疾病与肿瘤的发展之间存在关联。在孤立的半增生个体中也观察到癌症风险增加。我们严格审查了Beckwith-Wiedemann综合征和孤立性半增生中肿瘤监测的证据,并提出了当地实践指南。
  • 【寻求减肥手术的人的夜间饮食综合症和暴食症: 患病率和相关特征。】 复制标题 收藏 收藏
    DOI:10.1016/j.soard.2006.03.014 复制DOI
    作者列表:Allison KC,Wadden TA,Sarwer DB,Fabricatore AN,Crerand CE,Gibbons LM,Stack RM,Stunkard AJ,Williams NN
    BACKGROUND & AIMS: OBJECTIVE:To assess the prevalence of night eating syndrome (NES) and binge eating disorder (BED) and their related behavioral and psychological correlates in persons who sought bariatric surgery. RESEARCH METHODS AND PROCEDURES:A consecutive series of 215 persons with extreme obesity (82% women, 70% European American) completed the Weight and Lifestyle Inventory and a semistructured interview as part of a pre-surgery behavioral/psychological assessment. Diagnoses for NES and BED were based on graded diagnostic criteria. RESULTS:Percentages of participants who met diagnostic criteria for NES by interview were 1.9% for the strictest definition and 8.9% across all definitions of NES. After interview, full DSM-TR criteria for BED were met by 4.2%; an additional 1.4% reported binge eating at least once per week. Self-reported prevalence of NES and BED were higher. Those with NES or BED had significantly more symptoms of depression and a greater history of psychological complications than the remaining sample. DISCUSSION:The prevalence rates of NES and BED among this population of bariatric surgery candidates were lower than expected based on previous reports. Findings and hypotheses regarding lowered prevalence rates are discussed.
    背景与目标:
  • 【居住在夏威夷的日本男女的跌倒发生率。】 复制标题 收藏 收藏
    DOI:10.1016/s0895-4356(96)00430-1 复制DOI
    作者列表:Davis JW,Ross PD,Nevitt MC,Wasnich RD
    BACKGROUND & AIMS: :Japanese people in both Japan and in Hawaii have a lower incidence of hip fractures than white people in Hawaii or on the mainland of the United States. Hip fractures usually occur after a fall, and differing incidence rates of falls might contribute to the observed differences in hip fracture rates. To investigate this possibility we undertook a prospective study of falls among elderly Japanese men and women living in Hawaii using intensive surveillance methods similar to those used in studies of predominantly white populations. For our Japanese participants, the incidence rates of total falls were 139 per 1000 person years for men and 276 per 1000 person years for women. Age adjusted rate ratios of falls for predominantly white populations compared with our Japanese participants ranged from 1.8 to 2.3 for women and from 2.6 to 4.7 for men. The risk of injuries when they did fall, however, was not lower for our Japanese participants than reported for white participants. For our Japanese population, past falls, female gender, and daytime hours were associated with an increased incidence of falls.
    背景与目标: : 日本和夏威夷的日本人髋部骨折的发生率都比夏威夷或美国本土的白人低。髋部骨折通常发生在跌倒后,不同的跌倒发生率可能会导致观察到的髋部骨折发生率差异。为了调查这种可能性,我们使用了类似于以白人为主的研究中使用的强化监测方法,对居住在夏威夷的日本老年男性和女性的跌倒进行了前瞻性研究。对于我们的日本参与者,男性的总跌倒发生率为139/1000人年,女性为276/1000人年。与我们的日本参与者相比,以白人为主的年龄调整后的跌倒率比率为女性的1.8至2.3,男性的2.6至4.7。但是,我们的日本参与者跌倒时受伤的风险并不比白人参与者低。对于我们的日本人口,过去的跌倒,女性性别和白天的时间与跌倒的发生率增加有关。
  • 【社区获得性耐甲氧西林金黄色葡萄球菌对苯唑西林耐药所需的VraS/VraR双组分调节系统。】 复制标题 收藏 收藏
    DOI:10.1111/j.1574-6968.2006.00384.x 复制DOI
    作者列表:Boyle-Vavra S,Yin S,Daum RS
    BACKGROUND & AIMS: :Methicillin/oxacillin (Oxa) resistance in Staphylococcus aureus is primarily mediated by the acquired penicillin-binding protein (PBP2a) encoded by mecA. PBP2a acts together with native PBP2 to mediate oxacillin resistance by contributing complementary transpeptidase and transglycosylase activities, respectively. The VraS/VraR two-component regulatory system is inducible by cell-wall antimicrobials (beta-lactams, glycopeptides) and controls transcriptional induction of many cell-wall genes including pbp2 and itself. We investigated the role of VraS/VraR in the phenotypic expression of oxacillin resistance by inactivating vraS in community-acquired MRSA clinical isolates that lack functional genes encoding the mecA regulatory sequences mecI and mecR1. Inactivation of vraS abrogated oxacillin resistance, and complementation with the vraS operon restored the resistance phenotype. mecA transcription increased in the vraS mutants; however, PBP2a abundance was similar to that of the wild type. Although pbp2 transcription decreased in the vraS mutants, overexpression of the pbp2 operon did not restore resistance. These data demonstrate that although expressions of mecA and pbp2 are required for oxacillin resistance, they are not sufficient. Therefore, the vraS/vraR regulatory system plays a crucial role in allowing MRSA to respond to beta-lactams by regulation of a gene target other than the known effectors of methicillin resistance.
    背景与目标: : 金黄色葡萄球菌对甲氧西林/苯唑西林 (Oxa) 的耐药性主要由mecA编码的获得性青霉素结合蛋白 (PBP2a) 介导。PBP2a与天然PBP2一起通过分别贡献互补的转肽酶和转糖基化酶活性来介导苯唑西林抗性。VraS/VraR两组分调节系统可由细胞壁抗菌剂 (β-内酰胺,糖肽) 诱导,并控制许多细胞壁基因 (包括pbp2及其自身) 的转录诱导。我们通过在缺乏编码mecA调节序列mecI和mecr1的功能基因的社区获得性MRSA临床分离株中灭活VraS,研究了vraS/VraR在苯唑西林抗性表型表达中的作用。vraS的失活消除了苯唑西林的抗性,并与vraS操纵子互补恢复了抗性表型。vraS突变体中的mecA转录增加; 然而,PBP2a的丰度与野生型相似。尽管vraS突变体中的pbp2转录降低,但pbp2操纵子的过表达并不能恢复抗性。这些数据表明,尽管mecA和pbp2的表达对于苯唑西林抗性是必需的,但它们还不够。因此,vraS/vraR调节系统在允许MRSA通过调节除甲氧西林抗性的已知效应子以外的基因靶标来响应 β-内酰胺方面起着至关重要的作用。
  • 【全球女性人乳头瘤病毒患病率的年龄特异性曲线的变化。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22241 复制DOI
    作者列表:
    BACKGROUND & AIMS: :An inverse relationship between age and human papillomavirus (HPV) prevalence has been reported in many developed countries, but information on this relationship is scarce in many other parts of the world. We carried out a cross-sectional study of sexually active women from the general population of 15 areas in 4 continents. Similar standardised protocols for women's enrolment, cervical specimen collection and PCR-based assays for HPV testing were used. HPV prevalence in different age groups was compared by study area. 18,498 women aged 15-74 years were included. Age-standardised HPV prevalence varied more than 10-fold between populations, as did the shape of age-specific curves. HPV prevalence peaked below age 25 or 35, and declined with age in Italy, the Netherlands, Spain, Argentina, Korea and in Lampang, Thailand and Ho Chi Minh, Vietnam. This was not the case in Songkla, Thailand nor Hanoi, Vietnam, where HPV prevalence was low in all age groups. In Chile, Colombia and Mexico, a second peak of HPV prevalence was detected among older women. In the poorest study areas in Asia (Shanxi, China and Dindigul, India), and in Nigeria, HPV prevalence was high across all age groups. The substantial differences observed in age-specific curves of HPV prevalence between populations may have a variety of explanations. These differences, however, underline that great caution should be used in inferring the natural history of HPV from age-specific prevalences.
    背景与目标: : 在许多发达国家,已经报道了年龄与人乳头瘤病毒 (HPV) 患病率之间的反比关系,但是在世界许多其他地区,有关这种关系的信息很少。我们对来自4大洲15个地区的普通人群的性活跃女性进行了横断面研究。使用了类似的标准化方案,用于女性入组,宫颈标本收集和基于PCR的HPV检测方法。按研究区域比较了不同年龄组的HPV患病率。包括18,498名15-74岁的妇女。年龄标准化的HPV患病率在人群之间的变化超过10倍,年龄特定曲线的形状也是如此。HPV的患病率在25岁或35岁以下达到峰值,在意大利,荷兰,西班牙,阿根廷,韩国以及泰国南邦和越南胡志明市,随着年龄的增长而下降。泰国宋卡和越南河内的情况都不是这样,那里所有年龄组的HPV患病率都很低。在智利,哥伦比亚和墨西哥,在老年妇女中发现了HPV患病率的第二个高峰。在亚洲最贫困的研究地区 (中国山西和印度Dindigul) 和尼日利亚,HPV的患病率在所有年龄组中都很高。在人群之间HPV患病率的年龄特异性曲线中观察到的实质性差异可能有多种解释。然而,这些差异强调,在从年龄特异性患病率推断HPV的自然史时应格外小心。
  • 9 Obstructive sleep apnoea syndrome and genes. 复制标题 收藏 收藏

    【阻塞性睡眠呼吸暂停综合症和基因。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Kaparianos A,Sampsonas F,Karkoulias K,Spiropoulos K
    BACKGROUND & AIMS: :Obstructive sleep apnoea (OSA) is a complex disease entity strongly influenced by genetic factors, especially those that affect obesity and fat distribution, upper airway muscle tone, craniofacial morphology, ventilatory control and sleep, giving rise to the OSA phenotype. OSA can also be considered a metabolic syndrome which adversely affects multiple organ systems, especially the cardiovascular system and the brain. The most widely used clinical marker for the diagnosis of OSA is the apnoea-hypopnoea index, calculated by polysomnography. A percentage of 35 to 40% of its variance can be attributed to genetic factors. Therefore, the identification and elucidation of the genes implicated in the pathogenesis of OSA becomes a matter of extensive research and could lead to the development of therapeutic agents that can have a beneficial effect on the natural course of OSA.
    背景与目标: 阻塞性睡眠呼吸暂停 (OSA) 是一种复杂的疾病,受到遗传因素的强烈影响,尤其是那些影响肥胖和脂肪分布,上呼吸道肌张力,颅面形态,通气控制和睡眠的因素,从而引起OSA表型。OSA也可以被认为是一种代谢综合征,会对多器官系统 (尤其是心血管系统和大脑) 产生不利影响。诊断OSA最广泛使用的临床标志物是通过多导睡眠图计算的呼吸暂停-低通气指数。其方差的35% 至40% 的百分比可归因于遗传因素。因此,鉴定和阐明与OSA发病机理有关的基因已成为广泛研究的问题,并可能导致开发可对OSA自然过程产生有益作用的治疗剂。
  • 【新型anti-CD4单克隆抗体可分离人类免疫缺陷病毒感染和CD4细胞融合与病毒结合。】 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与病毒包膜糖蛋白gp120之间的相互作用与细胞结合。先前的研究已将gp120的高亲和力结合位点定位于CD4的第一个结构域,与该区域反应性的单克隆抗体 (mab) 与gp120结合竞争,从而阻止病毒的感染性和合胞体的形成。尽管对gp120与CD4的结合有详细的了解,但对导致膜融合和病毒进入的后续事件知之甚少。我们描述了两种与CD4的第三结构域反应的新mab,它们抑制了对HIV感染性和细胞融合至关重要的病毒结合之后的步骤。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被阻断。这些发现表明,除了病毒结合外,CD4可能在膜融合中起积极作用。
  • 【关系质量,激素避孕选择和青少年妇女不使用避孕套的发展关联。】 复制标题 收藏 收藏
    DOI:10.1016/j.jadohealth.2005.12.027 复制DOI
    作者列表:Sayegh MA,Fortenberry JD,Shew M,Orr DP
    BACKGROUND & AIMS: PURPOSE:Consistent condom use is critical to efforts to prevent sexually transmitted infections among adolescents, but condom use may decline as relationships and contraceptive needs change. The purpose of this research is to assess changes in condom non-use longitudinally in the context of changes in relationship quality, coital frequency and hormonal contraceptive choice. METHODS:Participants were women (aged 14-17 years at enrollment) recruited from three urban adolescent medicine clinics. Data were collected at three-month intervals using a face-to-face structured interview. Participants were able to contribute up to 10 interviews, but on average contributed 4.2 interviews over the 27-month period. Independent variables assessed partner-specific relationship quality (five items; scale range 5-25; alpha = .92, e.g., this partner is a very important person to me); and, number of coital events with a specific partner. Additional items assessed experience with oral contraceptive pills (OCP) use and injected depo medroxy-progesterone acetate (DMPA). The outcome variable was number of coital events without condom use during the past three months. Analyses were conducted as a three-level hierarchical linear growth curve model using HLM 6. The Level 1 predictor was time, to test the hypothesis that condom non-use increases over time. Level 2 predictors assessed relationship quality and coital frequency across all partners to assess hypotheses that participants' condom non-use increases over time as a function of relationship quality and coital frequency. Level 3 predictors assessed the participant-level influence of OCP or DMPA experience on time-related changes in condom non-use. RESULTS:A total of 176 women reported 279 sex partners and contributed 478 visits. Both average coital frequency and average condom non-use linearly increased during the 27-month follow-up. At any given follow-up, about 35% reported recent OCP use, and 65% reported DMPA use. HLM analyses showed that condom non-use increased as a function of time (beta = .12; p = .03, Level 1 analysis). Increased condom non-use over time was primarily a function of increased coital frequency (beta = .01; p = .00), although higher levels of relationship quality were associated with increased condom non-use at enrollment (beta = .44; p = .00, Level 2 analysis). The temporal rise in condom non-use significantly increased among DMPA users (beta = .06; p = .00) but not OCP users (Level 3 analysis) (beta = -.04; p = .06). CONCLUSIONS:Developmentally, relationship characteristics and coital frequency appear to have increasing weight in decisions about condom use. Hormonal contraceptive methods are not equivalently associated with the overall temporal decline in condom use. Future research associated with dual contraceptive/condom use should address differential factors associated condom use in combination with different hormonal methods.
    背景与目标:
  • 【与人类神经胶质瘤细胞系SNB-19获得性替莫唑胺抗性相关的遗传改变。】 复制标题 收藏 收藏
    DOI:10.1158/1535-7163.MCT-05-0428 复制DOI
    作者列表:Auger N,Thillet J,Wanherdrick K,Idbaih A,Legrier ME,Dutrillaux B,Sanson M,Poupon MF
    BACKGROUND & AIMS: :Gliomas are highly lethal neoplasms that cannot be cured by currently available therapies. Temozolomide is a recently introduced alkylating agent that has yielded a significant benefit in the treatment of high-grade gliomas. However, either de novo or acquired chemoresistance occurs frequently and has been attributed to increased levels of O6-methylguanine-DNA methyltransferase or to the loss of mismatch repair capacity. However, very few gliomas overexpress O6-methylguanine-DNA methyltransferase or are mismatch repair-deficient, suggesting that other mechanisms may be involved in the resistance to temozolomide. The purpose of the present study was to generate temozolomide-resistant variants from a human glioma cell line (SNB-19) and to use large-scale genomic and transcriptional analyses to study the molecular basis of acquired temozolomide resistance. Two independently obtained temozolomide-resistant variants exhibited no cross-resistance to other alkylating agents [1,3-bis(2-chloroethyl)-1-nitrosourea and carboplatin] and shared genetic alterations, such as loss of a 2p region and loss of amplification of chromosome 4 and 16q regions. The karyotypic alterations were compatible with clonal selection of preexistent resistant cells in the parental SNB-19 cell line. Microarray analysis showed that 78 out of 17,000 genes were differentially expressed between parental cells and both temozolomide-resistant variants. None are implicated in known resistance mechanisms, such as DNA repair, whereas interestingly, several genes involved in differentiation were down-regulated. The data suggest that the acquisition of resistance to temozolomide in this model resulted from the selection of less differentiated preexistent resistant cells in the parental tumor.
    背景与目标: : 神经胶质瘤是高度致命的肿瘤,目前可用的疗法无法治愈。替莫唑胺是最近引入的烷基化剂,在治疗高级别神经胶质瘤方面具有显着益处。然而,从头开始或获得的化学抗性经常发生,并且归因于O6-methylguanine-DNA甲基转移酶水平的升高或失配修复能力的丧失。然而,很少有神经胶质瘤过表达O6-methylguanine-DNA甲基转移酶或错配修复缺陷,这表明其他机制可能与替莫唑胺的耐药性有关。本研究的目的是从人神经胶质瘤细胞系 (SNB-19) 产生替莫唑胺抗性变体,并使用大规模基因组和转录分析来研究获得性替莫唑胺抗性的分子基础。两个独立获得的抗替莫唑胺的变体对其他烷基化剂 [1,3-双 (2-氯乙基)-1-亚硝基脲和卡铂] 没有交叉抗性,并且具有共同的遗传改变,例如2p区域的丢失和丢失染色体4和16q区域的扩增。核型改变与亲本SNB-19细胞系中先存的抗性细胞的克隆选择兼容。微阵列分析表明,17,000个基因中有78个在亲本细胞和替莫唑胺抗性变体之间差异表达。没有一个与已知的抗性机制 (例如DNA修复) 有关,而有趣的是,参与分化的几个基因被下调。数据表明,在该模型中获得对替莫唑胺的耐药性是由于在亲本肿瘤中选择了分化较少的耐药细胞。
  • 【在病因不明的原发性b细胞免疫缺陷儿童中鉴定人磷酸肌醇3激酶p110delta基因的变异。】 复制标题 收藏 收藏
    DOI:10.1111/j.1744-313X.2006.00627.x 复制DOI
    作者列表:Jou ST,Chien YH,Yang YH,Wang TC,Shyur SD,Chou CC,Chang ML,Lin DT,Lin KH,Chiang BL
    BACKGROUND & AIMS: :Our recent study demonstrated that defects in p110delta result in B-cell immunodeficiency that is very similar to that observed in BTK-deficient mice. We revealed that the p110delta fit the B-cell signal transduction complex and played a non-redundant role in the development and function of B cells. In humans, most children with primary B-cell immunodeficiency have mutations in the BTK, whereas a few have defects in the components of the B-cell signal transduction complex. But little is known about the genetic variation of p110delta in children with defects in B-cell immunodeficiency of unknown aetiology. Sixteen patients from 15 unrelated families and 112 normal controls underwent sequence analysis to identify genetic variations of the p110delta. Allele frequency in each group was also analysed and compared. We identified five single base-pair polymorphic nucleotide exchanges in both patient and control groups with similar allele frequencies, which did not contribute to the immunodeficiency. Three of them are novel (m.953A>G, m.1200C>T and m.1561A>G), and the m.953A>G and m.1561A>G nucleotide exchanges are non-synonymous (N253S and T456A, respectively). The novel m.1561A>G was in complete linkage disequilibrium with the known m.873A>G in our study of Taiwanese group. In addition, one novel single base-pair missense mutation, m.3256G>A (E1021K), was identified in one boy with typical clinical features of primary B-cell immunodeficiency and could not be found in either his family or the normal control population. By atomic structural analysis of the amino acid as well as the alignment comparison between species, it resulted in the replacement of the negative-charged amino acid E with the positive-charged amino acid K at codon 1021, located in the highly conservative and important catalytic functional domain. Our findings could shed light on further understanding the polymorphisms of p110delta in B-cell immunodeficiency and different populations. Moreover, the 3256G>A missense mutation raised the attention and warranted further extensive analysis to elucidate the role of p110delta in human immunodeficiency.
    背景与目标: : 我们最近的研究表明,p110delta的缺陷导致b细胞免疫缺陷,这与BTK缺陷小鼠中观察到的非常相似。我们揭示了p110delta符合b细胞信号转导复合物,并且在b细胞的发育和功能中起着非冗余的作用。在人类中,大多数患有原发性b细胞免疫缺陷的儿童在BTK中存在突变,而少数儿童在b细胞信号转导复合物的成分中存在缺陷。但是,对于病因不明的b细胞免疫缺陷儿童中p110delta的遗传变异知之甚少。来自15个无关家庭和112个正常对照的16名患者进行了序列分析,以鉴定p110delta的遗传变异。还对各组的等位基因频率进行了分析和比较。我们在患者组和对照组中鉴定出五个具有相似等位基因频率的单碱基对多态性核苷酸交换,这对免疫缺陷没有贡献。其中三个是新颖的 (m.953A>G,m.1200C>T和m.1561A>G),而m.953A>G和m.1561A>G核苷酸交换是非同义的 (分别为N253S和T456A)。在我们对台湾组的研究中,新颖的m.1561A>G与已知的m.873A>G完全处于连锁不平衡状态。此外,在一名具有原发性b细胞免疫缺陷典型临床特征的男孩中鉴定出一个新的单碱基对错义突变m.3256G>A (E1021K),在其家人或正常对照人群中均找不到。通过氨基酸的原子结构分析以及物种之间的比对比较,它导致负电荷氨基酸E被密码子1021位的正电荷氨基酸K取代,位于高度保守和重要的催化功能域。我们的发现可能有助于进一步了解b细胞免疫缺陷和不同人群中p110delta的多态性。此外,3256G>A错义突变引起了人们的注意,并需要进一步广泛的分析来阐明p110delta在人类免疫缺陷中的作用。
  • 【正常年轻和老年妇女肠道维生素d受体,钙吸收和血清1,25二羟基维生素d之间的关系。】 复制标题 收藏 收藏
    DOI:10.1359/jbmr.1997.12.6.922 复制DOI
    作者列表:Kinyamu HK,Gallagher JC,Prahl JM,DeLuca HF,Petranick KM,Lanspa SJ
    BACKGROUND & AIMS: The exact mechanism for the decrease in intestinal calcium absorption with age is not yet understood. A decrease with age in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein concentration are possible causes. The objective of this study was to examine the effect of age on these factors. Fifty-nine young women age 25-35 years were compared with 41 elderly women age 65-83 years who underwent measurements of VDR, calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic hormones. Calcium absorption by both tests was lower in the elderly women compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR protein concentration were not significantly different between the two age groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did not correlate with calcium absorption in young women or elderly women, nor did VDR correlate with serum 1,25(OH)2D and serum 25-hydroxyvitamin D. In summary, the decrease in calcium absorption cannot be explained by a decrease in intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium absorption tests only accounts for 12-30% of the variance in the age-related change in the calcium absorption tests. Other factors, not yet understood, are responsible for the decline in calcium absorption with age.

    背景与目标: 随着年龄的增长,肠道钙吸收减少的确切机制尚不清楚。血清1,25-二羟基维生素d (1,25(OH)2D) 随着年龄的增长而降低或肠道维生素d受体 (VDR) 蛋白浓度降低是可能的原因。这项研究的目的是检查年龄对这些因素的影响。将59名年龄在25-35岁之间的年轻女性与41名年龄在65-83岁之间的老年女性进行了比较,这些女性接受了VDR,使用20 mg和100 mg钙载体的钙吸收以及钙促激素的测量。与年轻女性相比,老年女性两种测试对钙的吸收均较低 (p <0.05)。血清1,25(OH)2D和十二指肠VDR蛋白浓度在两个年龄组之间没有显着差异。血清1,25(OH)2D与青年 (r = 0.35,p <0.007) 和老年妇女 (r = 0.58,p <0.0001) 的20 mg钙吸收试验相关,与老年人的100 mg钙吸收相关 (r = 0.32; p <0.05)。VDR与年轻女性或老年女性的钙吸收无关,也与血清1,25(OH)2D和血清25-羟基维生素d无关。总而言之,钙吸收的减少不能用肠道VDR的减少来解释。血清1,25(OH)2D与两种钙吸收测试之间的相关性仅占钙吸收测试中年龄相关变化的12-30%。其他尚未了解的因素是钙吸收随年龄下降的原因。
  • 15 Tietze's syndrome: a critical review. 复制标题 收藏 收藏

    【Tietze综合征: 批判性评论。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Aeschlimann A,Kahn MF
    BACKGROUND & AIMS: :A critical review of Tietze's syndrome and the relevant literature to date is presented. The disease has been characterized as a tender, non-suppurative swelling in the upper costosternal region. The etiology and pathology of the disease are still unknown. In the past decade new knowledge concerning rheumatic diseases affecting the anterior chest wall has modified our approach to this condition. Tietze's syndrome could be more a part of seronegative disease than has been previously recognized, even if the existence of this condition as an entity cannot be totally denied.
    背景与目标: : 提出了对Tietze综合征的重要评论和迄今为止的相关文献。该疾病的特征是在上胸骨区域的压痛,非化脓性肿胀。该病的病因和病理仍然未知。在过去的十年中,有关影响前胸壁的风湿性疾病的新知识改变了我们对这种情况的治疗方法。即使不能完全否认这种情况的存在,Tietze综合征也可能比以前认识到的更多是血清阴性疾病的一部分。

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