• 【电化学疗法对经典卡波西肉瘤中人疱疹病毒8动力学的影响。】 复制标题 收藏 收藏
    DOI:10.1186/s13027-017-0147-4 复制DOI
    作者列表:Starita N,Di Monta G,Cerasuolo A,Marone U,Anniciello AM,Botti G,Buonaguro L,Buonaguro FM,Tornesello ML
    BACKGROUND & AIMS: BACKGROUND:Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years. METHODS:A total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12-48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification. RESULTS:All KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10-7 to 6.9 × 10-4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No correlation was found between HHV8 subtypes and ECT complete response. CONCLUSIONS:ECT therapy has a significant effect on HHV8 kinetics in patients with classic KS. The complete remission of patients was accompanied by clearance of circulating virus.
    背景与目标: 背景:电化学疗法(ECT)已被证明是治疗皮肤和皮下卡波西肉瘤(KS)病变的有效方法。但是,尚无研究调查ECT治疗对人类8型疱疹病毒(HHV8)动力学的影响,后者被认为是KS的必要病因。我们旨在评估经典KS患者的HHV8病毒载量和表达水平,这些患者接受一种或多种ECT治疗,并且每半年进行长达四年的随访。
    方法:本研究共纳入27例经典KS患者。在ECT治疗之前获得了肿瘤活检和血液样本。在六个月的时间间隔内(12-48个月)收集更多的血液样本。通过实时评估所有样本中HHV8病毒载量和潜伏(ORF72和ORF73)和溶菌(K2,K8,K8.1,K10 / K10.1,K10.5 / K10.6和ORF16)基因的表达谱PCR。扩增HHV8 ORF26和K1区,并进行直接核苷酸测序,然后进行系统发育分析以鉴定变体。
    结果:在ECT治疗前收集的所有KS活检和46.4%的外周血单个核细胞(PBMC)均为HHV8 DNA阳性。 KS病变中的病毒载量为每细胞0.02至2.3拷贝,PBMC中每细胞的病毒载量为3.0×10-7至6.9×10-4拷贝。总体而言,潜在的ORF72和ORF73以及溶解性K2,K8和K10 / K10.1在所有KS活检中均表达。在KS样本中,ORF16 mRNA的检出率为71.4%,K8.1和K10.5 / K10.6 mRNA的检出率为57.1%。 ORF72,ORF73和K2转录本分别在ECT前收集的PBMC中扩增了37.5%,25%和25%。在第一次ECT会议之后,在六个月的随访中,27例患者中有20例(74.1%)获得了完全缓解,27例PBMC中有4例(14.8%)检测到HHV8 DNA。系统发育分析的ORF26扩增子表明,大多数病毒变体属于A / C(82.3%),很少属于C2(5.9%)或C3(11.8%)亚型。 K1 / VR1变异分为A(33.3%)和C(66.7%)HHV8进化枝。在HHV8亚型和ECT完全应答之间未发现相关性。
    结论:ECT治疗对经典KS患者的HHV8动力学有显着影响。患者的完全缓解伴随着循环病毒的清除。
  • 【基于单核苷酸多态性阵列的染色体核型分析在急性骨髓性白血病或骨髓增生异常综合症中,三体性8是唯一的染色体异常。】 复制标题 收藏 收藏
    DOI:10.1159/000343420 复制DOI
    作者列表:Hahm C,Mun YC,Seong CM,Han SH,Chung WS,Huh J
    BACKGROUND & AIMS: :The clinical heterogeneity of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with trisomy 8 as the sole abnormality may result from cytogenetically undetectable genetic changes. The purpose of this study was to identify hidden genomic aberrations not detected by metaphase cytogenetics (MC) using high-resolution single nucleotide polymorphism array (SNP-A)-based karyotyping in AML/MDS patients with a sole trisomy 8. The study group included 8 patients (3 AML and 5 MDS) and array-based karyotyping was done using whole-genome SNP-A (SNP 6.0 and SNP 2.7M). By SNP-A, additional genomic aberrations not detected by MC were identified in 2 patients: 1 AML patient exhibited a copy-neutral loss of heterozygosity (CN-LOH) of 3q21.1-q29 and 11q13.1-q25 and the other patient with MDS (refractory cytopenia with unilineage dysplasia) had CN-LOH of 2p25.3-p15. In particular, the latter patient progressed to AML 18 months after the diagnosis. In 3 patients, aberrations in addition to trisomy 8 were not identified by SNP-A. In the remaining 3 patients, SNP-A could not detect trisomy 8, while trisomy 8 was found in 25-67% of metaphase cells by MC. This study suggests that additional genomic aberrations may in fact be present even in cases of trisomy 8 as sole abnormality by MC, and SNP-A could be a useful karyotyping tool to identify hidden aberrations such as CN-LOH.
    背景与目标: :急性髓细胞性白血病(AML)或骨髓增生异常综合症(MDS)的8号三体症为唯一异常的临床异质性可能是由于细胞遗传学上无法检测到的遗传变化所致。这项研究的目的是使用高分辨率三核苷酸多态性阵列(SNP-A)基于核型分型的AML / MDS唯一三体性患者,鉴定中期细胞遗传学(MC)未检测到的隐藏基因组畸变。该研究组包括使用全基因组SNP-A(SNP 6.0和SNP 2.7M)进行了8例患者(3例AML和5例MDS)和基于阵列的核型分析。通过SNP-A,在2例患者中发现了MC未检测到的其他基因组异常:1例AML患者表现出3q21.1-q29和11q13.1-q25的拷贝中性杂合度(CN-LOH)丧失,另一例患者MDS(难治性血细胞减少症伴单系发育不良)患者的CN-LOH为2p25.3-p15。特别是,后者在诊断后18个月发展为AML。在3例患者中,SNP-A未鉴定到8号三体畸变。在剩下的3名患者中,SNP-A无法检测到8三体,而MC在25-67%的中期细胞中发现了8三体。这项研究表明,即使在三体性8病例中,由于MC唯一异常,实际上也可能存在其他基因组畸变,而SNP-A可能是一种有用的核型分析工具,可识别诸如CN-LOH之类的隐藏畸变。
  • 【胃造口术喂养的结构化满意度调查表(SAGA-8)的胃食管反流营养支持儿童的心理计量学特性。】 复制标题 收藏 收藏
    DOI:10.1111/jhn.12000 复制DOI
    作者列表:Martínez-Costa C,Calderón C,Pedrón-Giner C,Borraz S,Gómez-López L
    BACKGROUND & AIMS: BACKGROUND:To analyse the psychometric properties of the structured Satisfaction Questionnaire with Gastrostomy Feeding (SAGA-8) in parents/caregivers of children with home enteral nutrition (HEN) by gastrostomy tube (GT). METHODS:Eighty-six caregivers (mothers) of paediatric patients with HEN by GT were recruited. Patients suffered from neurological disease (61.6%) and other chronic diseases. The SAGA-8 scale, a structured questionnaire to explore satisfaction with HEN by GT, and the Caregiver Burden Inventory (Zarit) were completed. The discriminating power of each of the SAGA-8 items, internal consistency and external validity were evaluated. An exploratory factor analysis and Kaiser-Meyer-Olkin (KMO) was performed as well. RESULTS:Eighty-four percent of the families expressed high satisfaction with GT feeding. All eight items of SAGA-8 gave additional information. The exploratory factor analysis revealed that a significant part of the items' variability could be explained by two independent factors: Factor 1 (direct benefit), which compiled the variables related to the perception of children's overall improvement by GT feeding; Factor 2 (indirect benefit), which grouped the variables related to a decrease in respiratory infections, feeding time and institutional support. Results from KMO (0.628) indicated the high adequacy of the items assessed in the factorial analysis. Moreover, the questionnaire presented high internal consistency (0.76), and the external validation analysis confirmed the correlation between SAGA-8 and Zarit, thereby emphasising the approptiate use of the SAGA-8 to detect carers' satisfaction. CONCLUSIONS:The SAGA-8 questionnaire has a high discriminatory power to assess the degree of satisfaction experienced by parents/caregivers of children with HEN by GT and, subsequently, the patients' wellbeing.
    背景与目标: 背景:目的通过胃造口管(GT)分析胃肠道营养喂养(HEN)患儿父母/照顾者的胃造口喂养结构满意度调查表(SAGA-8)的心理计量学特征。
    方法:招募了86例小儿HEN患者的GT照护者(母亲)。患者患有神经系统疾病(61.6%)和其他慢性疾病。已完成SAGA-8量表,用于探索GT对HEN满意程度的结构化问卷以及Caregiver Burden清单(Zarit)。评估了每个SAGA-8项目的辨别力,内部一致性和外部有效性。还进行了探索性因素分析和Kaiser-Meyer-Olkin(KMO)。
    结果:84%的家庭对GT喂养表示高度满意。 SAGA-8的所有八项均提供了附加信息。探索性因素分析表明,项目差异的很大一部分可以由两个独立的因素解释:因子1(直接收益),该变量汇总了与GT喂养对儿童总体改善知觉有关的变量;因素2(间接收益),将与呼吸道感染减少,进食时间和机构支持有关的变量分组。 KMO(0.628)的结果表明,析因分析中所评估项目的充分性很高。此外,该问卷具有较高的内部一致性(0.76),并且外部验证分析证实了SAGA-8和Zarit之间的相关性,从而强调了合理使用SAGA-8来检测护理人员的满意度。
    结论:SAGA-8问卷具有很高的判别力,可以评估GT患儿的父母/监护人对HEN的满意程度,并随后评估患者的幸福感。
  • 【在日本患有局部前列腺癌的男性中,与健康相关的生活质量:用SF-8进行评估。】 复制标题 收藏 收藏
    DOI:10.1111/j.1442-2042.2008.02046.x 复制DOI
    作者列表:Sugimoto M,Takegami M,Suzukamo Y,Fukuhara S,Kakehi Y
    BACKGROUND & AIMS: OBJECTIVES:To evaluate health related quality of life (HRQOL) using the Medical Outcomes Study 8-items Short Form Health Survey (SF-8) questionnaire in Japanese patients with early prostate cancer. METHODS:A cross-sectional analysis was done in 457 patients with prostate cancer treated with radical prostatectomy, external beam radiotherapy, brachytherapy, androgen deprivation therapy, and watchful waiting or a combination these therapies. General HRQOL was measured using the Japanese version of the SF-8 questionnaire and disease-specific HRQOL was assessed using the Japanese version of the Extended Prostate Cancer Index Composite. RESULTS:The external beam radiotherapy group reported significantly lower values for the physical health component summary score (PCS) in comparison to the radical prostatectomy and brachytherapy groups (P < 0.05). In the analysis of both the PCS and the mental health component summary score (MCS) over time after treatment, higher scores with time were found in the radical prostatectomy group. No significant change over time after androgen deprivation therapy in the PCS was found. In contrast, the MCS was found to deteriorate in the early period, showing a significant increase over time. CONCLUSIONS:SF-8 in combination with the Extended Prostate Cancer Index Composite has shown to be a helpful tool in the HRQOL assessment of Japanese patients treated for localized prostate cancer.
    背景与目标: 目的:使用医疗结果研究8项简式健康调查(SF-8)问卷对日本早期前列腺癌患者进行健康相关生活质量(HRQOL)评估。
    方法:对457例前列腺癌患者进行横断面分析,这些患者接受了前列腺癌根治术,外照射,放疗,近距离放射疗法,雄激素剥夺疗法以及警惕的等待或这些疗法的联合治疗。普通HRQOL使用日文版SF-8问卷进行测量,而疾病特异性HRQOL使用日文版扩展前列腺癌指数复合材料进行评估。
    结果:与放射根治性前列腺切除术和近距离放射治疗组相比,外束放射治疗组报告的身体健康成分摘要评分(PCS)值明显更低(P <0.05)。在分析治疗后随时间变化的PCS和精神健康成分总评分(MCS)时,根治性前列腺切除术组随时间的推移发现了更高的评分。在PCS中,雄激素剥夺治疗后未发现随时间的显着变化。相反,发现MCS在早期恶化,显示随时间的推移显着增加。
    结论:SF-8与前列腺癌指数综合指数的组合已被证明是对接受局部前列腺癌治疗的日本患者进行HRQOL评估的有用工具。
  • 【TIM桶蛋白折叠的拓扑结构和序列:全局分析突出了功能未知的(betaalpha)8桶的复杂折叠机制中瞬态途径和稳定途径折叠中间体之间的分配】 复制标题 收藏 收藏
    DOI:10.1016/j.jmb.2007.06.018 复制DOI
    作者列表:Forsyth WR,Bilsel O,Gu Z,Matthews CR
    BACKGROUND & AIMS: :The relative contributions of chain topology and amino acid sequence in directing the folding of a (betaalpha)(8) TIM barrel protein of unknown function encoded by the Bacillus subtilis iolI gene (IOLI) were assessed by reversible urea denaturation and a combination of circular dichroism, fluorescence and time-resolved fluorescence anisotropy spectroscopy. The equilibrium reaction for IOLI involves, in addition to the native and unfolded species, a stable intermediate with significant secondary structure and stability and self-associated forms of both the native and intermediate states. Global kinetic analysis revealed that the unfolded state partitions between an off-pathway refolding intermediate and the on-pathway equilibrium intermediate early in folding. Comparisons with the folding mechanisms of two other TIM barrel proteins, indole-3-glycerol phosphate synthase from the thermophile Sulfolobus solfataricus (sIGPS) and the alpha subunit of Escherichia coli tryptophan synthase (alphaTS), reveal striking similarities that argue for a dominant role of the topology in both early and late events in folding. Sequence-specific effects are apparent in the magnitudes of the relaxation times and relative stabilities, in the presence of additional monomeric folding intermediates for alphaTS and sIGPS and in rate-limiting proline isomerization reactions for alphaTS.
    背景与目标: :通过可逆的尿素变性和环状结合的方法评估了链拓扑结构和氨基酸序列在指导由枯草芽孢杆菌iolI基因(IOLI)编码的未知功能的βα(8)TIM桶蛋白折叠中的相对贡献二向色性,荧光和时间分辨荧光各向异性光谱。除了天然和未折叠的物种外,IOLI的平衡反应还涉及具有明显二级结构和稳定性以及天然状态和中间状态的自缔合形式的稳定中间体。全局动力学分析显示,折叠初期,未折叠状态在非通路折叠中间体和通路平衡中间体之间分配。与其他两种TIM桶蛋白的折叠机制进行比较,即嗜热嗜盐菌(sulfolobus solfataricus)的吲哚-3-甘油磷酸合酶(sIGPS)和大肠杆菌色氨酸合酶(alphaTS)的α亚基,发现了惊人的相似之处,这些相似之处证明了它们的主导作用折叠中早期和晚期事件中的拓扑。在存在额外的αTS和sIGPS单体折叠中间体的情况下,以及在αTS的限速脯氨酸异构化反应中,序列特异性效应在弛豫时间和相对稳定性的大小上很明显。
  • 【小儿尿路结石:单中心的8年经验。】 复制标题 收藏 收藏
    DOI:10.1007/s11255-007-9234-6 复制DOI
    作者列表:Dursun I,Poyrazoglu HM,Dusunsel R,Gunduz Z,Gurgoze MK,Demirci D,Kucukaydin M
    BACKGROUND & AIMS: OBJECTIVE:The objective was to investigate the clinical features and metabolic and anatomic risk factors for kidney stone formation in our patient group. METHODS:Between 1998 and 2005, 179 children (94 girls, 85 boys) followed in our department because of urolithiasis were enrolled to participate in our study. Clinical presentation, urinary tract infection, stone localisation, positive family history, stone composition, presence of anatomic abnormalities and urinary metabolic risk factors, and treatment modality were evaluated retrospectively. RESULTS:The mean age at diagnosis of stone disease was 4.5 years (range 0.25-15.3 years). The mean follow-up duration was 8 months (range 1-98). The major clinical presentations of our patients were abdominal pain and/or flank pain in 100 children (55.9%) and macroscopic hematuria in 25 (14%). Urinary tract infection was detected in 20% of patients on admission. Forty-three children (24%) had a urinary tract abnormality and ureteropelvic junction obstruction was the most common abnormality. A family history of stone disease was recorded in 98 patients (54.7%). Stones were located within the renal parenchyma in 90 patients. Hypercalciuria and hyperuricosuria were detected in 42.3 and 54.8% respectively. Stone analysis was performed in 63 children and calcium oxalate was a major mineral. Surgical treatment was performed in 49 children and extracorporeal shock wave lithotripsy (ESWL) in 41 children. CONCLUSION:We think that urolithiasis remains a serious problem in children in our country. Family history of urolithiasis, urologic abnormalities (especially under the age of 5 years), metabolic disorders and urinary tract infections tend to indicate childhood urolithiasis.
    背景与目标: 目的:探讨本组患者肾结石形成的临床特征以及代谢和解剖危险因素。
    方法:在1998年至2005年之间,由于尿路结石而在我科随访的179名儿童(94名女孩,85名男孩)参加了我们的研究。回顾性评估临床表现,尿路感染,结石定位,阳性家族史,结石成分,解剖学异常和尿代谢危险因素的存在以及治疗方式。
    结果:诊断为结石病的平均年龄为4.5岁(范围为0.25-15.3岁)。平均随访时间为8个月(范围1-98)。我们患者的主要临床表现为100名儿童(55.9%)的腹痛和/或胁腹痛和25名儿童(14%)的肉眼血尿。入院时有20%的患者检测到尿路感染。 43名儿童(占24%)患有尿路异常,输尿管盆腔交界处梗阻是最常见的异常。记录了98例(54.7%)的家族结石病史。结石位于肾实质内的90例患者中。尿钙尿过多和尿尿尿过多的检出率分别为42.3和54.8%。对63名儿童进行了结石分析,草酸钙是主要矿物质。对49例儿童进行了手术治疗,对41例儿童进行了体外冲击波碎石术(ESWL)。
    结论:我们认为尿石症在我国儿童中仍然是一个严重的问题。尿石症的家族病史,泌尿系统异常(尤其是5岁以下),代谢异常和尿路感染往往表明儿童期尿石症。
  • 【抑制念珠菌物种生长的新型抗真菌剂:二氯8-喹啉醇。】 复制标题 收藏 收藏
    DOI:10.1023/a:1007120913871 复制DOI
    作者列表:Lentz DL,Gershon H,Marini H
    BACKGROUND & AIMS: :Five dichlorinated 8-quinolinols (2,5- 5,6-, 3,5-, 3,7-, and 4,5-dichloro-8-quinolinol) were tested against Candida albicans and C. tropicalis in Sabouraud dextrose broth with and without bovine serum. The 5,6-, 3,5-, and 3,7-dichloro-8-quinolinols proved to be more effective than the control, 5-fluorocytosine. In cytotoxicity tests employing baby hamster kidney (BHK) cells, all test agents proved to be more cytotoxic than the control. However, the minimum inhibitory concentration (MIC) of 3,5-dichloro-8-quinolinol to both fungi was only one tenth the cytotoxic dose, suggesting that the compound may be useful as a topical or systemic antifungal agent.
    背景与目标: :在Sabouraud葡萄糖肉汤中测试了五种二氯8-喹啉醇(2,5- 5,6-,3,5-,3,7-和4,5-二氯8-喹啉醇)对白色念珠菌和热带念珠菌的抵抗力有和没有牛血清。 5,6-,3,5-和3,7-二氯-8-喹啉醇被证明比对照的5-氟胞嘧啶更有效。在使用小仓鼠肾脏(BHK)细胞的细胞毒性测试中,所有测试药物均被证明比对照更具细胞毒性。但是,3,5-二氯-8-喹啉醇对两种真菌的最小抑制浓度(MIC)仅是细胞毒性剂量的十分之一,表明该化合物可用作局部或全身性抗真菌剂。
  • 【降钙素基因相关肽(CGRP)受体拮抗剂CGRP(8-37)对滑膜血流量的调节。】 复制标题 收藏 收藏
    DOI:10.1038/sj.bjp.0701237 复制DOI
    作者列表:McMurdo L,Lockhart JC,Ferrell WR
    BACKGROUND & AIMS: 1. The effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(8-37) on blood flow in the knee joint of the anaesthetized rat was investigated. 2. Synovial blood flow in both exposed and intact, skin-covered knees was measured by laser Doppler perfusion imaging. 3. Topical application of CGRP(8-37) caused a dose-dependent fall in synovial blood flow in the exposed knee joint of the rat. At low (1.5 nmol) doses of CGRP(8-37) there was no significant effect on synovial blood flow. In rats treated with 7.5 nmol CGRP(8-37) there was a fall in synovial blood flow (maximum effect at 10 min-28.8 +/- 4.6%; n=7), which returned to resting levels within 30 min.

    The highest dose (15 nmol) of antagonist used in this study caused a marked (maximum at 10 min-35.6 +/- 9.3%; n=8), and prolonged (up to 30 min) fall in blood flow. 4.

    Ten days after surgical denervation, CGRP(9-37) (15 nmol, topical) had no significant effect on blood flow in the rat exposed knee joint (change in flux at 10 min-5.1+/-3.6%; n=4). This suggests that CGRP(8-37) acts selectively to antagonize the actions of a neurally derived product, probably CGRP, on the rat synovial vasculature. 5.

    In skin-covered knee joints, intra-articular injection of CGRP(8-37) (15 nmol; bolus) elicited a significant fall in synovial blood flow (maximum effect at 10 min-15.5 +/- 5.8%; n=6). 6. CGRP (0.01, 0.1 or 1.0 nmol; topical) caused a dose-dependent increase in exposed knee joint blood flow, which was attenuated by co-administration of 1.5 nmol CGRP(8-37). For example, 1 nmol CGRP elicited a peak increase in flux at 10 min of 94.7 +/- 31.8% (n=8) and 28.8 +/- 8.9% (n=7) in the absence and presence of CGRP(8-37), respectively. The vasodilator responses induced by acetylcholine (ACh) (10 nmol, topical; n=4-5) or sodium nitroprusside (SNP) (10 nmol, topical; n=4-5) were unaltered in the presence of CGRP(8-37) (1.5 nmol, topical). 7. Thus, the CGRP receptor antagonist CGRP(8-37) elicits vasoconstriction in the rat synovium. This suggests that the endogenous, basal release of CGRP may play a physiological role in the regulation of blood flow in the rat knee joint.

    背景与目标: 1.研究了降钙素基因相关肽(CGRP)受体拮抗剂CGRP(8-37)对麻醉大鼠膝关节血流的影响。 2.通过激光多普勒灌注成像测量暴露的和完整的,皮肤覆盖的膝盖中的滑膜血流量。 3.局部应用CGRP(8-37)导致大鼠裸露的膝关节滑膜血流量呈剂量依赖性下降。在低剂量(1.5 nmol)的CGRP(8-37)下,滑膜血流没有明显影响。在用7.5 nmol CGRP(8-37)治疗的大鼠中,滑膜血流量下降(在10分钟时达到最大作用,即28.8 /-4.6%; n = 7),并在30分钟内恢复了静息水平。

    本研究中使用的最高剂量的拮抗剂(15 nmol)引起明显的症状(最大10min时为35.6 /-9.3%; n = 8),并导致血流持续时间延长(长达30分钟)。 4.

    去神经手术后十天,CGRP(9-37)(15 nmol,局部用)对大鼠裸露膝关节的血流没有明显影响(在10分钟时血流变化-5.1 /- 3.6%; n = 4)。这表明CGRP(8-37)选择性地拮抗神经源性产物(可能是CGRP)对大鼠滑膜脉管系统的作用。 5.

    在皮肤覆盖的膝关节中,关节腔内注射CGRP(8-37)(15 nmol;推注)引起滑膜血流量显着下降(在10 min-15.5时最大作用) 5.8%; n = 6)。 6. CGRP(0.01、0.1或1.0 nmol;局部用药)引起暴露的膝关节血流量呈剂量依赖性增加,并与1.5 nmol CGRP(8-37)并用可减弱这种作用。例如,在不存在和存在CGRP(8-37)的情况下,1 nmol CGRP在10分钟时引起的通量峰值分别为94.7 /-31.8%(n = 8)和28.8 /-8.9%(n = 7),分别。在存在CGRP(8-37)的情况下,乙酰胆碱(ACh)(10 nmol,局部; n = 4-5)或硝普钠(SNP)(10 nmol,局部; n = 4-5)诱导的血管舒张反应没有改变。 )(1.5 nmol,局部用)。 7.因此,CGRP受体拮抗剂CGRP(8-37)在大鼠滑膜中引起血管收缩。这表明CGRP的内源性基础释放可能在调节大鼠膝关节血流中起着生理作用。

  • 【血清型5和8胶囊表达的金黄色葡萄球菌等位基因遗传基因座包含侧翼常见基因的特定类型基因。】 复制标题 收藏 收藏
    DOI:10.1099/00221287-143-7-2395 复制DOI
    作者列表:Sau S,Bhasin N,Wann ER,Lee JC,Foster TJ,Lee CY
    BACKGROUND & AIMS: The nucleotide sequences of two gene clusters, cap5 and cap8, involved in the synthesis of Staphylococcus aureus type 5 and type 8 capsular polysaccharides (CPs), respectively were determined. Each gene cluster contained 16 ORFs, which were named cap5A through cap5P for type 5 CP and cap8A through cap8P for type 8 CP. The cap5 and cap8 loci were allelic and were mapped to the SmaI-G fragment in the standard SmaI map of Staph. aureus strain NCTC 8325. The predicted gene products of cap5A through cap5G and cap5L through cap5P are essentially identical to those of cap8A through cap8G and cap8L through cap8P, respectively, with very few amino acid substitutions. Four ORFs located in the central region of each locus are type-specific. A comparison of the predicted amino acid sequences of cap5 and cap8 with sequences found in the databases allowed tentative assignment of functions to 15 of the 16 ORFs. The majority of the capsule genes are likely to be involved in amino sugar synthesis; the remainder are likely to be involved in sugar transfer, capsule chain-length regulation, polymerization and transport.

    背景与目标: 确定了分别与金黄色葡萄球菌5型和8型荚膜多糖(CP)合成有关的两个基因簇cap5和cap8的核苷酸序列。每个基因簇包含16个ORF,对于5型CP,它们分别被命名为cap5A至cap5P,对于8 CP型,其命名为cap8A至cap8P。 cap5和cap8位点是等位基因,并在Staph的标准SmaI图中定位到SmaI-G片段。金黄色葡萄球菌菌株NCTC8325。cap5A至cap5G和cap5L至cap5P的预测基因产物分别与cap8A至cap8G和cap8L至cap8P相同,只有很少的氨基酸取代。位于每个基因座中心区域的四个ORF是特定于类型的。将cap5和cap8的预测氨基酸序列与数据库中发现的序列进行比较,可以将功能暂时分配给16个ORF中的15个。大多数的胶囊基因可能参与了氨基糖的合成。其余的可能与糖的转移,胶囊的链长调节,聚合和运输有关。

  • 【在含有卡波西氏肉瘤相关疱疹病毒/人类疱疹病毒-8的原发性渗出性淋巴瘤中,爱泼斯坦-巴尔病毒潜伏基因的表达。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Horenstein MG,Nador RG,Chadburn A,Hyjek EM,Inghirami G,Knowles DM,Cesarman E
    BACKGROUND & AIMS: Primary effusion (body cavity-based) lymphoma (PEL) is a recently recognized subtype of malignant lymphoma that exhibits distinctive clinical and biological features, most notably its usual infection with the Kaposi's sarcoma-associated herpesvirus (KSHV). The vast majority of cases also contain Epstein-Barr virus (EBV). This dual viral infection is the first example of a consistent dual herpesviral infection in a human neoplasm and provides a unique model to study viral interactions. We analyzed the pattern of EBV latent gene expression to determine the pathogenic role of this agent in PELs. We examined five PELs coinfected with EBV and KSHV by reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. EBER1 mRNA, a consistent marker of viral latency, was positive in all PEL cases, although at lower levels than in the non-PEL controls due to EBER1 expression by only a variable subset of lymphoma cells. Qp-initiated mRNA, encoding only EBNA1 and characteristic of latencies I and II, was positive in all PEL cases. Wp- and Cp-initiated mRNAs, encoding all EBNAs and characteristic of latency III, were negative in all cases. LMP1 mRNA, expressed in latencies II and III, was present in three cases of PEL, although at very low levels that were not detectable at the protein level by immunohistochemistry. Low levels of LMP2A mRNA were detected in all cases. BZLF1, an early-intermediate lytic phase marker, was weakly positive in four cases, suggesting a productive viral infection in a very small proportion of cells, which was confirmed by ZEBRA antigen expression. Therefore, PELs exhibit a restricted latency pattern, with expression of EBNA1 in all cases, and low LMP1 and LMP2A levels.

    背景与目标: 原发性积液(基于体腔的)淋巴瘤(PEL)是最近公认的恶性淋巴瘤亚型,具有独特的临床和生物学特征,最常见的是卡波西氏肉瘤相关疱疹病毒(KSHV)的常见感染。绝大多数病例还包含爱泼斯坦-巴尔病毒(EBV)。这种双重病毒感染是人类肿瘤中一致的双重疱疹病毒感染的第一个例子,并提供了研究病毒相互作用的独特模型。我们分析了EBV潜伏基因表达的模式,以确定这种药物在PEL中的致病作用。我们通过逆转录-聚合酶链反应(RT-PCR),原位杂交和免疫组化检查了五种同时感染EBV和KSHV的PEL。 EBER1 mRNA是病毒潜伏期的一个稳定标志,在所有PEL病例中均为阳性,尽管由于非淋巴瘤细胞仅由一个可变子集表达EBER1而水平低于非PEL对照。在所有PEL病例中,Qp启动的mRNA仅编码EBNA1,并具有I和II潜伏期特征。在所有情况下,Wp和Cp起始的mRNA编码所有EBNA并具有潜伏期III的特征,均为阴性。 LMP1 mRNA在潜伏期II和III中表达,存在于3例PEL病例中,尽管其水平非常低,而通过免疫组织化学检测却无法在蛋白质水平上检测到。在所有情况下均检测到低水平的LMP2A mRNA。 BZLF1是一种早期中间裂解相标志物,在4例病例中呈弱阳性,表明在极小比例的细胞中发生了生产性病毒感染,这可通过ZEBRA抗原表达得到证实。因此,PEL表现出受限制的等待时间模式,在所有情况下都具有EBNA1的表达,并且LMP1和LMP2A水平较低。

  • 【勘误表:Hopp,A.K。等。 NAD和ADP核糖基化对葡萄糖代谢的调节。 Cells 2019,8,890。】 复制标题 收藏 收藏
    DOI:10.3390/cells8111371 复制DOI
    作者列表:Hopp AK,Grüter P,Hottiger MO
    BACKGROUND & AIMS: :Change in References list order. [...].
    背景与目标: :更改参考列表的顺序。 [...]。
  • 【c-FLIP抑制在乳腺癌细胞中诱导不依赖配体的DR5-,FADD-,caspase-8-和caspase-9依赖性凋亡。】 复制标题 收藏 收藏
    DOI:10.1016/j.bcp.2008.09.007 复制DOI
    作者列表:Day TW,Huang S,Safa AR
    BACKGROUND & AIMS: :Cellular-FLICE inhibitory protein (c-FLIP) is an inhibitor of apoptosis downstream of the death receptors Fas, DR4, and DR5, and is expressed as long (c-FLIP(L)) and short (c-FLIP(S)) splice forms. We found that the knockdown of c-FLIP using small interfering RNA (siRNA) triggered ligand-independent caspase-8- and -9-dependent spontaneous apoptosis and decreased the proliferation of MCF-7 breast cancer cells. Further analysis revealed that an apoptotic inhibitory complex (AIC) comprised of DR5, FADD, caspase-8, and c-FLIP(L) exists in MCF-7 cells, and the absence of c-FLIP(L) from this complex induces DR5- and FADD-mediated caspase-8 activation in the death inducing signaling complex (DISC). c-FLIP(S) was not detected in the AIC, and using splice form-specific siRNAs we showed that c-FLIP(L) but not c-FLIP(S) is required to prevent spontaneous death signaling in MCF-7 cells. These results clearly show that c-FLIP(L) prevents ligand-independent death signaling and provides direct support for studying c-FLIP as a relevant therapeutic target for breast cancers.
    背景与目标: :细胞FLICE抑制蛋白(c-FLIP)是死亡受体Fas,DR4和DR5下游的凋亡抑制剂,表达为长(c-FLIP(L))和短(c-FLIP(S) )拼接形式。我们发现使用小干扰RNA(siRNA)敲低c-FLIP会触发不依赖配体的caspase-8和-9依赖性自发凋亡,并降低MCF-7乳腺癌细胞的增殖。进一步的分析表明,MCF-7细胞中存在由DR5,FADD,caspase-8和c-FLIP(L)组成的凋亡抑制复合物(AIC),并且该复合物中不存在c-FLIP(L)会诱导DR5。 -和FADD介导的caspase-8激活在死亡诱导信号复合物(DISC)中。在AIC中未检测到c-FLIP(S),并且使用剪接形式特异性siRNA,我们证明了c-FLIP(L)而非c-FLIP(S)是防止MCF-7细胞自发死亡信号所必需的。这些结果清楚地表明,c-FLIP(L)可以防止配体依赖性死亡信号传导,并为研究c-FLIP作为乳腺癌的相关治疗靶标提供了直接支持。
  • 【HIV-1整合酶的5-(1-H或1-烷基-5-氧代吡咯烷-3-基)-8-羟基-[1,6]-萘啶-7-羧酰胺抑制剂的合成。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2008.08.038 复制DOI
    作者列表:Melamed JY,Egbertson MS,Varga S,Vacca JP,Moyer G,Gabryelski L,Felock PJ,Stillmock KA,Witmer MV,Schleif W,Hazuda DJ,Leonard Y,Jin L,Ellis JD,Young SD
    BACKGROUND & AIMS: :HIV-1 integrase catalyzes the insertion of viral DNA into the genome of the host cell. Integrase inhibitor N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide selectively inhibits the strand transfer process of integration. 4-Substituted pyrrolidinones possessing various groups on the pyrrolidinone nitrogen were introduced at the 5-position of the naphthyridine scaffold. These analogs exhibit excellent activity against viral replication in a cell-based assay. The preparation of these compounds was enabled by a three-step, two-pot reaction sequence from a common butenolide intermediate.
    背景与目标: :HIV-1整合酶催化病毒DNA插入宿主细胞的基因组。整合酶抑制剂N-(4-氟苄基)-8-羟基-1,6-萘啶-7-羧酰胺选择性地抑制整合的链转移过程。将具有在吡咯烷酮氮上的各种基团的4-取代的吡咯烷酮引入到萘啶支架的5-位。这些类似物在基于细胞的测定中显示出优异的抗病毒复制活性。这些化合物的制备可通过一个三步,两锅的反应流程从一个常见的丁烯内酯中间体进行。
  • 【6至8岁儿童的总糖摄入量以及大量和微量营养素:ANIVA研究。】 复制标题 收藏 收藏
    DOI:10.3390/nu12020349 复制DOI
    作者列表:Morales-Suarez-Varela M,Peraita-Costa I,Llopis-Morales A,Picó Y,Bes-Rastrollo M,Llopis-Gonzalez A
    BACKGROUND & AIMS: :The objective of this study was to study the association between total sugar intake (TSI) levels of children aged 6-8 years old, nutrient intake and anthropometry. Food and beverage intakes were collected by a prospective three-day recall questionnaire. The 2237 children were distributed into three groups according to TSI percentiles. Mean TSI was 93.77 ± 25.72 g/day, 22%-25% of total caloric intake, with boys presenting an intake of 96.24 ± 24.34 g/day and girls 91.38 ± 26.78 g/day. Greater TSI was associated with higher body fat, parental education, energy intake, nutrients/1000 kcal, and lower weight z-scores, BMI z-scores, waist circumferences, and hip circumferences. Weight, height, and waist circumference had the highest R2 while body fat had the lowest. The percentage of total energy derived (%E) from protein decreased as the %E from TSI increased, while the opposite was true for carbohydrates and saccharides, while for fiber intake, the medium groups presented the highest intake/1000 kcal. For the remaining macronutrients studied, intake/1000 kcal decreased when the %E from TSI increased. Calcium, iodine, magnesium, vitamin B2, folate, and vitamin C intake increased as the %E from TSI increased, while the opposite was true for vitamin B12. Fiber, ω-6 PUFA, iodine, folate, vitamin D, and vitamin E intakes were insufficient across most of the sample. TSI levels in children were identified to exceed adult recommendations. It is not clear what the effect of up to an average of 21% of energy coming from total sugars has on childhood obesity and further research is needed in the pediatric population, however, opportunities exist to improve sugar intake patterns.
    背景与目标: :这项研究的目的是研究6-8岁儿童的总糖摄入(TSI)水平,营养摄入和人体测量学之间的关系。通过前瞻性三天召回问卷收集食物和饮料的摄入量。根据TSI百分位数,将2237名儿童分为三组。平均TSI为93.77±25.72 g /天,占总热量摄入的22%-25%,其中男孩摄入量为96.24±24.34 g /天,女孩摄入量为91.38±26.78 g /天。较高的TSI与较高的体脂,父母教育,能量摄入,营养素/ 1000大卡和较低的Z分数,BMI Z分数,腰围和臀围有关。体重,身高和腰围R2最高,而体脂最低。随着TSI的%E的增加,来自蛋白质的总能量的百分比(%E)降低,而碳水化合物和糖类则相反,而对于纤维的摄入,中型组的摄入量最高/ 1000 kcal。对于剩余的大量营养素,当TSI的%E升高时,摄入量/ 1000 kcal降低。随着TSI的%E升高,钙,碘,镁,维生素B2,叶酸和维生素C的摄入量也增加,而维生素B12则相反。大部分样品中纤维,ω-6PUFA,碘,叶酸,维生素D和维生素E的摄入量不足。确定儿童中的TSI水平超过成人推荐水平。目前尚不清楚平均高达21%的总糖分能量对儿童肥胖有何影响,儿科人群需要进一步研究,但是,仍有改善糖分摄入方式的机会。
  • 【心电图决定8焦耳电击对房室结消融疗效的决定因素。】 复制标题 收藏 收藏
    DOI:10.1093/oxfordjournals.eurheartj.a059947 复制DOI
    作者列表:Jordaens L,Van Wassenhove E,Clement L
    BACKGROUND & AIMS: :Factors determining the success of a single, low-energy, direct current-shock to achieve chronic complete heart block were studied in a consecutive group of 14 patients. A shock of 8 J was delivered by a modified device (Sirecust BS1, Siemens). If the first shock did not produce persistent complete block, multiple shocks were given. Standard 6 French U.S.C.I. catheters were used for all procedures. Chronic complete heart block was achieved with a single shock in six cases (43%; Group I); in eight others multiple shocks were needed (Group II). Neither polarity of the bipolar and of the distal His bundle recording nor the presence of sinus rhythm before the first shock were important factors to predict the outcome. The amplitude of the first recording of the bipolar His electrogram was 225 +/- 55 microV in Group I and 138 +/- 105 microV in Group II (P = 0.029). The duration of the HV interval before the first shock was 55 +/- 12 ms in Group I and 45 +/- 11 ms in Group II (NS). It is concluded that complete permanent heart block can be achieved with a single 8-J shock in 43% of the patients. The long-term success (follow-up at least 1 month, with a range of 1 to 8) of a single 8-J shock is predicted by a large amplitude of the bipolar and distal unipolar His bundle deflection, but not by its polarity or the HV interval.
    背景与目标: :在连续的14例患者中,研究了确定单个低能量,直流电休克成功实现慢性完全性心脏传导阻滞的因素。修改后的设备(Sirecust BS1,西门子)提供了8 J的电击。如果第一次电击未产生持续的完全阻塞,则给予多次电击。标准6法国U.S.C.I.导管用于所有程序。单例休克实现了慢性完全性心脏传导阻滞6例(43%; I组)。在其他八种情况下,则需要多次冲击(第二组)。第一次电击之前,双极和His束远端记录的极性以及窦性心律的出现都不是预测结果的重要因素。第一组双极His电图的第一次记录的幅度在I组为225 /-55 microV,在II组为138 /-105 microV(P = 0.029)。第一组电击之前,HV间隔的持续时间在I组为55 /-12 ms,在II组(NS)为45 /-11 ms。结论是,在43%的患者中,单次8-J休克可实现完全永久性心脏传导阻滞。单极8-J电击的长期成功(至少随访1个月,范围为1到8)是由双极和远端单极His束偏转的大幅度预测的,而不是由其极性决定的或HV间隔。

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