• 【长骨金刚烷瘤的细胞遗传学分析:骨纤维异常增生的常见组织发生的进一步指征。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-4608(96)00308-1 复制DOI
    作者列表:Hazelbag HM,Wessels JW,Mollevangers P,van den Berg E,Molenaar WM,Hogendoorn PC
    BACKGROUND & AIMS: Five adamantinomas of long bones were cytogenetically characterized to investigate the role of chromosomal aberrations in their histogenesis, as well as a putative relationship between adamantinoma and osteofibrous dysplasia (OFD). Three tumors had a classic histologic subtype, with abundant epithelium. Two of them revealed trisomies 7, 8, 12, and 19, combined with a balanced translocation, t(10;12), with centromere breakpoints in one tumor. The third showed a karyotype 51,XY, +X, +7, +12, +19, +21. The fourth tumor, of OFD-like subtype, showed trisomies 7, 8, and a small marker chromosome in a low percentage of cells. The fifth tumor, also of OFD-like subtype, displayed only a few keratin-positive cells from the multiple tissue blocks investigated. This latter tumor revealed a clonal abnormality with a karyotype 46,XX,t(2;11)(p23;q14)inv(11)(p14q14), which was confirmed with fluorescence in situ hybridization (FISH), using chromosome-specific library probes and chromosome 11 locus-specific probes. The trisomies 7, 8, and 12 also were described in OFD, which suggests a common histogenesis of OFD and adamantinoma. Our findings further support the probability of clonal origin of OFD. The OFD-like component may be an integral element of adamantinoma, rather than a tissue reaction to epithelial tumor cells.

    背景与目标: 对五个长骨的金刚烷瘤进行了细胞遗传学表征,以研究染色体畸变在其组织发生中的作用以及金丹汀瘤与骨纤维异常增生(OFD)之间的假定关系。三种肿瘤具有经典的组织学亚型,上皮丰富。他们中的两个揭示了三体性7、8、12和19,并结合了一个肿瘤中平衡的易位t(10; 12)和着丝点断点。第三个显示核型51,XY,X,7,12,19,21。第四个OFF样亚型肿瘤显示三体性7、8和小的标记染色体,细胞比例低。第五种肿瘤,也属于OFD样亚型,仅表现出所研究的多个组织块中的少数角蛋白阳性细胞。后一种肿瘤显示克隆型异常,核型为46,XX,t(2; 11)(p23; q14)inv(11)(p14q14),使用染色体特异性文库通过荧光原位杂交(FISH)进行了证实探针和11号染色体基因座特异性探针。在OFD中也描述了三体性7、8和12,这提示了OFD和金刚烷瘤的常见组织发生。我们的发现进一步支持了OFD克隆起源的可能性。类OFD成分可能是金刚烷瘤的组成部分,而不是对上皮肿瘤细胞的组织反应。

  • 【人PEBP2alphaA / CBFA1的转录本的cDNA克隆定位于6p12.3-p21.1,即颅骨发育不良的位点。】 复制标题 收藏 收藏
    DOI:10.1038/sj.onc.1201352 复制DOI
    作者列表:Zhang YW,Bae SC,Takahashi E,Ito Y
    BACKGROUND & AIMS: PEBP2/CBF is a heterodimeric transcription factor composed of alpha and beta subunits. There are at least three closely related genes, PEBP2alphaA/Cbfa1, AML1/PEBP2alphaB/Cbfa2 and PEBP2alphaC/Cbfa3, encoding the alpha subunit and one beta subunit encoding gene. Structural alterations of AML1 and the beta subunit gene by chromosome translocations are frequently associated with several types of human leukemia. Structural changes of any of these gene products would have potential to affect the function of others. In this study, we isolated the human PEBP2alphaA cDNA by which we mapped the gene to 6p12.3-p21.1. Human chromosome 6p21 is the locus for cleidocranial dysplasia, an autosomal dominant bone disease. Recent gene disruption study revealed that PEBP2alphaA/Cbfa1 plays an essential role in osteogenesis (Komori et al., Cell, 1997, in press). Therefore, a close relationship between human PEBP2alphaA/CBFA1 and this bone disease is strongly implicated.

    背景与目标: PEBP2 / CBF是由α和β亚基组成的异二聚体转录因子。至少有3个紧密相关的基因,分别编码α亚基和一个β亚基编码基因,即PEBP2alphaA / Cbfa1,AML1 / PEBP2alphaB / Cbfa2和PEBP2alphaC / Cbfa3。 AML1和β亚基基因通过染色体易位的结构改变通常与几种类型的人类白血病有关。这些基因产物中任何一种的结构变化都可能影响其他基因产物的功能。在这项研究中,我们分离了人PEBP2alphaA cDNA,将其定位到6p12.3-p21.1。人类染色体6p21是颅骨发育不良(常染色体显性遗传性骨疾病)的发生地。最近的基因破坏研究表明,PEBP2alphaA / Cbfa1在成骨中起着至关重要的作用(Komori等人,Cell,1997,印刷中)。因此,强烈暗示了人PEBP2alphaA / CBFA1与这种骨病之间的密切关系。

  • 【高频振荡反映了局灶性皮质发育不良患者的疾病活动。】 复制标题 收藏 收藏
    DOI:10.1111/epi.12262 复制DOI
    作者列表:Kerber K,LeVan P,Dümpelmann M,Fauser S,Korinthenberg R,Schulze-Bonhage A,Jacobs J
    BACKGROUND & AIMS: PURPOSE:The study analyzes the occurrence of high frequency oscillations in different types of focal cortical dysplasia in 22 patients with refractory epilepsy. High frequency oscillations are biomarkers for epileptic tissue, but it is unknown whether they can reflect increasingly dysplastic tissue changes as well as epileptic disease activity. METHODS:High frequency oscillations (80-450 Hz) were visually marked by two independent reviewers in all channels of intracranial implanted grid, strips, and depth electrodes in patients with focal cortical dysplasia and refractory epilepsy. Rates of high frequency oscillations in patients with pathologically confirmed focal cortical dysplasia of Palmini type 1a and b were compared with those in type 2a and b. KEY FINDINGS:Patients with focal cortical dysplasia type 2 had significantly more seizures than those with type 1 (p < 0.001). Rates of high frequency oscillations were significantly higher in patients with focal cortical dysplasia type 2 versus type 1 (p < 0.001). In addition, it could be confirmed that rates of high frequency oscillations were significantly higher in presumed epileptogenic areas than outside (p < 0.001). SIGNIFICANCE:Activity of high frequency oscillations mirrors the higher epileptogenicity of focal cortical dysplasia type 2 lesions compared to type 1 lesions. Therefore, rates of high frequency oscillations can reflect disease activity of a lesion. This has implications for the use of high frequency oscillations as biomarkers for epileptogenic areas, because a detailed analysis of their rates may be necessary to use high frequency oscillations as a predictive tool in epilepsy surgery.
    背景与目标: 目的:本研究分析了22例难治性癫痫患者在不同类型的局灶性皮质发育异常中发生高频振荡的情况。高频振荡是癫痫组织的生物标志物,但尚不清楚它们是否能反映出日益增生的组织变化以及癫痫疾病的活动。
    方法:在两名局灶性皮质发育不良和难治性癫痫患者的颅内植入网格,条带和深度电极的所有通道中,由两名独立审阅者视觉标记了高频振荡(80-450 Hz)。将经病理证实的1a和b型Palmini局灶性皮质发育异常的患者的高频振荡发生率与2a和2b型患者的发生高频振荡的发生率进行比较。
    主要发现:2型局灶性皮质发育不良的患者的癫痫发作明显多于1型(p <0.001)。 2型局灶性皮质发育不良患者的高频振荡发生率明显高于1型(p <0.001)。此外,可以确认的是,在假定的癫痫发生区域,高频振荡的发生率明显高于外部区域(p <0.001)。
    意义:高频振荡的活动反映了与1型病变相比,2型局灶性皮质发育异常病变的更高的致癫痫性。因此,高频振荡的速率可以反映病变的疾病活动。这对使用高频振荡作为癫痫发生区域的生物标记具有影响,因为可能需要对它们的发生率进行详细分析,才能将高频振荡用作癫痫手术的预测工具。
  • 【国家行政数据库中Barrett食管的高度不典型增生编码:一项基于人群的队列研究。】 复制标题 收藏 收藏
    DOI:10.1136/bmjopen-2016-014281 复制DOI
    作者列表:Chadwick G,Varagunam M,Brand C,Riley SA,Maynard N,Crosby T,Michalowski J,Cromwell DA
    BACKGROUND & AIMS: OBJECTIVES:The International Classification of Diseases 10th Revision (ICD-10) system used in the English hospital administrative database (Hospital Episode Statistics (HES)) does not contain a specific code for oesophageal high-grade dysplasia (HGD). The aim of this paper was to examine how patients with HGD were coded in HES and whether it was done consistently. SETTING:National population-based cohort study of patients with newly diagnosed with HGD in England. The study used data collected prospectively as part of the National Oesophago-Gastric Cancer Audit (NOGCA). These records were linked to HES to investigate the pattern of ICD-10 codes recorded for these patients at the time of diagnosis. PARTICIPANTS:All patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014 in England, who had data submitted to the NOGCA. OUTCOMES MEASURED:The main outcome assessed was the pattern of primary and secondary ICD-10 diagnostic codes recorded in the HES records at endoscopy at the time of diagnosis of HGD. RESULTS:Among 452 patients with a new diagnosis of HGD between 1 April 2013 and 31 March 2014, Barrett's oesophagus was the only condition coded in 200 (44.2%) HES records. Records for 59 patients (13.1%) contained no oesophageal conditions. The remaining 193 patients had various diagnostic codes recorded, 93 included a diagnosis of Barrett's oesophagus and 57 included a diagnosis of oesophageal/gastric cardia cancer. CONCLUSIONS:HES is not suitable to support national studies looking at the management of HGD. This is one reason for the UK to adopt an extended ICD system (akin to ICD-10-CM).
    背景与目标: 目的:在英国医院行政数据库(医院发作统计数据(HES))中使用的国际疾病分类第十次修订版(ICD-10)系统未包含针对食管高度不典型增生(HGD)的特定代码。本文的目的是研究如何在HES中对HGD患者进行编码,以及编码是否一致。
    地点:英国新诊断为HGD的患者的全国人群队列研究。该研究使用了前瞻性收集的数据作为国家食管胃癌审核(NOGCA)的一部分。这些记录与HES相关联,以调查在诊断时为这些患者记录的ICD-10代码的模式。
    参与者:2013年4月1日至2014年3月31日期间在英国诊断为HGD的所有新患者,并已向NOGCA提交了数据。
    评估的结果:评估的主要结果是在诊断HGD时内窥镜检查中记录在HES记录中的主要和次要ICD-10诊断代码的模式。
    结果:2013年4月1日至2014年3月31日期间,有452例新诊断为HGD的患者中,Barrett食管是200例(44.2%)HES记录中唯一编码的疾病。 59例患者(13.1%)的记录没有食道疾病。其余193例患者记录了各种诊断代码,其中93例诊断为Barrett食道,57例诊断为食道/胃card门癌。
    结论:HES不适合支持有关HGD管理的国家研究。这是英国采用扩展的ICD系统(类似于ICD-10-CM)的原因之一。
  • 【局灶性牙骨骨发育不良:系统评价。】 复制标题 收藏 收藏
    DOI:10.1259/dmfr/31641295 复制DOI
    作者列表:Macdonald-Jankowski DS
    BACKGROUND & AIMS: OBJECTIVES:To evaluate the principal features of focal cemento-osseous dysplasia (FocCOD) by systematic review (SR) and to compare their frequencies between four global groups. METHODS:Alternative names for FocCOD were used as search terms. The databases searched were the PubMed interface of Medline and LILACS (Literature Index for Latin-America and the Caribbean; Biblioteca Regional de Medicina (BIREME)). Only those reports of FocCODs which occurred in a series in the reporting authors' caseload were considered. All cases used radiographs and were confirmed fibro-osseous lesions histopathologically. RESULTS:Of the 20 series considered, 10 were included in the SR. Five SR-included series were of East Asian communities. 64% of all SR-included cases were found incidentally. FocCOD predominantly affects females and the mandible. The three predominant radiological presentations varied significantly between reports. CONCLUSIONS:The two at-risk global communities appear to be East Asians and those of black African origin. Although there appears to be little difference between East Asians and non-East Asians, the significant differences between them with regards to the predominant radiological presentation could suggest that either all communities vary in their presentation or that most, if not all, did not reflect the true frequency within their communities. Long-term follow-up of large series that would have revealed the long-term outcomes of FocCODs was lacking. This is necessary because of both FocCOD's predilection of edentulous areas, increasingly required for osseointegrated implants, and its wide differential diagnosis, which includes some lesions normally treated by surgery.
    背景与目标: 目的:通过系统评价(SR)评估局灶性骨水泥性骨发育不良(FocCOD)的主要特征,并比较其在四个全球性人群之间的发生频率。
    方法:使用FocCOD的替代名称作为搜索词。搜索的数据库是Medline和LILACS的PubMed界面(拉丁美洲和加勒比海文学索引;医学图书馆区域(BIREME))。仅考虑在报告作者案例中出现的一系列FocCOD报告。所有病例均用X线片检查,并在组织病理学上证实为纤维骨病变。
    结果:在考虑的20个系列中,有10个包含在SR中。五个包含SR的系列是东亚社区。在所有包含SR的案例中,有64%是偶然发现的。 FocCOD主要影响女性和下颌骨。报告之间的三个主要放射学表现差异很大。
    结论:两个高风险的全球社区似乎是东亚人和非洲黑人血统。尽管东亚人与非东亚人之间似乎没有什么区别,但是在主要的放射学表现方面,他们之间的显着差异可能表明,所有社区的表现都各不相同,或者大多数(如果不是全部)都没有反映出他们社区内的真实频率。尚缺乏对可能会揭示FocCOD长期结果的大系列药物的长期随访。这是必要的,因为FocCOD偏爱无牙区域(对骨整合植入物的要求越来越高)及其广泛的鉴别诊断(包括一些通常通过手术治疗的病变)。
  • 【溃疡性结肠炎监测中的不典型增生的窄带成像和凹坑模式评估:多发性与不典型增生相关的病变或肿块。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2006-10-01
    来源期刊:Gut
    DOI:10.1136/gut.2005.087171 复制DOI
    作者列表:East JE,Suzuki N,von Herbay A,Saunders BP
    BACKGROUND & AIMS: :A 62 year old man with longstanding ulcerative colitis and previous endoscopic excision of two dysplasia associated lesions or masses (DALMs) was admitted to our endoscopy unit for evaluation and resection of other possible DALMs. He had previously been offered and refused colectomy because of comorbidity from Parkinson's disease. He had multiple polypoid and sessile lesions which were assessed using a third generation prototype narrow band imaging (NBI) colonoscope with magnification. Selected lesions were either biopsied or resected with a combination of endoscopic submucosal dissection and endoscopic mucosal resection techniques. We correlated the pit pattern and vascular pattern intensity seen with magnification NBI with histology of both inflammatory and dysplastic lesions. Dysplastic areas showed Kudo pit patterns II, IIIL, and IV and high vascular pattern intensity. Non-dysplastic and dysplastic areas of recurrence immediately adjacent to the scar from a previous endoscopic mucosal resection site were also assessed. This is the first case report where NBI has been shown to help in DALM detection and to distinguish dysplastic from non-dysplastic mucosa in ulcerative colitis.
    背景与目标: :一名62岁的长期溃疡性结肠炎患者,之前曾接受内镜切除两个不典型增生相关的病变或肿物(DALM),被纳入我们的内窥镜部门,以评估和切除其他可能的DALM。由于帕金森氏病的合并症,他以前曾被提供并拒绝接受结肠切除术。他患有多息肉样和无蒂性病变,使用第三代原型窄带成像(NBI)结肠镜在放大下对其进行了评估。对选定的病变进行活检或结合内镜下黏膜下剥离术和内镜下黏膜切除术切除。我们将放大的NBI所见的凹坑模式和血管模式强度与炎性和异常增生性病变的组织学联系起来。增生异常区域显示工藤凹纹II,IIIL和IV和高血管纹强度。还评估了先前内镜黏膜切除部位紧邻疤痕的非增生和增生复发区域。这是第一个病例报告,其中NBI被证明有助于溃疡性结肠炎的DALM检测,并能将粘膜增生与非粘膜增生区分开。
  • 【内镜超声检查不到3 cm的侧支导管内乳头状黏液性肿瘤常发生高度不典型增生和腺癌。】 复制标题 收藏 收藏
    DOI:10.1007/s11605-012-2017-0 复制DOI
    作者列表:Wong J,Weber J,Centeno BA,Vignesh S,Harris CL,Klapman JB,Hodul P
    BACKGROUND & AIMS: BACKGROUND:Surgical resection for intraductal papillary mucinous neoplasm (IPMN) of the pancreas has increased over the last decade. While IPMN with main duct communication are generally recommended for resection, indications for resection of side-branch IPMN (SDIPMN) have been less clear. We reviewed our single institutional experience with SDIPMN and indications for resection. METHODS:Patients who underwent resection for IPMN were identified from a prospectively maintained IRB-approved database. Patients with main pancreatic duct communication were excluded. Outcome, clinical and pathologic characteristics were correlated with endoscopic ultrasound (EUS) findings. RESULTS:From 2000 to 2010, 105 patients who underwent preoperative EUS evaluation and resection for SDIPMN were identified. The mean age was within the sixth decade of life, and there was a slight female predominance (55 vs. 45 %). The most common presenting symptom was abdominal pain (N = 47, 45 %), followed by jaundice (N = 24, 23 %) and weight loss (N = 24, 23 %). Only ten patients (10 %) were asymptomatic at presentation; seven (70 %) had suspicious features on EUS. Of the total cohort, few patients had intracystic septations (N = 27, 26 %) or presence of mural nodules (N = 2, 2 %) on EUS. Of 39 patients who had invasive pancreatic ductal adenocarcinoma (PDAC) on final pathology, EUS-fine needle aspiration (EUS-FNA) demonstrated malignancy in only 21 (54 %). An additional seven (18 %) had EUS-FNA findings of atypia or concern for mucinous neoplasm. EUS evaluation of cyst size was correlated with final pathology. Of 70 patients with EUS cyst size <3 cm, 12 (17 %) had a preoperative EUS diagnosis of malignancy. Final pathology revealed 24 (34 %) to have PDAC: 1 of 7 (14 %) patients with cyst size <1 cm, 2 of 19 (11 %) with cyst size 1-2 cm, and 21of 44 (48 %) with cyst size 2-3 cm. Fifteen of 35 (43 %) patients with cyst size >3 cm had PDAC on final pathology. Of the patients with cyst size <3 cm, 16 (23 %) had high-grade dysplasia on final pathology: 3 of 7 (43 %) with cyst size <1 cm, 3 of 19 (16 %) with cyst size 1-2 cm, and 10 of 44 (23 %) with cyst size 2-3 cm. Seven of 35 (20 %) patients with cyst size >3 cm had high-grade dysplasia on final pathology. Although overall survival (OS) at 48 months stratified by EUS cyst size did not significantly differ between groups, patients with PDAC on final pathology had significantly worse OS compared to noninvasive pathology. A total of eight patients (8 %) developed recurrent disease, all of whom had PDAC on final pathology. CONCLUSION:EUS is a helpful modality for the diagnostic evaluation of SDIPMN. Considering the high incidence of malignancy as well as high-grade dysplasia in SDIPMN greater than 2 cm, EUS features should be used in conjunction with other clinical criteria to guide management decisions. Patients with SDIPMN greater than 2 cm that do not undergo surgical resection may benefit from more intensive surveillance.
    背景与目标: 背景:过去十年来,胰腺导管内乳头状粘液性肿瘤(IPMN)的手术切除有所增加。虽然通常建议使用IPMN与主导管通信进行切除,但对于旁支IPMN(SDIPMN)切除的指征尚不明确。我们回顾了我们在SDIPMN方面的单一机构经验以及切除的适应症。
    方法:从经过前瞻性维护的IRB批准的数据库中鉴定接受IPMN切除的患者。排除主要胰管沟通的患者。结果,临床和病理特征与内镜超声检查(EUS)相关。
    结果:从2000年至2010年,确定了105例接受了术前EUS评估并切除SDIPMN的患者。平均年龄在生命的第六十年以内,女性占主导地位(55%对45%)。最常见的症状是腹痛(N = 47,45%),其次是黄疸(N = 24,23%)和体重减轻(N = 24,23%)。就诊时仅10例(10%)无症状;七分(70%)的EUS具有可疑特征。在整个队列中,很少有患者在超声内镜下出现囊内分隔(N = 27,26%)或有壁结节(N = 2,2%)。在39例最终病理诊断为浸润性胰腺导管腺癌(PDAC)的患者中,EUS细针穿刺术(EUS-FNA)仅显示21例恶性肿瘤(54%)。 EUS-FNA发现另外7例(18%)为非典型性或粘液性肿瘤。 EUS对囊肿大小的评估与最终病理相关。 EUS囊肿大小<3 cm的70例患者中,有12例(17%)术前经EUS诊断为恶性。最终病理结果显示24(34%)患有PDAC:囊肿尺寸<1 cm的患者中有7(14%)1例,囊肿尺寸1-2 cm的患者中有19(11%)中的2人,囊肿尺寸为1-2 cm的患者中有21(44%)囊肿大小2-3厘米在35例(43%)囊肿尺寸大于3厘米的患者中,其最终病理结果为PDAC。囊肿大小<3 cm的患者中,最终病理表现为高度不典型增生:7例囊肿中的3个(43%)囊肿大小<1 cm,19例囊肿中的3例(16%)囊肿大小为1- 2厘米,44个中的10个(23%),囊肿大小2-3厘米。 35例囊肿大小> 3 cm的患者中有7例(20%)在最终病理上表现为高度不典型增生。尽管各组之间按EUS囊肿大小分层的48个月总生存率(OS)没有显着差异,但与无创病理学相比,具有最终病理学特征的PDAC患者的OS明显较差。共有8例患者(8%)患有复发性疾病,所有患者均在最终病理学上患有PDAC。
    结论:超声内镜对SDIPMN的诊断评价有帮助。考虑到SDIPMN中恶性肿瘤的高发率以及高度不典型增生大于2 cm,应将EUS功能与其他临床标准结合使用以指导管理决策。 SDIPMN大于2厘米且未进行手术切除的患者可受益于更深入的监测。
  • 【肝移植前后溃疡性结肠炎和原发性硬化性胆管炎结肠炎的不定性和低度异型增生的命运。】 复制标题 收藏 收藏
    DOI:10.1111/apt.12469 复制DOI
    作者列表:Eaton JE,Smyrk TC,Imam M,Pardi DS,Loftus EV Jr,Owens VL,Talwalkar JA
    BACKGROUND & AIMS: BACKGROUND:Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk of colorectal neoplasia, but it is unknown if liver transplantation (LT) alters neoplasia progression. AIM:To examine the natural history of indefinite dysplasia (IND) and low-grade dysplasia (LGD) that develop in patients with PSC-UC with and without LT. METHODS:We performed a retrospective review of patients with PSC and UC evaluated at our institution between 1993 and 2011 who were diagnosed with IND or LGD before or after LT for PSC. The primary end point was neoplasia progression or persistent LGD. RESULTS:Ninety-six patients (non-LT n = 63, LT n = 33) were examined. For the IND group, multifocal lesions were significantly associated with time to neoplasia progression [hazard ratio (HR), 3.5; 95% confidence interval (CI), 1.3-9.7], while 5-aminosalicylate (5-ASA) use was protective (HR, 0.2; 95% CI, 0.1-0.6). For patients with LGD, multifocal lesions were significantly associated with the primary end point (HR, 7.1; 95% CI, 1.7-28.3), while LT was protective (HR, 0.3; 95% CI, 0.1-0.9). CONCLUSIONS:In PSC-UC patients with IND, 5-ASA use was associated with a decreased the risk of neoplasia progression, regardless of transplant status. In contrast, multifocal IND and LGD were associated with neoplasia progression or persistent LGD. Patients who developed LGD following LT for PSC were less likely to have progressive neoplasia or persistent LGD, compared with those who had not been transplanted.
    背景与目标: 背景:原发性硬化性胆管炎(PSC)和溃疡性结肠炎(UC)的患结直肠癌的风险增加,但是尚不知道肝移植(LT)是否会改变肿瘤的发展。
    目的:研究患有或不伴有LT的PSC-UC患者发生的不确定性不典型增生(IND)和低度不典型增生(LGD)的自然史。
    方法:我们对1993至2011年间在我们机构评估的PSC和UC患者进行了回顾性评估,这些患者在LT进行PSC之前或之后被诊断为IND或LGD。主要终点是肿瘤发展或持续性LGD。
    结果:检查了96例患者(非LT n = 63,LT n = 33)。对于IND组,多灶性病变与肿瘤形成的时间显着相关[危险比(HR)为3.5; 95%置信区间(CI)为1.3-9.7],而5-氨基水杨酸酯(5-ASA)的使用具有保护性(HR,0.2; 95%CI,0.1-0.6)。对于LGD患者,多灶性病变与主要终点显着相关(HR,7.1; 95%CI,1.7-28.3),而LT具有保护性(HR,0.3; 95%CI,0.1-0.9)。
    结论:在患有IND的PSC-UC患者中,无论移植状态如何,使用5-ASA可降低肿瘤发展的风险。相反,多灶性IND和LGD与瘤形成进展或持续性LGD相关。与未移植的患者相比,LT进行PSC后发生LGD的患者发生进行性瘤形成或持续LGD的可能性较小。
  • 【软骨细胞分化和软骨膜矿化的解偶联是毛发-犀牛-指骨综合征中骨骼发育异常的基础。】 复制标题 收藏 收藏
    DOI:10.1093/hmg/ddn125 复制DOI
    作者列表:Napierala D,Sam K,Morello R,Zheng Q,Munivez E,Shivdasani RA,Lee B
    BACKGROUND & AIMS: :Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant craniofacial and skeletal dysplasia that is caused by mutations involving the TRPS1 gene. Patients with TRPS have short stature, hip abnormalities, cone-shaped epiphyses and premature closure of growth plates reflecting defects in endochondral ossification. The TRPS1 gene encodes for the transcription factor TRPS1 that has been demonstrated to repress transcription in vitro. To elucidate the molecular mechanisms underlying skeletal abnormalities in TRPS, we analyzed Trps1 mutant mice (Trps1DeltaGT mice). Analyses of growth plates demonstrated delayed chondrocyte differentiation and accelerated mineralization of perichondrium in Trps1 mutant mice. These abnormalities were accompanied by increased Runx2 and Ihh expression and increased Indian hedgehog signaling. We demonstrated that Trps1 physically interacts with Runx2 and represses Runx2-mediated trans-activation. Importantly, generation of Trps1(DeltaGT/+);Runx2(+/-) double heterozygous mice rescued the opposite growth plate phenotypes of single mutants, demonstrating the genetic interaction between Trps1 and Runx2 transcription factors. Collectively, these data suggest that skeletal dysplasia in TRPS is caused by dysregulation of chondrocyte and perichondrium development partially due to loss of Trps1 repression of Runx2.
    背景与目标: :Tricho-r​​hino-phalangeal综合征(TRPS)是常染色体显性遗传性颅面和骨骼发育异常,是由涉及TRPS1基因的突变引起的。患有TRPS的患者身材矮小,髋关节异常,锥形骨phy和生长板过早闭合,反映出软骨内骨化的缺陷。 TRPS1基因编码转录因子TRPS1,已证明在体外抑制转录。为了阐明TRPS骨骼异常的分子机制,我们分析了Trps1突变小鼠(Trps1DeltaGT小鼠)。生长板的分析表明延迟的软骨细胞分化和Trps1突变小鼠中软骨膜的加速矿化。这些异常伴随有Runx2和Ihh表达的增加以及印度刺猬信号的增加。我们证明了Trps1在物理上与Runx2相互作用并抑制Runx2介导的反式激活。重要的是,Trps1(DeltaGT /); Runx2(/-)双杂合子小鼠的产生拯救了单个突变体的相反生长板表型,证明了Trps1和Runx2转录因子之间的遗传相互作用。总体而言,这些数据表明TRPS中的骨骼发育异常是由于软骨细胞失调和软骨膜发育异常引起的,部分原因是Runx2的Trps1抑制丧失。
  • 【鞘氨醇激酶1抑制剂PF543的新生儿疗法可改善支气管肺发育不良小鼠模型中高氧诱导的气道重塑。】 复制标题 收藏 收藏
    DOI:10.1152/ajplung.00169.2020 复制DOI
    作者列表:Ha AW,Sudhadevi T,Ebenezer DL,Fu P,Berdyshev EV,Ackerman SJ,Natarajan V,Harijith A
    BACKGROUND & AIMS: :Hyperoxia (HO)-induced lung injury contributes to bronchopulmonary dysplasia (BPD) in preterm newborns. Intractable wheezing seen in BPD survivors is associated with airway remodeling (AWRM). Sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) signaling promotes HO-mediated neonatal BPD; however, its role in the sequela of AWRM is not known. We noted an increased concentration of S1P in tracheal aspirates of neonatal infants with severe BPD, and earlier, demonstrated that Sphk1-/- mice showed protection against HO-induced BPD. The role of SPHK1/S1P in promoting AWRM following exposure of neonates to HO was investigated in a murine model. Therapy using PF543, the specific SPHK1 inhibitor, during neonatal HO reduced alveolar simplification followed by reduced AWRM in adult mice. This was associated with reduced airway hyperreactivity to intravenous methacholine. Neonatal HO exposure was associated with increased expression of SPHK1 in lung tissue of adult mice, which was reduced with PF543 therapy in the neonatal stage. This was accompanied by amelioration of HO-induced reduction of E-cadherin in airway epithelium. This may be suggestive of arrested partial epithelial mesenchymal transition (EMT) induced by HO. In vitro studies using human primary airway epithelial cells (HAEpCs) showed that SPHK1 inhibition or deletion restored HO-induced reduction in E-cadherin and reduced formation of mitochondrial reactive oxygen species (mtROS). Blocking mtROS with MitoTempo attenuated HO-induced partial EMT of HAEpCs. These results collectively support a therapeutic role for PF543 in preventing HO-induced BPD in neonates and the long-term sequela of AWRM, thus conferring a long-term protection resulting in improved lung development and function.
    背景与目标: 高氧血症(HO)引起的肺损伤导致早产儿支气管肺发育不良(BPD)。在BPD幸存者中看到的顽固性喘息与气道重塑(AWRM)相关。鞘氨醇激酶1(SPHK1)/鞘氨醇-1-磷酸(S1P)信号传导促进HO介导的新生儿BPD。但是,其在AWRM后遗症中的作用尚不清楚。我们注意到患有严重BPD的新生儿气管抽吸物中S1P的浓度增加,并且更早地证明Sphk1-/-小鼠对HO诱导的BPD具有保护作用。在鼠模型中研究了SPHK1 / S1P在新生儿接触HO后促进AWRM的作用。在新生的HO中使用PF543(特异性SPHK1抑制剂)进行的治疗减少了成年小鼠的肺泡简化,继而减少了AWRM。这与减少对气道乙酰甲胆碱的气道高反应性有关。新生儿HO暴露与成年小鼠肺组织中SPHK1表达的增加有关,而在新生儿期用PF543治疗可降低这种表达。这伴随着HO诱导的气道上皮中E-钙粘蛋白的减少的改善。这可能暗示了HO诱导的部分上皮间质转化(EMT)被阻滞。使用人原代气道上皮细胞(HAEpCs)进行的体外研究表明,SPHK1的抑制或缺失可恢复HO诱导的E-钙粘蛋白的减少,并减少线粒体活性氧(mtROS)的形成。用MitoTempo阻断mtROS可减弱HO诱导的HAEpC的部分EMT。这些结果共同支持了PF543在预防新生儿HO诱导的BPD和AWRM的长期后遗症方面的治疗作用,从而提供了长期的保护,从而改善了肺的发育和功能。
  • 【射频消融在食管鳞状上皮不典型增生和早期瘤形成中的作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.gie.2016.08.045 复制DOI
    作者列表:Chen WC,Wolfsen H
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【视神经发育不良伴有双侧复杂性小眼球。】 复制标题 收藏 收藏
    DOI:10.3109/13816819609057113 复制DOI
    作者列表:Gündüz K,Günalp I,Saatçi I
    BACKGROUND & AIMS: An 8-month-old girl was examined because of corneal clouding and microphthalmos. The fundi of both eyes could not be visualized because of corneal clouding. Orbital and cranial computerized tomographic scanning and magnetic resonance imaging demonstrated bilateral microphthalmos and presumed retinal dysplasia, hypoplasia of the optic nerves and chiasm, agenesis of the septum pellucidum, thinning of corpus callosum, and a normal pituitary infundibulum. Cerebral cortex and white matter were unremarkable. Other ocular malformations were anterior segment dysgenesis in the right eye and congenital cataract or lens abnormality in the left eye. Endocrine studies revealed normal serum hormone levels. There were no colobomatous lesions and systemic anomalies suggestive of a coloboma syndrome. This case represents the rare association of septo-optic dysplasia with complex microphthalmos.

    背景与目标: 对一个8个月大的女孩进行了检查,原因是角膜混浊和小眼球。由于角膜混浊,无法看到两只眼睛的眼底。眼眶和颅骨计算机断层扫描和核磁共振成像显示双侧小眼睑和假定的视网膜发育异常,视神经和黑素瘤发育不全,透明膜中隔发育不全,call体变薄以及垂体正常漏斗。脑皮质和白质不明显。其他眼部畸形是右眼前节发育不全和左眼先天性白内障或晶状体异常。内分泌研究显示血清激素水平正常。没有大疱性病变和全身异常提示大肠癌综合征。这种情况代表了视神经发育不良与复杂的小眼球症的罕见关联。

  • 【炎症性肠病中与发育异常相关的病变或肿块的识别和适当处理-经验确实很重要。】 复制标题 收藏 收藏
    DOI:10.1016/j.gie.2007.02.006 复制DOI
    作者列表:Baumgart DC
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【SLC35A3相关骨骼发育异常的人类病例。】 复制标题 收藏 收藏
    DOI:10.1002/ajmg.a.38374 复制DOI
    作者列表:Edmondson AC,Bedoukian EC,Deardorff MA,McDonald-McGinn DM,Li X,He M,Zackai EH
    BACKGROUND & AIMS: :Researchers have identified a subset of Holstein having a range of skeletal deformities, including vertebral anomalies, referred to as complex vertebral malformation due to mutations in the SLC35A3 gene. Here, we report the first case in humans of SLC35A3-related vertebral anomalies. Our patient had prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Clinical exome sequencing revealed a novel missense homozygous mutation in SLC35A3. Follow-up biochemical analysis confirmed abnormal protein glycosylation, consistent with a defective Golgi UDP-GlcNAc transporter, validating the mutations. Congenital disorders of glycosylation, including SLC35A3-CDG, can present as a wide phenotypic spectrum, including skeletal dysplasia. Previously reported patients with SLC35A3-CDG have been described with syndromic autism, epilepsy, and arthrogryposis.
    背景与目标: 研究人员已经确定了荷斯坦因的一个子集,该子集具有一系列骨骼畸形,包括椎骨异常,这是由于SLC35A3基因突变导致的复杂椎体畸形。在这里,我们报告人类中与SLC35A3相关的椎骨异常的第一例。我们的患者在产前被诊断出脊椎异常,包括整个脊柱中的蝴蝶和半椎骨,以及c裂,微棘突,卵圆孔未闭,动脉导管未闭,后胚胎毒素,短肢,弯曲状,触角外翻,摇臂底足和面部畸形,包括眼球突出,痣红斑和杯状左耳。临床外显子组测序显示SLC35A3中有一个新的错义纯合突变。后续生化分析证实了异常的蛋白质糖基化,与有缺陷的高尔基UDP-GlcNAc转运蛋白相一致,证实了突变。先天性糖基化疾病(包括SLC35A3-CDG)可以表现为广泛的表型谱,包括骨骼发育不良。先前报道的SLC35A3-CDG患者已被证明患有自闭症,癫痫和关节炎。
  • 【髋部发育不良后,Salter股骨头缺血性坏死标准与Kalamchi的预后分类之间的相关性。】 复制标题 收藏 收藏
    DOI:10.1302/0301-620X.99B8.BJJ-2016-1070.R1 复制DOI
    作者列表:Tsukagoshi Y,Kamegaya M,Kamada H,Saisu T,Morita M,Kakizaki J,Tomaru Y,Yamazaki M
    BACKGROUND & AIMS: AIMS:The aim of this study was to evaluate the correlation between Salter's criteria and Kalamchi's classification of avascular necrosis in patients treated for developmental dysphasia of the hip (DDH). PATIENTS AND METHODS:The study involved a retrospective analysis of 123 patients (123 hips) with DDH treated by operative and non-operative reduction before the age of two years, with a minimum follow-up of ten years. Salter's criteria (S1 to S4) were determined from radiographs obtained at one to two years post-reduction, whilst the Kalamchi grade was determined from radiographs obtained at ten or more years of age. Early post-reduction radiographs were also used to evaluate the centre-head distance discrepancy (CHDD) and the occurrence of a dome-shaped deformity of the proximal femoral metaphysis (D-shaped metaphysis). The prognosis was described as good (Kalamchi grade K0 or KI), fair (Kalamchi grade KII) or poor (Kalamchi grade KIII or KIV) for analysis and correlation with the early Salter criteria, CHDD and D-shaped metaphysis. RESULTS:S1 and S2 criteria were predictive of a poor prognosis. The outcome following S3, S4 and S3 + S4 varied; 18 (40%) had a good prognosis, 17 (38%) a fair prognosis and ten (22%) a poor prognosis. A CHDD ≥ 10% and a D-shaped metaphysis were also predictive of a poor prognosis. CONCLUSION:The Salter criteria were predictive of the Kalamchi grade of avascular necrosis in patients with DDH aged ten or more years after reduction of the hip. Cite this article: Bone Joint J 2017;99-B:1115-20.
    背景与目标: 目的:本研究的目的是评估髋部发育不良(DDH)患者的Salter标准与卡拉姆奇血管坏死分类之间的相关性。
    病人和方法:该研究包括对年龄在2岁之前接受手术和非手术复位治疗的123例DDH患者(123髋)的回顾性分析,最少随访10年。索尔特标准(S1至S4)是根据还原后一到两年的放射线照片确定的,而卡拉马奇等级是根据十岁或以上年龄的放射线照片确定的。早期的复位后X光片也被用于评估中心头距离差异(CHDD)和股骨近端干physi端(D形干physi端)的圆顶形畸形的发生。对于早期Salter标准,CHDD和D形干meta端的分析和相关性,预后被描述为好(Kalamchi K0或KI级),中等(Kalamchi KII级或差)(Kalamchi KIII级或KIV级)。
    结果:S1和S2标准可预示不良预后。 S3,S4和S3,S4之后的结果有所不同; 18例(40%)的预后良好,17例(38%)的预后良好,十例(22%)的预后不良。 CHDD≥10%和D形干physi端也预示不良预后。
    结论:Salter标准可预测髋关节复位后10岁或10岁以上DDH患者的Kalamchi级无血管坏死。引用本文:Bone Joint J 2017; 99-B:1115-20。

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