Journal of Neuropathology & Experimental Neurology最新文献_第7页

Elevated Expression of the Cerebrospinal Fluid Disease Markers Chromogranin A and Clusterin in Astrocytes of Multiple Sclerosis White Matter Lesions 多发性硬化症白质病变星形胶质细胞中脑脊液疾病标志物嗜铬粒蛋白A和聚簇蛋白的表达升高

Journal of Neuropathology & Experimental Neurology

Pub Date : 2016-01-01 DOI: 10.1093/jnen/nlv004

Marvin M. van Luijn, M. van Meurs, M. Stoop, E. Verbraak, A. Wierenga-wolf, M. Melief, K. Kreft, R. Verdijk, B. '. ’t Hart, T. Luider, J. Laman, R. Hintzen

Using proteomics, we previously identified chromogranin A (CgA) and clusterin (CLU) as disease-related proteins in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). CgA and CLU are involved in cell survival and are implicated in neurodegenerative disorders and may also have roles in MS pathophysiology. We investigated CgA and CLU expression in lesions and nonlesional regions in postmortem brains of MS patients and controls and in the brains of marmosets with experimental autoimmune encephalomyelitis. By quantitative PCR, mRNA levels of CgA and CLU were elevated in white matter but not in grey matter of MS patients. In situ analyses showed greater expression of CgA and CLU in white matter lesions than in normal-appearing regions in MS patients and in the marmosets, primarily in or adjacent to perivascular spaces and inflammatory infiltrates. Both proteins were expressed by glial fibrillary acidic protein-positive astrocytes. CgA was more localized in astrocytic processes and endfeet surrounding blood vessels and was abundant in the superficial glia limitans and ependyma, 2 CSF-brain borders. Increased expression of CgA and CLU in reactive astrocytes in MS white matter lesions supports a role for these molecules as neuro-inflammatory mediators and their potential as CSF markers of active pathological processes in MS patients.

利用蛋白质组学，我们先前在多发性硬化症(MS)患者的脑脊液(CSF)中发现了嗜铬粒蛋白A (CgA)和聚簇蛋白(CLU)作为疾病相关蛋白。CgA和CLU参与细胞存活，与神经退行性疾病有关，也可能在MS病理生理中起作用。我们研究了CgA和CLU在MS患者和对照组死后大脑病变和非病变区域以及实验性自身免疫性脑脊髓炎狨猴大脑中的表达。通过定量PCR, MS患者白质中CgA和CLU mRNA水平升高，而灰质中无升高。原位分析显示，在MS患者和狨猴的白质病变中，CgA和CLU的表达高于正常区域，主要是在血管周围间隙和炎症浸润内或附近。这两种蛋白均由胶质原纤维酸性蛋白阳性星形胶质细胞表达。CgA多局限于血管周围的星形细胞突起和终足，并大量存在于浅表胶质细胞边界和室管膜，2 csf -脑边界。在MS白质病变的反应性星形胶质细胞中，CgA和CLU的表达增加，支持了这些分子作为神经炎症介质的作用，以及它们作为MS患者活跃病理过程的CSF标志物的潜力。

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引用次数: 19

Meningiomas With Rhabdoid Features Lacking Other Histologic Features of Malignancy: A Study of 44 Cases and Review of the Literature. 缺乏其他恶性肿瘤组织学特征的横纹肌瘤：44 个病例的研究和文献综述。

Journal of Neuropathology & Experimental Neurology

Pub Date : 2016-01-01 Epub Date: 2015-12-07 DOI: 10.1093/jnen/nlv006

Rachael A Vaubel, Selby G Chen, David R Raleigh, Michael J Link, Michael R Chicoine, Igor Barani, Sarah M Jenkins, Patrice Abell Aleff, Fausto J Rodriguez, Peter C Burger, Sonika Dahiya, Arie Perry, Caterina Giannini

The behavior of rhabdoid meningiomas otherwise lacking malignant features remains unknown as most of the originally reported aggressive cases showed anaplastic histologic features independently of rhabdoid phenotype. We studied 44 patients with rhabdoid meningiomas lacking anaplastic features. Median age at diagnosis was 48.6 years (range 10-79). Location was supratentorial in 28 (63.6%), skull base in 15 (34.1%), and spinal in 1 (2.3%). Tumor grade was otherwise World Health Organization grade I (n = 22, 50%) or II (n = 22, 50%). Rhabdoid cells represented <20% of the tumor in 12 cases (27.3%), 20% to 50% in 18 (40.9%), and >50% in 14 (31.8%). Median clinical follow-up, available for 38 patients, was 5.0 years (range 0.17-14.2). Recurrence occurred in 9 patients (5-year recurrence-free survival, 73.7%) with a significantly higher risk in subtotally resected tumors (p = 0.043). Rhabdoid cell percentage was not associated with recurrence. Six patients died (4 of disease, 2 of unclear causes); 5-year overall survival was 86.7%, a mortality in excess of that expected in grade I-II meningiomas but much lower than originally reported. Review of 50 similar previously reported cases confirmed our findings. We suggest that rhabdoid meningiomas be graded analogously to nonrhabdoid tumors, with caution that some may still behave aggressively and close follow-up is recommended.

由于最初报道的侵袭性病例大多表现为无弹性组织学特征，而非横纹表型，因此缺乏恶性特征的横纹状脑膜瘤的表现仍然未知。我们对 44 例缺乏无弹性特征的横纹肌脑膜瘤患者进行了研究。确诊时的中位年龄为48.6岁（10-79岁不等）。肿瘤位置为胸膜上28例（63.6%）、颅底15例（34.1%）和脊柱1例（2.3%）。肿瘤分级为世界卫生组织I级（22例，50%）或II级（22例，50%）。14例（31.8%）中横纹肌细胞占50%。38名患者的中位临床随访时间为5.0年（0.17-14.2年不等）。9名患者出现复发（5年无复发生存率为73.7%），次全切除肿瘤的复发风险明显更高（P = 0.043）。横纹肌细胞百分比与复发无关。6名患者死亡（4人死于疾病，2人死因不明）；5年总生存率为86.7%，死亡率超过了I-II级脑膜瘤的预期，但比最初报道的要低得多。对之前报道的 50 例类似病例的回顾证实了我们的研究结果。我们建议对横纹肌脑膜瘤进行类似于非横纹肌脑膜瘤的分级，但要注意有些肿瘤仍可能具有侵袭性，建议进行密切随访。

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引用次数: 0

The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas 免疫组织化学替代物在胶质瘤中诊断特征分子遗传改变的应用

Journal of Neuropathology & Experimental Neurology

Pub Date : 2016-01-01 DOI: 10.1093/jnen/nlv009

J. Tanboon, E. Williams, D. Louis

A number of key mutations that affect treatment and prognosis have been identified in human gliomas. Two major ways to identify these mutations in a tumor sample are direct interrogation of the mutated DNA itself and immunohistochemistry to assess the effects of the mutated genes on proteins. Immunohistochemistry is an affordable, robust, and widely available technology that has been in place for decades. For this reason, the use of immunohistochemical approaches to assess molecular genetic changes has become an essential component of state-of-the-art practice. In contrast, even though DNA sequencing technologies are undergoing rapid development, many medical centers do not have access to such methodologies and may be thwarted by the relatively high costs of sending out such tests to reference laboratories. This review summarizes the current experience using immunohistochemistry of glioma samples to identify mutations in IDH1, TP53, ATRX, histone H3 genes, BRAF, EGFR, MGMT, CIC, and FUBP1 as well as guidelines for prudent use of DNA sequencing as a supplemental method.

许多影响治疗和预后的关键突变已经在人类胶质瘤中被确定。在肿瘤样本中识别这些突变的两种主要方法是直接询问突变DNA本身和免疫组织化学来评估突变基因对蛋白质的影响。免疫组织化学是一种廉价、强大、广泛可用的技术，已经存在了几十年。因此，使用免疫组织化学方法来评估分子遗传变化已成为最先进实践的重要组成部分。相比之下，尽管DNA测序技术正在快速发展，但许多医疗中心无法获得这种方法，而且将这种测试送到参考实验室的费用相对较高，可能会阻碍这种方法的发展。本文综述了目前使用神经胶质瘤样本免疫组织化学鉴定IDH1、TP53、ATRX、组蛋白H3基因、BRAF、EGFR、MGMT、CIC和FUBP1突变的经验，以及谨慎使用DNA测序作为补充方法的指南。

引用次数: 82

Simultaneous Quantification of Unmyelinated Nerve Fibers in Sural Nerve and in Skin 同时定量测定腓肠神经和皮肤无髓神经纤维

Journal of Neuropathology & Experimental Neurology

Pub Date : 2016-01-01 DOI: 10.1093/jnen/nlv005

M. Duchesne, L. Magy, L. Richard, P. Ingrand, J. Neau, S. Mathis, J. Vallat

Peripheral polyneuropathies are common and their diagnosis may be challenging. We compared the results from sural-nerve and skin biopsies in 33 patients with a polyneuropathy and neuropathic pain examined in our hospital over a 6-year period. The biopsies were all from the same lower limb of each patient. Intraepidermal nerve fiber (IENF) densities in the skin were determined by fluorescence microscopy; unmyelinated fiber densities in sural-nerve biopsies (UFNB) were determined by electron microscopy. There was no correlation with age or gender in either biopsy type; there was a weak trend to correlation between UFNB density and IENF density, possibly because of the small sample size. The sensitivity of detection of quantitative abnormalities of unmyelinated fibers was better in the skin than in the nerves. Proximal and distal IENF densities were strongly correlated; and counts of UFNB were highly reproducible. Thus, quantification of unmyelinated fibers in sural-nerve and skin biopsies seem to be complementary. Sural-nerve biopsy may be required to confirm a specific diagnosis, to identify lesion mechanisms, and to devise therapeutic strategies, whereas skin biopsy seems to be more efficient in the follow-up of length-dependent polyneuropathies and in the diagnosis of neuropathic pain.

周围多发性神经病是常见的，他们的诊断可能具有挑战性。我们比较了6年来在我院检查的33例多发性神经病变和神经性疼痛患者的腓肠神经和皮肤活检结果。每个病人的活检都来自同一个下肢。荧光显微镜下测定皮肤表皮内神经纤维(IENF)密度;电镜法测定腓肠神经活检(ubnb)中无髓鞘纤维密度。两种活检类型均与年龄或性别无关;ubnb密度与IENF密度相关性不明显，可能是样本量较小的原因。皮肤对无髓鞘纤维定量异常的检测灵敏度高于神经。近端和远端IENF密度密切相关;UFNB计数具有高重复性。因此，腓肠神经和皮肤活检中无髓鞘纤维的定量似乎是互补的。可能需要腓肠神经活检来确认特定的诊断，确定病变机制，并制定治疗策略，而皮肤活检似乎在长度依赖性多神经病变的随访和神经性疼痛的诊断中更有效。

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引用次数: 10

Increased Expression and Cellular Localization of P2X7R in Cortical Lesions of Patients With Focal Cortical Dysplasia P2X7R在局灶性皮质发育不良患者皮质病变中的表达和细胞定位增加

Journal of Neuropathology & Experimental Neurology

Pub Date : 2016-01-01 DOI: 10.1093/jnen/nlv003

Yujia Wei, W. Guo, Fei-Ji Sun, W. Fu, Dahai Zheng, Xin Chen, Song Li, Zhen-le Zang, Chun-Qing Zhang, Shiyong Liu, Hui Yang

Focal cortical dysplasias (FCDs) are major brain malformations that commonly lead to medically intractable epilepsy. The purinergic ionotropic P2X7 receptor (P2X7R) is an atypical P2X subtype that gates calcium and sodium ions. Previous animal studies have suggested that P2X7R is a contributing factor in epileptogenesis. This study aimed to define the distribution and expression of P2X7R in 35 FCD patient-surgical-resection specimens relative to autopsy control samples (n = 8). Immunohistochemical colocalization assays revealed that P2X7R was primarily expressed in neurons, astrocytes, and microglia. In FCD samples, P2X7R protein levels were increased in abnormal cell types such as dysmorphic neurons and balloon cells, which are characteristic of FCD. By real-time PCR and Western blotting, P2X7R mRNA and protein expression levels were elevated in FCD patient samples vs control samples; P2X7R expression was also higher in FCDII vs FCDIa patient samples. Because interleukin-1&bgr; is a downstream factor of the P2X7R signaling pathway, we determined that there was also moderate-to-strong interleukin-1&bgr; expression in the dysmorphic neurons, balloon cells, and microglia in FCD patient lesions. These results indicate that increasing P2X7R levels may contribute to the pathogenesis of human FCD and that P2X7R represents a potential anti-epileptogenic target.

局灶性皮质发育不良(FCDs)是主要的大脑畸形，通常导致医学上难治性癫痫。嘌呤能嗜电性P2X7受体(P2X7R)是一种非典型的P2X亚型，可抑制钙离子和钠离子。先前的动物研究表明P2X7R是癫痫发生的一个促进因素。本研究旨在确定35例FCD患者手术切除标本中P2X7R相对于尸检对照标本的分布和表达(n = 8)。免疫组织化学共定位分析显示P2X7R主要在神经元、星形胶质细胞和小胶质细胞中表达。在FCD样本中，P2X7R蛋白水平在异常细胞类型中升高，如畸形神经元和球囊细胞，这是FCD的特征。通过实时荧光定量PCR和Western blotting检测，FCD患者标本中P2X7R mRNA和蛋白表达水平较对照组升高;P2X7R在FCDII和FCDIa患者样本中的表达也更高。因为interleukin-1&bgr;是P2X7R信号通路的下游因子，我们确定也存在中强白介素-1;FCD患者病变中畸形神经元、球囊细胞和小胶质细胞的表达。这些结果表明，P2X7R水平的升高可能与人类FCD的发病机制有关，P2X7R可能是一个潜在的抗癫痫靶点。

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引用次数: 11

Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy 慢性创伤性脑病早期病理性Tau构象和磷酸化的特征

Journal of Neuropathology & Experimental Neurology

Pub Date : 2016-01-01 DOI: 10.1093/jnen/nlv001

N. Kanaan, K. Cox, Victor E. Alvarez, T. Stein, Sharra Poncil, A. Mckee

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 in tau occurs early and correlates with cognitive decline in patients with Alzheimer disease (AD). We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. Notably, the TauC3 epitope, which is abundant in AD, was relatively sparse in CTE. Together, these results provide the first description of PAD exposure, TOC1 reactive oligomers, phosphorylation of S422, and TauC3 truncation in the tau pathology of CTE.

慢性创伤性脑病(CTE)是一种神经退行性脑病，发生在重复性头部损伤后。其他tau疾病的一些证据表明，tau寡聚物的形成诱导神经毒性，并且tau寡聚物介导的神经毒性涉及通过暴露tau中的n端基序(磷酸酶激活域(PAD))诱导轴突功能障碍。此外，tau蛋白422丝氨酸磷酸化发生较早，并与阿尔茨海默病(AD)患者的认知能力下降相关。我们对固定脑切片进行免疫组织化学和免疫荧光分析，并对新鲜脑提取物进行生化分析，以表征9-11例CTE患者、非痴呆老年对照和AD (Braak VI)患者大脑中pad暴露的tau (TNT1抗体)、tau寡聚物(TOC1抗体)、S422位点磷酸化的tau (pS422抗体)和D421位点截断的tau (TauC3抗体)的存在。所有3种早期tau标志物(即TNT1, TOC1和pS422)均存在于CTE中，并在血管周围tau病变中显示广泛的共定位，这被认为是CTE的诊断。值得注意的是，在AD中丰富的TauC3表位在CTE中相对较少。总之，这些结果首次描述了PAD暴露、TOC1反应性低聚物、S422磷酸化和CTE tau病理中的TauC3截断。

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引用次数: 86

Neuropathological Characteristics of Brachial Plexus Avulsion Injury With and Without Concomitant Spinal Cord Injury. 伴有或不伴有脊髓损伤的臂丛神经撕脱伤的神经病理学特征

Journal of Neuropathology & Experimental Neurology

Pub Date : 2016-01-01 DOI: 10.1093/jnen/nlv002

Zarina S Ali, Victoria E Johnson, William Stewart, Eric L Zager, Rui Xiao, Gregory G Heuer, Maura T Weber, Arka N Mallela, Douglas H Smith

Neonatal brachial plexus avulsion injury (BPAI) commonly occurs as a consequence of birth trauma and can result in lifetime morbidity; however, little is known regarding the evolving neuropathological processes it induces. In particular, mechanical forces during BPAI can concomittantly damage the spinal cord and may contribute to outcome. Here, we describe the functional and neuropathological outcome following BPAI, with or without spinal cord injury, in a novel pediatric animal model. Twenty-eight-day-old piglets underwent unilateral C5–C7 BPAI with and without limited myelotomy. Following avulsion, all animals demonstrated right forelimb monoparesis. Injury extending into the spinal cord conferred greater motor deficit, including long tract signs. Consistent with clinical observations, avulsion with myelotomy resulted in more severe neuropathological changes with greater motor neuron death, progressive axonopathy, and persistent glial activation. These data demonstrate neuropathological features of BPAI associated with poor functional outcome. Interestingly, in contrast to adult small animal models of BPAI, a degree of motor neuron survival was observed, even following severe injury in this neonatal model. If this is also the case in human neonatal BPAI, repair may permit functional restoration. This model also provides a clinically relevant platform for exploring the complex postavulsion neuropathological responses that may inform therapeutic strategies.

新生儿臂丛神经撕脱伤（BPAI）通常是产伤的结果，可导致终生发病；然而，人们对其诱发的神经病理变化过程却知之甚少。特别是，BPAI 期间的机械力可能会同时损伤脊髓，并可能导致结果。在此，我们描述了一种新型儿科动物模型在发生或未发生脊髓损伤的 BPAI 后的功能和神经病理学结果。28 天大的仔猪接受了单侧 C5-C7 BPAI，并进行了或未进行有限脊髓切开术。撕脱后，所有动物都表现出右前肢单瘫。损伤延伸至脊髓会导致更大的运动障碍，包括长束征。与临床观察结果一致的是，脊髓切断术导致了更严重的神经病理学改变，包括更多的运动神经元死亡、进行性轴突病变和持续的神经胶质激活。这些数据表明，BPAI 的神经病理学特征与不良的功能预后有关。有趣的是，与成年小动物模型相比，即使在这种新生儿模型中受到严重损伤，也能观察到一定程度的运动神经元存活。如果人类新生儿 BPAI 的情况也是如此，那么修复可能允许功能恢复。该模型还为探索惊厥后复杂的神经病理反应提供了一个与临床相关的平台，可为治疗策略提供参考。

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引用次数: 0

Transmission of Soluble and Insoluble &agr;-Synuclein to Mice 可溶性和不溶性&agr;-Synuclein在小鼠体内的传递

Journal of Neuropathology & Experimental Neurology

Pub Date : 2015-12-01 DOI: 10.1097/NEN.0000000000000262

D. Jones, M. Delenclos, Ann-Marie T Baine, M. DeTure, M. Murray, D. Dickson, P. McLean

Abstract The neurodegenerative synucleinopathies, which include Parkinson disease, multiple-system atrophy, and Lewy body disease, are characterized by the presence of abundant neuronal inclusions called Lewy bodies and Lewy neurites. These disorders remain incurable, and a greater understanding of the pathologic processes is needed for effective treatment strategies to be developed. Recent data suggest that pathogenic misfolding of the presynaptic protein, &agr;-synuclein (&agr;-syn), and subsequent aggregation and accumulation are fundamental to the disease process. It is hypothesized that the misfolded isoform is able to induce misfolding of normal endogenous &agr;-syn, much like what occurs in the prion diseases. Recent work highlighting the seeding effect of pathogenic &agr;-syn has largely focused on the detergent-insoluble species of the protein. In this study, we performed intracerebral inoculations of the sarkosyl-insoluble or sarkosyl-soluble fractions of human Lewy body disease brain homogenate and show that both fractions induce CNS pathology in mice at 4 months after injection. Disease-associated deposits accumulated both near and distal to the site of the injection, suggesting a cell-to-cell spread via recruitment of &agr;-syn. These results provide further insight into the prion-like mechanisms of &agr;-syn and suggest that disease-associated &agr;-syn is not homogeneous within a single patient but might exist in both soluble and insoluble isoforms.

神经退行性突触核蛋白病包括帕金森病、多系统萎缩和路易体病，其特征是存在大量的称为路易体和路易神经突的神经元包涵体。这些疾病仍然无法治愈，需要对病理过程有更深入的了解，才能制定有效的治疗策略。最近的数据表明，突触前蛋白&agr;-突触核蛋白(&agr;-syn)的致病性错误折叠以及随后的聚集和积累是疾病过程的基础。据推测，错误折叠的异构体能够诱导正常内源性&agr;-syn的错误折叠，就像在朊病毒疾病中发生的那样。最近强调致病性&agr;-syn的播种效应的工作主要集中在不溶于洗涤剂的蛋白质种类上。在本研究中，我们将人类路易体病脑匀浆的萨科齐不溶或萨科齐可溶部分进行脑内接种，结果表明，在注射后4个月，这两部分均可诱导小鼠中枢神经系统病变。疾病相关沉积物在注射部位附近和远端积聚，表明通过招募&agr;-syn进行细胞间扩散。这些结果进一步深入了解了&agr;-syn的朊病毒样机制，并表明疾病相关的&agr;-syn在单个患者中不是均匀的，而可能存在于可溶性和不溶性亚型中。

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引用次数: 31

A New Mouse Model of Limb-Girdle Muscular Dystrophy Type 2I Homozygous for the Common L276I Mutation Mimicking the Mild Phenotype in Humans 模拟人类轻度表型的常见L276I突变的2I型四肢带状肌营养不良小鼠纯合模型

Journal of Neuropathology & Experimental Neurology

Pub Date : 2015-12-01 DOI: 10.1097/NEN.0000000000000260

T. Krag, J. Vissing

Abstract Limb-girdle muscular dystrophy type 2I (LGMD2I) is caused by mutations in the Fukutin-related protein (FKRP) gene, leading to inadequate glycosylation of &agr;-dystroglycan, an important protein linking the extracellular matrix to the cytoskeleton. We created a mouse model of the common FKRP L276I mutation and a hemizygous FKRP L276I knockout model. We studied histopathology and protein expression in the models at different ages and found that homozygous FKRP L276I mice developed a mild progressive myopathy with increased muscle regeneration and fibrosis starting from 1 year of age. This was likely caused by progressive loss of &agr;-dystroglycan–specific glycosylation, which was decreased by 78% at 20 months. The homozygous FKRP knockout was embryonic lethal, but the hemizygous L276I model resembled the homozygous FKRP L276I model at comparable ages. These models emphasize the importance of FKRP in maintaining proper glycosylation of &agr;-dystroglycan. The mild progression in the homozygous FKRP L276I model resembles that in patients with LGMD2I who are homozygous for the L276I mutation. This animal model could, therefore, be relevant for understanding the pathophysiology of and developing a treatment strategy for the human disorder.

2I型肢体肌营养不良症(LGMD2I)是由福克汀相关蛋白(FKRP)基因突变引起的，导致&agr;-肌营养不良蛋白糖基化不足，而&agr;-肌营养不良蛋白是连接细胞外基质与细胞骨架的重要蛋白。我们建立了常见的FKRP L276I突变小鼠模型和半合子FKRP L276I敲除模型。我们研究了不同年龄模型的组织病理学和蛋白表达，发现纯合子FKRP L276I小鼠从1岁开始出现轻度进行性肌病，肌肉再生和纤维化增加。这可能是由于&agr;-糖醛酸异常特异性糖基化的逐渐丧失引起的，在20个月时减少了78%。纯合子FKRP敲除具有胚胎致死性，但半合子L276I模型在相当年龄时与纯合子FKRP L276I模型相似。这些模型强调了FKRP在维持&agr;-三聚糖酐适当糖基化中的重要性。纯合子FKRP L276I模型的轻度进展类似于L276I突变纯合子的LGMD2I患者。因此，这种动物模型可能与理解人类疾病的病理生理学和开发治疗策略有关。

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引用次数: 19

Primary Central Nervous System Histiocytic Sarcoma Arising After Precursor B-Cell Acute Lymphoblastic Leukemia 前体b细胞急性淋巴母细胞白血病后发生的原发性中枢神经系统组织细胞肉瘤

Journal of Neuropathology & Experimental Neurology

Pub Date : 2015-12-01 DOI: 10.1097/NEN.0000000000000258

Alan F Brown, H. Fan, J. Floyd, J. Henry, Russell A Higgins

Abstract Histiocytic sarcomas (HSs) are rare malignant neoplasms derived from histiocytes that may be associated with other hematolymphoid neoplasms. Histiocytic sarcomas rarely occur in the CNS and have not previously been reported in conjunction with prior B-cell lymphoblastic leukemia. We report the case of a 23-year-old man who presented with primary CNS HS 7 years after achieving remission for precursor B-cell acute lymphoblastic leukemia (B-ALL). Molecular studies revealed clonal immunoglobulin heavy-chain (IGH) gene rearrangement within the HS, suggesting linkage to his previous B-ALL. Previously reported post-ALL HSs show a strong predilection for young males (male-to-female ratio, 20:1), whereas cases of primary CNS HS without previous ALL affected older adults with balanced sex predilection. The patient's survival at 60 months exceeds expectations when compared with that of other reported cases of de novo primary CNS HS (n = 18) and post-ALL HS at all sites (n = 19). In addition, we discuss the potential relationship between B-ALL and HS posed by other authors.

组织细胞肉瘤(HSs)是一种罕见的起源于组织细胞的恶性肿瘤，可能与其他血淋巴肿瘤有关。组织细胞肉瘤很少发生在中枢神经系统，以前没有报道与既往b细胞淋巴母细胞白血病合并。我们报告一例23岁的男性在前体b细胞急性淋巴母细胞白血病(B-ALL)缓解7年后出现原发性中枢神经系统综合征。分子研究显示，HS内克隆性免疫球蛋白重链(IGH)基因重排，提示与先前的B-ALL有关。先前报道的ALL后HS表现出强烈的年轻男性偏好(男女比例为20:1)，而没有ALL前的原发性中枢神经系统HS病例影响的是性别偏好平衡的老年人。与其他报道的原发性中枢神经系统HS (n = 18)和all后所有部位HS (n = 19)的新生病例相比，患者的60个月生存率超过预期。此外，我们还讨论了其他作者提出的B-ALL与HS之间的潜在关系。

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引用次数: 11