Searching for Serum Antibodies to Neuronal Proteins in Patients With Myalgic Encephalopathy/Chronic Fatigue Syndrome

PurposeA role for the immune system in causing myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is long suspected, but few studies have looked for specific autoantibodies that might contribute to the symptoms. Our aim was to look for evidence of antibodies to neuronal proteins in patients with ME/CSF.MethodsSera samples from 50 patients and 50 healthy individuals were sent coded to the Neuroimmunology Laboratory in Oxford. Screening for antibody binding to neuronal tissue was performed on brain tissue and neuronal cultures. Specific serum antibodies were assessed by antigen-specific cell-based assays and radioimmunoassays. After antibody testing, the associations between seropositive status and clinical data were investigated.FindingsOverall, 8 patients and 11 participants were found to have some serum immunoreactivity toward neuronal or neuromuscular junction proteins, but only 1 patient and 2 participants had specific serum antibodies. Nevertheless, seropositive status in patients with ME was associated with shorter duration since onset and a more severe disease.ImplicationsThe results indicate no overall increased frequency of antibodies to neuronal proteins in ME/CSF and no evidence of a specific antibody that might be causative or contribute to clinical features in patients. However, the association of seropositive status with shorter duration of disease and more severe symptoms suggests a possible role of antibodies at onset in some patients and should be the focus of future studies.     

EEG dipole analysis of motor-priming foreperiod activity reveals separate sources for motor and spatial attention components

OBJECTIVE: This study employed EEG source localisation procedures to study the contribution of motor preparatory and attentional processing to foreperiod activity in an S1-S2 motor priming task. METHODS: Behavioural and high-density event-related potential (ERP) data were recorded in an S1-S2 priming task where participants responded to S2 with a left or right-hand button press. S1 either provided information about response hand (informative) or ambiguous information (uninformative). RESULTS: Responses were significantly faster in informative trials compared with uninformative trials. Dipole source analysis of foreperiod lateralized ERPs revealed sources of motor preparatory activity in the dorsolateral premotor cortex (PMd) in line with previous work. In addition, two spatial attention components (ADAN, LDAP) were identified with generators in the PMd and occipitotemporal visual areas in the middle temporal (MT) region, respectively. Separation of motor-related and attentional PMd source locations was reliable along the rostral-caudal axis. CONCLUSIONS: The presence of attentional components in a motor priming paradigm supports the premotor theory of attention which suggests a close link between attention and motor preparatory processes. Separation of components in the premotor cortex is in accord with a functional division of PMd into rostral (higher-order processing) and caudal (motor-related processing) areas as suggested by imaging work. SIGNIFICANCE: A prime for response preparation is a trigger for separate, but closely linked, attention-related activity in premotor areas.     

肺癌患者FLK-1、LRP和MDR1的表达与临床研究

目的:探讨血管内皮生长因子受体 (Flk 1),肺耐药蛋白 (LRP)基因以及多药耐药基因 (MDR1)蛋白与肺癌患者临床及病理指标的关系。方法:用免疫组化技术(ABC法)对原发性肺癌组织中三种基因的表达进行检测。结果: 70例肺癌中,非小细胞肺癌MDR1阳性率 49. 2% (29 /59),明显高于小细胞肺癌 (SCLC) 18. 2% (2 /11)(P<0. 05);非小细胞肺癌LRP阳性率 69. 5% (41 /59),明显高于小细胞肺癌 27. 3% (3 /11) (P<0. 05)。腺癌中MDR1与LRP的表达明显高于鳞癌(P<0. 05)。LRP与Flk 1在NSCLCs中共同表达 49. 2% (29 /59),LRP的表达与肺癌的组织学分级相关,MDR1和LRP的表达与肺癌的组织学类型有关,Flk 1与TNM分期相关,均有统计学意义(P<0. 05)。Flk 1 LRP均阳性、FLK 1 LRP MDR1均阳性、中药治疗、复发与患者的生存率有关(P<0. 05)。结论:FLK 1、LRP和MDR1基因蛋白产物的检测对肺癌患者的诊治和预后评估有积极意义。     

Cenani–Lenz syndrome and other related syndactyly disorders due to variants in LRP4, GREM1/FMN1, and APC: Insight into the pathogenesis and the relationship to polyposis through the WNT and BMP antagonistic pathways

Cenani–Lenz (C–L) syndrome is characterized by oligosyndactyly, metacarpal synostosis, phalangeal disorganization, and other variable facial and systemic features. Most cases are caused by homozygous and compound heterozygous missense and splice mutations of the LRP4 gene. Currently, the syndrome carries one OMIM number (212780). However, C–L syndrome‐like phenotypes as well as other syndactyly disorders with or without metacarpal synostosis/phalangeal disorganization are also known to be associated with specific LRP4 mutations, adenomatous polyposis coli (APC) truncating mutations, genomic rearrangements of the GREM1‐FMN1 locus, as well as FMN1 mutations. Surprisingly, patients with C–L syndrome‐like phenotype caused by APC truncating mutations have no polyposis despite the increased levels of β catenin. The LRP4 and APC proteins act on the WNT (wingless‐type integration site family) canonical pathway, whereas the GREM‐1 and FMN1 proteins act on the bone morphogenetic protein (BMP) pathway. In this review, we discuss the different mutations associated with C–L syndrome, classify its clinical features, review familial adenomatous polyposis caused by truncating APC mutations and compare these mutations to the splicing APC mutation associated with syndactyly, and finally, explore the pathophysiology through a review of the cross talks between the WNT canonical and the BMP antagonistic pathways.     

肺耐药蛋白在子宫内膜癌中表达及其临床意义

目的 探讨肺耐药蛋白(LRP)在子宫内膜癌治疗中的作用及预后关系。方法 采用免疫组化染色SP法，检测30例石蜡包埋的子宫内膜癌中LRP的表达，并对应用化疗后的效果进行分析。结果 (1)LRP阳性表达率80％(24／30)；(2)LRP表达阳性者的化疗有效率约为45．8％，明显低于LRP表达阴性者(83．3％)；(3)LRP的表达与腹水相关，与患者年龄、临床分期、组织分级无关；(4)LRP表达阴性患者预后明显优于阳性。结论 LRP是评价子宫内膜癌化疗耐药性和预后可靠指标。     

Clinical Phenotype and Relevance of LRP5 and LRP6 Variants in Patients With Early-Onset Osteoporosis (EOOP)

Reduced bone mineral density (BMD; ie, Z-score ≤−2.0) occurring at a young age (ie, premenopausal women and men <50 years) in the absence of secondary osteoporosis is considered early-onset osteoporosis (EOOP). Mutations affecting the WNT signaling pathway are of special interest because of their key role in bone mass regulation. Here, we analyzed the effects of relevant LRP5 and LRP6 variants on the clinical phenotype, bone turnover, BMD, and bone microarchitecture. After exclusion of secondary osteoporosis, EOOP patients (n = 372) were genotyped by gene panel sequencing, and segregation analysis of variants in LRP5/LRP6 was performed. The clinical assessment included the evaluation of bone turnover parameters, BMD by dual-energy X-ray absorptiometry, and microarchitecture via high-resolution peripheral quantitative computed tomography (HR-pQCT). In 50 individuals (31 EOOP index patients, 19 family members), relevant variants affecting LRP5 or LRP6 were detected (42 LRP5 and 8 LRP6 variants), including 10 novel variants. Seventeen variants were classified as disease causing, 14 were variants of unknown significance, and 19 were BMD-associated single-nucleotide polymorphisms (SNPs). One patient harbored compound heterozygous LRP5 mutations causing osteoporosis-pseudoglioma syndrome. Fractures were reported in 37 of 50 individuals, consisting of vertebral (18 of 50) and peripheral (29 of 50) fractures. Low bone formation was revealed in all individuals. A Z-score ≤−2.0 was detected in 31 of 50 individuals, and values at the spine were significantly lower than those at the hip (−2.1 ± 1.3 versus −1.6 ± 0.8; p = .003). HR-pQCT analysis (n = 34) showed impaired microarchitecture in trabecular and cortical compartments. Significant differences regarding the clinical phenotype were detectable between index patients and family members but not between different variant classes. Relevant variants in LRP5 and LRP6 contribute to EOOP in a substantial number of individuals, leading to a high number of fractures, low bone formation, reduced Z-scores, and impaired microarchitecture. This detailed skeletal characterization improves the interpretation of known and novel LRP5 and LRP6 variants. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

P-GP170、LRP与Ki-67在甲状腺乳头状癌中的表达及临床意义

 目的　检测多药耐药基因蛋白P 糖蛋白 (P GP170 )和肺耐药蛋白 (LRP)与抗核抗体Ki 6 7在甲状腺乳头状癌中的表达及临床意义。方法　采用免疫组化SP法检测P GP170、LRP、Ki 6 7在 6 4例甲状腺乳头状癌和 2 0例甲状腺腺瘤中的表达。结果　 3种抗体在甲状腺乳头状癌中均呈高表达 ,在甲状腺腺瘤中呈低表达。与甲状腺腺瘤相比有显著性差异 (P <0 .0 1)。P GP170、LRP、Ki 6 7三者呈显著相关性 (LRP与Ki 6 7r =0 .4 2 ,LRP与P GP170r =0 .4 2 ,Ki 6 7与P GP170r =0 .6 5 ,P <0 .0 1)。结论甲状腺乳头状癌标记指数高、耐药性强、化疗敏感性低。在化疗中同时给予耐药抑制剂 ,可以提高化疗敏感性和化疗效果。     

肺耐药蛋白表达与食管鳞癌临床病理特征的关系

目的　研究肺耐药蛋白(LRP)在食管鳞癌组织中的表达情况及其与临床病理特征和预后的关系。方法　应用Elivision二步免疫组织化学法观察51例食管鳞癌组织和18例癌旁正常粘膜组织(距离癌组织>2cm)中LRP的表达情况,结合临床病理指标包括患者年龄、肿瘤大小、临床分期和淋巴结转移以及生存情况进行统计学分析。结果　肿瘤大于5cm者LRP的阳性率明显高于5cm以下者(P<0. 05),食管鳞癌中LRP表达阳性率高于癌旁正常食管鳞状上皮,高年龄组的LRP阳性率较低年龄组高,有淋巴结转移者LRP阳性率高于无转移者,生存期短者( <3年)的阳性率高于生存期长者( >3年),但P均>0. 05。结论　LRP表达与食管鳞癌肿瘤大小之间存在显著相关性,临床检测LRP阳性不能作为判断食管鳞癌转移和预后的独立指标,但提示LRP表达阳性患者可能有预后差的趋势。