106 research outputs found
Humoral response to neurofilaments and dipeptide repeats in ALS progression
Abstract Objective To appraise the utility as biomarkers of blood antibodies and immune complexes to neurofilaments and dipeptide repeat proteins, the products of translation of the most common genetic mutation in amyotrophic lateral sclerosis (ALS). Methods Antibodies and immune complexes against neurofilament light, medium, heavy chains as well as polyâ(GP)â(GR) dipeptide repeats were measured in blood samples from the ALS Biomarkers (nâ=â107) and the phenotypeâgenotype biomarker (nâ=â129) studies and in 140 healthy controls. Target analyte levels were studied longitudinally in 37 ALS cases. Participants were stratified according to the rate of disease progression estimated before and after baseline and C9orf72 genetic status. Survival and longitudinal analyses were undertaken with reference to matched neurofilament protein expression. Results Compared to healthy controls, total neurofilament proteins and antibodies, neurofilament light immune complexes (pâ<â0.0001), and neurofilament heavy antibodies (pâ=â0.0061) were significantly elevated in ALS, patients with faster progressing disease (pâ<â0.0001) and in ALS cases with a C9orf72 mutation (pâ<â0.0003). Blood neurofilament light protein discriminated better ALS from healthy controls (AUC: 0.92; pâ<â0.0001) and faster from slower progressing ALS (AUC: 0.86; pâ<â0.0001) compared to heavyâchain antibodies and lightâchain immune complexes (AUC: 0.79; pâ<â0.0001 and AUC: 0.74; pâ<â0.0001). Lower neurofilament heavy antibodies were associated with longer survival (Logârank Chiâsquare: 7.39; pâ=â0.0065). Increasing levels of antibodies and immune complexes between time points were observed in faster progressing ALS. Conclusions We report a distinctive humoral response characterized by raising antibodies against neurofilaments and dipeptide repeats in faster progressing and C9orf72 genetic mutation carriers ALS patients. We confirm the significance of plasma neurofilament proteins in the clinical stratification of ALS
Loss of heterozygosity at 7p in Wilms' tumour development
Chromosome 7p alterations have been implicated in the development of Wilms' tumour (WT) by previous studies of tumour cytogenetics, and by our analysis of a constitutional translocation (t(1;7)(q42;p15)) in a child with WT and radial aplasia. We therefore used polymorphic microsatellite markers on 7p for a loss of heterozygosity (LOH) study, and found LOH in seven out of 77 informative WTs (9%). The common region of LOH was 7p15â7p22, which contains the region disrupted by the t(1;7) breakpoint. Four WTs with 7p LOH had other genetic changes; a germline WT1 mutation with 11p LOH, LOH at 11p, LOH at 16q, and loss of imprinting of IGF2. Analysis of three tumour-associated lesions from 7p LOH cases revealed a cystic nephroma-like area also having 7p LOH. However, a nephrogenic rest and a contralateral WT from the two other cases showed no 7p LOH. No particular clinical phenotype was associated with the WTs which showed 7p LOH. The frequency and pattern of 7p LOH demonstrated in our studies indicate the presence of a tumour suppressor gene at 7p involved in the development of Wilms' tumour. © 2000 Cancer Research Campaig
Basic Atomic Physics
Contains reports on five research projects.Joint Services Electronics Program Contract DAAL03-92-C-0001Joint Services Electronics Program Grant DAAH04-95-1-0038National Science Foundation Grant PHY 92-21489U.S. Navy - Office of Naval Research Grant N00014-90-J-1322National Science Foundation Grant PHY 92-22768U.S. Army - Office of Scientific Research Grant DAAL03-92-G-0229U.S. Army - Office of Scientific Research Grant DAAL01-92-6-0197U.S. Navy - Office of Naval Research Grant N00014-89-J-1207Alfred P. Sloan FoundationU.S. Navy - Office of Naval Research Grant N00014-90-J-1642U.S. Navy - Office of Naval Research Grant N00014-94-1-080
Strategies of Bacterial Over Expression of Membrane Transporters Relevant in Human Health: The Successful Case of the Three Members of OCTN Subfamily
Fabrication of Pyramidal Patterned Sapphire Substrates for High-Efficiency InGaN-Based Light Emitting Diodes
Cardiomyocytes overexpressing TNFâα attract migration of embryonic stem cells via activation of p38 and câJun aminoâterminal kinase
Clearance kinetics of CD34+ cells from peripheral blood: an independent predictor of hematologic recovery after high-dose chemotherapy and hematopoietic stem cell transplantation
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