Search results for " sequence"
showing 10 items of 3643 documents
Cloning of the human NCNF gene.
1998
We have cloned from a cDNA library of human testis tissue the human homologue to the mouse nuclear orphan receptor NCNF (neuronal cell nuclear factor). The open reading frame encodes a protein of 480 amino acids, the sequence of which (EMBL accession no. X99975) is 98.3% identical to the mouse homologue. Northern blot analysis of adult human tissues revealed a broad pattern of tissue expression. Similar to NCNF expression in mouse testis, two transcript forms of the single copy gene are expressed in human tissues. The two transcript forms which differ only in their 3'UTR, result in human from differential polyadenylation, in mouse from alternative splicing. Based on the high level of sequen…
IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
2018
GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 ca…
Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation
2014
Intrathecal oligoclonal bands of the cerebrospinal fluid are considered the most important immunological biomarkers of multiple sclerosis. They typically consist of clonally expanded IgG antibodies that underwent affinity maturation during sustained stimulation by largely unknown antigens. In addition, ∼40% of patients with multiple sclerosis have oligoclonal bands that consist of expanded IgM antibodies. We investigated the molecular composition of IgM- and IgG-chains from cerebrospinal fluid of 12 patients with multiple sclerosis, seven patients with other neurological diseases, and eight healthy control subjects by high-throughput deep-sequencing and single-cell PCR. Further, we studied …
Characterization of target antigens from anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis type-I.
1997
The occurrence of anti-neutrophil cytoplasmic antibodies (ANCA) has been described in sera of patients with autoimmune hepatitis (AIH). The significance of this finding remains uncertain and the nature of the target antigen(s) has not yet been defined. We studied 32 sera from patients with AIH type-I and prepared extracts of human neutrophils to identify the target antigen(s). A 43 kDa dominant immunoreactive protein was found and identified as the cytoskeletal component actin. Initial studies to define the antigenic determinants identified three different actin domains.
Reliability of measuring the fat content of the lumbar vertebral marrow and paraspinal muscles using MRI mDIXON-quant sequence
2018
PURPOSE We aimed to assess the reliability of measuring the fat content of the lumbar vertebral marrow and the paraspinal muscles using magnetic resonance imaging (MRI) mDIXON-Quant sequence. METHODS Thirty-one healthy volunteers were included. All participants underwent liver mDIXON-Quant imaging on a 3.0 T Philips MRI scanner by observer A. Within two weeks, observer B repeated the scan. After the examination, each observer independently measured the fat content of the third lumbar vertebra (L3), and the psoas (PS), erector spinae (ES), and multifidus (MF) muscles on central L3 axial images. After two weeks, each observer repeated the same measurements. They were blinded to their previous…
Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1-PDGFB ) study with therapeutic implications.
2009
Aims: To analyse the presence of collagen type I alpha 1–platelet-derived growth factor beta (COL1A1–PDGFB) transcripts in 20 cases of dermatofibrosarcoma protuberans (DFSP) and to assess the relationship between COL1A1 breakpoints and clinical and histopathological variables. Methods and results: Multiplex reverse transcriptase-polymerase chain reaction was carried out using frozen tissue. Our series contained 14 men and six women. Histologically, most cases were of conventional type (n = 9), followed by fibrosarcoma (n = 4), Bednar tumour (n = 2), sclerosing (n = 2), myoid (n = 1) and atrophic (n = 1) DFSP, and giant cell fibroblastoma (n = 1). Immunohistochemistry revealed CD34 express…
Overexpression of human homologs of the bacterial DnaJ chaperone in the synovial tissue of patients with rheumatoid arthritis
1999
Objective To study the expression of the chaperone family of J proteins in the synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis. Methods Rabbit antibodies specific for a synthetic peptide (pHSJ1: EAYEVLSDKHKREIYD), representing the most conserved part of all J domains thus far identified—among them the Drosophila tumor suppressor Tid56—were used in immunohistochemical analyses of frozen sections of synovial tissue and immunoblotting of protein extracts of adherent synovial cells. IgG specific for Tid56 was also used. Results Both antisera predominantly and intensely stained synovial lining cells from RA patients; other cells did not stain or stained only faintly.…
Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus
2006
We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection ( TAAD) and patent ductus arteriosus (PDA)(1,2) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocal…
Successful application of preimplantation genetic diagnosis for hypokalaemic periodic paralysis.
2009
Hypokalaemic periodic paralysis is a rare dominant inherited disease where a person suffers sudden falls of circulating potassium concentrations, producing muscle weakness and sometimes severe paralysis. Attacks can occur as frequently as several times a day or once in a year. The age of onset is usually adolescence but symptoms can appear as early as 10 years of age. Muscle weakness can compromise vital functions such as breathing or swallowing and heart arrhythmias are also frequent during attacks. Preimplantation genetic diagnosis, an early form of prenatal diagnosis for couples at risk of transmitting inherited diseases, was used to prevent the transmission of this disease. Six polymorp…
Identification of a peptide mimicking the binding pattern of an antiphospholipid antibody
2006
Our objective was to characterize monoclonal antiphospholipid antibodies (APL) and identify disease-associated antigens in patients with the antiphospholipid syndrome (APS). We used the monoclonal antibody HL-5B, derived from a patient with APS suffering from multiple ischemic events, to screen a 12-mer peptide phage display library (New England Biolabs, London, England). The identified phage clones were sequenced and the derived consensus peptide was synthesized. The peptide was used to perform competitive inhibition experiments for their ability to inhibit the binding of the monoclonal antibody and of serum antibodies to cardiolipin and phosphatidylserine. Additionally patients and contro…