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A clonal expression biomarker associates with lung cancer mortality
An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage1. Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types2–6. Here, we analyze multi-region whole-exome and RNA sequencing
COSCA (Core Outcome Set for Cardiac Arrest) in Adults : An Advisory Statement From the International Liaison Committee on Resuscitation
Cardiac arrest effectiveness trials have traditionally reported outcomes that focus on survival. A lack of consistency in outcome reporting between trials limits the opportunities to pool results for meta-analysis. The COSCA initiative (Core Outcome Set for Cardiac Arrest), a partnership between patients, their partners, clinicians, research scientists, and the International Liaison Committee on R
Monoclonal Antibodies against Pancreatic Islet‐Cell‐Surface Antigens Selected by Flow Cytofluorometry
BALB/c mice were immunized with human islets of Langerhans and spleen cells from two mice. found to develop cell‐surface antibodies against insulin‐producing rat islet tumour RIN‐5F cells, were fused with mouse myeloma cells. Antibody‐producing hybrids were cloned on the basis of their production of surface antibodies reactive with paraformaldehyde‐fixed RIN‐5F cells by indirect immunofluorescence
A deletion in a rat major histocompatibility complex class I gene is linked to the absence of β2-microglobulin-containing serum molecules
Class I major histocompatibility antigens are composed of a heavy chain that is noncovalently associated with β2-microglobulin (β2m). Most class I molecules are membrane bound, but mouse and rat cDNA clones and genes without a functional code for the transmembrane amino acids have been identified. The membrane-associated class I molecules are important in the control of cell-mediated cytotoxicity,
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Islet cell antibodies in insulin-dependent (type 1) diabetic children treated with plasmapheresis
Plasma levels of islet cell cytoplasmic and cytotoxic antibodies were determined in 10 children with insulin-dependent diabetes mellitus (IDDM) treated with plasmapheresis shortly after diagnosis, and in 9 children with IDDM treated by conventional means alone. Islet cell cytoplasmic antibody (ICA) titers were determined by indirect immunofluorescence using unfixed sections of human pancreas, and
Identification of an HLA-DQ β-chain related genomic sequence associated with insulin-dependent diabetes
Restriction fragment length polymorphism detected by a cDNA probe for an HLA-DQ β-chain gene has revealed an HLA-DR4 linked BamH1 3.7 kb fragment which is rarely found among insulin-dependent diabetic patients. The present analysis demonstrates that the BamH1 3.7 kb fragment present on an HLA-DR4 positive chromosome in a healthy individual contains coding sequences for an HLA-DQ β-chain gene and t
Molecular biology of Type 1 (insulin-dependent) diabetes mellitus
Islet cell antibodies and cellular immunity in human diabetes.
In vitro lymphocyte recognition of islet cells following in vivo priming with allogeneic murine pancreatic islets
Lymphocytes from patients with insulin-dependent diabetes have been shown to be sensitized to pancreatic tissue antigens. Mice immunized with homologous pancreatic islets have been found to develop glucose intolerance and insulitis. Since lymphocytes may be involved in diabetogenesis, we wished to determine if lymph node cells from islet-immunized mice can recognize and respond to islet cells in v
Is there an autoimmune component in insulin-dependent diabetes?
A β-cell glycoprotein of Mr 40 000 is the major rat islet cell immunogen following xenogenic immunisation
An antiserum (R2) was raised in a rabbit against dispersed Sprague Dawley rat islet cells. The R2 antiserum contains islet cell surface antibodies, which mediate complement-dependent cytotoxicity against islet cells resulting in a block of glucose induced insulin release. Immunoprecipitation and gel electrophoretic analysis showed that R2 specifically recognizes an Mr 40 000 glycoprotein present i
Autoantibodies to a 64-kilodalton islet cell protein precede the onset of spontaneous diabetes in the BB rat
Spontaneous insulin-dependent diabetes mellitus (IDDM) in the BB rat is associated with the presence of antibodies to a 64-kilodalton rat islet cell protein. These protein antibodies appeared in young animals and remained for as long as 8 weeks before the clinical onset of IDDM. Antibodies to a 64-kilodalton human islet cell protein were found to be associated with human IDDM. Detection of the ant
LHC Dark Matter Working Group: Next-generation spin-0 dark matter models
Dark matter (DM) simplified models are by now commonly used by the ATLAS and CMS Collaborations to interpret searches for missing transverse energy (ET miss). The coherent use of these models sharpened the LHC DM search program, especially in the presentation of its results and their comparison to DM direct-detection (DD) and indirect-detection (ID) experiments. However, the community has been awa
Inhibition of insulin release after passive transfer of immunoglobulin from insulin-dependent diabetic children to mice
We used the mouse passive transfer model to test whether islet cell antibodies affect β-cell function. The immunoglobulin (Ig) fraction of plasma from 5 islet cell surface antibody-positive, newly diagnosed insulin-dependent diabetic children or of a pool of plasma from 12 normal subjects was injected daily (7–16 mg IgG/day) for 14 days into normal immunosuppressed BALB/c mice. Insulin secretory r
Role of islet cell antibodies in the pathogenesis of type I diabetes.
Detection of HLA-D/DR-related DNA polymorphism in HLA-D homozygous typing cells.
Sequences of different sizes are generated when DNA from homozygous HLA-Dw/DR typing cells are digested with restriction endonuclease and analyzed by hybridization with a HLA-D region class II antigen beta-chain cDNA probe. The patterns of hybridization were highly polymorphic but one endonuclease, BamHI, defined sequences unique to all HLA-Dw/DR specificities 1-8 except HLA-Dw/DR 2 and 6; however
B‐Cell Function and Islet Cell and Other Organ‐Specific Autoantibodies in Relatives to Insulin‐Dependent Diabetic Patients
ABSTRACT The pancreatic B‐cell function (glucose tolerance, C‐peptide release) and organ‐specific autoantibodies, including islet cell cytoplasmic and cell surface (mouse), were studied in 45 first‐degree relatives of patients with insulin‐dependent diabetes mellitus diagnosed before the age of 30 years. Compared to 107 healthy persons without any family history of either insulin‐dependent or non‐
Analysis of islet cell antibodies on frozen sections of human pancreas
The sensitivity and specificity of the assay for islet cell cytoplasmic antibodies in human serum were examined using cryostat sections from fresh frozen pancreas. The specificity of the assay was close to 100% while the sensitivity was 40%-98% depending on the pancreas used. Inter-observer variation was 12-27%. End-point titres of islet cell antibodies varied with the sensitivity of each pancreas