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An H-2 alloantiserum preserves β-cell function in mice made diabetic by low-dose streptozotocin

The pancreatic β-cell mass and function in C57BL/KsJ mice is markedly reduced the day after the last injection of five daily injections of a subdiabetogenic, 40 mg/kg, dose of streptozotocin (STZ). In this study, we prepared an H-2 alloantiserum by injecting C57BL/6J mice (H-2b) with spleen lymphocytes from C57BL/KsJ (H-2(d)) mice. The alloantiserum given on five consecutive days, 5 h before each

Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case–control pairs from 20 prospective cohorts included in the inte

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

Insulin release and pancreatic insulin is reduced in young prediabetic BB rats

The pancreases of approximately 50 days old diabetes-prone BB/Hagedorn (BB/H) and of the genetically closely related, but non-diabetic BB w-subline (control BB) rats were perfused to determine the capacity of D-glucose to release insulin before the expected development of diabetes. The BB/H rats were from a colony with 82-84% incidence of insulin-dependent diabetes mellitus (IDDM) by 140 days of a

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,

Isolation of a rat immune response gene identical to an alleged mouse A class II β-chain pseudogene

A human HLA-DQ β-chain cDNA was used as a probe to identify and isolate a rat major histocompatibility antigen β-chain gene from a genomic library constructed in the vector λ Charon 28 using Wistar rat DNA (RT1u). The isolated exon of the rat gene (RT1.Bβ2) encoding a β-chain second domain was found to share 93% nucleotide homology with a mouse A β2 exon. Although the genomic organization of this

Increased reduction in fasting C-peptide is associated with islet cell antibodies in Type 1 (insulin-dependent) diabetic patients

A cohort of 82 patients with Type 1 (insulin-dependent) diabetes was followed prospectively for 24 months, and 54 of them for 30 months, to study the relationship between fasting levels of immunoreactive C-peptide and titres of islet cell antibodies. After diagnosis, fasting C-peptide rose temporarily for 1-6 months of insulin therapy and declined continuously thereafter. While islet cell antibodi

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

Diffusion of C-peptide but not proinsulin from islets in frozen sections of human pancreas identified by monoclonal antibodies

Human proinsulin (HPI) and C-peptide (HCP) were visualized by specific monoclonal antibodies (Mab's) in the conventional indirect immunofluorescent assay for ICA (islet cell cytoplasmic antibodies) on frozen sections of human pancreas. Two different Mab's, GS-9A8 (anti-HPI, mouse IgG1) and GN-ID4 (anti-HPI/HCP, rat IgG2A), showed intense islet cell cytoplasmic staining. In contrast to the anti-HPI

Immune complexes in insulin-dependent diabetes

Circulating immune complexes (IC) were studied in 40 newly-diagnosed insulin-dependent diabetics (IDDM), 40 long duration IDDM, and 16 healthy controls. IC were detected by the solid-phase Clq test (SP-Clq). IDDM patients at diagnosis (25%) showed a higher incidence of IC compared to the long duration IDDM patients (15%) and the control group (7%). There was no difference in the prevalence of circ

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

Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2) : A randomized clinical trial—Rationale and design

Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore

Cortisone fails to affect levels of islet cell surface antibodies and incidence of diabetes in the BB rat

Cortisone acetate (250 µg/kg·day) was given by im injections to 40 21-day-old diabetes-prone BB rats. The animals were followed longitudinally to determine islet cell surface antibodies (ICSA), as an expression of an abnormal immune reaction against the pancreatic islet cells and plasma glucose to estimate the degree of metabolic control. ICSA were detected 10-150 days before the diagnosis of diab

Locus-specific detection of HLA-DQ and -DR antigens by antibodies against synthetic N-terminal octapeptides of the β chain

Antibodies against synthetic peptides representing the class-II antigen HLA-DR and -DQ β chain N-terminal sequences were prepared in rabbits. The two octapeptides only share two amino acids and enzyme-linked immuno-assays showed the antisera only to bind to its own antigen. Both peptide antisera detected a 29 kDa component in immunoblots of Raji and AL-34 cell plasma membrane proteins separated by

A prospective analysis of islet-cell cytotoxic antibodies in insulin-dependent diabetic children. Transient effects of plasmapheresis

We determined the effects of plasmapheresis on cytotoxic antibodies to islet cells in 10 children (aged 11-16 yr) with newly diagnosed insulin-dependent diabetes mellitus (IDDM), as well as the plasma levels of antibodies over the next 30 mo and their relation to serum C-peptide concentrations. Complement-dependent, antibody-mediated cytotoxicity (C'AMC) in plasma was measured in a 51Cr release as

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

Islet cell surface and lymphocyte antibodies often precede the spontaneous diabetes in the BB rat

The diabetic syndrome of the BB rat shows many homologies with that of human insulin-dependent diabetes and evidence that the onset of the disease is associated with the presence of autoantibodies, including islet cell surface antibodies. In this study, sera were sampled serially from weaning to 157 days of age from 26 BB rats in two low-incidence litters, and 22 rats of three high-incidence litte