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Antibodies to an Mr 64,000 Human Islet Cell Protein in the Prediabetic Period of IDDM Patients
Islet cell and 64k autoantibodies are associated with plasma IgG in newly diagnosed insulin-dependent diabetic children
There is a high prevalence of islet cell antibodies (ICA) and autoantibodies detected against an islet cell protein of M(r) 64,000 at the time of clinical diagnosis of insulin-dependent diabetes (IDDM). In view of the biphasic immune response after antigen presentation, the purpose of this study was to determine the presence of ICA and antibodies against the 64,000 islet antigen after separation o
A simple assay for the detection of antibodies to endocrine islet cell surface antigens
A simple and sensitive immunoradiometric assay for the detection of islet cell surface antibodies (CIRMA) has been developed. Live, transformed islet cells derived from a liver metastasis of a transplantable islet cell tumor were grown in removable microtiter wells and incubated with antibody. Cell-bound antibodies were quantitated using 125I-labelled second antibodies. The assay was used to detec
Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones
A liver metastasis (MSL) with a remarkable in vitro proliferation potential has been identified in an NEDH rat carrying a transplantable x-ray-induced islet cell tumor. Two insulin-secreting cell lines, MSL-G and MSL-H, with doubling times of 3-5 d were established by repeated limiting dilution cloning. In vivo inoculation of MSL-G cells induced severe hypoglycemia caused by a small but highly het
Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity
Column perfusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L-phenylalanine nor L-serine methyl ester, stimulate insulin secretion. In the presence of L-glutamine, however,
Panel discussion I : diagnosis, classification, and value of screening for diabetes mellitus.
Islet cell and other organ-specific autoantibodies in healthy first-degree relatives to insulin-dependent
The presence of organ-specific autoantibodies including islet cell surface, cytoplasmic and cytotoxic as well as thyroid-gastric antibodies were determined in healthy, non-diabetic, first-degree relatives to 30 insulin-dependent diabetic (IDDM) children. Thirty healthy families without family-history of diabetes mellitus served as controls. The prevalence of organ-specific autoantibodies among the
Secretin and its C-terminal hexapeptide potentiates insulin release in mouse islets
Peptides representing the C-terminal end of secretin were synthetized and their effects tested along with secretin on column-perifused isolated mouse pancreatic islets. Insulin release induced by 10 mmol/l D-glucose was potentiated by secretin tested in a concentration range of 0.01-10 μg/ml; the maximal effect was obtained with 1 μg/ml secretin. This effect was mimicked by 50-500 μg/ml NH2-Leu-Le
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
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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
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