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Detection of islet cell autoantibodies in newly diagnosed diabetic patients using insulin-producing Syrian hamster cells.

An insulin-producing cell line, Clone-16, of hamster origin, was characterized for islet hormone production and for reactivity with islet cell surface (ICSA) and islet cell cytoplasmic (ICA) antibodies in sera from children with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM). The Clone-16 cells have a doubling time of about 50-60 hr. The cells produced 63 ± 3 ng (mean ± SD) im

Prolonged incubation in the two-colour immunofluorescence test increases the prevalence and titres of islet cell antibodies in Type 1 (insulin-dependent) diabetes mellitus

The conventional indirect immunofluorescence test of islet cell antibodies was recently improved by the development of a two-colour immunofluorescence assay using a monoclonal proinsulin antibody to detect islet B cells. The aim of this study was to test whether in this new assay the prevalence and titre of ICA were affected by the time of incubation carried out in the presence of aprotinin (Trasy

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,

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