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  • Keywords Type I diabetes  (2)
  • A 23187  (1)
  • Actin filament  (1)
  • 1
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; insulitis ; ICA ; GAD ; biopsy ; immunohistochemistry ; HLA typing.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To determine whether the clinical heterogeneity observed in the development of Type I (insulin-dependent) diabetes mellitus correlates with immunohistochemical differences observed at diagnosis. Methods. Patients (n = 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I), underwent pancreatic biopsy for immunohistological analysis. These patients were divided into two groups based on the presence or absence of islet immunological abnormalities (insulitis or hyperexpression of MHC class I antigens or both). The patients were also HLA typed and tested for islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD-Ab). All patients were followed monthly for 2 years and their fasting plasma glucose, haemoglobin A1C and daily insulin doses were recorded. The clinical course of patients with islet immunological abnormalities was compared with that of patients without those abnormalities. Results. Patients with and without islet immunological abnormalities did not differ with regard to HLA type or islet cell antibodies. Antibodies to glutamic acid decarboxylase correlated with the presence of insulitis and MHC class I hyperexpression. These local immunological abnormalities were also associated with higher haemoglobin A1C values (p 〈 0.05) and a trend towards greater insulin requirements. Further, patients with the islet abnormalities had higher fasting plasma glucose concentrations 2 years after the biopsy than at the time of the biopsy (p 〈 0.05). Conclusion/interpretation. The heterogeneous clinical course observed following diagnosis in patients with Type I diabetes correlates with islet immunological abnormalities. Insulitis and hyperexpression of MHC class I correlate with deteriorating glycaemic control. [Diabetologia (1999) 42: 574–578]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; Fas ; Fas ligand ; insulitis ; human pancreas ; apoptosis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Type I (insulin-dependent) diabetes results mainly from T-cell-mediated autoimmune destruction of pancreatic beta cells. Cytotoxic T lymphocytes destroy target cells via a perforin-based or Fas-based mechanism. Our previous study indicated that the Fas-Fas ligand (FasL) pathway is required for the development of autoimmune diabetes in the NOD mouse. We now investigated whether or not the Fas-FasL system is involved in the beta-cell destruction in human Type I diabetes. Methods. We immunohistochemically analysed pancreas biopsy specimens of 13 recent-onset patients. Results. Pancreatic islets were identified but showed various degrees of reduction in beta-cell volume in all patients. Out of 13 patients 6 had insulitis. In these 6 patients Fas was expressed in both the islets and infiltrating cells but not in either cell type in the 7 other patients without insulitis. Double immunostaining showed that Fas was positive in 92.2 to 97.7 % of beta cells but only in 17.6 to 46.7 % of alpha cells in Fas-positive, insulin-remaining islets. We found FasL was expressed exclusively in islet-infiltrating cells in patients with insulitis. Double immunostaining revealed that the most prevalent phenotype of FasL-positive cells was CD8, which was followed by macrophages and CD4. Conclusion/interpretation. The interaction between Fas on beta cells and FasL on infiltrating cells might trigger selective apoptotic beta-cell death in inflamed islets, leading to immune-mediated Type I diabetes. [Diabetologia (1999) 42: 1332–1340]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0878
    Keywords: Thyroid ; Colloid reabsorption ; Actin filament ; Micropinocytosis ; Freeze-fracture ; Freeze substitution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The mechanism of the luminal colloid reabsorption and the fate of reabsorbed colloid droplets were studied ultracytochemically in epithelial cells of thyroid cells of TSH-treated mice. The luminal colloid is reabsorbed by micropinocytosis as well as phagocytosis into the follicle epithelial cell. Almost all the pinocytotic pits and vesicles are coated and often closely associated with actin filaments demonstrated by use of heavy meromyosin (HMM). This suggests the involvement of the actin filament system in making and transporting coated vesicles for micropinocytosis of the luminal colloid. Freeze-fracture images show aggregates of intramembrane particles on the P-face of the small depressions corresponding to the initial site for coated pits. The reabsorbed colloid droplets fuse with one another and with lysosomes. At the initial stage of this fusion, the limiting membranes of adjoining droplets fuse in a limited area to become pentalaminar, and then become trilaminar. Eventually, the membranes at the fusion point disappear, and the contents of both droplets become continuous. Freeze-fracture images reveal the disappearance of the intramembrane particles at the initial site where the fusion occurs. Examination of thin-sectioned tissue treated by rapid-freeze substitution fixation, shows clearly delineated cell organelles, and the rounded mitochondria have a characteristically high electron-dense matrix. Just beneath the limiting membrane of each colloid droplet, there always exists a low electron-dense layer about 10 nm thickness. The lysosomes are sometimes seen wrapped around the colloid droplet.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 229 (1983), S. 129-136 
    ISSN: 1432-0878
    Keywords: A 23187 ; Anterior pituitary ; Calcium influx ; Multigranular exocytosis ; Coated pits
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In order to study the fine structural effect of calcium influx on secretory activity of rat anterior pituitary cells, small pieces of anterior pituitary were incubated in Krebs' medium containing the calcium ionophore A23187 (0.15 mM) and were examined electron microscopically. Marked changes were present in all types of secretory cells incubated for 3, 12 and 20 min in the medium containing calcium and A23187. Secretory granules tended to accumulate in the peripheral cytoplasm of the secretory cells, and more numerous images of granule release by exocytosis were observed in somatotroph (STH cell), luteotroph (LTH cell), thyrotroph (TSH cell), corticotroph (ACTH cell), type 1 gonadotroph (Type 1 GTH cell), and type 2 gonadotroph (Type 2 GTH cell). In addition to the increase in the number of exocytoses of single granules, the simultaneous extrusion of multiple granules, “multigranular exocytosis”, was often observed in all kinds of secretory cells, especially the ACTH-cells. Large numbers of granule cores were often located in large vacuole-like or channel-like structures, irregular in shape and size, which were open to the intercellular or pericapillary space. Some parts of the membrane of the vacuole-like or channel-like structures were coated. These observations are interpreted to suggest that the calcium influx stimulates the extrusion of the secretory granules by single or multigranular exocytosis.
    Type of Medium: Electronic Resource
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