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1.
Metabolism ; 42(7): 854-9, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8345795

RESUMEN

We determined the natural history of the widespread pancreatic islet beta-cell destruction that precedes the onset of spontaneous putative autoimmune diabetes mellitus in NOD mice. For this purpose, we performed both histological and immunocytochemical examinations of pancreata retrieved from mice at 2 through 30 weeks of age. An overexpression of la antigens was identified on islet beta cells at 4 weeks of age, without evidence of mononuclear cell infiltration. The abnormal expression of la antigens was age-related and was associated with hyperexpression of class I antigens and progressive islet cell histologic damage after 17 weeks of age. Immunocytochemical examination of islet cell infiltrate showed that the number of macrophages did not increase during the early phase of islet cell damage in these mice. The L3T4/Lyt-2 ratio increased after 7 weeks of age, but was 1:1 in the late stage of insulitis. These findings suggest that widespread islet beta-cell destruction is a process that begins primarily with derangements of the pancreatic beta-cell immune pattern, which may trigger a mononuclear cell reaction.


Asunto(s)
Diabetes Mellitus Tipo 1/patología , Islotes Pancreáticos/patología , Animales , Femenino , Antígenos de Histocompatibilidad Clase II/análisis , Islotes Pancreáticos/inmunología , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Endogámicos NOD
3.
J Endocrinol Invest ; 14(8): 629-33, 1991 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1774448

RESUMEN

A simple method for assaying DNA content of in vitro culture maintained pancreatic islets is described. By employing lyophilization of the islets and subsequent fluorometric analysis, we have been able to measure DNA from relatively small cell samples. The method may result advantageous, over others, previously reported, since it is less subject to experiment-related interfering conditions. This procedure, which is easy and reliable, even for very low DNA concentrations, seems to be very useful for culture maintained pancreatic islets, since in vitro work conducted with this endocrine tissue is usually associated with small size cell samples. The method may help for a simple assessment of the viable islet cell mass in in vitro studies.


Asunto(s)
ADN/análisis , Islotes Pancreáticos/química , Hidróxido de Amonio , Animales , Células Cultivadas , Detergentes , Perros , Femenino , Liofilización , Hidróxidos , Linfocitos/química , Masculino , Octoxinol , Polietilenglicoles , Ratas , Ratas Endogámicas Lew , Estándares de Referencia , Espectrometría de Fluorescencia , Porcinos
4.
J Endocrinol Invest ; 16(11): 869-73, 1993 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8144863

RESUMEN

We have studied the effects of long-term treatment with azathioprine (AZA) vs cyclosporin A (CSA) vs placebo (PL), in three groups of 10 week old, prediabetic NOD mice. One of 8 AZA, none of 8 CSA and 7 of 11 PL treated mice developed overt diabetes (IDDM). Quantitative morphometric analysis conducted on mouse pancreatic histologic sections documented that extent and degree of islet beta-cell damage were incomparably less severe in the mice that received AZA or CSA compared to those treated with PL. Since early and prolonged treatment with AZA seems to prevent the onset of DM in NOD mice as nearly effectively as CSA, AZA, which is significantly safer than CSA, could replace the latter as a potential approach for the immunotherapy of IDDM.


Asunto(s)
Azatioprina/uso terapéutico , Diabetes Mellitus Tipo 1/prevención & control , Animales , Ciclosporina/uso terapéutico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patología , Femenino , Islotes Pancreáticos/patología , Masculino , Ratones , Ratones Endogámicos NOD , Páncreas/patología
5.
Clin Exp Immunol ; 107(2): 341-6, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9030873

RESUMEN

The diagnostic specificity of recombinant 21-hydroxylase autoantibodies (21OH-Ab) for Addison's disease was tested in adult patients with either Graves' disease (GD), insulin-dependent diabetes mellitus (IDDM), or polyendocrinopathy, as well as in healthy controls. Using a radiobinding assay with in vitro translated recombinant human 21-hydroxylase, we found 21OH-Ab in 24/28 (86%) idiopathic Addison patients, and using an immunofluorescence assay we found adrenal cortex autoantibodies (ACA) in 12/28 (43%) patients (P = 0.002). All the 12 ACA-positive sera were also positive for 21OH-Ab and ACA were found in 11/15 (73%) patients with less than 15 years and in 1/13 (8%) patients with 15-38 years of disease duration (P = 0.002). 21OH-Ab were present in 3/92 (3%) patients with GD, in 1/180 (0.6%) with IDDM and in 0/106 healthy subjects. The 21OH-Ab-positive GD and IDDM patients were also positive for ACA. None of 17 patients with polyendocrinopathy, but without Addison's disease, had 21OH-Ab. None of the 180 Belgian IDDM patients had Addison' s disease or developed an adrenal insufficiency at follow up. In two out of three Graves patients, the presence of 21OH-Ab was associated with clinical and biochemical signs of adrenal insufficiency. Of the 89 21OH-Ab-negative patients with GD none had Addison's disease at the time of blood sampling, and 79 were followed up for 5.6-7.5 years and none developed clinical signs of adrenal insufficiency. We conclude that the presence of 21OH-Ab in patients with endocrine autoimmune diseases is highly specific for Addison's disease.


Asunto(s)
Enfermedad de Addison/inmunología , Poliendocrinopatías Autoinmunes/inmunología , Esteroide 21-Hidroxilasa/inmunología , Enfermedad de Addison/epidemiología , Corteza Suprarrenal/inmunología , Adulto , Especificidad de Anticuerpos , Autoanticuerpos/inmunología , Bélgica/epidemiología , Diabetes Mellitus Tipo 1/inmunología , Enfermedad de Graves/inmunología , Humanos , Italia/epidemiología , Poliendocrinopatías Autoinmunes/epidemiología , Valor Predictivo de las Pruebas , Prevalencia , Proteínas Recombinantes/inmunología
6.
Horm Metab Res ; 28(7): 319-22, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8858375

RESUMEN

X-linked adrenoleukodystrophy (ALD) is a frequent cause of adrenal insufficiency in young-adult patients with Addison's disease. As the contribution of an autoimmune process in the destruction of steroid cells in ALD is unclear, the aim of the present study was to evaluate the occurrence of adrenal-, thyroid- and islet-specific and non organ-specific autoantibodies in adult ALD patients. In all 5 patients, Addison's disease was the first manifestation of ALD. None of the ALD patients were positive for adrenal cortex autoantibodies in an indirect immunofluorescence assay, or for 21-hydroxylase autoantibodies in a radiobinding assay with recombinant human antigen. Similarly, we found neither non-organ specific autoantibodies (such as anti-nuclear, anti-ribosomal, anti-mitochondria, anti-smooth-muscle, anti-liver/kidney microsomal or anti-reticulin autoantibodies), nor islet-cell antibodies or glutamic acid decarboxylase (GAD65 or GAD67) autoantibodies, nor thyroglobulin autoantibodies in the sera of the 5 ALD patients. Two out of five patients were positive for thyroid microsomal autoantibodies. One of the two latter thyroid antibody-positive patients had clinical symptoms of hypothyroidism, and the other presented high levels of circulating TSH but no clinical signs or symptoms of hypothyroidism. Our study demonstrates that adult ALD is not immediately associated with the presence of adrenal autoantibodies and suggests that adrenal insufficiency is not mediated by an autoimmune process in adult ALD patients.


Asunto(s)
Glándulas Suprarrenales/inmunología , Adrenoleucodistrofia/inmunología , Autoanticuerpos/inmunología , Enfermedades Genéticas Congénitas/genética , Enfermedad de Addison/inmunología , Enfermedad de Addison/metabolismo , Corteza Suprarrenal/citología , Corteza Suprarrenal/inmunología , Adulto , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/fisiopatología , Técnica del Anticuerpo Fluorescente , Glutamato Descarboxilasa/inmunología , Humanos , Persona de Mediana Edad , Esteroide 21-Hidroxilasa/inmunología , Esteroide 21-Hidroxilasa/metabolismo , Glándula Tiroides/inmunología , Cromosoma X/genética
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