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Biomedical subjects

E Colle

Publications and source records attributed to E Colle.

At least 55 records · Page 3Linked to original sources
PubMed1985

Association of spontaneous thyroiditis with the major histocompatibility complex of the rat.

Overt insulin-dependent diabetes mellitus in the rat is associated with the u haplotype of the rat major histocompatibility complex (MHC), RT1. Thyroiditis of sufficient severity to result in elevation of TSH levels is seen in Buffalo rats (RT1b). In order to examine the association of autoimmune thyroid disease with MHC gene products, we have crossed inbred Buffalo rats with diabetic BB rats and examined the RT1 genotype, the histology of thyroid and pancreatic tissue, and two indices of thyroid function. The data indicate that animals having pancreatic lymphocytic infiltration and insulinopenic overt diabetes mellitus had at least one RT1u haplotype. All but one animal having severe histological thyroid lymphocytic infiltration had at least one RT1b haplotype. Rats with severe thyroiditis had higher mean TSH levels than rats with normal histology or rats with mild thyroiditis. We conclude that gene products of the rat MHC affect the severity of spontaneous organ-specific autoimmune disease in terms of clinically apparent as well as tissue inflammatory disease.

Animals↗
PubMed1984

Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages.

Spleen cells of diabetes-prone BB Wistar rats were found to generate excessively low proliferative responses, and interleukin 2 (IL-2) levels in response to T-dependent mitogens. This abnormality was not due solely to abnormal T cell numbers since: (a) addition of BB spleen cells of BB splenic macrophages to normal major histocompatibility complex (MHC)-matched Wistar Furth (WF) spleen cells resulted in severe suppression of concanavalin A (Con A)-, phytohemagglutinin (PHA)-, and pokeweed mitogen (PWM)-mediated proliferation, and IL-2 production; (b) macrophage depletion from BB spleen cells, but not B cell or T cell depletion, removed completely the suppressive effects of BB cells on WF cells; (c) macrophage depletion greatly enhanced the response of BB lymphocytes to T-dependent mitogens. Although suppressor macrophages could also be found in the spleen of WF control rats they were present in much smaller numbers than in the spleen of BB rats. The suppressive effect of BB macrophages was partially reduced by addition of the prostaglandin synthetase inhibitor indomethacin to cultures. Furthermore, indomethacin (but not catalase or PMA) considerably augmented IL-2 secretion of Con A-stimulated BB spleen cells, but had little effect on WF spleen cells. In contrast, prostaglandins E1 and E2 (PGE1 and PGE2) suppressed IL-2 production. While IL-2 secretion was severely depressed in BB rats unstimulated and lipopolysaccharide (LPS)-stimulated IL-1 secretion by splenic macrophages was normal. BB macrophages did not inactivate IL-2. Low IL-2 production and macrophage-mediated suppression were features of all BB rats tested.

Animals↗
PubMed1984

Pancreatic cellular infiltrates in autoimmune-prone New Zealand Black mice.

Healthy New Zealand Black (NZB) mice of both sexes (age 19-31 weeks) were studied to determine the magnitude of pancreatic beta cell injury related to mononuclear cell infiltration of islets. This investigation was undertaken following the description of spontaneous cellular immune reactions against islets in four strains of autoimmune-prone mice, including NZB mice [1]. Studies included complete autopsies with histological examination, determination of the pancreatic content of immunoreactive insulin, and the measurement of the plasma glucose concentration. Mononuclear cell infiltrates were identified in the lung, liver, kidney, salivary gland, mesentery, and pancreas. In the latter site, the infiltrates were situated in fibrous septae about ducts, ductules, and venules rather than islets. Only islets contiguous to infiltrates were involved, and then but focally. Insulitis, as manifest by the envelopment and permeation of islets by mononuclear cells, was not observed. In none was there a significant reduction of beta cells or pancreatic insulin content, neither was hyperglycaemia manifest. This study reveals that, although NZB mice are subject to autoimmune phenomena and widespread mononuclear cell infiltrates, beta cell injury and insulitis are not consistent features of this strain.

Animals↗
PubMed1984

Isolation of T-lymphocyte lines with specificity for islet cell antigens from spontaneously diabetic (insulin-dependent) rats.

T-lymphocyte lines specific for islet cell antigens were isolated from the spleen and pancreas of newly diabetic BB rats or from the related strain BBUF. These cell lines were grown in continuous culture with interleukin-2 (IL-2) containing medium for greater than 60 days. Such T-lymphocytes responded by proliferation and IL-2 secretion in the combined presence of islet cell antigens and major histocompatibility (MHC)-matched antigen-presenting cells. By fluorescence-activated cell sorter (FACS) analysis the cells were W3/13+, W3/25+, and OX8-. Thus, both functionally and by cell-surface-marker analysis they appear to be of the T-helper phenotype. The long-term growth and study of anti-islet T-lymphocyte lines will permit a detailed analysis of the role of T-lymphocytes in the pathogenesis of IDDM.

Animals↗
PubMed1983

Abnormal immunoregulation in patients with insulin dependent diabetes mellitus and their healthy first degree relatives.

Autoantibodies, cell-mediated autoimmunity, and impaired suppressor T cell function, suggesting abnormal immunoregulation, have been implicated in the pathogenesis of juvenile-onset insulin dependent diabetes mellitus (IDDM). To examine one of the parameters of immunoregulation, and to explore its relationship to the disease, we tested suppressor cell function in IDDM patients, their clinically healthy relatives, and in normal unrelated controls. 9/15 IDDM had impaired suppressor cell function compared to 1/8 age-matched healthy sibs (p less than 0.04) and to 0/9 unrelated controls (p less than 0.005). There was no correlation between abnormal suppressor cell function and the patient's age, sex, preprandial blood glucose levels, age at the time of diagnosis, or duration of the disease. However, there was a trend for a higher proportion of HLA Dr3 positive diabetics to have abnormal suppressor cell function compared to DR3 negative patients. Impaired suppressor cell function was also found in 5/23 clinically healthy first degree relatives; 4/5 were related to a diabetic who demonstrated abnormal suppressor cell function. These findings raise the possibility that underlying familial, probably genetically determined abnormalities in immunoregulation, acting in concert with other environmental or genetic factors, may contribute to disease susceptibility in IDDM.

Child↗
PubMed1983

Spontaneous diabetes mellitus syndrome in the rat. III. Pancreatic alterations in aglycosuric and untreated diabetic BB Wistar-derived rats.

The pancreatic alterations in aglycosuric and untreated diabetic BB Wistar-derived rats are described. A common finding, often seen in young aglycosuric rats, is that of discrete foci of periductular and/or acinar aggregates of lymphocytes and macrophages. Sites of periductular mononuclear cell infiltrates usually lack endocrine cells. In contrast, foci of acinar infiltrates, although distinct from the predominant endocrine cell mass in the islets of Langerhans, often contain small numbers of alpha and/or beta cells. It is suggested that these clusters of endocrine cells may in some way be antigenically different from those resident in the principal islets and thus serve as an additional target for the immune system in rats bearing the BB genome. The development of overt diabetes requires a massive destruction of beta cells within the islets of Langerhans. Two forms of diabetes mellitus emerge in untreated animals. The more common, designated unstable diabetes, is severe and lethal unless treated with insulin. Less commonly, a stable type of diabetes mellitus ensues for which insulin therapy is not mandatory. In each, the concentration of pancreatic immunoreactive insulin is profoundly decreased, although relatively greater amounts are present in the stable form. Unstable diabetic rats demonstrate a reduction in the concentration of pancreatic immunoreactive glucagon and somatostatin, suggesting that alpha and delta cells also sustain injury in this model of insulin-dependent diabetes mellitus.

Age Factors↗
PubMed1983

Spontaneous diabetes mellitus syndrome in the rat. IV. Immunogenetic interactions of MHC and non-MHC components of the syndrome.

We have examined the frequency of three phenotypic characteristics of the syndrome of spontaneous diabetes (overt IDDM, lymphocytic infiltration of the pancreas, and depression of T lymphocytes) in the offspring of crosses between IDDM BB rats and rats of strains with the same and different RT1 genotypes. On the basis of these observations we propose that there are at least three components of the diabetic syndrome in the rat: (1) a requirement for the RT1u haplotype from the BB strain or a gene in close linkage with the gene coding for this haplotype, (2) a susceptibility for development of insular, periductular, or intraacinar lymphocytic infiltration in the pancreas, and (3) a susceptibility to depression of T lymphocytes. Interactions between these components as well as with other genetic and environmental factors contribute to the full expression of the syndrome.

Animals↗
PubMed1983

Lymphoproliferative lesions in BB Wistar rats.

Fifteen percent of long-term diabetic BB Wistar rats developed abdominal B cell lymphoproliferative lesions which ranged from minute mesenteric aggregates of plasma cells and lymphocytes to malignant lymphoma with features of immunoblastic sarcoma or plasma-cell lymphoma. Lymph nodes in younger BB Wistar rats, both diabetic and nondiabetic, demonstrated variable degrees, often extensive, of paracortical and medullary replacement by plasmacytoid lymphocytes and/or plasma cells. This study documents morphologic abnormalities in lymph nodes of BB Wistar rats, thus providing additional evidence of altered immunity in this model.

Animals↗
PubMed1983

Episodic hypoglycemia with psi-hydroxy fatty acid excretion.

We present case histories of two young children with episodes of hypoglycemia, elevation of SGOT, low insulin levels, increased urinary excretion of psi-hydroxy fatty acids (5-hydroxyhexanoic, 7-hydroxyoctanoic and 9-hydroxydecanoic), traces of the corresponding psi-ketoacids and elevations of urinary adipic, suberic, and sebacic acids. The ratio of psi-hydroxy fatty acids to 3-hydroxybutyric in the urine of these patients is higher than in patients of similar ages with similar illnesses. These acids persisted while the patients were well. Increased urinary psi-hydroxy fatty acids could be reproduced by a load of medium chain triglycerides without precipitating other clinical symptoms. Three children with hypoglycemia were found not to excrete measurable amounts of these unusual acids while ill. A medium chain triglyceride load in one of these children after recovery failed to elicit psi-hydroxy acid excretion. Small amounts of urinary 5-hydroxyhexanoic acid only were found in two patients with acute Reye's syndrome and in three of five severely ill children with starvation ketonuria. In this last group, no urinary psi-hydroxyacids could be detected after recovery. Normal children do not excrete measurable amounts (less than 1 mg/g creatinine) of these psi-hydroxyacids.

Aspartate Aminotransferases↗
PubMed1983

Spontaneous diabetes mellitus syndrome in the rat. II. T lymphopenia and its association with clinical disease and pancreatic lymphocytic infiltration.

We have studied the occurrence of two phenotypic components (pancreatic lymphocytic infiltration [PLI] of the pancreas and T lymphocytopenia) of the spontaneous insulin-dependent diabetic syndrome (IDDM) in the progeny of hybrids obtained by crossing BB diabetic rats with rats of inbred strains differing from the BB rat at the major histocompatibility complex, RT1. Both PLI and T lymphopenia were seen in animals with all three possible genotypes in both (BUF x BB) and (LEW x BB) lines. PLI was seen in all IDDM animals. T lymphopenia was strongly associated with overt IDDM in both lines (chi 2 = 22.28, p = 0.00002 and chi 2 = 19.28, p less than 0.00001). In addition, T lymphopenia was associated with PLI with and without IDDM in both lines (chi 2 = 8.32, p = 0.0039 an chi 2 = 3.95, p = 0.0467). Not all animals exhibiting PLI without overt IDDM had depressed T cells. Not all animals with T lymphopenia had PLI with or without IDDM. In both lines, the overt IDDM occurred only in animals with at least one RT1 u haplotype derived from the BB rat, confirming our previously reported association of IDDM and RT1. We interpret this evidence to suggest that the overt IDDM syndrome requires one MHC-linked gene and at least two non-MHC-linked genes, which determine susceptibility to PLI and to circulating T lymphocyte depression.

Animals↗
PubMed1982

Daytime pulsatile growth hormone secretion during childhood and adolescence.

Spontaneous GH secretory patterns were studied in 91 subjects (84 children, 2-18 yr old, at various stages of pubertal development and 7 healthy adults). Plasma GH was determined every 20 min for 6 h (0900-1500 h), and at least 1 spontaneous GH secretory episode (peak, greater than or equal to 5 ng/ml) was evident in 61 children and 5 of 7 adults. There was no significant difference in the mean number of GH secretory episodes or the mean 6-h plasma GH levels in 40 children with short stature compared to those in children of the same sex and pubertal maturation with normal or tall stature. The mean number of GH secretory episodes observed during the sampling period was significantly less in Tanner Stage II males (1.3 +/- 0.15) than in Tanner Stage III males (2.1 +/- 0.20; P less than 0.05). Also, the mean 6-h plasma GH level and the amplitude of the highest GH peak in Tanner Stage III (or greater) boys were greater than those in the prepubertal, early pubertal, or adult male subjects. Among females there was no difference in the number of peaks, mean 6-h plasma GH, or mean peak amplitude in prepubertal, pubertal, or adult subjects. Furthermore, there was no significant difference in overall mean 6-h plasma GH levels between male and female subjects. The frequency of GH secretory bursts was greater between 0830-0930 and 1330-1430 h. The GH secretory profiles were not different in children fed 1 or 2 meals. Children failing to show spontaneous peaks had GH deficiency secondary to central nervous system pathology (n = 10), psychosocial GH deficiency (n = 4), estrogen-dependent GH deficiency (n = 2), and optic nerve hypoplasia (n = 3). There were 2 false negatives and 2 children who were not retested. Pulsatile GH secretion is present during the daytime in children of all ages and stages of puberty. Determination of spontaneous GH secretory bursts is a safe and effective method for assessing GH deficiency.

Adolescent↗
PubMed1982

Dynamic time course studies of the spontaneously diabetic BB Wistar rat. III. Light-microscopic and ultrastructural observations of pancreatic islets of Langerhans.

The pancreatic islet alterations were studied in spontaneously diabetic BB Wistar rats and in young (50 and 65 days old) normoglycemic BB rats with the use of light microscopy, immunohistochemistry, and electron microscopy. Three groups of diabetic rats were delineated: 1) early diabetes (1-3 days after detection of glycosuria), 2) stable diabetes (41-63 days after detection), and 3) unstable diabetes (7-22 days after detection). In early diabetes islets were extensively infiltrated by "activated" lymphocytes and macrophages, and B cells demonstrated marked degranulation, injury, and necrosis. Although no consistent changes were recorded in A cells, D cells appeared to be decreased in number. In stable and unstable diabetes, islets were small and markedly depleted of B cells, although more insulin-containing cells were identified in the stable group. The number of A and D cells appeared normal in the stable group, although some A cells appeared altered ultrastructurally. In the unstable group both A and D cells appeared decreased, and ultrastructurally altered A cells were again noted. These findings suggest that although B cells appear to be the principal islet target in this model, A and D cells also sustain cellular injury. Variable degrees of insulitis, B cell degranulation, and necrosis were documented in 65-day-old normoglycemic BB rats, suggesting that the destructive process in the islets is initiated well in advance of the onset of the clinical syndrome. The pancreases from many diabetic and normoglycemic BB rats also demonstrated mononuclear cell infiltrates distinct from insulitis in periductular and/or acinar locations. These infiltrates, not present in controls, appear to represent an additional morphologic expression of the process responsible for initiating the diabetic state.

Animals↗
PubMed1981

Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.

A syndrome of spontaneous diabetes mellitus has been previously described in a partially inbred rat strain called BB Wistar. We have determined whether there is major histocompatibility complex (MHC) linkage as well as other predisposing haplotype-associated factors of development. BB rats are RT1 (MHC) genotype u/u. Using BB x Lewis F1 hybrid matings, an F2 study analyzed 128 rats from 8 primary and 3 additional litters from a breeding pair producing a diabetic offspring. 4 of 128 F2 rats, all from the 48 progeny of same breeding pair, became clinically diabetic. The four diabetics were all genotype u/u (P = 0.03). In the primary F2 litters, haplotype distribution was not different from the 1:2:1 expected ratio. However, in the four litters from the from the F1 breeding pair producing diabetics, there was an increased number of u/u animals. Two-way analysis of variance revealed significant differences in pancreatic insulin content between litters (diabetics excluded), P less than 0.001, and between haplotypes P less than 0.007 with heterozygous u/u less than 1/1 progeny. The glucagon content showed no significant differences. These data demonstrate (a) MHC linkage with spontaneous diabetes in this rat model; (b) penetrance similar to the human disease; and (c) a possible association of MHC haplotype with pancreatic inflammation as well as insulin content in nondiabetic F2 siblings.

Animals↗