Biomedical subjects

E Clauser

Publications and source records attributed to E Clauser.

112 records · Page 7Linked to original sources

PubMedDate not supplied

Vasopressin receptors modulate the pharmacological phenotypes of Cushing's syndrome.

We have examined the expression profiles of the different vasopressin receptors (V1, V2, V3) that can be expressed in the three different types of tumors associated with Cushing's syndrome. V3 (V1b) receptor cDNA was cloned from a pituitary tumor responsible for Cushing's disease. We show that it is overexpressed in these tumors and can respond to DD-AVP. High expression of the V3 receptor on highly differentiated, ACTH-secreting, bronchial carcinoid tumors explain why these non-pituitary tumors occasionally respond to vasopressin, mimicking a "pituitary-like" behavior. A retrospective analysis showed that vasopressin induced an ACTH-independent cortisol rise in 27% of the adrenocortical tumors responsible for Cushing's syndrome. V1 mRNA was detected in normal adrenal cortex and in all tumors. Adenomas had significantly higher levels than carcinomas. V1 mRNA levels were higher in responders than in non-responders. One adenoma which had a brisk cortisol response in vivo, also had in vitro cortisol responses that were inhibited by a specific V1 antagonist. In situ hybridization showed the presence of V1 mRNA in the normal human adrenal cortex where the signal predominated in the compact cells of the zona reticularis. A positive signal was also present in the tumors with high V1 mRNA levels determined by RT-PCR; its distribution pattern was heterogeneous and showed preferential association with compact cells. High-and not ectopic-expression of the V1 receptor occurs in a minority of adrenal cortical tumors which become directly responsive to vasopressin stimulation.

Adrenal Cortex Neoplasms↗

PubMedDate not supplied

Similarity of HLA-DQ profiles in adult-onset type 1 insulin-dependent diabetic patients with and without extra-pancreatic auto-immune disease.

Some insulin-dependent diabetic patients present with auto-immune diseases involving extra pancreatic tissues (type 1b diabetes mellitus). The genetic specificity of this syndrome, as opposed to insulin dependent diabetes mellitus (IDDM) free of such associations (Type 1a IDDM) is not clearly established. We have analyzed the HLA-DQB1 and DQA1, loci, after PCR amplification of genomic DNA, in 44 Type 1b IDDM patients, 78 Type 1a IDDM patients and 105 control subjects. No essential difference in HLA-DQ profiles appeared between Type 1b and Type 1a IDDM patients. Both diabetic groups displayed a significant enrichment in DQB1 alleles negative for aspartate at position 57 (Type 1b: 83%; Type 1a: 89%; controls 48%; p < 0.001 vs both patient groups) and in DQB1 Asp 57 negative homozygosity: 71% of Type 1b; 80% of Type 1a; 25% of controls (p < 0.01). This enrichment in DQB1 Asp 57 negative alleles was accounted for by DQB1* 0201 in the Type 1b group, and by DQB1 % 0201 and 0302 in the Type 1a patients. Conversely, alleles DQB1* 0602 and 0301 (DQB1 Asp 57 positive) were protective. Both diabetic groups also displayed a significant enrichment in DQA1 alleles positives for arginine at position 52 (65% of Type 1b; 76% of Type 1a; 50% of control subjects; p < 0.01 and 0.001, respectively, vs controls), and in DQA1 Arg 52 positive homozygotes (48% of Type 1b, 58% of Type 1a, 22% of control subjects; p < 0.01). All differences between diabetic groups and the control group were more pronounced in the case of Type 1a than of Type 1b patients. The HLA-DQ genes shared by Type 1a and Type 1b patients must therefore be closely associated with islet autoimmunity. Genetic differences between Type 1a and Type 1b syndromes, if any, must be investigated in other MHC and non-MHC regions of the genome.

Adult↗

PubMedDate not supplied

[Diabetogenic tropical pancreatitis].

The tropical calcifying pancreatitis and/or fibrous pancreatitis are responsible for a number of cases of juvenile insulin-dependent diabetes in the Third World countries. World wide distributed in the tropical areas of Asia, Africa and South America, they can also be observed in Europe, in migrants from these countries. Intensive epidemiological and biochemical studies are currently developed in order to shed light on the many obscure points. Classification of the typical calcifying pancreatitis and the related syndromes is a matter of debate. The pathological basis is calcification of the pancreas and echography of the gland may become a cheap convenient relatively specific tool for epidemiology. The clinical syndrome consists of chronic painful pancreatic episodes since childhood, associated with pancreatic exocrine insufficiency, followed by the onset, during adolescence, of diabetes mellitus, which is most of the times insulin dependent. Patients' history is free of chronic alcoholism, but includes constantly chronic caloric and proteic malnutrition. Although insulin dependent this diabetes in not prone to ketosis, due presumably to carnitine deficiency and relative glucagon deficiency (or suppressibility). Insulin resistance is traditionally noted, the pathophysiology of which is unknown. The mechanism of calcification appearance is also undetermined. Either a deficiency in pancreatic stone protein, or the toxic effect of cyanogen glucosides present in cassava and other tropical foodstuffs, or the malnutrition-related deficiency in sulphur-containing aminoacids may be causal factors. No valid experimental model of the disease is available.

Calcinosis↗

PubMedDate not supplied

[Angiotensin II receptors: classification, structure, and signal transduction].

Angiotensin II (AngII), a circulating vasoactive peptide, interacts with specific membrane-bound receptors on the target tissues (vessels, kidneys and adrenal gland). Using new pharmacological tools and molecular cloning, these receptors have been classified in two types, called AT1 et AT2, whereas two subtypes, called AT1A et AT1B, have been identified for the rodent AT1 receptors, but not in humans. All these receptors present a seven hydrophobic transmembrane domain structure, which is classical for G protein coupled receptors. The interspecies molecular homology of these AngII receptors is high (> 90 per cent identity) within the same type of receptor, but is rather low (approximately 35 per cent identity) between the two types of receptors. The AT1 receptors are responsible for most of the AngII physiological actions and are coupled to a Gq protein, which activates a phospholipase C producing second messengers which activate protein kinases C and mobilize calcium intracellular stores. More recently, a strong interaction of this receptor has been demonstrated with the signalling pathways of the tyrosine kinases. The molecular mechanisms and the physiological importance of these interactions remain to be elucidated. The intracellular signalling (Gi coupling and tyrosine phosphatase activation) and the physiological actions (cellular differentiation, apoptosis) of the AT2 receptors are more controversial.

Angiotensin II↗