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Biomedical subjects

G Edan

Publications and source records attributed to G Edan.

At least 37 records · Page 2Linked to original sources

Functional properties of human thyroid follicles cultured within collagen gel.

Cultures of human thyroid follicles embedded in collagen gel were performed to investigate certain functional properties under bovine thyrotropin (TSH) stimulation. Follicles obtained from normal glands responded to increasing concentrations of TSH administered on day 4 in culture and for 3 days by increased amounts of cyclic AMP (cAMP), thyroglobulin (Tg) and triiodothyronine (T3) and by decreased levels of thyroxine (T4). Effect was maximal at 2000 microU/ml TSH (cAMP) or 200 microU/ml (Tg, T3, T4). When methimazole or propylthiouracil (PTU) were added, the T3 levels decreased. Follicle lumens contained a periodic acid-Schiff substance which was identified by immunoreaction as Tg. Thyroid follicles obtained from Graves' disease glands gave modified results with an earlier and intensified T3 response and no increase in Tg. These data show that (1) Tg and T3 are secretory products of functional follicles giving a cAMP-mediated response to TSH. (2) The detected T3 also derives from T4 5'-deiodination inhibited by PTU. (3) Intensified T3 response in Graves' follicles is probably due to enhanced conversion of T4 to T3.

Cells, Cultured

[Anomalies of cellular immunity in Graves' disease treated by synthetic antithyroid drugs: effects on prognosis].

The involvement of humoral immunity mechanism in etiology of Graves' disease was observed for the first time in 1956. Twenty years later cellular auto-immune dysfunction was also described. To day, there is evidence for suppressor T cell deficiency and decrease in T suppressor lymphocytes in Graves' disease and cell mediated immunity might be one of the most important point in the pathogenesis of Graves disease. For the future, cellular auto-immune dysfunction might be used to predict the evolution of the disease and to choice the best therapeutic scheme.

Antithyroid Agents

A study of 609 HLA haplotypes marking for the hemochromatosis gene: (1) mapping of the gene near the HLA-A locus and characters required to define a heterozygous population and (2) hypothesis concerning the underlying cause of hemochromatosis-HLA association.

We compared 609 haplotypes carrying the idiopathic hemochromatosis allele with 475 control haplotypes. Four haplotypes were more frequent in hemochromatosis: A3, B7 (actually A3, CW., B7, Bfs, DR2); A3, B14 (actually A3, CW., B14, BfF, DRW6); A11, B35; and A11, B5. The linkage disequilibrium for A3, B7 and A3, B14 (and probably also for A11, B5) was undeniably stronger in hemochromatosis than in controls. Two haplotypes--A3, B12 and A3, B15--were more frequent in hemochromatosis, without linkage disequilibrium. Four haplotypes in linkage disequilibrium in hemochromatosis--i.e., A2, B12; A1, B8; A9, B7; and A29, B12--were also found to have the same frequency and strength of linkage in controls. The dual observation (1) that haplotypes carrying A3 without either B7 or B14 were highly significantly more frequent in hemochromatosis than in controls and (2) that haplotypes carrying B7 or B14 but not A3 had the same frequency in hemochromatosis and controls led to the formal conclusion that only A3 is an independent marker for the hemochromatosis allele, B7 and B14 being involved only owing to the haplotypic mode of marking; the hemochromatosis allele can thus be mapped closer to locus A than to locus B. Our findings fit well with the hypothesis that the hemochromatosis mutation was a rare if not unique event that produced an ancestral HLA marking that was subsequently modified by recombinations and geographical scattering due to migrations.

Alleles

Assays for thyrotropin-receptor binding and thyroid-stimulating antibodies in sera from patients with Graves' disease.

We compared the activities of thyroid-stimulating antibodies (TSAb) measured in cultures of human thyrocytes and the values for thyrotropin-receptor antibodies (TRAb) as measured with a commercial kit based on use of radiolabeled receptors. Sera were obtained from patients with Graves' disease before, during, and after therapy with carbimazole (1-methyl-2-thio-3-carbethoxyimidazole). We found a significant correlation between the measurements of these two antibodies in patients: before treatment (r = 0.74, p less than 0.01, n = 44), after three months of treatment (r = 0.76, p less than 0.01, n = 21), and during relapse after the drug was discontinued (r = 0.64, p less than 0.01, n = 19). In all three situations, our TSAb technique was more sensitive than the TRAb method. We conclude that, even though the TRAb technique is simpler and quicker, this commercial kit is too insensitive to replace measurement of TSAb in fresh human thyrocyte cultures for management of drug therapy of patients with Graves' disease.

Adult

Is the HLA-linked haemochromatosis allele implicated in idiopathic refractory sideroblastic anaemia?

In order to assess the previously reported association of HLA-linked idiopathic haemochromatosis with idiopathic refractory sideroblastic anaemia (IRSA), the prevalence of HLA-A3 antigen in a group of 22 patients with IRSA was compared to that observed in healthy controls and in patients with homozygous idiopathic haemochromatosis and to that calculated for a population heterozygous for idiopathic haemochromatosis. The prevalence of A3 in patients with IRSA (0.23) was quite similar to that observed in controls (0.29) and significantly different from that observed in homozygous (0.73; P less than 10(-5] and heterozygous (0.57; P less than 10(-3] haemochromatosis. Serum iron, transferrin saturation, serum ferritin and liver iron concentration showed no difference in IRSA patients with or without A3. It is concluded that there is neither systematic association between the haemochromatosis allele and IRSA nor systematic implication of such an allele in the development of iron overload observed in IRSA.

Aged

Gallium-67 imaging in muscular sarcoidosis.

A case is presented of sarcoid myopathy in which radiogallium was seen to accumulate in the sites of muscle involvement. Uptake of the radiotracer disappeared following institution of corticosteroid therapy. The exceptional nature of this case contrasts with the high frequency of biopsy evidence of sarcoid muscle disease but is consistent with the rarity of clinical evidence of sarcoid granulomas in muscle. Gallium-67 imaging can be used to determine the extent of muscle involvement and, through evaluation of uptake intensity, the degree of disease activity before and after treatment.

Adult

[Peripheral distribution of lymphocyte subpopulations in Basedow's disease. Decrease in suppressor T-lymphocytes].

The distribution of B- and T-lymphocyte subpopulations was studied in peripheral blood of 45 patients with untreated Graves' disease and 45 sex- and age-matched healthy controls. Blood samples were taken at the same hour in all subjects. The following tests were performed: HTLA and E (AET) for relative T-lymphocyte count, complement receptor (EAC) and surface immunoglobulins (IgS, IgG, IgM, IgA, kappa, lambda) for relative B-lymphocyte count. In 23 subjects of each group the subpopulations of T-lymphocytes were defined by their reactivity with monoclonal antibodies OKT8 (T-suppressor cells) and OKT4 (T-helper cells). Compared with the control group, patients with Graves' disease showed a decrease in the number of T-lymphocytes (HTLA: P less than 0.05: EAET: P less than 0.001) a decrease in T-suppressor cells (P less than 0.01), and no significant difference in B-lymphocytes and T-helper cells. Thus, the main lymphocyte characteristic in Graves' disease is a decrease in the relative value of T-cells, specifically affecting T-suppressor cells.

Adult

An HLA-All association with the hemochromatosis allele?

Two hundred and seventy-four patients with hemochromatosis and 1005 controls were HLA-typed, and HLA haplotypes were determined for 163 patients and 123 controls. The increased frequency of antigen A3 and haplotypes A3, B7 and A3, B14 in patients with hemochromatosis was confirmed. After correction for the space taken up by A3, a significant increase in All was found. This increase could not be explained by cross reaction between A3 and All. All showed a phenotype association and a haplotype link with Bw35. The genetic significance of this increased All frequency is discussed.

Alleles

[Demonstration by iron overloading study and HLA genotyping of recessive transmission of idiopathic haemochromatosis in two pseudodominant pedigrees (author's transl)].

We studied iron overloading and HLA genotype in two families with overt forms of idiopathic haemochromatosis in two successive generations. In each family the spouse of the patient with overt haemochromatosis in the first generation had clinical and laboratory signs of moderate iron overload and a HLA haplotype A3, B14 and A3, B7 respectively--which is frequently associated with the haemochromatosis gene. This specific HLA haplotype had been transmitted to the second generation patient with overt disease, which thus could be considered as having received a haemochromatosis gene from each parent. Although the finding of cases of overt disease in successive generation firstly suggests a dominant transmission the genetical analysis of these families lead to further strong argument in favour of recessive inheritance of idiopathic haemochromatosis.

Adolescent

Idiopathic hemochromatosis and iron overload in alcoholic liver disease: differentiation by HLA phenotype.

HLA A and B antigens were determined in two groups of patients: 38 patients with idiopathic hemochromatosis (IH) and 22 patients with iron overload accompanying alcoholic liver disease (AH). As previously described, HLA A3 and HLA B14 antigens appeared more frequently in the IH group (76.3 and 28.9%, respectively) than in a control group of 204 subjects (27 and 3.4%). In the AH group the frequency of A3 (22.7%) and B14 (13.6%) was not significantly different from that observed in controls. The frequency of A3 was significantly lower in the AH group than in the IH group (P less than 0.001). On this basis a clear difference appears between the two conditions with iron overload, and genetic analysis of the results rules out the hypothesis that AH would be a heterozygous form of IH exposed by alcohol.

Adult

Renal scintigraphy in insulin-dependent diabetes mellitus: early glomerular and urologic dysfunction.

Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous injection of 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-Hippuran in 115 insulin-dependent diabetic patients with albumin excretion rates (AER) less than 200 micrograms/min, and in 45 normal subjects. Separate kidney function and urinary elimination were estimated by renography. GFR was increased in the diabetic patients (152 +/- 24 ml/min/1.73 m2 vs. 128 +/- 15) and correlated significantly with RPF (r = 0.5; p less than 10(-9)). No relationship was found between GFR and the duration of diabetes, blood glucose, HbA1c, or AER. Fifty patients were hyperfiltering with RPF and filtration fraction higher than those in the normofiltering group. Slow intrarenal or pyeloureteral elimination, either unilateral or bilateral, was observed in 3 controls and 60 diabetic subjects (24 hyperfiltering; 36 normofiltering) and did not disappear with the patient in the standing position. In these 60 patients, mean age, duration of diabetes, blood glucose, HbA1c, 24 h albumin excretion rate, and frequency of peripheral or autonomic neuropathy did not differ from patients with normal scintigraphy; GFR was lower in the group with slow elimination, but not significantly so. 99mTc-DTPA renal uptake was symmetric in all the controls; asymmetric renal uptake with asymmetric GFR was observed in 13 patients (7 hyperfiltering; 6 normofiltering) and often associated with slower elimination. No evidence for renal stenotic atheroma or parenchymatous disease was found on the angiopyeloureterography. The results suggest that incipient uropathy is a very common phenomenon that occurs irrespective of glomerular dysfunction.

Diabetes Mellitus, Type 1

[Clinical and biological symptoms of T. gambiense tryponosomiasis in the meningo-encephalitic period (author's transl)].

Main clinical symptoms are reviewed in the first part of the article. They consist in mental alertness disorder, motorial confusion and quite constantly in reflexes and abnormal movements due to brain stem lesion. The author reports on 22 cases. No correlation appears between prognosis and epileptiform seizures. Bertran's prognostical score has given contradictory indications. Neujan's criteria have not been very reliable to select treatment schedule. No correlation has been observed between biological data on the one hand and clinical symptoms as well as lethal evolution on the other hand.

Adolescent