Biomedical subjects

J M Csicsmann

Publications and source records attributed to J M Csicsmann.

2 recordsLinked to original sources

PubMed1986

Familial dysalbuminaemic hyperthyroxinaemia: studies of albumin binding and implications for hormone action.

The abnormal intermediate-affinity T4 binding to albumin which is characteristic of familial dysalbuminaemic hyperthyroxinaemia (FDH) is dependent on buffer, temperature, and ionic composition. Scatchard analysis of T4-binding to isolated albumin preparations from FDH subjects showed that half the circulating albumin showed the higher-affinity T4 binding site, assuming one site per molecule. Using dextran-charcoal separation at 4 degrees C the T4 affinity (Kd) of purified albumin from FDH subjects was 7.5 nmol/l in phosphate and 17 nmol/l in Tris-Cl- buffer. T4 binding to FDH albumin was inhibited by a range of substances in the order: 8-anilino-1-naphthalene sulphonic acid greater than merthiolate greater than propylthiouracil greater than methyl-thiouracil greater than carbimazole greater than salicylate greater than barbitone. Binding of T4 was competitively inhibited by low concentrations of dithiothreitol (DTT). The effect of DTT 0.1-0.5 nmol/l was reversed by removal of DTT by dialysis. Competition with a range of iodothyronines indicated that the 3', 5'-iodine atoms are most important for binding to this site. Serum binding of salicylate, frusemide, fenclofenac and barbituric acid, and a range of steroid hormones was similar in FDH and normal sera. Serum levels of sex hormone binding globulin (SHBG), were not significantly different from sex-matched controls. Nuclear [125I]-T3 binding sites in circulating lymphocytes from two FDH subjects showed affinities (Kd) of 59 and 79 pmol/l (normal 67 +/- 7 pmol/l, n = 6). These findings suggest that the highly specific binding anomaly of FDH is due to a disulphide-dependent structural change in albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Protein Disorders↗

PubMed1982

Familial euthyroid thyroxine excess: characterization of abnormal intermediate affinity thyroxine binding to albumin.

The abnormal high capacity T4 binding site of familial euthyroid T4 excess was separable from prealbumin and T4-binding globulin but not from albumin. We therefore compared T4 binding by albumin preparations isolated from the sera of normal and affected subjects. By equilibrium dialysis, albumin from affected subjects showed an extra T4 binding site (Kd approximately 50 nM) in addition to the T4 binding sites of normal albumin (Kd approximately 4 microM). Comparison of the estimated capacity of the additional site (200 microM) with the molar concentration of albumin suggested that only about one third of albumin molecules from affected subjects contained the extra binding site. Estimates of affinity and capacity were used to derive combining powers for the diverse classes of serum T4 binding sites. From these estimates, it appears that the presence of the abnormal site accounts for the approximate doubling of normal mean total T4 (from approximately 100 nM or 7.7 micrograms/dl to approximately 200 nM or 15.5 micrograms/dl), in order to maintain a normal free T4 in the face of the increased T4 association with albumin. Studies of [125I]T4 displacement from albumin of affected subjects showed low T3 affinity and competition by barbitone. Relative molar concentrations to give equivalent displacement of [125I]T4 were: 3,3',5,5'-tetraiodothyroacetic acid, 0.4; T4, 1.0; rT3, 4; 8-anilinonaphthalene sulfonic acid, 10; T3, 80; salicylate, 200; and barbitone, 40,000. Studies with dithiothreitol suggested that disulfide bonds were critical in maintaining the T4-albumin association. These findings indicate that familial T4 excess is due to abnormal intermediate affinity, sulfhydryl-sensitive T4 binding sites that are inseparable from the albumin found in affected subjects.

Barbital↗