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Biomedical subjects

A Haeberli

Publications and source records attributed to A Haeberli.

78 records · Page 5Linked to original sources
PubMed1978

Transformation of normal follicles into thyrotropin-refractory "cold" follicles in the aging mouse thyroid gland.

Autoradiographs of thyroid glands of aging mice demonstrate the gradual appearance of "cold" follicles which fail to iodinate the intraluminar iodoproteins even after intense exogeneous or endogeneous TSH stimulation. "Cold" follicles first appear at the age of 5 months. They may account for 80% of all thyroid follicles in 13-month-old mice. Morphologically, the "cold" follicles are characterized by a larger than normal colloid volume and a comparatively flat epithelium for any given follicle size. Old thyroids are twice as large as young ones. They contain twice as much normally iodinated thyroglobulin/mg wet weight. The total number of cells per gland remains constant throughout the life time. This is probably also true for the total number of follicles. The iodide pump, as judged by the tissue to serum ratio, remains normal and TSH-responsive. Yet, it is not established whether this is due to a higher activity of the pump in normal follicles or to preservation of inorganic iodide transport in "cold" follicles. Pinocytosis is defective in "cold" follicles and is poorly responsive to TSH stimulation. Furthermore, diffusion of iodocompounds is severely impaired in the colloid of "cold" follicles. It is suggested that the primary defect in the pathogenesis of "cold" follicles in old mice is the gradual failure of endocytosis to respond to normal TSH stimulation. Because exocytosis and iodination would first proceed normally, the follicular lumina would become overdistended up to a point where the apical membrane is functionally impaired. With this sequence of events, "cold" follicles would have impaired iodination while being metabolically as active as hot ones. Thus, several puzzling reports on high metabolic activity of "cold" tissue could possibly be interpreted.

Aging↗
PubMed1975

Relationship between iodination and the polypeptide chain composition of thyroglobulin.

Thyroglobulin was isolated from thyroid glands of normal guinea pigs and from animals treated with thiouracil. These preparations were fractionated by isopyknic centrifugation in RbCl into proteins of varying iodine content. When the disulfide bonds of these protein fractions were reduced and analyzed by polyacrylamide gel electrophoresis in Na dodecyl-SO4, t hree species were observed with molecular weights of 295,000 (A), 210,000 (B), and 110,000 (C). Species A comprised 80% of the protein in thyroglobulin of 0.04% iodine and 13% in thyroglobulin of 0.68% iodine content. Species C showed the opposite relationship, comprising 10% of the low and 70% of the high iodine thyroglobulin. Species B was relatively independent of the iodine content and represented approximately 20% of the protein. Iodine analysis of these proteins showed species A to be lowest and species C highest. It appears that the subunit composition of thyroglobulin depends on the degree of iodination and that species A should be the only one present in the absence of iodination.

Animals↗
PubMed1975

Elementary chain composition of guinea pig thyroglobulin.

Thyroglobulin obtained from guinea pigs was examined by Na dodecyl-SO4-polyacrylamide gel electrophoresis after reduction and alkylation. In contrast to thyroglobulin from other mammalian sources, only three groups of polypeptide chains accounted for 95% or more of the protein. Determinations of the molecular weights of these purified proteins by equilibrium centrifugation in 6 M guanidine HCl gave values of 295,000 (species A), 210,000 (species B), and 110,000 (species C). Molecular weights determined by gel filtration in 6 M guanidine HCl gave similar results. Due to the large size of the polypeptides, satisfactory molecular weights could not be obtained from Na dodecyl-SO4-polyacrylamide gel electrophoresis. Amino acid analysis of the three species was similar to that of whole thyroglobulin. Only slightly higher level of lysine and histidine and a lower level of glutamic acid were seen in species C. The iodine contents were found to range from 0.07 to 0.12 to 0.20% for species A, B, and C, respectively.

Amino Acids↗
PubMed1975

Autoradiographic localization of slow turnover iodocompounds within the follicular cells of the rat thyroid gland.

In addition to thyroglobulin, several low molecular wt iodinated glycopeptides are present in the thyroid gland. Some of these compounds are considered to be slowly metabolized remnants of intracellular lysis of engulfed colloid droplets. In this paper we present autoradiographic evidence obtained by light microscopy, suggesting that breakdown products of thyroglobulin digestion can indeed be located within the thyroid cells. The thyroid glands of rats were labeled with 125I to approach isotopic equilibrium. The tracer was then withdrawn from the otherwise unchanged high-iodine diet, and thyroidal radioactivity was washed out for 80 days. Autoradiographs of glands containing 10% or less of the tracer present at equilibrium showed the bulk of 125I within the follicular cells while the colloid was only slightly labeled. An additional finding was the presence of dense radioactive inclusions in the lumina of many follicles. They are assumed to represent clusters of thyroglobulin molecules not readily available to pinocytosis. In addition to autoradiographic evidence, the identity of intracellularly located radioactivity with slow-turnover enzyme-resistant iodocompounds is supported by double labeling experiments, using 125I as the "old" tracer, accumulating within the cells, and 131I as the "new" label representing intraluminal 19 S thyroglobulin. Experimental manipulations which tended to deplete the thyroid of thyroglobulin, increased the 125I/131I ratio in the gland as predicted by the working hypothesis. Thus, this paper describes a new kind of autoradiographic ring reaction due to a hitherto barely considered intracellular organic iodine pool.

Animals↗
PubMedDate not supplied

Dose- and shear rate-dependent effects of heparin on thrombogenesis induced by rabbit aorta subendothelium exposed to flowing human blood.

The effect of heparin on thrombogenesis induced by the subendothelium of rabbit aorta was investigated in 24 healthy volunteers after intravenous injection of different doses (0, 1000, 2500, and 5000 IU). By using an ex vivo perfusion chamber system, the interaction between flowing blood and exposed subendothelium was measured at low (50 s-1), intermediate (650 s-1), and high (2600 s-1) wall shear rates. The low shear rate simulated blood flow in venous, the intermediate shear rate in arterial, and the high shear rate in small or stenosed arterial vessels. Deposition of fibrin, platelets, and platelet thrombi on vascular subendothelium (SE) was quantified by morphometrical and immunological techniques. Fibrin deposition prevailed at low shear rates and was only minimal at high shear rates (30 +/- 1% vs. 1 +/- 0.4% coverage of SE with fibrin, means +/- SEM, p less than 0.001). In contrast, the interaction of platelets with SE was more intense at high compared to low shear rates, as indicated by higher platelet adhesion (54 +/- 5% vs. 4 +/- 1% coverage of SE with platelets, p less than 0.001) and platelet thrombus volumes (4.8 +/- 1.3 vs. 0.5 +/- 0.1 microns 3/microns 2, p less than 0.001). Fibrin deposition on SE was inhibited by heparin in a dose-dependent manner and was abolished after high doses. In addition, high doses of heparin reduced the height and volume of platelet thrombi at low and intermediate wall shear rates, but no effect was found at the high shear rate. Our data show that heparin inhibits the formation of both fibrin and platelet thrombi on vascular subendothelium. The lack of effect of heparin on platelet thrombus formation at high shear rates indicates that thrombin modulates the growth rate and/or stability of platelet thrombi at low and intermediate shear rates, whereas additional factors may control platelet thrombus growth and stability at high shear conditions.

Adult↗