In order to examine the specificity of the autoantibody response to thyroid peroxidase (TPO, previously identified as thyroid microsomal antigen) in autoimmune thyroid disease, we examined reactivity of sera from 45 Hashimoto's and 48 Graves' patients to native thyroid microsomes, denatured and reduced human TPO and several recombinant fragments of human TPO corresponding to amino acids 457-933 of the native protein. Both Graves' and Hashimoto's sera bound native, denatured and reduced TPO at significantly greater rate than normal controls, and no differences were noted between the two disorders in binding to these forms of the autoantigen. Binding was also noted to two recombinant fragments of TPO, corresponding to amino acids 513-633 and 633-933 in TPO. The frequency of autoantibodies to the TPO AA(633-933) region was not significantly different in Hashimoto's vs. Graves' disease patients (58% vs. 65% respectively), and appeared to relate to evidence of glandular inflammation in the Graves' patients (presence of anti-thyroglobulin antibodies and elevated anti-microsomal antibody levels). In contrast, antibodies to the TPO AA(513-633) fragment were significantly more common and of higher titer in Hashimoto's vs. Graves' disease patients, and did not correlate with any measure of glandular inflammation. These results identify two specific regions of TPO autoantibody binding and indicate that there are differences in the autoantibody response to TPO in Hashimoto's and Graves' diseases.
Following administration of uranium parenterally into rats in an acute dose, the increase in protein excretion consisted not only of an increase in the normally occurring albumin but to a greater extent an increase in the various globulins. At the height of proteinuria, the electrophoretic pattern of the excreted proteins strongly resembled the pattern of the serum proteins. The appearance of these serum-like urinary proteins suggests a defect in the glomerulus filtration apparatus and provides further evidence that the glomerulus, as well as the tubule, is altered by uranium administration.
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