ABSTRACT
A recent report has identified a new autoantigen called D1 that appears to be associated with Graves' ophthalmopathy and is expressed in the thyroid and eye muscle. To better characterize the tissue specificity and disease relevance of this antigen, we evaluated the expression of D1 RNA in various human tissues using a reverse transcriptase polymerase chain reaction assay. These studies indicate a wide tissue distribution of the messenger RNA for this antigen, including the thyroid, eye muscle, parathyroid, spleen, skeletal muscle, and uterus. There were variations in the relative amounts of specific message for D1 in the different tissues, with the uterus, thyroid, and eye muscle having the greatest amount of product per microgram of total RNA. A maltose binding protein-D1 fusion protein was expressed in Escherichia coli, purified, and used to assess serologic reactivity to D1 by Western blot. Autoantibodies to this antigen were noted in 19 of 24 (78%) of Hashimoto's disease patients, 26 of 41 (63%) of Graves' disease patients, and in 9 of 17 (53%) of normal controls. Sixty percent of Graves' disease patients with clinical ophthalmopathy had antibodies to D1, as did 63% of Graves' patients without signs or symptoms of clinical ophthalmopathy. There was no correlation between reactivity to D1 and either clinical measures of hyperthyroidism or antibody titers to thyroid peroxidase or thyroglobulin. The presence of autoantibodies to this antigen in patients with Hashimoto's disease, in Graves' disease patients without ophthalmopathy and in normal controls indicate that serologic recognition of this antigen is not restricted to patients with ophthalmopathy. In addition, the expression of messenger RNA for this antigen in multiple types of cells questions the tissue specificity of this autoantigen.
Subject(s)
Autoantigens/biosynthesis , Autoimmune Diseases/immunology , Graves Disease/immunology , Thyroiditis, Autoimmune/immunology , Adult , Autoantibodies/biosynthesis , Autoantibodies/immunology , Autoantigens/genetics , Autoantigens/immunology , Base Sequence , Blotting, Western , Eye Diseases/etiology , Eye Diseases/immunology , Female , Graves Disease/complications , Humans , Male , Molecular Sequence Data , Polymerase Chain Reaction , RNA, Messenger/biosynthesis , Recombinant Fusion Proteins , Thyroid Gland/immunologyABSTRACT
A major focus of past and recent research in hypertension has been on the characterization of the nature of the vasculature changes which lead to the observed increase in total peripheral resistance responsible for the elevation of arterial pressure. Here we survey recent evidence which suggests that altered handling of calcium is a primary membrane defect in hypertension. Evidence for the primacy of this defect is provided by studies demonstrating a reduced ability of the membrane to bind calcium in diverse tissues from hypertensive animals. The reduced calcium binding ability appears to be responsible for a greater membrane permeability to monovalent and divalent cations. This greater permeability contributes to the increased sensitivity to vasoconstrictor stimuli of vascular smooth muscle in hypertension.
Subject(s)
Hypertension/physiopathology , Ion Channels/physiology , Muscle, Smooth, Vascular/physiopathology , Animals , Cell Membrane Permeability , RatsABSTRACT
Ross River virus was isolated from two out of four seronegative serum samples obtained from epidemic polyarthritis patients in Australia. Virus isolated from each patient was found to be phenotypically diverse. These isolations suggest that previous failure to isolate virus from epidemic polyarthritis patients in this country may have been due to failure to obtain material (serum) from patients early enough in the course of the disease and to the use of relatively insensitive isolation techniques.
