ABSTRACT
Analysis of nine mouse monoclonal antibodies (mAbs) to the thyrotropin receptor (TSHR) with TSH antagonist activity showed that only one of the mAbs (RSR B2) was an effective antagonist of the human thyroid stimulating autoantibody M22. Crystals of B2 Fab were analyzed by x-ray diffraction and a crystal structure at 3.3 A resolution was obtained. The surface charge and topography of the B2 antigen binding site were markedly different from those of the thyroid-stimulating mAb M22 and these differences might contribute to the different properties of the two mAbs. B2 (but not other mouse TSHR-specific mAbs) was also an effective antagonist of thyroid stimulating autoantibody activity in 14 of 14 different sera from patients with Graves' disease. 125I-labeled B2 bound to the TSHR with high affinity (2 x 10(10) L/mol) and patient serum TSHR autoantibodies inhibited labeled B2 binding to the receptor in a similar way to inhibition of labeled TSH binding (r = 0.75; n = 20). Furthermore, labeled B2 binding was inhibited by patient serum TSHR autoantibodies with TSH antagonist activity and also by mouse and human thyroid stimulating mAbs. Overall, mAb B2 is a powerful antagonist of thyroid stimulating autoantibodies (and TSH) thus resembling closely patient serum TSH antagonist TSHR autoantibodies. Furthermore, B2 might have potentially important in vivo applications when tissues containing the TSHR (including those in the orbit) need to be made unresponsive to stimulating autoantibodies.
Subject(s)
Antibodies, Monoclonal/immunology , Autoantibodies/immunology , Graves Disease/immunology , Receptors, Thyrotropin/immunology , Thyrotropin/immunology , Animals , Antibodies, Monoclonal/chemistry , CHO Cells , Cricetinae , Crystallography, X-Ray , Graves Disease/therapy , Humans , Immunoglobulin Fab Fragments/chemistry , Immunoglobulin Fab Fragments/immunology , Iodine Radioisotopes , Mice , Protein Structure, Tertiary , Receptors, Thyrotropin/metabolism , Thyrotropin/metabolismABSTRACT
The topographic distribution of epidurally recorded flashed visual evoked potentials (VEPs) in unanesthetized rabbits was studied using 2 montages. VEPs with linked ears reference and source derivation were compared. With the linked-ears reference, N34 of VEPs which consisted of slow potentials and superimposed oscillations were recorded diffusely over the head. When source derivation was used, the slow negative potentials of N34 present on the recordings in P3 and P4 were not obtained in F3, Fz and F4. In a digital filtering study of the oscillatory potentials, N34 in oscillatory potentials which were recorded diffusely over the head were localized to the visual cortex by source derivation. It was concluded that N34 in the oscillatory potentials generated from the visual cortex are enhanced and localized with source derivation.
Subject(s)
Brain Mapping , Electroencephalography/methods , Evoked Potentials, Visual , Visual Cortex/physiology , Animals , Female , Rabbits , Time FactorsABSTRACT
A case of primary megaureter in a 59-year-old man which might shed light on the etiology and pathology is described. Intravenous urography and the computed tomography showed a left marked hydro-nephro-ureter which compressed the bladder and right ureter. In the left ureter, dilated portions stretched beyond dilated portions; that is, five non-dilated portions lay among four dilated portions. On histological examination of this specimen, all dilated portions showed aplasia of muscle in which muscle bundles were not observed, while all non-dilated portions including ureterovesical junction showed normal muscle layers. A case presentation and brief review of the literature were made.
