A Genomic Point Mutation in the Extracellular Domain of the Thyrotropin Receptor in Patients with Graves’ Ophthalmopathy

Orbital and pretibial fibroblasts are targets of autoimmune attack in Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD). The fibroblast autoantigen involved in these peripheral manifestations of Graves' disease and the reason for the association of GO and PTD with hyperthyroidism are unknown. RNA encoding the full-length extracellular domain of the TSH receptor has been demonstrated in orbital and dermal fibroblasts from patients with GO and normal subjects, suggesting a possible antigenic link between fibroblasts and thyrocytes. RNA was isolated from cultured orbital, pretibial, and abdominal fibroblasts obtained from patients with severe GO (n = 22) and normal subjects (n = 5). RNA was reverse transcribed, and the resulting cDNA was amplified by the polymerase chain reaction, using primers spanning overlapping regions of the entire extracellular domain of the TSH receptor. Nucleotide sequence analysis showed an A for C substitution in the first position of codon 52 in 2 of the patients, both of whom had GO, PTD, and acropachy. Genomic DNA isolated from the 2 affected patients, and not from an additional 12 normal subjects, revealed the codon 52 mutation by direct sequencing and AciI restriction enzyme digestions. In conclusion, we have demonstrated the presence of a genomic point mutation, leading to a threonine for proline amino acid shift in the predicted peptide, in the extracellular domain of the TSH receptor in two patients with severe GO, PTD, acropachy, and high thyroid-stimulating immunoglobulin levels. RNA encoding this mutant product was demonstrated in the fibroblasts of these patients. We suggest that the TSH receptor may be an important fibroblast autoantigen in GO and PTD, and that this mutant form of the receptor may have unique immunogenic properties

Tissue eosinophilia and eosinophil degranulation in Riedel's invasive fibrous thyroiditis.

The etiology of Riedel's invasive fibrous thyroiditis (IFT) has remained obscure. This rare disorder has been confused in the past with the more common fibrous variant of Hashimoto's disease. The typical histological features of IFT, in particular the presence of an invasive fibrosclerotic process in conjunction with a prominent chronic inflammatory infiltrate, suggest that the release of fibrogenic cytokines and other factors from these cellular infiltrates may play an important role in the pathogenesis of this condition. Our observations in routinely processed tissue sections obtained from patients with documented IFT of striking tissue eosinophilia led us to hypothesize that eosinophils and their products may play a role in the evolution of this disease. Immunofluorescence staining with affinity-purified polyclonal rabbit antibody directed against human eosinophil granule major basic protein revealed marked tissue eosinophilia and abundant extracellular deposition of major basic protein in all specimens from 16 patients with IFT. By contrast, only occasional eosinophils and no extracellular major basic protein were detected in control thyroid tissues obtained from patients with multinodular goiter, Graves' disease, Hashimoto's disease, and normal thyroid tissue. The presence of marked eosinophil infiltration and extracellular major basic protein deposition in IFT and other associated fibrosclerotic conditions suggests a role for eosinophils and their products in propagating the fibrogenesis seen in IFT

Analysis of testbed airborne multispectral scanner data from Superflux II

A test bed aircraft multispectral scanner (TBAMS) was flown during the James Shelf, Plume Scan, and Chesapeake Bay missions as part of the Superflux 2 experiment. Excellent correlations were obtained between water sample measurements of chlorophyll and sediment and TBAMS radiance data. The three-band algorithms used were insensitive to aircraft altitude and varying atmospheric conditions. This was particularly fortunate due to the hazy conditions during most of the experiments. A contour map of sediment, and also chlorophyll, was derived for the Chesapeake Bay plume along the southern Virginia-Carolina coastline. A sediment maximum occurs about 5 nautical miles off the Virginia Beach coast with a chlorophyll maximum slightly shoreward of this. During the James Shelf mission, a thermal anomaly (or front) was encountered about 50 miles from the coast. There was a minor variation in chlorophyll and sediment across the boundary. During the Chesapeake Bay mission, the Sun elevation increased from 50 degrees to over 70 degrees, interfering with the generation of data products

Active and passive microwave measurements in Hurricane Allen

The NASA Langley Research Center analysis of the airborne microwave remote sensing measurements of Hurricane Allen obtained on August 5 and 8, 1980 is summarized. The instruments were the C-band stepped frequency microwave radiometer and the Ku-band airborne microwave scatterometer. They were carried aboard a NOAA aircraft making storm penetrations at an altitude of 3000 m and are sensitive to rain rate, surface wind speed, and surface wind vector. The wind speed is calculated from the increase in antenna brightness temperature above the estimated calm sea value. The rain rate is obtained from the difference between antenna temperature increases measured at two frequencies, and wind vector is determined from the sea surface normalized radar cross section measured at several azimuths. Comparison wind data were provided from the inertial navigation systems aboard both the C-130 aircraft at 3000 m and a second NOAA aircraft (a P-3) operating between 500 and 1500 m. Comparison rain rate data were obtained with a rain radar aboard the P-3. Evaluation of the surface winds obtained with the two microwave instruments was limited to comparisons with each other and with the flight level winds. Two important conclusions are drawn from these comparisons: (1) the radiometer is accurate when predicting flight level wind speeds and rain; and (2) the scatterometer produces well behaved and consistent wind vectors for the rain free periods