RESUMEN

Activity of autoantibodies to the thyrotropin receptor in the serum of patients with active Graves's disease was compared when the patients' IgG was purified by three different procedures: ammonium sulfate precipitation (I), a modified batch diethylaminoethyl cellulose method (II), and affinity chromatography on Protein A-Sepharose CL-4B (III). IgG extracted by I was significantly less potent in inhibiting binding of 125I-labeled thyroid membranes than that prepared by either II or III, and was significantly less effective than II in stimulating adenyl cyclase activity in thyroid membrane. Thyroglobulin, a serum protein whose concentration is increased in patients with various thyroid diseases, was coprecipitated in amounts sufficient to significantly inhibit binding only when method I was used, but not with either of the other two procedures. Evidently method I is inferior to either of the other two when used for purification of autoantibodies to the thyrotropin receptor. Method II used in this study, being faster and more economical than I and of equivalent efficacy, is a feasible alternative method for clinical use.

Asunto(s)

RESUMEN

Thyrotropin (TSH)-receptor autoantibodies were assessed by measurement of 125I-bTSH binding inhibition in 32 patients with juvenile-onset Graves' disease (one of whom was studied twice) and 16 normal control subjects. Thirteen (76.5%) of 17 thyrotoxic patients had significantly elevated TSH binding-inhibitory immunoglobulin (TBII) activity compared with eight (50%) of 16 patients who were in clinical remission and none of the control subjects. Mean TBII activity was significantly greater in thyrotoxic patients than in individuals in remission, except in one unusual patient in whom there was a discordance between TBII activity and in vitro thyroid-stimulatory activity. In eight euthyroid patients who were followed up for at least five months while not receiving treatment, assessment of TBII activity did not predict who would or would not suffer relapse at a later date. Thus, TBIIs are secreted in excess in juvenile Graves' disease, the titer decreasing as the disease remits. The TBII assay cannot be used as the sole predictor of when antithyroid medication can be withdrawn safely, however.

Asunto(s)

RESUMEN

Whole human plasma contains a factor that inhibits the binding of bovine TSH to human thyroid membranes. To determine whether this activity is attributable to the presence of small amounts of immunoglobulin G (IgG) molecules that bind specifically to the thyroid, we have extracted from normal human plasma by a process of selective membrane adsorption a subfraction of IgG that is much more potent in TSH binding inhibition that the starting IgG. The enriched fraction was shown to be IgG by multiple criteria: precipitation in ammonium sulfate, elution by the anion exchange resin DEAE-cellulose, and electrophoresis in sodium dodecyl sulfate-urea polyacrylamide gel. Pretreatment with staphylococcal protein A, with specifically binds IgG, completely removed its activity. Significant TSH binding inhibition was retained under salt conditions, which have been shown to optimize the sensitivity and specificity of the TSH receptor. The enriched fraction was not an antimicrosomal or antithyroglobulin antibody, and did not bind to the TSH label. A similar enriched subfraction of bovine TSH binding inhibitory IgG could be prepared using membranes obtained from kidney and liver, suggesting that the membrane antigen with which it bound was not thyroid specific. These data indicate that in the plasma of individuals presumed to be free of thyroid disease there circulates low concentrations of an IgG which reacts with a thyroid membrane antigen(s). It may be an autoantibody or a normal constituent of plasma with specific binding properties.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Roles of ovarian progesterone secretion and maternal nutrition in fetal development were investigated in a species that normally experiences considerable embryonic and fetal mortality. Pregnancies were maintained in 81% of Yorkshire pigs during prolonged starvation (e.g., 40 days; 0 kcal/day, water only) in either the middle third (days 30-70) or last third (days 70-110) of gestation compared with 100% in full-fed controls (7,028 kcal/day). In spite of severe maternal deprivation, fetal survival rates averaged 65% in starved dams and 63% in controls; mean number of living fetuses was 9.9 in starved and 9.6 in control dams. Fetal growth was reduced by maternal starvation during the middle third, but not the last third of pregnancy. Placental insufficiency was the primary cause of reduced fetal growth and resulted in abortion in a few of the dams. Progesterone in peripheral serum of dams starved either during middle or late pregnancy was maintained at levels similar (P greater than 0.05) to those in controls. Abortion occurred in starved dams only when serum progesterone concentrations dropped to less than 10 ng/ml within 3 days before loss of conceptuses.

Asunto(s)

RESUMEN

Pregnancies in pigs were sustained during periods of prolonged starvation in spite of maternal body weight losses exceeding 40 kg. Maternal stores of protein were made available for feto-placental development during starvation of the dam. Concentrations of maternal serum proteins, urea nitrogen, electrolytes, and iron were determined in sequential blood samples of healthy Yorkshire pigs during a prolonged period of 40 days inanition (water only) in either the middle third (days 30-70) or last third (days 70-110). Serum protein levels remained similar to full-diet controls throughout these two periods, whereas serum concentrations of albumin and urea N increased primarily during the last third of gestation in starved dams. Serum Na+ levels declined during prolonged inanition while Ca2+ increased and K+ remained unchanged. It was only near term that Fe2+ levels decreased in those dams starved during a period of 40 days in the last third of pregnancy. These results indicated that maternal serum components were sustained at adequate levels to maintain normal development of conceptuses during prolonged starvation in either the middle third or last third of pregnancy in the pig.

Asunto(s)