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Biomedical subjects

B C Nisula

Publications and source records attributed to B C Nisula.

At least 91 records · Page 5Linked to original sources
PubMed1980

The inverse relationship between serum dopamine-beta-hydroxylase activity and thyroid function.

Serum dopamine-beta-hydroxylase (DBH) activity is inversely related to thyroid status in both humans and rats. The low level of serum DBH activity in hyperthyroid rats is accompanied by a rapid rate of disappearance of enzyme activity after the injection of exogenous bovine DBH. Conversely, the high level of serum DBH activity in hypothyroid rats is accompanied by a slow rate of exogenous DBH disappearance. These results suggest that the extraneuronal disposal pathway for DBH is an important factor in the regulation of the level of DBH activity in altered thyroid function in both humans and rats.

Adrenal Medulla↗
PubMed1980

Testosterone-estradiol binding globulin binds to 2-methoxyestradiol with greater affinity than to testosterone.

This report describes the unexpected observation that testosterone-estradiol binding globulin (TeBG) binds 2-methoxyestradiol better than it binds either testosterone or 17 beta-estradiol. As determined by competitive displacement of 3H-testosterone from TeBG adsorbed onto a solid phase matrix of Con A-Sepharose, the relative binding activities of 2-methoxyestradiol, testosterone and 17 beta-estradiol for TeBG were 2.0, 1.0 and 0.32, respectively. In contrast, 2-methoxyestradiol, which is known to bind with low affinity to estrogen receptors, had only low affinity binding to the androgen receptor, as determined by competitive displacement of 3H-dihydrotestosterone using 64-24 rat mammary tumor cells. 2-Methoxyestradiol is the first example of a naturally occurring steroid which binds with high affinity to TeBG but with low affinity to both androgen and estrogen receptors.

2-Methoxyestradiol↗
PubMed1979

Measurement of the testosterone binding parameters for both testosterone-estradiol binding globulin and albumin in individual serum samples.

This report describes a solid phase method for the characterization of testosterone binding to both albumin and testosterone-estradiol binding globulin (TeBG). TeBG is adsorbed from serum samples onto a solid phase matrix of concanavalin A covalently linked to 4B Sepharose. The binding of testosterone is then examined both in the presence and absence of the endogenous serum albumin. Analysis of the resulting Scatchard plots permits determination of the TeBG binding capacity, TeBG association constant and a parameter of albumin binding equivalent to the product of its affinity and capacity for binding testosterone. Results showed that the TeBG capacity was lower in men than in women (18.4 +/- 5.8 vs. 33.1 +/- 19.2 nM, p less than 0.01). The association constant was greater in men (1.59 +/- 0.35 vs. 1.19 +/- 0.32 x 10(9)M-1, 10(9)M-1, p less than 0.01). There was no difference in the albumin binding parameter (43.8 +/- 18.3 vs. 46.6 +/- 15.5, NS). These parameters can then be used to calculate the distribution of the circulating testosterone into albumin bound, TeBG bound and unbound fractions.

Adult↗
PubMed1979

Metabolic clearance rates of the subunits of human chorionic gonadotropin in man.

Highly purified preparations of the alpha- and beta-subunits of hCG (hCG alpha and hCG beta) were injected iv in normal subjects. After rapid injection, the disappearance of both subunits from serum was nonlinear when plotted on a semilog graph. A two-component exponential curve was fitted for each subject, and the curve parameters were used to estimate the MCR, apparent initial volume of distribution (Vd), and half-times of disappearance of the rapid and slow phase for each subunit. The Vd of hCG beta was indistinguishable from that of hCG alpha (1958 +/- 131 vs. 1729 +/- 99 ml/m2, respectively). The rapid phase half-time for hCG beta was significantly longer than that of hCG alpha (41.2 +/- 1.7 vs. 13.0 +/- 0.9 min; P less than 0.001), and the slow phase half-time of hCG beta was also significantly longer than that of hCG alpha (236 +/- 41 vs. 76 +/- 19 min; P less than 0.01). The estimated MCR of hCG alpha was 49.7 +/- 1.6 ml/min.m2; this value was significantly greater than that of hCG beta (19.0 +/- 0.7 ml/min.m2; P less than 0.001). No significant differences between sexes in parameters determined for the subunits were observed. Continuous infusion of subunits at a rate of 2.7 microgram/min achieved a steady state blood level of hCG beta that was significantly greater than that of hCG alpha (59.1 +/- 7.8 vs. 24.4 +/- 0.7 ng/ml; P less than 0.02) and gave a MCR of hCG alpha that was 3 times greater than the MCR of hCG beta (72.2 +/- 4.9 vs. 21.6 +/- 2.8 ml/min.m2; P less than 0.001). We conclude that the hCG subunits have similar Vds, but since hCG alpha has much shorter half-times of disappearance in both rapid and slow phases, the MCR of hCG alpha is much greater than that of hCG beta.

Adult↗
PubMed1979

A sensitive, convenient radioimmunoassay procedure which demonstrates that serum hTSH is suppressed below the normal range in thyrotoxic patients.

A highly sensitive radioimmunoassay procedures for the measurement of serum hTSH is described which permits delineation of the entire range of values in normal subjects (0.5-4.5 microU/ml). The procedure involves the concentration of hTSH from serum by adsorption to concanavalin A covalently bound to 4B Sepharose, Lactoperoxidase iodination of hTSH, and disequilibrium assay conditions. This method utilizes commonly available radioimmunoassay materials and is convenient to perform. Our results with this assay show that patients with thyrotoxicosis of a variety of etiologies have serum hTSH levels suppressed well below the normal range.

Adolescent↗
PubMed1979

Cyclophosphamide in the management of advanced Graves' ophthalmopathy. A preliminary report.

Three patients with advanced Graves' ophthalmopathy were treated with cyclophosphamide. All had proptosis and diplopia. One patient had disabling iatrogenic Cushing's syndrome from steroid treatment of the ophthalmopathy and had undergone bilateral orbital decompression before cyclophosphamide therapy; steroids could not subsequently be withdrawn. When cyclophosphamide was administered to the cushingoid patient, withdrawal of glucocorticoid therapy was then possible. Diplopia completely resolved in two patients and improved in the third coincident with administration of cyclophosphamide. Deteriorating visual acuity resolved in one patient. Chemosis improved in the two affected patients. Proptosis was unchanged in all three patients. Cyclophosphamide deserves further study as a therapeutic agent in Graves' disease.

Administration, Oral↗
PubMed1978

Highly sensitive radioimmunoassay for chorionic gonadotropin in human urine.

The value of RIAs that measure hCG levels in human urine has been limited principally because of cross-reactivity with human LH. Recently, antisera generated to antigenic determinants on the intact hCG beta subunit and its carboxyl-terminal peptide have been shown to exhibit substantially reduced human LH cross-reactivity. To take maximal advantage of these antisera and to minimize interference by nonspecific substances in urine, a procedure for extracting and concentrating hCG from 24-h urine samples was developed. The procedure involves preparation of a standard kaolin-acetone urine concentrate and adsorption of the hCG in the concentrate to Concanavalin A covalently linked to agarose for purification and subsequent RIA. In urine samples obtained from patients with gestational trophoblastic disease, there was a direct correlation between hCG levels measured by RIA and those estimated by mouse uterine weight bioassay. In individual subjects, hCG levels were determined in serum and urine obtained the same day. When hCG was clearly detectable in the serum at levels greater than 1 ng/ml, the quantity of hCG measured in the urine concentrate exceeded 500 ng/24 h. The concentrates prepared from the urine of normal persons contained an hCG-like glycoprotein substance with antigenic determinants similar to those of the carboxyl-terminal peptide of hCG beta. As the range of hCG immunoreactivity measured in the urine concentrates of normal subjects was 6-52 ng/24 h, specific and sensitive detection of urinary hCG could be accomplished in patients whose sera contained hCG undetectable by conventional RIA. Partial purification and concentration of urinary hCG by this procedure with subsequent RIA provides a sensitive and reliable method for detecting hCG in urine.

Antibody Specificity↗
PubMed1978

Thyroid-stimulating activity of chorionic gonadotropin and luteinizing hormone.

While recent evidence indicates that the hCG molecule has intrinsic thyroid-stimulating activity (TSA), it is not clear whether a thyrotropic molecule other than hCG accounts for some of the TSA apparent in the crude or highly purified hCG. To determine if a thyrotropic factor is excluded from crude urinary hCG during purification of hCG, the ratio of interstitial cell-stimulating activity (ICSA) to TSA was determined in the starting material used for hCG preparation as well as in the highly purified hCG preparation. The ratio of the two biological activities did not change significantly during purification, suggesting that no factor present in crude hCG other than hCG itself accounts for the TSA. The highly purified hCG preparation was gel-filtered on Sephadex G-100 and the main protein peak was divided into three fractions. The ratio of TSA to ICSA was the same in each fraction, further indicating that these activities are intrinsic to the same molecule. If hCG has intrinsic thyrotropic activity, as these data indicate, then thyrotropic activity would be expected to be a secondary biological activity of LH, since there are strong structural and functional similarities between LH and hCG. In order to assess the LH molecule for intrinsic TSA, an LH preparation with minimal TSH contamination was prepared by recombining subunits exhibiting minimal TSH immunoreactivity. The LH molecule formed from the recombination of highly purified hCG alpha and ovine LH beta subunits exhibited TSA in the bioassay that was 25 times greater than that expected based on the immunoreactive TSH contamination. There was no evidence to support the existance of a thyrotropic factor other than hCG in either crude or highly purified hCG preparations. Our finding that a hybrid LH molecule structurally similar to hCG with potent ICSA also exhibits intrinsic TSA further extends and supports the hypothesis that TSA is an intrinsic property of the hCG molecule.

Animals↗
PubMed1978

Serum dopamine-beta-hydroxylase activity does not reflect sympathetic activation during hypoglycemia.

The relationship between serum dopamine-beta-hydroxylase (DBH) activity and sympathetic nervous system activation in response to insulin-induced hypoglycemia was investigated in healthy young male and female volunteers. Serum DBH activity and glucose levels were measured in blood samples obtained 30 min before and 90 min after the iv administration of regular insulin or placebo. All subjects developed significant hypoglycemia in response to the insulin and manifested signs of sympathetic activation, including increased heart rate, diaphoresis, and lightheadedness. However, despite obvious clinical manifestations of increased sympathetic activity, none of the subjects exhibited a significant alteration in serum DBH activity either in comparison to baseline or placebo values. These data question the suitability of serum DBH measurements for assessing adrenomedullary function in man.

Dopamine beta-Hydroxylase↗
PubMed1978

Radioimmunoassay for partially degraded thyrotropin.

A radioimmunoassay for partially pepsin degraded bovine thyrotropin (bTSH) was developed and used to examine human thyrotropin (hTSH) preparations and sera obtained from patients with Graves' ophthalmopathy for the presence of cross-reactivity. As little as 4 microunits of the hTSH (68/38) reference preparation produced inhibition of binding in the radioimmunoassay, but none of the sera obtained from patients with Graves' disease (n = 26) contained detectable cross-reactivity. These data indicate that there is a substantial amount of partially degraded thyrotropin in human pituitary extracts, but none detectable in the sera of patients with Graves' ophthalmopathy.

Cross Reactions↗
PubMed1977

A new method for the assessment of thyroxine metabolism in the rat.

A new method for assessing thyroxine (T4) metabolism in the rat has been devised and the results that it yields have been compared to those obtained by other methods for assessing peripheral T4 metabolism. The new method uses a simple analysis of the kinetics of exogenous T4 metabolism in rats chronically treated with daily injections of exogenous labeled T4 to determine T4 clearance rates via both fecal and deiodinative pathways. Fecal clearance rates of endogenously labeled hormone measured in rats brought into approximate 125I/127I specific activity equilibrium by administration of iodide of know specific activity in the drinking water were nearly the same as those determined with this new method. Furthermore, total T4 clearance rate determined with the new method agreed well with that measured by the standard single injected technique utilizing radioactive T4. These results indicate that quantitation of the clearance rate of endogenous T4 via not only the fecal, but also the deiodinative, pathway for T4 disposal can be achieved with this new method. In rats made hyperthyroid with exogenous T4, clearance rates of T4 via both deiodinative and fecal pathways were markedly increased. This result supports the concept that hyperthyroidism increases the activity of the tissue mechanisms for metabolizing T4.

Animals↗
PubMed1976

Effect of a large dose of thyrotrophin releasing factor on pituitary and thyroid function in patients with Parkinsonism.

Thyrotrophin releasing factor (TRF) was given intravenously in doses of 0-5 mg and 20 mg to six patients with Parkinsonism treated with L-dopa. Plasma thyrotrophin (TSH), prolactin, lutenizing hormone (LH), follicle stimulating hormone (FSH), thyroxine (T4) and triiodothyronine (T3) were measured before and after TRF infusion. The observation that FSH and LH did not change in response to either dose of TRF confirmed specificity of the effects TRF for certain anterior pituitary functions. The plasma TSH and prolactin levels achieved after 20 mg TRF were considerably greater and were maintained longer than those after 0-5 mg TRF. However, despite a seven fold increase in the overall TSH response, the T4 and T3 responses to 20 mg TRF were not significantly greater than those to 0-5 mg TRF. The explanation for this discrepancy between immunoreactive TSH levels and apparent biologic effect is unclear.

Adult↗
PubMed1976

Follicle stimulating activity of human chorionic gonadotropin: effect of dissociation and recombination of subunits.

The follicle stimulating activity (FSA) and interstitial cell stimulating activity (ICSA) of highly purified human chorionic gonadotropin (hCG), its alpha and beta subunits, and hCG generated by subunit recombination were determined by ovarian weight and ventral prostate weight bioassays. Whereas highly purified hCG exhibited both FA and ICSA, its separated subunits were essentially devoid of both activities. ICSA and FSA, indistinguishable from that of the highly purified hCG, were restored by recombination of the hCG subunits. These observations are consistent with the hypothesis that the FSA and ICSA found in highly purified hCG preparations are properties of the hCG molecule.

Animals↗