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B C Nisula

Publications and source records attributed to B C Nisula.

At least 73 records · Page 4Linked to original sources
PubMed1983

Characterization of a carboxyterminal peptide fragment of the human choriogonadotropin beta-subunit excreted in the urine of a woman with choriocarcinoma.

We have observed low-molecular weight carboxyterminal fragments of the human choriogonadotropin (hCG) beta-subunit in the urines of several women with choriocarcinoma, and we have characterized one fragment in detail. Its apparent molecular weight by gel chromatography on Sephadex G-100 was 14,200. The fragment was not adsorbed to concanavalin A-Sepharose, indicating that it lacked the asparagine-linked carbohydrate groups of intact hCG beta. It was active in radioimmunoassays (RIA) using antisera either to the hCG beta carboxyterminal peptide (CTP) or to the desialylated hCG beta CTP (hCG beta as-CTP), indicating the presence of not only the hCG beta carboxyterminus but also desialylated O-serine-linked carbohydrate side chains on the fragment. It lacked luteinizing hormone/choriogonadotropin radioreceptor activity and hCG beta conformational immunoreactivity (SB6 RIA). On Sephadex G-100 gel chromatography, the elution profiles of this fragment and the hCG beta as-CTP(115-145) prepared by trypsin digestion of as-hCG were essentially indistinguishable (apparent molecular weights 14,200 and 14,000, respectively). The immunological characteristics of the fragment in both hCG beta CTP and hCG beta as-CTP RIA were indistinguishable from those of the hCG beta as-CTP(115-145) glycopeptide. Carboxyterminal fragments of hCG beta were evident in urine specimens obtained from 10 of 11 patients with choriocarcinoma but not in those obtained from normal subjects who were given an intravenous infusion of highly purified hCG. Of six pregnant women, only the one at term excreted carboxyterminal fragments of hCG beta and then only in trace amounts. We conclude that hCG beta carboxyterminal fragments, including one that is indistinguishable from the tryptic glycopeptide hCG beta as-CTP(115-145), can occur naturally in the urine of patients with choriocarcinoma.

Choriocarcinoma↗
PubMed1983

Metabolic clearance rate of dopamine beta-hydroxylase in the rat.

The metabolic clearance rate (MCR) of both bovine and rat dopamine beta-hydroxylase (DBH) preparations was measured using two complementary procedures, pulse-dose injection and constant infusion of enzyme into the rat circulation. Rats that received injections of DBH activity had plasma DBH activity levels similar to those of controls by 24 hr after a pulse dose of rat DBH. The DBH MCR computed by stochastic analysis of the disappearance curve of injected DBH activity was about 1.0 ml/hr/100 g body weight; the mean transit time of DBH was about 8 hr. The disappearance curve of heterologous enzyme (bovine DBH) was more rapid than that of the rat, yielding an MCR of about 8 ml/hr/100 g body weight. MCR values obtained with the constant-infusion technique were similar to those obtained with the pulse-dose technique. These kinetic parameters are consistent with the time frame for altered plasma DBH activity observed with pharmacological and endocrinological factors. These data support the conclusion that plasma DBH turnover time is measured in hours, not days.

Animals↗
PubMed1982

Regulation and inheritance of dopamine-beta-hydroxylase.

Dopamine-beta-hydroxylase (DBH) is unique among the catecholamine biosynthetic enzymes in that release from sympathoadrenal cells during neurotransmission is an integral part of the enzyme's physiology. Because of this unique attribute, the metabolic pathways regulating DBH cannot depend solely upon intraneuronal processes. This manuscript summarizes evidence relating to the regulation of DBH metabolism in the rat. Levels of DBH in the circulation, which derive from release of sympathoadrenal cellular enzyme stores, are genetically determined; even though inherited, circulating DBH levels bear no apparent consistent relationship to cellular enzyme levels or to sympathoadrenal function. These findings suggest that processes regulating neuronal release of DBH are separate from other processes regulating disposal of the circulating enzyme. We have evaluated the circulating DBH disposal pathways by standard metabolic techniques. Our data strongly suggest that clearance of DBH from the circulatory compartment is a main, and perhaps the primary, disposal mechanism for cellular enzyme stores.

Animals↗
PubMed1982

Familial thyroid hormone resistance.

Three phenotypically normal family members were discovered to have elevated thyroid function (T4, free T4, T3, 123I uptake), but were clinically euthyroid. Further evaluation of pituitary and peripheral indices of thyroid hormone action was consistent with the diagnosis of peripheral resistance to thyroid hormone. Basal metabolic rate, serum cholesterol, pulse wave arrival time (QKd), and serum sex hormone binding globulin levels were all normal. Serum TSH was inappropriately elevated for the degree of thyroid hormone excess, while serum alpha subunit levels were normal. TSH responses to TRH (200 micrograms) were commensurate with the basal TSH levels, and decreases in TSH were observed after T3, dexamethasone, and bromocriptine administration. Analysis of thyroid hormone binding to an extract of mononuclear leukocyte nuclei disclosed no abnormalities. The reason for these patients' resistance to thyroid hormones remains to be elucidated. The proper diagnosis of this syndrome may be difficult. Assessment of pituitary TSH secretory dynamics and peripheral indices of thyroid hormone action should be performed in all hyperthyroxinemic patients who do not have obvious symptoms and signs of thyrotoxicosis.

Adolescent↗
PubMed1982

Evidence of excessive androgen secretion by both the ovary and the adrenal in patients with idiopathic hirsutism.

Fifteen patients with idiopathic hirsutism, who had no attenuated adrenal hyperplasia, obesity, enlarged ovaries, or amenorrhea, were studied. Excessive androgen secretion by adrenal tissue was suggested by the finding of increased levels of dehydroepiandrosterone sulfate, which decreased after dexamethasone administration but did not change after human chorionic gonadotropin (hCG) injection. Excessive androgen secretion by ovarian tissue was suggested by the finding that testosterone and androstenedione levels were elevated, correlated significantly with the levels of luteinizing hormone, decreased with administration of estrogen-progestagen, and increased after hCG injection. Notably, free testosterone levels, which were significantly increased, were only partially suppressed during dexamethasone or estrogen-progestagen administration. These results provide further evidence that both the adrenals and the ovaries secrete androgens excessively in patients with idiopathic hirsutism.

Adrenal Glands↗
PubMed1982

Circulating dopamine-beta-hydroxylase in the rat: importance of altered disposal pathways in experimental diabetes.

Circulatory dopamine-beta-hydroxylase (DBH) activity was increased as much as 6-fold in rats with streptozotocin-induced diabetes mellitus. The increased enzymatic activity correlated with increased DBH protein as assessed by neutralization with homologous antiserum. The high levels of circulating DBH activity induced by streptozotocin was associated with a markedly slowed disappearance of enzyme activity after the i.v. injection of exogenous bovine DBH or exogenous rat DBH. Treatment of streptozotocin-treated rats with insulin prevented the increase in circulating DBH activity and reduced the initial half-time of disappearance of bovine DBH in a dose-related manner; the correlation between the initial half-time of disappearance of the bovine enzyme and the circulating DBH activity level was strongly positive. These results indicate that a reduction in the metabolic clearance rate of circulating DBH is a major factor accounting for the increase in serum DBH activity in the streptozotocin-diabetic rat.

Animals↗
PubMed1981

Improved monitoring of gestational trophoblastic neoplasia using a highly sensitive assay for urinary human chorionic gonadotropin.

A radioimmunoassay for urinary human chorionic gonadotropin (hCG) which used antiserum to the hCG beta carboxy-terminal peptide was employed to detect hCG production in women with gestational trophoblastic disease. The urinary hCG assay was considerably more effective in detecting increased hCG production, and, hence, persistent tumor burden, than the commonly used serum hCG beta subunit radioimmunoassay. In two women treated for choriocarcinoma, urinary hCG levels remained distinctly elevated for 2 to 6 weeks, even though the serum hCG level was undetectable; in both cases, the urinary hCG radioimmunoassay reliably predicted the eventual reappearance of hCG in the serum. In six women whose disease remitted, the urinary hCG level declined to the normal range during chemotherapy, and remained there afterward. In eight patients who had been in remission for periods of from 1 to 14 years, urinary hCG levels were in the normal range. We conclude that this highly sensitive and reliable method for the detection of hCG production improves the ability to diagnose persistent trophoblastic disease.

Adult↗
PubMed1981

Metabolic and renal clearance rates of purified human chorionic gonadotropin.

The metabolic clearance rate (MCR) and renal clearance rate (RCR) of human chorionic gonadotropin (hCG) were measured in healthy young men and women using techniques of continuous intravenous infusion and rapid intravenous injection of unlabeled, highly purified hCG. Seven subjects received 4 d of infusion at a rate of 0.2 microgram/min, followed by an additional 4 d of infusion at 0.8 microgram/min. Mean serum levels of hCG established at these rates of infusion were 61.1 +/- 3.3 and 237 +/- 16 ng/ml, respectively (mean +/- SEM). The MCR determined at the low infusion rate was not significantly different from that determined at the higher infusion rate (1.83 +/- 0.09 vs. 1.95 +/- 0.14 ml/min per m2). The mean MCR for all subjects was 1.88 +/- 0.08 ml/min per m2. The MCR was not significantly different between men amd women (2.04 +/- 0.13 vs. 1.76 +/- 0.07 ml/min per m2). The RCR also did not vary between low and high infusion rates (0.40 +/- 0.03 vs. 0.40 +/- 0.04 ml/min per m2). The mean RCR for all subjects was 0.40 +/- 0.02 ml/min per m2. There was no difference in RCR between men and women (0.42 +/- 0.05 vs. 0.39 +/- 0.03 ml/min per m2). Six subjects were given 1.0 mg of highly purified hCG by rapid intravenous injection. Initial serum levels of hCG were 300-400 ng/ml, and the subsequent disappearance curve was multiexponential over 8-10 d. The disappearance curve of hCG in each subject was fitted to a biexponential equation. The rapid component t1/2 was 5.97 +/- 0.63 h and the slow component t1/2 was 35.6 +/- 8.0 h. We conclude that the MCR of purified hCG in man is about 2 ml/min per m2 and the RCR is 0.4 ml/min per m2; these parameters are concentration independent and do not differ significantly between healthy young men and women.

Adolescent↗
PubMed1981

Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma.

This report describes a model of steroid transport in human plasma. The binding affinities of 21 endogenous steroids for both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG) were determined under equilibrium conditions using a solid phase method at physiological pH and temperature. A computer program was used to solve the complex equilibrium interactions between these steroids and TeBG, CBG, and albumin. In this manner, we calculated the plasma distribution of each steroid into TeBG-bound, CBG-bound, albumin-bound, and unbound fractions in normal men, normal women during both the follicular and luteal phases of the ovarian cycle, and women during the third trimester of a normal pregnancy.

Adrenal Cortex Hormones↗
PubMed1981

Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma.

This report describes the binding of 70 synthetic compounds to both testosterone-binding globulin (TeBG) and corticosteroid-binding globulin (CBG). The ability of each compound to displace [3H]testosterone from TeBG and [3H]cortisol from CBG adsorbed from a plasma pool onto a solid phase matrix of Concanavalin A-Sepharose was determined under equilibrium conditions at physiological pH and temperature. From these data, the association constants of the compounds for binding to both TeBG and CBG were calculated and used to predict whether endogenous steroid transport would be altered by the therapeutic administration of the drug. Computer simulation predicted that by interacting with TeBG, therapeutic levels of danazol, methyltestosterone, fluoxymesterone, and norgestrel could displace 83%, 48%, 43%, and 16%, respectively, of the concentration of testosterone bound to TeBG in a normal man. Similarly, by interacting with CBG, therapeutic levels of prednisolone could decrease the concentration of cortisol bound to CBG by approximately 32% in both men and women, and despite relatively low affinity binding to TeBG (5 X 10(5) M-1), prednisolone could also displace small amounts of testosterone from TeBG. These results indicate that binding to steroid transport proteins should be considered among the in vivo effects of drugs on endogenous steroid hormone levels.

Binding, Competitive↗
PubMed1981

Convenient radioimmunoassay for urinary human choriogonadotropin without interference by urinary human lutropin.

We have devised a radioimmunoassay (RIA) for human choriogonadotropin (hCG) in first morning-voided urine specimens. Concanavalin A, a lectin, is used to extract and concentrate the hCG from urine. A high-affinity antiserum is used, directed to the hCG beta carboxy-terminal peptide, a unique immunological determinant not shared by the beta subunit of human lutropin. This ensures that urinary human lutropin-related molecules, which interfere with RIAs involving antisera to the intact hCG beta subunit, will not cross react in this assay. A concentrations of hCG as low as 0.4 microgram/L can be detected in the first morning-voided urine. The effective sensitivity of this assay for the unequivocal detection of hCG production is somewhat better than that achieved with the serum hCG RIA involving antisera to the hCG beta subunit. The improved specificity and sensitivity of this assay, and the greater convenience of collecting samples of urine rather than blood, are clinical useful advantages of this approach to assessing hCG production in humans.

Adult↗
PubMed1980

Thyroid function in gestational trophoblastic neoplasia: evidence that the thyrotropic activity of chorionic gonadotropin mediates the thyrotoxicosis of choriocarcinoma.

An investigation was made of thyroid function in 20 patients with gestational trophoblastic neoplasia. Two patients were judged to be overtly thyrotoxic on the basis of the symptoms and physical findings; both patients had widely metastatic choriocarcinoma, markedly increased serum T4 levels (21.4 and 27.7 micrograms/100 ml), and extremely high levels of serum human chorionic gonadotropin (hCG) (3,220 and 6,720 IU/ml) relative to those of normal gestation(< 100 IU/ml). Three other patients had moderately increased serum T4 levels (13 to 17.1 micrograms/100 ml), moderately increased serum hCG levels (110 to 310 IU/ml), and findings on clinical examination which suggested euthyroidism. Using the mouse thyroid bioassay, we found that the biologic characteristics of the thyroid-stimulating factor were those of purified hCG, and that the levels of thyroid-stimulating activity in both serum and urine correlated closely with the levels of hCG. These results provide evidence that the thyroid-stimulating activity intrinsic to the hCG molecule plays the central pathophysiologic role in choriocarcinoma-associated thyrotoxicosis.

Adolescent↗