PubMed Health⌕ Search

Biomedical subjects

B B Bercu

Publications and source records attributed to B B Bercu.

At least 37 records · Page 2Linked to original sources
PubMed1992

Dextrothyroxine in the treatment of generalized thyroid hormone resistance in a boy homozygous for a defect in the T3 receptor.

The dextroisomer of thyroxine (D-T4) has been shown to have suppressive effects on pituitary TSH secretion in euthyroid individuals and patients with mild thyroid hormone resistance. We treated a 3-year-old boy with D-T4 who was homozygous for a T3 receptor defect, resulting in a complex clinical picture of tissue-specific hyperthyroidism and hypothyroidism. There was no evidence of significant alteration in thyroid physiology, including serum concentrations of basal and TRH stimulated TSH or echocardiographic parameters measuring systolic time interval. We conclude that D-T4 at a daily dose of 6 mg (0.65 mg/kg) was ineffective in this boy with homozygous dominant negative thyroid hormone resistance.

Child, Preschool↗
PubMed1992

Role of selected endogenous peptides in growth hormone-releasing hexapeptide activity: analysis of growth hormone-releasing hormone, thyroid hormone-releasing hormone, and gonadotropin-releasing hormone.

The purpose of this study was to evaluate the contribution of endogenous GH-releasing hormone (GHRH) to exogenous GH-releasing hexapeptide (GHRP-6) activity, and to determine whether TRH or GnRH are endogenous analogs of GHRP-6. The activity of GHRP-6, a synthetic GH secretagogue, was significantly attenuated in rats administered GHRH antiserum or alpha-methyl-rho-tyrosine to reduce endogenous GHRH concentrations, and also in rats administered 5-50 micrograms/kg of [N-Ac-Tyr1,D-Arg2]-GRF 1-29 amide to block pituitary GHRH receptors. However, GHRP-6 activity was potentiated in rats administered 150 micrograms/kg [N-Ac-Tyr1,D-Arg2]-GRF 1-29 amide, presumably due to partial agonist activity of the GHRH receptor antagonist at the higher dose. These data show that endogenous GHRH contributes to full expression of exogenous GHRP-6 activity in vivo. Like TRH, a subthreshold dose of GHRP-6 was significantly more effective in hypothyroid rats than in euthyroid rats. However, suprathreshold doses of GHRP-6 were less effective in hypothyroid rats. Unlike TRH, GHRP-6 had no effect on GH and prolactin release from GH3 cells, and TRH and GnRH were poor competitors for 3H-GHRP-6 binding sites on pituitary membranes. A GnRH receptor antagonist did not block GHRP-6 activity in vivo, and GnRH administered alone or in combination with GHRP-6, did not stimulate GH release. The results of this study suggest that synergy between GHRH and GHRP-6 seen in pharmacological studies is physiologically relevant, and that TRH and GnRH are not endogenous analogs of GHRP-6.

Animals↗
PubMed1992

Effects of coadministered growth hormone (GH)-releasing hormone and GH-releasing hexapeptide on maladaptive aspects of obesity in Zucker rats.

The purpose of this study was to determine the effect of chronic pharmacological stimulation of the pituitary gland on GH hyposecretion and other maladaptive aspects of obesity. Obese Zucker rats were coadministered GH-releasing hormone (GHRH; 3 micrograms/kg) and GH-releasing hexapeptide (GHRP-6; 300 micrograms/kg), a potent combination of synergistic GH secretagogues, once daily for 60 consecutive days. Although pituitary weights and GH concentrations were higher in obese rats administered the peptides than in obese rats administered saline, stimulated GH secretion was lower in obese rats than in lean rats. However, compared to those in lean rats, plasma insulin-like growth factor-I and insulin concentrations were higher in the obese rats regardless of treatment. The GH secretagogues did not alter food intake or body weight gain in sexually mature obese rats, whereas body weight gain was significantly increased when they were administered to prepubertal obese rats. Although glucose tolerance was impaired in both groups of obese rats, it improved in obese rats administered GHRH and GHRP-6 compared to that in obese rats administered saline. On the other hand, plasma cholesterol concentrations were elevated in obese rats administered the GH secretagogues but not saline. In conclusion, the results of this study suggest that hyposensitivity to GHRH and GHRP-6 in obese Zucker rats results from high concentrations of plasma insulin-like growth factor-I that negatively feedback on stimulated GH secretion. Nonetheless, daily episodes of endogenous GH secretion resulting from chronic coadministration of GH secretagogues significantly influenced the pituitary gland as well as lipid and carbohydrate metabolism.

Animals↗
PubMed1992

Hypothalamo-hypophyseal thyroid and gonadal function before and after erythropoietin therapy in dialysis patients.

We examined the effects of administration of two hypothalamic neurohormones, TRH and GnRH, for 3 days in five anemic male dialysis patients and five age-matched normal male volunteers. Patients on chronic hemodialysis have abnormal hypothalamo-hypophyseal thyroid and gonadal functions, including blunted TSH response to TRH, hyperprolactinemia, elevated basal levels of LH with exaggerated response to GnRH, and depressed FSH secretory response to GnRH. After correction of anemia with exogenous erythropoietin, these dialysis patients were given a single injection of the same hypothalamic hormones. The repeat studies after the correction of anemia showed normalization of 1) the TSH response to TRH, 2) basal GH and PRL levels, and 3) the FSH response to GnRH. Although these patients appear to have biochemical evidence of testicular failure, the gonadotropin response (FSH) to GnRH was not exaggerated. In addition, there was no increase in total T4 and free T4 after TRH administration. Although a free T3 response to TRH was present, it was remarkably blunted compared to that of controls. At the present time, it is not known whether these hormonal responses after the correction of anemia are due to better oxygenation or a trophic action of the erythropoietin.

Erythropoietin↗
PubMed1992

Variable transcriptional activity and ligand binding of mutant beta 1 3,5,3'-triiodothyronine receptors from four families with generalized resistance to thyroid hormone.

Mutations in the gene encoding the human beta 1 T3 receptor (hTR beta 1) have been associated with generalized resistance to thyroid hormone (GRTH). We measured the T3-binding affinity and transcriptional regulatory capacity of the mutant hTR beta 1 from four unrelated kindreds with GRTH. These mutations are contained in different functional regions of the ligand-binding domain. The T3 affinity of the mutant receptors correlated well with the degree of impairment of their trans-activating function in a transient cotransfection system in HeLa cells; two mutant receptors with undetectable ligand affinity showed no transcriptional activity, whereas the two other mutants characterized by a 2- and 5-fold reduction in T3 affinity required 5- and 15-fold higher T3 concentrations for half-maximal activity in the cotransfection assay, respectively. All of the mutant hTR beta 1s were able to inhibit the function of transfected normal hTR beta 1 and endogenous retinoic acid receptor in activating a palindromic positive T3 response element (TRE). In the partially functional mutants this dominant negative effect could be completely reversed by increased T3 concentrations. The dominant negative potency did not depend on the type of TRE used; mutant hTR beta 1s were able to inhibit normal receptor function to the same degree on a dimer-permissive palindromic TRE as on a nondimer-permissive inverted repeat of two identical half-sites separated by five spacer bases. However, the dominant negative potency was dependent on the absolute amount of receptor expression vector transfected. The expression of normal and mutant hTR beta 1 was assessed by immunocytochemistry. The hTR beta 1 protein levels in HeLa cells paralleled the amount of transfected expression vector. Moreover, all the mutant receptors were properly expressed in the nuclei of the transfected cells. These data suggest that different mutations in the ligand-binding domain of the human hTR beta 1 result in a variable degree of functional impairment, which may partially explain the phenotypic differences between kindreds with GRTH. Our findings suggest that competition for binding to the TRE and possibly the binding of limiting accessory factors may be more important in mediating the dominant negative effect than the formation of normal/mutant T3 receptor dimers.

Base Sequence↗
PubMed1991

Robust growth hormone (GH) secretion in aged female rats co-administered GH-releasing hexapeptide (GHRP-6) and GH-releasing hormone (GHRH).

Aging is associated with a blunted growth hormone (GH) secretory response to GH-releasing hormone (GHRH), in vivo. The objective of the present study was to assess the effects of aging on the GH secretory response to GH-releasing hexapeptide (GHRP-6), a synthetic GH secretagogue. GHRP-6 (30 micrograms/kg) was administered alone or in combination with GHRH (2 micrograms/kg) to anesthetized female Fischer 344 rats, 3 or 19 months of age. The peptides were co-administered to determine the effect of aging upon the potentiating effect of GHRP-6 on GHRH activity. The increase in plasma GH as a function of time following administration of GHRP-6 was lower (p less than 0.001) in old rats than in young rats; whereas the increase in plasma GH secretion as a function of time following co-administration of GHRP-6 and GHRH was higher (p less than 0.001) in old rats than in young rats (mean Cmax = 8539 +/- 790.6 micrograms/l vs. 2970 +/- 866 micrograms/l, respectively; p less than 0.01). Since pituitary GH concentrations in old rats were lower than in young rats (257.0 +/- 59.8 micrograms/mg wet wt. vs. 639.7 +/- 149.2 micrograms/mg wet wt., respectively; p less than 0.03), the results suggested that GH functional reserve in old female rats was not linked to pituitary GH concentration. The differential responses of old rats to individually administered and co-administered GHRP-6 are important because they demonstrate that robust and immediate GH secretion can occur in old rats that are appropriately stimulated. The data further suggest that the cellular processes subserving GH secretion are intact in old rats, and that age-related decrements in GH secretion result from inadequate stimulation, rather than to maladaptive changes in the mechanism of GH release.

Aging↗
PubMed1991

Sex differences in growth hormone (GH) secretion by rats administered GH-releasing hexapeptide.

The purpose of this study was to compare GH secretion after the administration of GH-releasing hexapeptide (GHRP-6) in conscious male and female rats. Plasma GH was significantly elevated in female rats (six of six) compared to male rats (three of six) 15 min after administration of a single sc injection of GHRP-6 (0.5 mg/kg). In male rats, GHRP-6 administration was associated with suppression of episodic GH secretion and desensitization to a second injection administered 6 h later, whereas in female rats, GH secretion occurred after both GHRP-6 injections. After 14 consecutive days of administering GHRP-6 twice per day, mean plasma GH concentrations in males decreased from 110 +/- 91 to 2.8 +/- 0.6 ng/ml (P less than 0.05) and in females increased from 170 +/- 53 ng/ml to 361 +/- 81 ng/ml (P less than 0.05). Desensitization to GHRP-6 in conscious male rats was not observed in pentobarbital-anesthetized male rats, suggesting that GHRP-6 administration enhanced somatostatin release in the conscious state. After 14 consecutive days of GHRP-6 administration, the mean pituitary GH concentration in female rats was significantly lower than that in male rats (5.1 +/- 0.2 vs. 12.9 +/- 1.2 micrograms/mg, respectively). Lower pituitary GH concentrations in females correlated with higher GH secretion after GHRP-6 administration. Desensitization to GHRP-6 in male rats is attributed to neurohumoral factors producing their unusual pattern of episodic GH secretion, and the response is probably not typical of other species.

Animals↗
PubMed1991

Homozygosity for a dominant negative thyroid hormone receptor gene responsible for generalized resistance to thyroid hormone.

Generalized resistance to thyroid hormones (GRTH) commonly results from mutations in the T3-binding domain of the c-erbA beta thyroid hormone receptor gene. We have reported on a novel deletion mutation in c-erbA beta in a kindred, S, with GRTH. One patient from this kindred was the product of a consanguineous union from two affected members and was homozygous for the beta-receptor defect. This patient at 3.5 weeks of age had unprecedented elevations of TSH, free T4, and free T3 (TSH, 389 mU/L; free T4, 330.8 pmol/L; free T3, 82,719 fmol/L). He displayed a complex mixture of tissue-specific hyperthyroidism and hypothyroidism. He had delayed growth (height age, 1 3/12 yr at chronological age 2 9/12 yr) and skeletal maturation (bone age, 4 months), and developmental delay (developmental age, 8 months), but he was quite tachycardic. The homozygous patient of kindred S is markedly different from a recently reported patient with no c-erbA beta-receptor. This difference indicates that a dominant negative form of c-erbA beta in man can inhibit at least some thyroid hormone action mediated by the c-erbA alpha-receptors.

Adolescent↗
PubMed1991

A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in a patient with generalized thyroid hormone resistance: isolation and characterization of the mutant receptor.

Different point mutations have been identified in the T3-binding domain of the c-erbA beta thyroid hormone receptor gene that are associated with variant phenotypes of generalized thyroid hormone resistance (GTHR). In most cases of GTHR, heterozygotes are affected; a single mutant allele results in the inhibition of the function of normal thyroid hormone receptors. We report here a novel genetic abnormality, a 3-basepair (bp) deletion in the T3-binding domain of the beta-receptor in a kindred, S, with GTHR. One patient, S1, was the product of a consanguineous union of two heterozygotes and was homozygous for this defect. Heterozygotes from kindred S harbored a CAC deletion at nucleotides 1295-1297, which resulted in the deduced loss of amino acid residue threonine at codon 332, and they displayed elevated free T4 levels and inappropriately normal TSH levels characteristic of other kindreds with GTHR. However, patient S1, who had two mutant alleles, had markedly elevated TSH and free T4 levels and displayed profound abnormalities in brain development and linear growth. A fibroblast c-erbA beta cDNA extending from codon 175 to stop codon 457 was cloned from patient S1, sequenced, and used to create a full-length mutant cDNA. The kindred S mutant receptor was synthesized in vitro and did not bind T3. This mutant receptor did bind with similar avidity as the wild-type human beta-receptor to thyroid hormone response elements of the human TSH beta (-12 to 43 bp) and rat GH (-188 to -160 bp) genes. Kindred S showed the effect in man of heterozygous and homozygous expression of a dominant negative form of c-erbA beta.

Alleles↗
PubMed1990

Linear growth response to exogenous growth hormone in children with short stature.

Response to growth hormone (GH) therapy was evaluated in 38 short children (28 males and 10 females; less than 1% in height for chronologic age [CA]) who were clinically categorized into three groups based on their endogenous mean 24-hour GH concentration (mean 24-hour GH) and peak GH response to two or more provocative agents (peak GH). All patients were treated with biosynthetic somatropin (human growth hormone) (0.15 to 0.30 mg/kg per week) injected subcutaneously three to seven times per week for a mean duration of 12.5 months. Group 1 consisted of 17 subjects (CA, 12.5 +/- 2.9 years [mean +/- SD]; bone age, 9.4 +/- 2.9 years; height velocity [HV], 3.4 +/- 1.8 cm/y; peak GH, 5.8 +/- 2.6 micrograms/L; mean 24-hour GH, 1.7 +/- 0.6 micrograms/L; and insulinlike growth factor-I, 0.40 +/- 0.24 U/mL. Group 2 consisted of 10 subjects (CA, 11.7 +/- 2.7 years; bone age, 9.2 +/- 3.0 years; HV, 3.4 +/- 1.6 cm/y; peak GH, 16.4 +/- 5.2 micrograms/L; mean 24-hour GH, 1.7 +/- 0.5 micrograms/L; and insulinlike growth factor-I, 0.49 +/- 0.27 U/mL. Group 3 consisted of 11 subjects (CA, 12.7 +/- 2.2 years; bone age, 10.2 +/- 2.4 years; HV, 3.5 +/- 1.5 cm/y; peak GH, 22.5 +/- 8.6 micrograms/L; mean 24-hour GH, 3.8 +/- 1.1 micrograms/L; and insulinlike growth factor-I, 1.07 +/- 0.69 U/mL. Following administration of somatropin, an increase (delta) in HV of 2.0 cm/y or greater occurred in 94% (16/17) of the group I subjects (delta HV of 5.1 +/- 2.6 cm/y), in 90% (9/10) of the group 2 subjects (delta HV of 4.3 +/- 2.2 cm/y), and in 73% (8/11) of group 3 subjects (delta HV of 3.7 +/- 2.3 cm/y). However, regardless of provoked and/or endogenous GH secretory dynamics, 88% of the children whose pretreatment HV was 2.0 cm/y or less, 94% whose pretreatment HV was between 2.0 and 4.0 cm/y, and 79% whose pretreatment HV was greater than 4.0 cm/y increased their HVs to 2.0 cm/y or greater while they were receiving somatropin. Significant negative correlations were observed between delta HV and pretreatment HV (r = -.67), delta HV and GH concentration expressed as a 24-hour area under the curve (r = -.33), and delta HV and peak GH (r = -.34).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Response to growth hormone-releasing hormone in adult renal failure patients on hemodialysis.

Exogenous synthetic growth hormone-releasing hormone (GHRH [hpGRF-40]), 1 microgram/kg body weight, was administered intravenously (IV) to eight men with chronic renal failure on chronic hemodialysis and to seven men matched for age (control group). Basal and stimulated growth hormone (GH) concentrations following GHRH (hpGRF-40) in renal failure patients were significantly higher than in controls. Basal prolactin and somatomedin C/insulin-like growth factor-1 (SmC/IGF-1) concentrations were significantly higher in the renal failure patients compared with controls. Following GHRH there was no further increase in serum concentration of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, SmC/IGF-1, or cortisol. GH appears to be the only pituitary hormone where there is an exaggerated response to its specific releasing hormone in adults with renal failure.

Adult↗
PubMed1990

Height screening in the community. The commercialization of growth. The role of the pediatrician.

The availability of unlimited but costly supplies of biosynthetic growth hormone has led to pressure for pharmacologic use (as opposed to replacement therapy in proven deficiency states). Commercial and altruistic motives have converged to promote community height screening among individuals who have been perceived by themselves or parents as short. This does not meet accepted criteria for health screening. Height screening of large populations of children yields few unrecognized medical conditions. If the goal of community screening is to identify abnormally short individuals (less than 3%) who might benefit from growth hormone treatment and if the unproven assumption is correct that stature correlates with success and happiness, then those less likely to appear for screening need to be recruited to avoid elitist domination. The annual cost of such growth promotion would be greater than $10 billion, with no evidence for substantial health benefits. Growth monitoring of all children through improved height measurement in schools and in physicians offices, as part of health supervision, is a more sound community approach than height screening.

Body Height↗
PubMed1989

Pooled prolactin measurements in the evaluation of short children.

PRL secretion was determined in 63 children undergoing evaluation of GH status. Children were assigned to 1 of 3 groups based on GH studies: group 1, those with abnormal GH responses to provocative testing (n = 23); group 2, children with normal GH responses to provocative testing and mean 24-h GH concentrations below 2.5 micrograms/L (n = 14); or group 3, those with normal stimulated GH secretion and mean 24-h GH concentrations of 2.5 micrograms/L or more (n = 26). Serum PRL concentrations were measured in daytime (0800-1600 h), nighttime (2200-0600 h), and 24-h pools of serum specimens obtained every 20 min over a 24-h period. Mean (+/- SD) daytime (17.5 +/- 14.3 micrograms/L) and 24-h (19.2 +/- 13.0 micrograms/L) pool PRL concentrations were significantly higher in group 1 than in group 3 (daytime, 6.7 +/- 2.3; 24 h, 10.2 +/- 2.5 micrograms/L; P less than 0.01). Mean nighttime pool PRL concentrations did not differ among groups. Mean nighttime pool PRL values were significantly higher (P less than 0.01) than daytime pool values in group 3 (nighttime pool, 13.6 +/- 3.6 micrograms/L; night to day ratio, 2.2 +/- 1.0) and group 2 (16.8 +/- 9.0 micrograms/L; night to day ratio, 2.5 +/- 1.5), but not within group 1 (21.4 +/- 13.5 micrograms/L; night to day ratio, 1.4 +/- 0.5). The mean peak and increment in PRL concentrations after an iv bolus of insulin-TSH-LHRH were not different among groups. The mean decrement in serum PRL level after L-dopa ingestion was greater in group 1 than in group 3 (P less than 0.05). Two children in group 2 and 10 in group 1 had significantly elevated daytime pool PRL concentrations (greater than 11.3 micrograms/L; 2 SD above the mean value for group 3). Two additional children in group 2 and 2 in group 1 had elevated 24-h (greater than 15.2 micrograms/L) pool PRL concentrations. One child in group 2 and 3 in group 1 had low 24-h PRL concentrations (less than 5.2 micrograms/L; less than 2 SD below the mean of group 3). Fourteen of 20 children with elevated daytime and/or 24-h pool PRL levels or low 24-h pool PRL values had structural or radiation-associated insults to the hypothalamic-pituitary axis evident in the history or with brain-imaging techniques; 1 had microphallus with panhypopituitarism and 5 children had no structural abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1988

Usefulness of serum thyrotropin-binding inhibitory index measurements in infantile hypothyroidism. Relationship to serum thyrotropin concentrations.

Transplacental passage of thyrotropin (TSH)-binding inhibitory immunoglobulins may result in transient congenital hypothyroidism. We measured serum TSH-binding inhibitory index (TBII) in 11 infants with abnormal screening findings using a commercially available kit. Two of the infants, who were siblings, had markedly elevated TBII values (90% and 100%, respectively), as did their mother (89%, 100%), and had a clinical course consistent with transient antibody-mediated hypothyroidism. Four other infants had a borderline or mildly elevated TBII that was not present in maternal serum, suggesting that endogenous TSH was being measured in this assay. The TBII was measured in the sera of 18 additional children with primary hypothyroidism and in human TSH standards from 25 to 2000 mU/L. Increasing concentrations of TSH were associated with a linear increase in TBII. Measurement of TBII by this method may identify infants with transient antibody-mediated hypothyroidism, although simultaneous assessment of maternal serum is necessary.

Antibodies↗
PubMed1988

Papillary-follicular carcinoma arising in a thyroglossal duct cyst in a 12-year-old child.

Carcinoma of a thyroglossal duct cyst is a rare occurrence, first reported by Ucherman in 1910. Less than 100 cases have been reported. most cases have been papillary carcinoma. We report the uncommon occurrence of a mixed papillary-follicular carcinoma in thyroglossal duct cyst in a 12-year-old girl. The controversy regarding surgical management is reviewed.

Adenocarcinoma↗