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Biomedical subjects

H Guyda

Publications and source records attributed to H Guyda.

At least 19 recordsLinked to original sources

Human embryos produce transforming growth factors alpha activity and insulin-like growth factors II.

OBJECTIVE: To assess whether growth factors are produced by early human embryos in culture. DESIGN: We studied various growth factors in the culture media of human embryos (n = 6) cultured from days 3 to 8 after fertilization. MAIN OUTCOME MEASURES: Four growth factors were measured: Insulin growth factors I and II (IGF-I and IGF-II), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) activity. RESULTS: Nonconditioned INRA Menezo B2 (Biomerieux, S.A., Paris, France) culture medium contained significant levels of TGF alpha activity (5.2 ng/mL) and low levels of IGF-I (1.02 ng/mL) and IGF-II (2.8 ng/mL), whereas EGF was below detection of our assay. With human embryo, the culture media contained lower TGF alpha activity on days 3 and 4 after fertilization (2.5 ng/mL and 2.8 ng/mL, P less than 0.05). From days 5 to 8 after fertilization, a significant increase in TGF alpha activity and IGF-II was detected (TGF alpha activity: day 5: 3.7 ng/mL; day 6: 4.4 ng/mL; day 7: 6.4 ng/mL; day 8: 8.4 ng/mL) (IGF-II: day 5: 3.4 ng/mL; day 6: 3.1 ng/mL; day 7: 4.1 ng/mL; day 8: 4.2 ng/mL). Epidermal growth factor was undetectable, and IGF-I did not vary significantly. CONCLUSION: Transforming growth factor alpha activity and IGF-II are produced by human embryos in culture at a time when they could play a role in morula to blastocyst transformation.

Analysis of Variance

Partial short arm deletions of the X chromosome and spontaneous pubertal development in girls with short stature.

Five additional examples of partial deletion of the short arm of the X chromosome are reported. All of the patients had short stature. The presence of the other stigmata of Turner syndrome, including ovarian dysfunction, appeared to depend on the location of the deletion. Chromosomal analysis of girls with short stature (less than 140 cm), normal pubertal development, and regular menses may reveal that minor deletions of the short arm of the X chromosome are more frequent than has been previously reported.

Adolescent

Effect of naloxone or levallorphan on serum prolactin concentrations and apomorphine-induced growth hormone secretion.

Naloxone HCl (0.8 mg intravenously; n=9) or levallorphan tartrate (0.25 mg subcutaneously; n=5) had no effect on basal prolactin or growth hormone secretion in normal men. Neither narcotic antagonist inhibited the growth hormone secretory response to apomorphine HCl (0.75 mg subcutaneously). These findings suggest that narcotic antagonists do not block dopamine receptors in the hypothalamic-pituitary axis in man and that if these agents have antischizophrenic properties then these are not mediated by dopamine receptor blockade.

Apomorphine

Effect of clozapine on apomorphine-induced growth hormone secretion and serum prolactin concentrations in schizophrenia.

Clozapine had no effect on basal serum growth hormone concentrations in 10 schizophrenic patients but significantly inhibited the apomorphine-induced growth hormone increase that occurred in 7 subjects. Clozapine caused a slight (17%) but significant elevation in basal serum prolactin levels. These data suggest that in man clozapine, like other neuroleptics, blocks dopamine receptors, at least in the hypothalamic-pituitary axis.

Adult

Effect of benztropine on haloperidol-induced prolactin secretion.

The effect of benztropine on haloperidol-induced prolactin secretion was investigated in 10 normal male volunteers. Benztropine had no effect on basal prolactin secretion but significantly enhanced the increased induced by haloperidol. The magnitude of the enhancement, however, was relatively small. These data suggest that in man cholinergic mechanisms have no effect on basal prolactin secretion but exert a weak inhibitory effect under conditions of dopamine receptor blockade. Differences in intrinsic anticholinergic properties may account for some of the variations in potency of different neuroleptics in increasing circulating prolactin concentrations.

Adult

Modification of a screening program for neonatal hypothyroidism.

From our experience in the screening of 212,000 newborn infants, we have devised a flow chart for processing T4 and TSH measurements obtained from initial filter paper blood spots. To date, all infants with thyroid dysfunction or TBG deficiency have been detected. Of the population screened, 1.84% require a spot TSH determination, and 1.1% require repeat determinations of T4.

Filtration

Bromocriptine: effect on serum prolactin and growth hormone in psychogeriatric hospital patients.

Serum prolactin (PRL) and human growth hormone (HGH) were assessed before, and three hours after oral administration of 2.5 mg of bromocriptine in 39 hospitalized geriatric patients with organic brain syndrome. Serum PRL concentrations decreased significantly irrespective of initial values (also in the 7 geriatric control subjects), but HGH levels were low in all patients and did not change during the three hours after administration of bromocriptine. Closer scrutiny of the HGH responses to bromocriptine in 5 patients and 5 controls showed that the serum HGH response was more variable among the patients than among the controls. The findings are discussed in relation to neuroendocrine changes associated with aging, institutional living, and mental disease.

Aged

Effect of lithium on hypothalamic-pituitary dopaminergic function.

The effect of lithium on apomorphine-induced growth hormone secretion and haloperidol-induced prolactin secretion was examined in eight male subjects without history of manic-depressive illness. Lithium had no effect on baseline or drug-induced changes in serum growth hormone or prolactin concentrations. These data suggest that lithium does not alter hypothalamic-pituitary dopamine receptor function.

Adult

Increased plasma somatomedin reactivity in chronic renal failure as determined by acid gel filtration and radioreceptor assay.

Plasma Somatomedin (SM) reactivity has been determined in patients with chronic renal failure and in normal children by radioreceptor assay (RRA) following acid gel filtration on Sephadex G-100. Total small molecular weight SM reactivity was obtained by the summation of all values between Kav 0.55 to 0.75. The mean SM reactivity (+/-SE) for the renal failure group (N = 9) was 154 +/- 10 ng/ml and for the normal subjects (N = 9) was 91 +/- 5 ng/ml (p less than .001). The renal failure group also had significantly increased mean levels of insulin, GH and PRL, but individual increases were not always concordant. Our data reveal that small molecular weight SM reactivity as determined by RRA of column eluates is increased in chronic renal failure compared to normal controls. Thus SM reactivity is not low in chronic renal failure, supporting the suggestion that peripheral antagonism to SM action contributes to the growth failure observed in these patients.

Adolescent

Opiates, prolactin, and the dopamine receptor.

The administration of a dopamine antagonist, chlorpromazine, and two opiates, morphine and methadone, resulted in a significant rise in serum PRL within 90-150 min. Prior administration of dopamine receptor agonists (apomorphine, levodopa, aand bromocriptine) blocked this effect. In contrast, cyproheptadine, a serotonin antagonist, did not. We suggest that the opiates induce hyperprolactinemia in man via dopamine receptor blockade.

Apomorphine

The effect of a slightly acidic somatomedin peptide (ILAs) on the sulphation of proteoglycans from articular and growth plate chondrocytes in culture.

Chondrocyte cultures were prepared from rabbit growth plate (GPC) and articular (ARC) chondrocytes. These two cell types have distinct morphological characteristics. The cells reached maximum numbers by days 10 and 21 for ARC and GPC, respectively. The proteoglycans (PG) contained in the cellular pool were extracted and purified by DEAE cellulose chromatography. The effect of a partially purified somatomedin peptide with insulin-like activity on [35S]sulphate incorporation into PG was evaluated. In both ARC and GPC a significant stimulation of [35S]sulphate uptake into PG subunits was obtained with 1 ng Eq./ml of somatomedin peptide. In order to obtain the same stimulatory effect with porcine insulin, a 1000-fold greater concentration was required. The electrophoretic patterns of the PG subunits on acrylamide-agarose electrophoresis were identical on control incubations and after stimulation with the somatomedin peptide. These data demonstrate in vitro biological activity of this peptide on well differentiated articular and epiphyseal growth plate chondrocytes in culture. These cultures appear to provide a sensitive biological assay for somatomedin peptides.

Animals

The syndrome of basal encephalocele and hypothalamic-pituitary dysfunction.

We documented hypothalamic-pituitary dysfunction in three patients with congenital herniation of the brain through the base of the skull (basal encephalocele). All had growth hormone deficiency, although one has attained normal height. One had diabetes insipidus. Two had hypogonadotropic hypogonadism. Prolactin secretion was elevated in one, normal in another, and borderline low in the third. Two patients were euthyroid, but in response to thyrotropin-releasing hormone (TRH) injection, one patient's thyrotropin (TSH) level increased to levels exceeding normal while the other's did not attain normal levels. In the third patient, TSH response to TRH went from subnormal to normal after treatment with growth hormone and thyroxine. No patient had evidence of ACTH deficiency. These heterogeneous findings do not permit assignment of an unequivocal anatomic or functional site to the endocrine defect(s). Pituitary function should be evaluated in all patients with basal encephalocele, and this entity should be considered in the differential diagnosis of central endocrine malfunction.

Adult

Effect of somatostatin on thyrotropin, prolactin, growth hormone and insulin responses to thyrotropin releasing hormone and arginine in healthy, hypothyroid and acromegalic subjects.

The effect of somatostatin on the thyrotropin (TSH), prolactin, growth hormone (GH) and insulin responses to the combined administration of thyrotropin releasing hormone (TRH) and arginine was studied in six healthy subjects, three hypothyroid patients and three acromegalic patients. Similar inhibition by somatostatin of the TSH and insulin responses was observed in the three groups. While the tetradecapeptide had no significant effect on the prolactin response in the healthy and acromegalic subjects, it caused an unexpected inhibition of the prolactin response in two of the hypothyroid subjects. Contrary to the findings in the healthy and hypothyroid subjects, somatostatin did not inhibit the GH response in the acromegalic patients. Normal inhibition by somatostatin of the insulin response, followed by a rebound in insulin secretion, was observed in all subjects. These preliminary data indicate increased sensitivity of the prolactin-secreting cells to somatostatin in hypothyroidism and suggest that decreased responsiveness of the somatotrophs to somatostatin could play a role in the pathogenesis of acromegaly.

Acromegaly

Short term culture of human midterm and term placenta: parameters of hormonogenesis.

Monolayer cultures of human midterm and term placentae have been established following trypsin dispersion of placental minces. Maintenance of endocrine function was monitored by the concentrations of specific hormones in the culture media. At either gestational age the cultures 1) secret estradiol-17beta(1) and estrone (in a ratio of about 1:20) and aromatize 3H- or 14C-dehydroepiandrosterone sulfate and 14C-androstenedione, estrogen production being markedly enhanced by addition of dehydroepiandrosterone (10(-6)7) to the culture medium; 2) metabolize 3H-pregnenolone to progesterone and 14C-cortisol to cortisone; and 3) produce increasing amounts of chorionic gonadotropin and decreasing amounts of placental lactogen during the first week in culture. It is proposed that the model is highly suited to the study of factors affecting hormonogenesis by the human placenta whether they be of maternal or of fetal origin.

Chorionic Gonadotropin

Dopaminergic function in two patients with catalepsy.

Apomorphine HC1 (2 mg subcutaneously), a dopamine receptor agonist, was administered to two schizophrenic patients with catalepsy. In one of these patients the clinical response to apomorphine was compared with that of sodium amytal and the growth hormone response apomorphine (0.75 mg subcutaneously) was compared with that of 25 control subjects. Apomorphine had no effect whereas sodium amytal caused rapid disappearance of catatonic symptoms including catalepsy. The peak growth hormone response to apomorphine was similar to that of controls. These data suggest that unlike experimental catalepsy in animals, catalepsy associated with schizophrenia may not be dependent on impaired dopaminergic function. Further case studies as well as the use of other dopamine receptor agonists are required before definite conclusions can be drawn.

Adult