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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

Stereospecificity of the dopamine receptor mediating the growth hormone response to apomorphine in man. Short communication.

The stereospecificity of the D-2 receptor mediating the growth hormone (GH) response to apomorphine (Apo) and the D-2 receptor regulating prolactin (PRL) secretion were investigated in 10 normal men by examining the effects of cis-flupenthixol (cis-Fx) and trans-flupenthixol (trans-Fx). cis-Fx (1 mg six hourly times four doses) antagonized the GH response to Apo HCl (0.5 mg sc) and increased basal serum PRL concentrations whereas the trans-isomer showed no effect. These findings (a) provide further evidence that the GH response to Apo is mediated by stimulating dopamine (DA) receptors, and, (b) demonstrate stereospecificity of the DA receptor mediating the GH response to Apo and the DA receptor regulating PRL secretion.

Adult

The effect of methyltestosterone on the growth hormone response to the dopamine receptor agonist, apomorphine.

1. There is some evidence that androgens affect dopaminergic function in animals and man. We investigated the effect of methyltestosterone (MT) (30 mg po) on the growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine (Apo) HC1 (0.5 mg sc), in 9 normal men. MT was given 2 hr before Apo. 2. The peak plasma MT concentration was present 1 hr after administration (19.9 +/- 19.5 ng/ml; X +/- SD); the concentration at 4 hr was 7.2 +/- 4.9 ng/ml. At the time of Apo administration, plasma MT varied from 6.0-24.1 ng/ml. 3. There was no significant effect of MT on Apo-GH secretion (interaction F(7,56) = 1.08; p = NS). The mean individual peak GH concentration after Apo alone was 20.2 +/- 11.9 (X +/- SD) vs 22.2 +/- 9.9 ng/ml when MT preceded Apo (p = NS). 4. These results suggest that exogenous androgens do not affect DA receptor function in males with normal androgenic function. Lack of effect due to an insufficient dose or duration of administration of MT cannot be excluded.

Adolescent

Transforming growth factor-alpha and the ontogeny of epidermal growth factor receptors in rat kidney.

Epidermal growth factor exerts potent receptor-mediated mitogenic effects on a variety of target cells in vitro, but its importance in normal organ development is not yet fully understood. We report that the specific high-affinity receptors for EGF/TGF-Alpha increase dramatically in late gestational rat kidney (from 2.3% at 16 days gestation to 6.4% at term) and then fall toward basal adult levels (< 1% binding) during the first week of post-natal life. This post-natal fall-off in EGF binding corresponds temporally to the period when replication of rat kidney DNA begins to slow (4-7 days of post-natal life). EGF mRNA is not detectable in rat kidney by Northern analysis until the second week of post-natal life, but high levels of transforming growth factor-alpha are demonstrable by specific radioimmunoassay in extracts of fetal kidney (52.2 +/- 8.2 pmoles/gram kidney) and amniotic fluid (4.49 +/- 0.75 pmoles/ml). We speculate that induction of EGF-receptors in fetal rat kidney may confer responsiveness to local transforming growth factor-alpha and dictate the rate of hyperplastic renal growth in the perinatal period.

Amniotic Fluid

Effect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients.

Insulinlike growth factor I (IGF-I) has been shown to be a potent mitogen for breast cancer cells in vitro, and IGF-I receptors have been demonstrated on human primary breast neoplasms. In a randomized, placebo-controlled study, we document that administration of the antiestrogen tamoxifen to patients with breast cancer was associated with a statistically significant (P = .002) reduction in the serum level of IGF-I. The mean IGF-I level was 1.4 U/mL in the placebo-treated group and 0.9 U/mL in the tamoxifen-treated group. Because serum IGF-I level is growth hormone (GH) dependent and because data suggest that the pubertal surge in GH and IGF-I levels is sex steroid dependent, we speculate that the mechanism underlying our observation may involve blockade by tamoxifen of estrogen action in the hypothalamic-pituitary axis. We conclude that tamoxifen treatment reduces IGF-I levels and that this reduction may contribute to the therapeutic effect of the drug.

Aged

Effect of some peptides on dopaminergic function in man.

Thyrotropin-releasing hormone (TRH) (200 micrograms iv) and 1-desamino-8-D-arginine vasopressin (DDAVP) (4 micrograms iv) antagonized the growth hormone (GH) response to apomorphine HCl (Apo) (0.5 mg sc) in 10 normal men. Apo had no effect on basal prolactin (PRL) levels but antagonized the PRL response to TRH. DDAVP plus Apo decreased PRL compared to placebo or DDAVP alone. These observations are compatible with (a) an inhibitory effect of TRH on hypothalamic and pituitary lactotrophe dopamine (DA) function (b) a facilitory effect of DDAVP on lactotrophe DA function and an inhibitory effect on hypothalamic DA function. Whether these are direct or indirect effects on DA mechanisms is unclear.

Adolescent

Abnormal food-seeking behavior after surgery for craniopharyngioma.

Three patients are described in whom surgical removal of a craniopharyngioma was followed by extreme hyperphagia resulting in obesity and abnormal food-seeking behavior, including foraging for food, stealing food or stealing money for food. These behaviors resemble those seen in the Prader-Willi syndrome but contrast with those noted in bulimia. This deviant behavior was a major factor in the poor outcome of surgery. Attempts at rehabilitation were unsuccessful.

Adolescent

Effect of estrogen on the growth hormone response to the alpha-adrenergic agonist clonidine in women with menopausal flushing.

The serum GH response to the alpha 2-adrenergic receptor agonist clonidine (0.15 mg, iv) was measured in 8 postmenopausal women with hot flushes before and during treatment with the conjugated estrogen premarin (1.25 mg, orally daily for 4 weeks), 9 normal premenopausal women, and 12 normal men. The men had a significantly greater GH response than did the age-matched premenopausal women (P less than 0.05). The mean individual peak GH response was significantly higher in the premenopausal compared with the postmenopausal women (P less than 0.05). Premarin decreased the number of hot flushes (P less than 0.01), but had no effect on the GH response to clonidine. These results suggest that estrogens do not enhance alpha 2-adrenergic mechanisms that regulate GH secretion and that improvement in menopausal flushing after estrogen therapy is not mediated by an effect on central alpha 2-adrenergic function.

Adrenergic alpha-Agonists

Effect of naloxone on menopausal flushes, skin temperature, and luteinizing hormone secretion.

The effect of naloxone (1.4 mg/hr for 3 hours) on subjectively experienced menopausal flushes, skin temperature, and luteinizing hormone secretion was investigated in seven women in a double-blind, saline-controlled, crossover study. Naloxone had no effect on the number of subjective flushes, episodic skin temperature elevation, luteinizing hormone pulses, variability of luteinizing hormone secretion, or total luteinizing hormone secretion. This study suggests that a naloxone-sensitive opioid mechanism is not active in modulating luteinizing hormone secretion in the postmenopausal woman and that opioid receptor blockade is not effective in altering the frequency of menopausal flushes.

Climacteric

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