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Biomedical subjects

R B Jaffe

Publications and source records attributed to R B Jaffe.

At least 109 records · Page 6Linked to original sources
PubMed1990

Human recombinant activin-A inhibits proliferation of human fetal adrenal cells in vitro.

Activins and inhibins are dimeric peptides which are structurally and functionally related to transforming growth factor-beta (TGF-beta). The mRNA for the activin and inhibin subunits is expressed in the adrenal gland. Because members of the TGF-beta superfamily have effects on mitogenesis, we examined the effect of recombinant human activin-A (rh-activin-A) on proliferation of midgestation human fetal adrenal cells in vitro. Dose-dependent growth inhibition by rh-activin-A was obtained, with an ED50 of 1 ng/ml. Rh-activin-A inhibited basal and epidermal growth factor (EGF)-stimulated fetal zone cell proliferation, but did not alter basic fibroblast growth factor (bFGF)-stimulated growth. TGF-beta combined with rh-activin-A demonstrated additive inhibition of fetal adrenal growth. These findings suggest a potential autocrine or paracrine role for activin-A in modulating the growth and/or subsequent involution of the human fetal adrenal gland.

Activins↗
PubMed1990

Regulation of mineralocorticoid secretion by the superfused fetal monkey adrenal gland: lack of stimulation of aldosterone by ACTH.

The rhesus monkey fetal adrenal secretion of mineralocorticoids was studied in vitro. Superfusion of fetal adrenal minces (n = 6) demonstrated that the fetal adrenal secretes aldosterone as well as desoxycorticosterone, 18 hydroxydesoxy corticosterone, and 18 hydroxycorticosterone. Addition of 250 ng/ml ACTH to the superfusion medium did not result in stimulation of aldosterone, but did increase these other mineralocorticoids. These data indicate that aldosterone production is not readily stimulated by ACTH in the fetal rhesus monkey, although other steroids in the mineralocorticoid pathway are.

18-Hydroxycorticosterone↗
PubMed1989

Angiocardiographic evaluation of right ventricular size and morphology in tricuspid atresia.

The potential for right ventricular growth and physiological repair in tricuspid atresia may influence the type of Fontan procedure. To evaluate preoperative right ventricular assessment, we compared the right ventricular size and morphology determined by selective right ventricular catheterization with axial left ventricular angiography. In seven consecutive patients with tricuspid atresia and ventriculo-arterial concordance, the right ventricular volume was 12.8 +/- 9.4 cc, with a predicted normal volume (based on body surface area) of 31 +/- 16 cc, 43% (range 24-78%) of normal. Right ventricular injection outlined a right ventricular area twice that visualized from an axial left ventricular injection (33.2 vs. 16.5 cm). All patients had a well developed but small trabecular portion of the right ventricle, often unopacified with left ventricular injection. Subinfundibular narrowing adjacent to the ventricular septal defect was invariably present, creating, in effect, a two-chambered right ventricle. Selective right ventriculography demonstrates the unique morphology of the right ventricle in patients with tricuspid atresia not visualized by axial left ventriculography.

Angiocardiography↗
PubMed1989

Low aromatase activity and gene expression in human fetal testes.

Because of previous indications that estradiol (E2) plays a role in the regulation of testicular testosterone (T) production in some species, the production of E2 and aromatase gene expression in human fetal testes were investigated. Testicular minces from 14 fetuses (fetal age 15-23 weeks) were incubated with and without 200 ng/ml highly purified hCG, and the production of E2 and T was measured by RIA. Basal T production was high at 15-18 weeks of gestation and decreased thereafter. Estradiol production was low in all testes. Aromatase mRNA (P-450 arom messenger ribonucleic acid) was not detectable in fetal testicular tissues when studied by Northern and dot blot techniques. Placenta and fetal liver expressed aromatase mRNA, but fetal ovary contained only miniscule amounts. HCG significantly stimulated the production of both T and E2 in the testes of older fetuses (19-23 weeks), but the testicular E2 production of the youngest fetuses (15-18 weeks) did not increase significantly after hCG stimulation. These results indicate that aromatase activity and gene expression are very low in human fetal testes. These findings suggest that E2 may not play a major role in testicular T production in the human fetus.

Aromatase↗
PubMed1989

Partial loss of responsiveness of human fetal pituitary cells to hGHRH after chronic exposure.

Synthetic hGHRH was incubated with dispersed pituitary cells from 14 human fetuses at 14-23 weeks of fetal age. After at least three days following plating the cells on an extracellular matrix in serum-containing medium, 3 h incubation with hGHRH in serum-free medium induced a significant increase in GH secretion into the medium at concentrations of hGHRH of 0.01 nmol/l or higher. After 24 h exposure to 0.5 nmol/l hGHRH, subsequent incubation with 0.5 nmol/l hGHRH for 3 h induced significantly lower GH secretion into the medium compared to the GH secretion by cells exposed previously to medium alone. In contrast, when the subsequent exposure to hGHRH was at 10-fold higher concentrations than the concentration present in the initial exposure, GH secretion into the medium did not significantly decrease compared to previously untreated cells. These results suggest that desensitization (down-regulation) of GHRH receptors on somatotropes may be involved in the mechanism by which prior GHRH exposure inhibits GH secretion in response to subsequent GHRH administration. Such desensitization seems to occur in the human fetus but is incomplete. The desensitization may be overcome by increasing the GHRH concentrations with subsequent exposure, suggesting that cellular GH depletion is not responsible for the decreased responsiveness observed.

Cells, Cultured↗
PubMed1989

An enzyme-linked immunosorbent assay to study human relaxin in human pregnancy and in pregnant rhesus monkeys.

A sensitive and specific double-antibody enzyme-linked immunoassay, using a synthetic analogue of human relaxin for standard and immunogen, was developed for the measurement of human relaxin (hRLX) in serum and plasma. No cross-reactivity was observed for human insulin, human insulin-like growth factor-I, hGH, human chorionic gonadotropin, hFSH, hLH or human prolactin. The assay was used to monitor RLX concentrations in samples from men, non-pregnant and pregnant women, and in pregnant rhesus monkeys infused with hRLX. RLX was not detected in serum from men nor from non-pregnant women, while a concentration of 600 ng/l was measured in pooled sera from two pregnant women (pregnancies achieved by in-vitro fertilization). Immunoreactive RLX (1.1 micrograms/g) was found in human corpora lutea taken from ectopic pregnancies at 7 weeks. In an experiment with a pregnant rhesus monkey infused with human RLX analogue, less than 1.5% of the maternal concentration was measured in the fetal circulation. Even though preliminary, these data suggest a low level of transfer of human analogue relaxin across the placenta in a rhesus monkey. Further studies of the physiology of RLX in human pregnancy will be facilitated by the availability of this immunoassay.

Amino Acid Sequence↗
PubMed1989

Percutaneous drainage of traumatic pancreatic pseudocysts in children.

In the past, children with pancreatic pseudocysts have been managed surgically. We report seven children 3-13 years old with posttraumatic pancreatic pseudocysts who were managed with percutaneous catheter drainage. All procedures were performed with local anesthesia and intramuscular sedation under sonographic or CT guidance. Two of the pseudocysts were drained via a transgastric approach, the other five via direct transcutaneous access to the pseudocyst. The catheters were in place an average of 25 days (range, 8-66). There were no serious complications. Six patients became asymptomatic with return of the serum amylase to normal and resolution of the pseudocyst on follow-up sonograms. One patient, in whom the catheter became dislodged after 2 weeks, became asymptomatic, but he had a residual 2-cm pancreatic pseudocyst that resolved over the next 6 weeks. Our experience suggests that percutaneous drainage is a safe and effective method of treatment for traumatic pancreatic pseudocysts in children.

Adolescent↗
PubMed1989

Use of a gonadotropin-releasing hormone agonist analogue for treatment of cyclic auditory dysfunction.

A patient with cyclic luteal phase high-frequency hearing loss is described. This was documented by pre- and post-menstrual audiograms indicating a 40-dB hearing loss in the luteal phase. This had been long-standing and was resistant to oral contraceptive therapy. A gonadotropin-releasing hormone agonist (nafarelin) was used to inhibit ovarian function and was successful in preventing loss of hearing for the 6-month treatment period.

Adult↗
PubMed1988

Use of an agonistic analog of gonadotropin-releasing hormone (nafarelin) to treat leiomyomas: assessment by magnetic resonance imaging.

The purposes of this study were to investigate the effect of a superactive agonistic analog of gonadotropin-releasing hormone, nafarelin, on uterine leiomyomas and to assess the use of magnetic resonance imaging in monitoring uterine and myoma size. Eleven women with uterine leiomyomas were treated with 800 micrograms of nafarelin per day for 6 months. Serum gonadotropin and estradiol concentrations were suppressed during treatment. The mean +/- SEM serum luteinizing hormone level decreased from 11.1 +/- 1.4 to 5.6 +/- 0.42 mlU/ml and follicle-stimulating hormone from 9.5 +/- 0.66 to 7.5 +/- 0.72 mlU/ml by 3 months of treatment (p less than 0.01). The estradiol level decreased from a pretreatment follicular phase mean +/- SEM of 43 +/- 8.3 to 19.8 +/- 3.1 (p less than 0.05) and 14.8 +/- 2.2 pg/ml (p less than 0.01) at 3 and 6 months of treatment, respectively. Mean pretreatment androgen levels (testosterone, androstenedione, and dehydroepiandrosterone sulfate) were low in these women and did not change significantly during treatment. Ten women had magnetic resonance imaging, which provided excellent resolution of individual uterine myomas. As assessed by magnetic resonance imaging, the largest myoma decreased in size in nine of 10 women; the mean decrease was 46% +/- 9%. Uterine volume decreased in all 10 patients; the mean decrease was 57% +/- 7%. In several women myomas reenlarged after discontinuance of nafarelin treatment. Posttreatment myomectomy was carried out in four women; there was minimal blood loss and no surgical complications. These data indicate that suppression of ovarian estrogen production with nafarelin is associated with a decrease in uterine myoma size in many women but that myomas may regrow with reinstitution of ovarian function. Magnetic resonance imaging is an excellent method by which to monitor treatment as changes in the size of the uterus, as well as individual myomas, can be assessed. The optimal use of gonadotropin-releasing hormone analogs may be in perimenopausal women or as presurgical treatment to decrease uterine and myoma size to facilitate myomectomy.

Adult↗
PubMed1988

Effect of preovulatory estradiol concentrations on luteinizing hormone diurnal secretory patterns: a hypothesis for the timing of the luteinizing hormone surge.

The effect of preovulatory estradiol concentrations on 24-hour patterns of luteinizing hormone secretion was studied in six women with normal menstrual cycles. Blood samples were collected every 15 minutes for 24 hours before and after 7 days of estradiol benzoate administration, which achieved mean (+/- SE) estradiol concentrations of 424 +/- 54 pg/ml. The luteinizing hormone pulse frequency decreased significantly during sleeping hours both before (p less than 0.05) and after (p less than 0.005) estradiol benzoate administration. After estradiol benzoate, there also was diurnal variation in overall mean luteinizing hormone concentrations, which markedly increased secretion in the morning hours. The diurnal changes in luteinizing hormone secretion varied inversely with those of prolactin. These findings are consonant with the observation that the onset of the preovulatory luteinizing hormone surge in women occurs most frequently in the early morning hours.

Adult↗
PubMed1988

Influence of preovulatory estradiol concentration on diurnal and pulsatile prolactin secretion patterns.

We evaluated the effect of preovulatory concentrations of estradiol on the 24-hour profile of prolactin secretion in women with regular menstrual cycles. An estradiol preparation was chosen to allow comparison with physiologic events. Estradiol benzoate, 1 mg intramuscularly, was administered for 7 days to achieve estradiol concentrations just above preovulatory levels (424 +/- 54 pg/ml); 24-hour mean prolactin concentrations increased threefold (14.0 +/- 2.1 to 40.6 +/- 7.1 ng/ml). Prolactin pulse frequency increased significantly (p less than 0.001) during waking hours after estradiol benzoate administration. The diurnal pattern of prolactin secretion was maintained with estradiol benzoate, although the sleep acrophase often reached high concentrations (86 +/- 11 ng/ml). These results suggest in women with regular menstrual cycles: (1) that estrogen administration that achieves slightly greater than preovulatory estradiol concentrations can stimulate prolactin release, (2) that estradiol may elevate prolactin by increasing its pulsatile secretion, (3) that estradiol does not alter the diurnal pattern of prolactin secretion, (4) that estradiol concentrations just above preovulatory levels can be associated with markedly elevated prolactin concentrations.

Adult↗
PubMed1988

Low-dose dopamine infusions do not ablate luteinizing hormone pulses in women.

The effect of dopamine on the secretion of luteinizing hormone in 15 euprolactinemic and 15 hyperprolactinemic women was investigated using infused doses of dopamine that achieved circulating levels from 2 to 100 times basal physiologic concentrations. The normal women were studied in the early follicular phase of the cycle. Different concentrations of dopamine were maintained at each dose level for 2 hours. Blood samples were obtained every 15 minutes and concentrations of dopamine, luteinizing hormone, follicle-stimulating hormone, and prolactin quantified. Mean basal concentrations of estradiol were 53 +/- 19 pg/ml in the euprolactinemic and 33 +/- 12 pg/ml in the hyperprolactinemic women; mean prolactin levels were 8.1 +/- 3.9 ng/ml in euprolactinemic and 183 +/- 174 ng/ml in hyperprolactinemic women; mean basal dopamine concentrations were 323 +/- 308 pg/ml in euprolactinemic and 337 +/- 232 pg/ml in hyperprolactinemic women. All doses of dopamine achieved some degree of prolactin suppression, but doses that achieved nanomolar circulating concentrations did not significantly affect luteinizing hormone secretion. Eight of the women in each group exhibited high-amplitude luteinizing hormone pulses, which persisted during the dopamine infusions. Neither the amplitude nor frequency of luteinizing hormone release correlated with basal estradiol, luteinizing hormone, or prolactin levels. We conclude that low doses of dopamine infused into the peripheral circulation do not achieve significant suppression of luteinizing hormone release. In some women during the early follicular phase of the menstrual cycle and in some amenorrheic hyperprolactinemic women, luteinizing hormone is secreted in a pulsatile manner characterized by high-amplitude low-frequency bursts. These bursts of luteinizing hormone were not influenced by elevations in circulating dopamine concentrations sufficient to suppress prolactin.

Adult↗