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Biomedical subjects

R B Jaffe

Publications and source records attributed to R B Jaffe.

At least 163 records · Page 9Linked to original sources
PubMed1983

A radioimmunoassay for dehydroepiandrosterone sulfate in the circulation of rhesus monkeys.

A radioimmunoassay for dehydroepiandrosterone sulfate (DHAS) was established and validated for use in the rhesus monkey. The validation demonstrated the co-migration of immunoreactive material with tritiated dehydroepiandrosterone after hydrolysis and indicated the absence of other interfering steroids in the measurement. The application of this assay to perinatal samples verified that there are microgram quantities of DHAS present in the circulation. The measurement of circulating concentrations of DHAS in male and female rhesus monkeys at different stages of development demonstrated the absence of increases associated with puberty in this macaque species. Concentrations of DHAS were similar in adult males and females, but were elevated in pregnant females (p less than 0.05). Adult males had increased DHAS concentrations after GnRH administration (p less than 0.05), but no change was detected in infant male monkeys. Cortisol and DHAS responses of both infant and adult males occurred at a similar dose of ACTH (0.05 mU per kg versus 0.015 mU per kg, infant and adult, respectively). These data demonstrate the validity of the DHAS measurement in the rhesus monkey and suggest that the secretion of DHAS from infant and adult adrenals is generated by a similar stimulus. Since there was no evidence of gonadal secretion of DHAS in the infant, changes in either adrenal secretion and/or metabolic clearance of DHAS probably account for the microgram concentrations found during the perinatal period.

Adrenocorticotropic Hormone↗
PubMed1983

Changes in gonadotrope responsivity to gonadotropin releasing hormone during development of the rhesus monkey.

To assess the changing responsiveness of pituitary gonadotropes to gonadotropin releasing hormone (GnRH) during development, 5 male and 5 female rhesus monkeys were studied. Three monkeys of each sex were tested periodically with a subcutaneous injection of 500 micrograms of GnRH dissolved in 50% polyvinylpyrrolidone (PVP) beginning at 2 to 4 weeks of age and continuing into young adulthood. The remaining 4 monkeys received injections of the vehicle (PVP) alone and served as controls. Serum concentrations of bioactive luteinizing hormone (LH) were determined by an interstitial cell testosterone bioassay, and follicle-stimulating hormone (FSH) levels were measured by radioimmunoassay. Baseline FSH levels in the 5 female neonatal monkeys were higher than those of the 5 male neonatal monkeys during the first 2 months of life. In both sexes, FSH concentrations decreased with age, and FSH was barely detectable by 6 months. Baseline LH values in the 5 female monkeys declined during the first 6 months of the study and were undetectable (less than 0.5 micrograms/ml) at 6 months of age. Baseline LH levels in 4 of the 5 neonatal males also declined to undetectable concentrations by 6 months of age. During the first 3 months of life, there was a striking increase in the serum concentrations of both LH and FSH following GnRH. Although the LH responses to GnRH (delta LH) were similar in males and females of comparable ages, the FSH responses (delta FSH) were considerably greater in the female monkeys. In the males, the delta LH exceeded the delta FSH, whereas in the females, the delta FSH were greater than the delta FSH. In both sexes, the delta LH and delta FSH generally were greatest in the youngest monkeys and decreased gradually with increasing age. By 6 months, the gonadotropin responses to GnRH either were undetectable (males) or very small (females). After 6 months there was no longer an increase in serum gonadotropins after GnRH in either sex until 1.5-4 years (females) or 3 years (males) of age. The delta LH in response to GnRH in the male monkeys 3-5 years of age were comparable to the responses during the first month after birth. Serum concentrations of FSH in the adult males, however, did not increase after GnRH. In the female monkeys, serum levels of LH and FSH increased after GnRH at 1.5 years (1 monkey) and 4 years (2 monkeys) of age. The delta LH were similar to those of the 1- to 2-month-old female monkeys. The delta FSH, however, were variable and were approximately 20% of the neonatal response. In these young adult female monkeys the delta LH exceeded the delta FSH.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1983

Cellular localization of chorionic gonadotropin in human fetal kidney and liver.

Earlier, we reported that second trimester human fetal kidney and, to a much lesser extent, human fetal liver were capable of synthesizing and secreting the beta-subunit of hCG. Recently, we also have shown that these tissues, likewise, synthesize and secrete the alpha-subunit of hCG. The hCG produced is biologically active. To determine the cellular localization of these peptides, immunocytochemical studies were performed on human fetal tissues using antibodies against beta hCG, alpha hCG, and the intact hormone. Placental syncytiotrophoblast served as an immunopositive control. In the human fetal kidney, the ascending (thick) limb of the loop of Henle, distal convoluted tubule, and occasional cells in the collecting ducts were distinctly immunopositive for both beta hCG and the alpha-subunit. Small amounts of light positive staining occurred in only a few hepatocytes. Placental syncytiotrophoblast was routinely positive for both subunits, but fetal lung and striated muscle were negative. These immunocytochemical results indicate that immunoreactive beta hCG as well as the alpha-subunit are present in placental syncytiotrophoblast, in the distal renal nephron, and in a limited population of hepatocytes. The qualitative number and intensity of immunopositive cells closely correlate with the quantitative amounts of their hCG subunit synthesis. Taken together with our previous biosynthetic data, the immunocytochemical localization reported here indicates the probable cellular sites of alpha- and beta hCG synthesis in these tissues. The presence of comparable alpha- and beta-subunit staining in identical cell populations suggests that both hCG subunits and, therefore, perhaps intact hCG are produced at these same cellular sites during fetal life.

Chorionic Gonadotropin↗
PubMed1983

Changes in fetal rhesus monkey plasma dehydroepiandrosterone sulfate: relationship to gestational age, adrenal weight and preterm delivery.

These studies were performed to assess the concentrations of dehydroepiandrosterone sulfate (DHAS) in the rhesus monkey fetal circulation from midgestation through the neonatal period, to determine the relation between changes in fetal adrenal size and DHAS levels both during gestation and after surgical stress, and to explore possible relations between changes in the concentration of DHAS in the fetal circulation and the initiation of labor. When plasma DHAS was quantified in cord blood and in serial samples from chronically catheterized rhesus monkey fetuses, a significant increase in plasma DHAS concentration occurred after 150 days gestational age (404 +/- 37 vs. 1093 +/- 159 ng/ml), and an additional increase was found after 159 days (2246 +/- 712 ng/ml). A diurnal change in fetal plasma DHAS occurred in chronically catheterized fetuses, with evening samples having higher values than morning samples. Further, there was an increase in plasma DHAS concentrations in the 4-5 days after fetal surgery. A significant increase in fetal plasma DHAS concentration occurred in the newborn rhesus monkey. Although plasma DHAS concentrations remained significantly higher than in the late gestation fetus, they decreased by approximately half within the first 2 weeks of life. A close correlation existed between fetal plasma DHAS and fetal adrenal weight in control fetuses delivered by hysterotomy and fetuses that were delivered 5 days after fetal surgery. Adrenal weights in the latter were significantly higher than those in comparably aged fetuses delivered by hysterotomy that had not undergone the stress of fetal surgery. The possible relationship between the increase in plasma DHAS and the initiation of labor was studied by monitoring the changes in daily morning DHAS concentrations in long term catheterized fetuses and comparing these values to the mean cross-sectional DHAS values corresponding to that gestational age. In all but one case, the values of DHAS, although they increased preceding delivery, were still within the range found in fetuses of the same gestational age that were not in labor. These data indicate that increases in DHAS are intimately related to parallel increases in fetal adrenal weight, that there are striking increases in DHAS levels near the end of gestation, that an increase in DHAS is a component of the fetal response to surgical stress, and that there is no immediately apparent, direct relationship between fetal DHAS and preterm delivery.

Adrenal Glands↗
PubMed1983

Fetoplacental endocrine and metabolic physiology.

This article deals with the formation and metabolism of steroid hormones in pregnancy and the proposed functions of these hormones; the formation of the polypeptide and neuropeptide hormones of fetus and placenta and their regulatory roles in pregnancy homeostasis; and the fetal thyroid gland and its regulation. It also focuses on the role played by the endocrine system in allowing the pregnancy to function as a heterograft and in initiating the process of labor.

Adrenal Glands↗
PubMed1983

Prolactin-secreting pituitary adenomas.

Prolactin-secreting pituitary adenoma is a common cause of gynecologic problems that include oligomenorrhea, infertility, amenorrhea and galactorrhea. Diagnosis requires a combination of endocrine testing and radiologic evaluation. The diagnosis of macroadenomas is usually straightforward and these large tumors may be associated with mass effects such as severe headache, nerve palsies or visual changes. Microadenomas may be more subtle in presentation, and the diagnosis of hyperprolactinemia without radiologic evidence of a tumor frequently is problematic. The management of prolactin-secreting adenoma remains controversial, with no clear consensus or indication for surgical versus medical treatment. Surgical intervention is a realistic option for those patients who have access to an experienced neurosurgeon and who have tumor characteristics that offer a reasonable hope for cure. Many questions remain to be answered, including the cause, natural history of development and the optimum treatment for individual cases.

Adenoma↗
PubMed1982

Cortisol-cortisone interrelationship in the late gestation rhesus monkey fetus in utero.

The metabolic interrelationship between cortisol (F) and cortisone (E) was studied in four long term catheterized rhesus monkey fetuses in utero during the last third of gestation. The MCR of E (50.8 +/- 5.4 liters/day) was greater than that of F (22.4 +/- 2.1, P less than 0.005) as was the plasma concentration (187.9 +/- 5.0 vs 86.1 +/- 2.5 ng/ml, P less than 0.001). The production rate of E (9.6 +/- 1.4 mg/day) was several-fold greater than for F (1.9 +/- 0.2, P less than 0.005). Of all fetal F, 79.5 +/- 7.0% was metabolized to E, and 43.4 +/- 3.9% originated from E within the fetal circulation. A significant mass of F was infused in these experiments because of the low specific activity of [14C]F. Nevertheless, the fetus was able to maintain F concentrations in the normal range. The MCR of F was similar to that which we previously found using trace amounts of [3H]F. This indicates that the fetus regulates the amount of F in the fetal compartment, probably by decreasing fetal; adrenal secretion rate. We conclude that F in the primate fetus is extensively oxidized to E. We conclude also that E is produced and metabolized much more extensively than is F. Reduction of E back to F could be an important source of fetal F, and increasing activity of this pathway, if present, could contribute to the increase in fetal F levels observed in late gestation in the primate.

Animals↗
PubMed1982

Isolation and identification of human fetal adrenal medullary cells in vitro.

A rapid method for the partial separation of human fetal adrenal medullary cells is described. Enzymatically dissociated human fetal adrenal cells were centrifuged on a preformed gradient of colloidal Silica particles (Percoll) in isotonic Earle's balanced salt buffer. This procedure leads to the formation of five fractions containing nonviable cells and debris, predominantly fetal zone cells, predominantly definitive zone cells and clumps of medullary cells, isolated medullary cells, and red blood cells. The medullary cells were then pooled and plated on plastic culture dishes coated with an extracellular matrix produced by cultured bovine corneal endothelial cells. Medullary cells plated on extracellular matrix demonstrated extensive neurite formation, facilitating their identification. Further identification of the cells as medullary in origin was confirmed using a specific catecholamine fluorescence technique.

Adrenal Medulla↗
PubMed1981

Fetal tissue can synthesize a placental hormone. Evidence for chorionic gonadotropin beta-subunit synthesis by human fetal kidney.

Metabolically active tissues from second trimester human fetuses were examined for their ability to synthesize the placental hormones chorionic gonadotropin and chorionic somatomammotropin. During short-term incubation studies both placenta and fetal kidney were found to synthesize and secrete the beta-subunit of chorionic gonadotropin, whereas its synthesis was not observed in fetal liver, lung or muscle. In addition, chorionic somatomammotropin synthesis and secretion was demonstrated with placental tissue but could not be detected in any of the fetal tissues examined. These observations constitute the first evidence that the genome of a fetal tissue directs the synthesis of what is considered a placental hormone.

Chorionic Gonadotropin↗
PubMed1981

Control of proliferation of human fetal adrenal cells in vitro.

The influence of fibroblast growth factor (FGF) and epidermal growth factor (EGF) on the proliferation of cultured human fetal adrenal cells has been examined. Separated human definitive zone and fetal zone adrenal cells plated at low density in the presence of 10% serum and maintained on plastic culture dishes proliferated slowly. If the cultures were exposed to either FGF or EGF, the growth rate of the cells from each zone increased significantly. Half-maximal stimulation of cell proliferation for both zones occurred at a concentration of 3 X 10(-11) M for EGF and 8 X 10(-9) M for FGF. In addition, 125I-labeled EGF binding to both definitive and fetal zone cells demonstrated high affinity (Kd = 10(-9) M). To investigate the influence of an extracellular matrix (ECM) on cell proliferation, separated fetal adrenal cells maintained on plastic culture dishes were compared with cells maintained on a recently described ECM prepared from bovine corneal endothelial cells. Fetal adrenal cells maintained on the ECM had a significantly higher growth rate than cells maintained on plastic alone. These results demonstrate 1) the mitogenic role of EGF and FGF for human fetal adrenal cells, and 2) that the type of substrate upon which fetal adrenal cells are maintained has a profound influence on their proliferation.

Adrenal Glands↗
PubMed1981

Infants of diabetic mothers: radiographic manifestations.

The radiographic findings of a series of infants of diabetic mothers and a review of the literature are presented to illustrate the wide spectrum of abnormalities that may be seen with this condition. Congenital anomalies of the spine and skeletal, genitourinary, and cardiovascular systems and visceral situs inversus are significantly more frequent among infants of diabetic mothers than normal. The most specific anomaly is sacral agenesis. Renal vein thrombosis and adrenal hemorrhage are also more common and may be diagnosed by sonography. Over one-half of the cases of the small left colon are associated with maternal diabetes and may be diagnosed and treated with a contrast enema. The incidence of the respiratory distress syndrome is higher in infants of diabetic mothers than other premature infants, and the disease may occur in the presence of reliable indicators of lung maturity. Other common causes of dyspnea include cardiomyopathy, congenital heart disease, wet lung syndrome, hyperviscosity syndrome, and persistence of fetal circulation. Echocardiography is the most valuable adjunct in differentiating cardiac from pulmonary problems.

Birth Weight↗
PubMed1980

Prolactin-secreting pituitary adenomas. III. Frequency and diagnosis in amenorrhea-galactorrhea.

Hypocycloidal tomograms of the sella turcica and serum prolactin concentrations were obtained in 146 women with amenorrhea, galactorrhea, or both to diagnose prolactin-secreting pituitary adenomas. Findings suggesting an adenoma, ie, abnormal tomogram and elevated serum prolactin concentration, were found in 24.6% (16/65) of previously unscreened patients and 59.2% (48/81) of prescreened patients. The combination of an abnormal tomogram and elevated prolactin level was relatively specific for an adenoma, as 91% (42/46) of women with these findings who underwent surgery had histologically confirmed tumors. Tumors occurred in women from 15 to 45 years of age, with amenorrhea or galactorrhea ranging from less than six months to more than 20 years in duration. Some women in this series also had obesity, rapid weight loss, polycystic ovarian syndrome, amenorrhea following discontinuance of oral contraceptive use, or emotional stress.

Adenoma↗