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Biomedical subjects

J Vaughan

Publications and source records attributed to J Vaughan.

At least 91 records · Page 5Linked to original sources
PubMed1992

Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice.

CRF is released in response to various stressors and regulates ACTH secretion and glucocorticoid production. CRF overproduction has been implicated in affective disorders, such as depression and anorexia nervosa, and may lead to Cushing's syndrome. To test whether CRF overproduction leads to Cushing's syndrome and to develop an animal model of chronic pituitary-adrenal activation, the CRF gene was expressed under control of the metallothionein promoter in transgenic mice. CRF transgenic animals exhibit endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis, such as elevated plasma levels of ACTH and glucocorticoids. These animals display physical changes similar to those of patients with Cushing's syndrome, such as excess fat accumulation, muscle atrophy, thin skin, and alopecia. These findings indicate that chronic production of excess CRF results in sustained stimulation of pituitary corticotrope cells, resulting in elevated ACTH and consequent glucocorticoid overproduction, a condition that leads to the development of Cushing's syndrome. Analysis of CRF mRNA distribution revealed that transgene expression is primarily restricted to cells that express the endogenous CRF gene and does not follow the pattern predicted of a metallothionein-regulated gene. These results suggest that DNA elements located outside of the CRF promoter but present within the CRF intron, coding, or 3'-flanking regions may contribute to the cell type specificity of CRF gene expression.

Animals↗
PubMed1992

Effects of porcine follicular fluid, inhibin-A, and activin-A on goldfish gonadotropin release in vitro.

Inhibin and activin are important reproductive regulators in mammalian species and have been demonstrated to be highly conserved in structure. The present study examines the effects of porcine follicular fluid (pFF; a crude inhibin and activin preparation) and purified porcine inhibin-A and activin-A on goldfish gonadotropin-II (GTH-II) release. In studies using primary cultures of dispersed goldfish pituitary cells in static incubation, treatments with pFF, inhibin-A, and activin-A for 10 h caused dose-dependent increase in GTH-II release. In perifusion studies using goldfish pituitary fragments, basal GTH-II release was significantly elevated after 12-h exposure to 500 micrograms/ml pFF. Furthermore, GnRH-induced GTH-II secretion was potentiated by pretreatment with pFF. When pFF was applied in the form of 5-min pulses, a rapid dose-related stimulation of GTH-II was observed. Similarly, challenges with 2-min pulses of 15, 150, and 1500 pM inhibin-A and activin-A stimulated GTH-II release by goldfish pituitary fragments in a rapid and dose-dependent manner. This acute stimulatory action of inhibin on goldfish GTH-II release was completely abolished after pretreatment with specific inhibin antibodies. The acute actions of inhibin and activin on GTH-II release are probably not due to the release of endogenous GnRH from nerve terminals in the pituitary fragments or binding to the GnRH receptors. First, a specific GnRH antagonist did not block the actions of inhibin and activin. Second, dopamine, a potent inhibitor of GnRH-stimulated GTH-II secretion in goldfish, was only partially effective in decreasing inhibin- and activin-induced GTH-II release. Third, the stimulatory effects of inhibin and GnRH on GTH-II release were additive. These lines of evidence also indicate that the mechanisms mediating inhibin and activin stimulation of goldfish GTH-II release may be somewhat different from those of GnRH. These results demonstrate that in contrast with the usual inhibitory effects of inhibin on GTH release in mammals, both inhibin and activin exert long term and acute stimulatory actions on GTH-II release in the goldfish.

Activins↗
PubMed1992

Prenatal pericardiocentesis: its role in the management of intrapericardial teratoma.

A fetus with intrapericardial teratoma had a large pericardial effusion diagnosed by echocardiography. Cardiac tamponade, a common cause of fetal death, was averted by intrauterine pericardiocentesis. Planned obstetric and neonatal management permitted surgical treatment before cardiorespiratory distress developed. The tumor was completely excised and the infant is asymptomatic.

Adult↗
PubMed1991

Reduced amounts of cartilage collagen fibrils and growth plate anomalies in transgenic mice harboring a glycine-to-cysteine mutation in the mouse type II procollagen alpha 1-chain gene.

We have generated transgenic mice harboring a glycine-to-cysteine mutation in residue 85 of the triple helical domain of mouse type II collagen. The offspring of different founders displayed a phenotype of severe chondrodysplasia characterized by short limbs and trunk, cranio-facial deformities, and cleft palate. The affected pups died of acute respiratory distress caused by an inability to inflate lungs at birth. Staining of the skeleton showed a severe retardation of growth for practically all bones. Light microscopic examination indicated a decrease in cartilage matrix density, a severe disorganization of growth plate architecture, and the presence of streaks of fibrillar material in the cartilage matrix. Electron microscopic analysis showed a pronounced decrease in the number of typical thin cartilage collagen fibrils, distension of the rough endoplasmic reticulum of chondrocytes, and the presence of abnormally large banded collagen fibril bundles. The level of expression of the mutant type II procollagen alpha 1 chain transgene in cartilage tissues was approximately equal to that of the endogenous gene in two of the strains. We propose that the principal consequence of the mutation is a considerable reduction in density of the typical thin cartilage collagen fibrils and that this phenomenon causes the severe disorganization of the growth plate. We also postulate that the abnormal thick collagen fibrils are probably related to a defect in crosslinking between the collagen molecules. The cartilage anomalies displayed by these transgenic mice are remarkably similar to those of certain human chondrodysplasias.

Animals↗
PubMed1991

Further predictors of renal dysplasia in fetal obstructive uropathy: bladder pressure and biochemistry of 'fresh' urine.

Urine was aspirated on two consecutive days from the dilated bladder of nine fetuses with lower urinary tract obstruction. Gestational age ranged from 17 to 35 weeks. Renal dysplasia was diagnosed histologically in four fetuses, whereas the other five had normal renal histology or only partial dysplasia. Urinary sodium (Na+) and osmolality (Osm) decreased significantly in the second urine sample 1 day after bladder emptying (median decrease: Na+ = -11.3 per cent; Osm = -13.3 per cent). Although there were no significant differences between fetuses with or without renal dysplasia, normalization of an initially raised urine Na+ concentration occurred at the second sample in a fetus with partially normal renal histology, thus correcting a false-positive diagnosis of dysplasia. Bladder pressure was measured at the time of the first urine sampling in seven fetuses and in a further eight with bladder outlet obstruction undergoing a single urine aspiration at 18-28 weeks. Bladder pressure was increased above the reference range in 8 of 15 fetuses with urinary obstruction, but there was no correlation between pressure and the degree of impairment of renal function. Although no conclusive clinical guidelines can be drawn from this study for the evaluation of fetal renal function, these findings suggest that, in lower urinary tract obstruction, tubular reabsorption is impeded by the standing pressure in the urinary tract and that improvement of renal function may occur following relief of obstruction.

Electrolytes↗
PubMed1991

Effect of recombinant inhibin on luteinizing hormone and follicle-stimulating hormone secretion in the rat.

We investigated the effect of the iv injection of recombinant human (rh) inhibin on FSH and LH secretion in the female rat under various experimental circumstances. Rh inhibin caused dose-related decreases in mean plasma FSH, but not LH, levels in ovariectomized female rats 14 days old and older. The duration of this inhibition was proportional to the dose of rh inhibin, but no consistent changes in FSH secretion were observed until 4 h after treatment. Maximum suppression of FSH release was observed at about 15 micrograms rh inhibin/kg BW and lasted 8-10 h. Measurement of the area under the curve from 4-12 h after injection of inhibin indicated a dose-related decrease in total FSH secreted. When blood samples were withdrawn every 10 min to evaluate pulsatile gonadotropin release, analysis of FSH pulse parameters indicated that rh inhibin (25 micrograms/kg) interfered with pulse frequency, amplitude, and peak levels in both intact and ovariectomized rats. In contrast, pulsatile LH secretion was not measurably altered. These results demonstrate that rh inhibin acts primarily at the level of the pituitary to inhibit all parameters of FSH secretion and suggest that this effect is at least not entirely mediated by changes in GnRH receptors.

Aging↗
PubMed1991

Transforming growth factor-beta: role in mediating serum-induced endothelin production by vascular endothelial cells.

Studies were performed to characterize the identity of the factors present in calf serum that stimulate endothelin (ET) production by vascular endothelial cells in culture. Two putative candidates responsible for the ET-releasing activity present in serum are members of the transforming growth factor-beta (TGF beta) superfamily, TGF beta 1 and activin A. TGF beta 1 antiserum was used to block the actions of TGF beta 1, and follistatin was used to block the actions of activin. Treatment of serum with TGF beta 1 antiserum attenuates ET production by vascular endothelial cells. TGF beta 1 antiserum (1 microliters) completely prevents the release of ET produced by 0.1% and 0.3% serum. Follistatin is a potent inhibitor of activin-induced ET release but does not alter serum-induced ET production. Because serum-induced ET release is dependent on TGF beta, it may be a physiological regulator of ET production by vascular endothelial cells.

Activins↗
PubMed1991

Localization and secretion of inhibin/activin subunits in the human and subhuman primate fetal gonads.

Little is known about the ability of the fetal primate gonads to produce inhibin/activin. We investigated the presence of the alpha-, beta A-, and beta B-subunits of inhibin/activin in fetal human (16-23 weeks gestational age) and rhesus monkey (days 150-157 of gestation; term = 165 days) testes and ovaries by immunocytochemistry. The regulation of alpha-inhibin secretion by gonadotropins was studied in fetal testicular cultures. In the human fetal testis, alpha-subunit immunostaining was found in interstitial and intratubular cells, while beta A- and beta B-subunit immunostaining occurred in clusters of Leydig cells that were clearly demarcated from groups of Leydig cells that were immunonegative. In the late gestational monkey testis, the alpha-subunit was localized in tubular cells, and the beta B-subunit was present in the tubules and interstitium. Testicular cells from midgestation human testes secreted detectable immunoreactive alpha-inhibin in response to FSH and hCG stimulation; alpha-inhibin levels were significantly higher after hCG than FSH. In contrast, levels of alpha-inhibin secreted by rhesus monkey testicular cells were significantly increased by FSH, but not hCG. In the ovary, only weak beta B-subunit immunoreactivity was detected in granulosa cells of a few primary follicles from midgestational human fetal ovaries. In contrast, all three subunits were found in granulosa cells of numerous primary and secondary follicles in the late gestation rhesus monkey ovary. In light of recent evidence that inhibins/activins have actions on gonadal differentiation and growth modulation in vitro, as well as endocrine effects on the fetal pituitary, we propose that these proteins may have intragonadal and endocrine roles in human and subhuman intrauterine gonadal development.

Activins↗
PubMed1991

Analysis of information processing stages using event-related potentials.

The event-related potential (ERP) was recorded to identify the time epochs during which different independent variables have their effects on stages in a memory search task. Stimulus intensity, memory set size and response type were varied. For the most part, the order and timing of effects (evaluated by Principal Components Analysis of within-subjects ERP differences) were consistent with the presumed underlying stages, except for early effects of response type prior to memory set effects (suggesting precategorical target recognition). The usefulness of this type of analysis for the investigation of information processing stages is discussed.

Adult↗
PubMed1991

Uterine-peritoneal amniotic fluid leakage: an unusual complication of intrauterine shunting.

Bilateral pleuroamniotic shunting was performed at 33 weeks' gestation in a fetus with bilateral hydrothorax, hydrops, and gross polyhydramnios. The procedure was successful, but acute amniotic fluid leakage into the maternal peritoneal cavity occurred soon after. This produced marked maternal discomfort and transient oligohydramnios, with consequent fetal distress. Expectant management was adopted in view of fetal lung immaturity. Resolution of maternal ascites occurred within 24 hours and the fetal heart rate normalized as amniotic fluid reaccumulated. The pregnancy progressed uneventfully thereafter.

Adult↗
PubMed1991

Diagnostic and therapeutic transabdominal amnioinfusion in oligohydramnios.

We report our experience with 92 antenatal amnioinfusion procedures. In order to facilitate ultrasound visualization, a diagnostic infusion was attempted at a median of 22 weeks (range 16-36) in 61 pregnancies with oligohydramnios in the absence of ruptured membranes on clinical examination. The procedure was successful in 58 (95%). Infusion (mean volume 181 mL, range 40-64) significantly increased (P less than .001) the deepest pool of amniotic fluid to a mean of 3.2 cm. Suspected fetal anomalies were then confirmed in 27 of 30 cases, whereas kidneys were clearly demonstrated in three fetuses suspected of renal agenesis. In addition, previously unsuspected anomalies were identified in five. Vaginal leakage indicating ruptured membranes occurred in 16 women. Leakage occurred in zero of 24 patients with, compared to 16 of 35 without, fetal urinary disorders (chi 2 = 15.1, P less than .001), which does not support the recent suggestion that amnioinfusion causes rather than unmasks rupture of the membranes. Membranous detachment was observed by ultrasound in 13 patients, 11 of whom leaked vaginally. Information obtained at amnioinfusion led to a change of etiologic diagnosis in eight (13% of subjects). Forty serial infusions were performed in nine women as a pilot study to prevent oligohydramnios sequelae. There were no skeletal deformities; three neonates survived, and five of the six perinatal deaths had normal lung-body weight ratios. Overall, only two of 89 infusions (2.2%) were complicated by clinical amnionitis. Our findings support a role for amnioinfusion in oligohydramnios.

Amnion↗
PubMed1990

Endothelin releasing activity in calf serum and porcine follicular fluid.

Bovine calf serum (CS) and porcine follicular fluid (PFF) added to bovine aortic endothelial cells (BAEC) in culture stimulate endothelin (ET) release. Sorbent extraction of acidified calf serum and PFF using Bond Elut C18 yields a product with an activity 30% that of the starting material. Fractionation of Bond Elut C18 extracted CS or PFF using HPLC yields peaks of activity with retention times similar to those of TGF beta and activin A, respectively. TGF beta is 10-fold more potent than activin A to stimulate ET release from BAECs. The observation that TGF beta and activin A are dose-additive but not effect-additive to stimulate ET release is compatible with the conclusion that these two substances act through a similar mechanism. Thus, TGF beta and/or activin A-related peptides may contribute to the ET releasing activity observed in acidified Bond Elut C18 extracted CS and PFF. The identity of ET-releasing activity in native CS and PFF remains to be established.

Activins↗
PubMed1990

Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures.

We show that mammalian and Xenopus activins induce dorsal axial mesoderm and anterior structures in explants of Xenopus blastula cells that would otherwise form epidermis. The induced explants of animal cap cells can form notochord, muscle, neural tissue, and eyes all arranged in a rudimentary axial pattern. Activin A shares inductive properties and antigenic determinants with PIF, an inducing factor recently isolated from mouse macrophage culture supernatants. Genes encoding Xenopus activin beta A and beta B chains were cloned. Activin beta B transcripts are first detected in Xenopus blastula, whereas activin beta A transcripts do not appear until the late gastrula stage. Recombinant Xenopus activin beta B protein induces mesodermal and neural tissues similar to those induced by mammalian activin A and PIF. Furthermore, ectopic expression of Xenopus activin beta B produces a second body axis in embryos injected with synthetic mRNA. Our results suggest that early induction and axial patterning are accomplished by endogenous activin B, not activin A, in Xenopus.

Activins↗
PubMed1990

Activin is a nerve cell survival molecule.

The structures of five neurotrophic molecules have so far been published. Nerve growth factor, fibroblast growth factor and purpurin, have been identified as nerve-cell survival molecules. More recently, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor have been cloned and sequenced. As all these proteins stimulate the survival of ciliary or sensory neurons, a new cell survival assay is required if novel neurotrophic molecules are to be discovered. P19 teratoma cells differentiate to nerve-like cells in the presence of 5 x 10(-7) M retinoic acid (RA). But when P19 cells are plated in N2 synthetic medium without being exposed to RA, they die within 48 h. In an attempt to identify a molecule(s) that can substitute for RA in promoting P19 survival, we assayed serum-free growth-conditioned media for their ability to promote P19 survival. One cell line from the rat eye secreted a molecule that promoted the survival of P19 cells and some types of nerve cell. We identified this molecule as activin, better known for its role in hormone secretion.

Activins↗
PubMed1990

Identical IgM antibodies recognizing a glycine-alanine epitope are induced during acute infection with Epstein-Barr virus and cytomegalovirus.

We studied antibody production in serial serum samples from patients with acute Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Sera were analyzed both by enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide (P62) derived from the glycine-alanine repeating region of the Epstein-Barr nuclear antigen (EBNA-1) and by immunoblotting. In prior studies, we have shown that patients with acute EBV infection make IgM antibodies that react with this peptide, that recognize a viral-specific protein (EBNA-1), and that bind with a number of proteins present in uninfected cells; however, antibody binding to these autoantigens was inhibited by the peptide. IgG antibodies reactive with the peptide did not appear until months after the disease and were specific for the EBNA-1 protein. We now find that patients with acute CMV infection but not those with acute infections from a variety of other nonherpes organisms also produce IgM antibodies that recognize the EBV-derived peptide P62. These antibodies also appear to recognize the same cellular proteins as the EBV-induced IgM antibodies. The IgM antibodies appeared in all acutely infected CMV patients studied and occurred both in patients with previous EBV infections and in one patient studied who had not previously been exposed to EBV. It appears that infection with EBV or CMV can induce the synthesis of a very similar or identical set of IgM antibodies.

Amino Acid Sequence↗
PubMed1990

Student nurse attitudes towards different teaching/learning methods.

Student nurse attitudes towards ten different teaching/learning methods were measured using the Osgood semantic differential scale. A variety of variables such as gender, age, and type of training being undertaken were considered. Analysis of variance showed that no difference in attitudes existed when including these variables, which suggested that the nurses could be considered as a single homogeneous group. Since the nurses could be considered as a single homogeneous group, it was then possible to compare the ten teaching methods for this single group. These teaching methods were found to fall into four distinct groups, with student centred activities generating more favourable attitudes from the student nurses than teacher centred activities. The least favoured teaching method being the lecture.

Attitude↗
PubMed1990

Steroid hormones modulate the release of immunoreactive gonadotropin-releasing hormone from cultured human placental cells.

The aim of the present study was to evaluate whether steroid hormones or opiate receptor agonists participate in the mechanisms regulating the release of immunoreactive GnRH (irGnRH) from cultured human placental cells. No significant changes in irGnRH concentrations were found in the culture medium after 48-h incubation of estradiol, estriol, or progesterone. Both estriol and estradiol augmented, while progesterone decreased, the irGnRH release induced by 8-bromo-cAMP. The stimulatory effect of estriol or estradiol was reversed by the concomitant addition of progesterone. The secretagogue effect of activin on irGnRH release from cultured placental cells was increased by the presence of estriol and reduced by the addition of progesterone. The action of estriol was counteracted by both tamoxifen, an estrogen antagonist, and progesterone. The inhibitory effect of progesterone was completely reversed by RU 486, a specific receptor antagonist. The addition of morphine, methionine-enkephalin, or UP50, 488H which preferentially bind mu-, delta-, and kappa-opiate receptors, respectively, did not decrease basal irGnRH release from cultured human placental cells. However, both morphine and UP50, 488H significantly inhibited 8-bromo-cAMP-induced GnRH release. The present results showed that steroid hormones and opiate receptor agonists influence irGnRH release from human cultured cells, suggesting that local interaction between steroids and peptides modulates irGnRH release from human placenta.

8-Bromo Cyclic Adenosine Monophosphate↗