Association between confined placental trisomy, fetal uniparental disomy, and early intrauterine growth retardation.
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Female↗
Biomedical subjects
J Vaughan
Publications and source records attributed to J Vaughan.
The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization.
In addition to a nonadecapeptide homologous to the teleost melanin-concentrating hormone (MCH), the amino acid sequence predicted from a rat prepro-MCH (ppMCH) cDNA suggested that at least one (neuropeptide EI, or NEI), and possibly a second (NGE), additional neuropeptide may be encoded by this precursor. Cross-reactivity with epitopes of NEI or NGE can account for reported localization of alpha-MSH, rat CRF, and human GRF in rat dorsolateral hypothalamic neurons. We have used antisera raised against rat MCH and NEI in immunohistochemical studies at the light and electron microscopic levels, along with hybridization histochemical localization of ppMCH mRNA, to define the organization of this system. As expected, ppMCH mRNA is prominently expressed in cells in the lateral hypothalamic area and zona incerta. The MCH and NEI peptides were extensively colocalized in neurons in both of these areas. In addition, smaller cell groups in the olfactory tubercle and pontine tegmentum were also positively hybridized for ppMCH mRNA and immunostained for MCH and NEI. Fibers stained for MCH and NEI were similarly, and very broadly, distributed throughout the central nervous system in patterns that generally conformed with known projection fields of the lateral hypothalamic area and zona incerta. A differential distribution was seen in at least one region, the interanterodorsal nucleus of the thalamus, which contained a prominent terminal field stained for MCH but not NEI. At the electron microscopic level, MCH-stained perikarya displayed a prominent staining associated with the Golgi apparatus; this was not encountered in NEI-stained cells. Both peptides were distributed similarly in terminals in the lateral hypothalamic area and median eminence, with staining associated principally with dense-cored vesicles. The results suggest that ppMCH-derived peptides may serve as neurotransmitters or modulators of prominence in a surprisingly expansive projection field of incerto-hypothalamic neurons. The terminal distributions of this system seem most compatible with functional roles in generalized arousal and sensorimotor integration, processes previously implicated as being subject to modulation by the lateral hypothalamic area.
Animals↗
Effect of activin A on globin gene expression in purified human erythroid progenitors.
The regulatory control of human erythropoiesis through a purified protein, activin A, was examined. Previous studies using mixed populations of bone marrow cells suggested that activin A has an indirect effect on cellular proliferation and DNA synthesis of erythroid progenitors through the mediation of accessory cells. In present studies, the cultures of purified erythroid progenitors were used to examine the effect of activin A on globin gene expression. Human erythroid burst-forming units (BFU-E) were partially purified from peripheral blood, and after 8 days of culture the cells generated consisted mainly of erythroid colony-forming units (CFU-E). It was found that the subsequent 7-day cultures of these purified progenitors yielded similar numbers and size distributions of erythroid colonies, regardless of the presence of activin A in the cultures. In addition, these erythroid progenitor cells were responsive, in terms of stimulation of DNA synthesis, to the addition of erythropoietin, but not to treatment by activin A. Therefore, once the erythroid progenitors are depleted of accessory cells, activin A has little effect on both the proliferation and the DNA synthesis of these progenitors. However, when these purified erythroid progenitors were cultured in the presence of activin A, the levels of all alpha, beta, and epsilon globin transcripts and hemoglobins were significantly increased. In addition, disuccinimidyl suberate was found to chemically cross-link 125I-activin A to cell surface binding proteins (45 to 54 Kd) in both purified erythroid progenitors and K562 cells. The labeling of these binding proteins was specifically inhibited by the presence of unlabeled activin A, but not transforming growth factor-beta. These results suggest that, in addition to its indirect effect on DNA synthesis and cellular proliferation of erythroid progenitors, activin A directly affects the levels of globin mRNAs and hemoglobins in developing human erythroid cells through its specific surface binding receptor(s).
Activins↗
Time course of movement planning: selection of handgrips for object manipulation.
A goal of research on the cognitive control of movement is to determine how movements are chosen when many movements are possible. We addressed this issue by studying how subjects reached for a bar to be moved as quickly as possible from a home location to a target location. Ss generally grabbed the bar in a way that afforded a comfortable posture at the target location (the end-state comfort effect) and with the thumb toward the end of the bar that would be aligned with the target (the thumb-toward bias). The data suggested that subjects chose handgrips by retrieving instances of previous reaches, not by carrying out computations that treated candidate reaches as new behavioral events.
Acceleration↗
Fetal breathing movements in oligohydramnios are not increased by aminoinfusion.
OBJECTIVE: To determine whether fetal breathing movements (FBM) in pregnancies with oligohydramnios change with restoration of amniotic fluid volume. DESIGN: A prospective experimental study. SETTING: Fetal Medicine Unit, tertiary referral hospital. SUBJECTS: 16 women with singleton pregnancies complicated by severe oligohydramnios. INTERVENTIONS: Restoration of amniotic fluid volume by transabdominal amnioinfusion. Controls comprised pregnancies in which infused fluid leaked vaginally, so that oligohydramnios was not corrected. MAIN OUTCOME MEASURES: Change in total breathing movements, change in FBM incidence derived from 40 min recordings immediately before and after amnioinfusion. RESULTS: There was no significant difference in the change in total breathing movements or in the change in incidence of FBM between the 10 pregnancies in which amniotic fluid volume was restored, and the other six in which fluid leaked after infusion and volume was not restored. In both groups, there was no significant change with infusion in number of FBM (mean change -72, 95% CI -218 to +74 in the fluid-retained group and -64, 95% CI -273 to +145 in the fluid-leaked group) and incidence of FBM (median change -2.5%, range -27 to +10 in the fluid retained group and -4.5%, range -34 to +15 in the fluid-leaked group). CONCLUSIONS: This study suggests that restitution of amniotic fluid volume in human pregnancies complicated by severe oligohydramnios does not acutely alter the incidence of FBM. These data support an increasing literature suggesting that impairment of fetal breathing is not the mechanism for oligohydramnios-related pulmonary hypoplasia.
Amnion↗
Determination of twin zygosity by DNA hybridisation to wild type bacteriophage M13.
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Bacteriophage M13↗
Regulation of FSH beta messenger ribonucleic acid levels in the rat by endogenous inhibin.
This study investigated the role of endogenous inhibin in regulating FSH beta mRNA levels subsequent to the gonadotropin surge in the immature, estradiol (E2)-treated female rat. Rats which undergo FSH surges on day 29 have low to undetectable levels of FSH beta mRNA at 0900 h on day 30, whereas those treated simultaneously with E2 and progesterone (P) implants to block these surges have considerably higher levels of FSH beta mRNA. In view of the profound inhibitory effect of inhibin on FSH beta mRNA, we examined the possibility that increased inhibin secretion is responsible for the decline in FSH beta mRNA levels on the morning after the FSH surge by immunoneutralization of endogenous inhibin. Twenty-eight day-old rats which received E2 and blank (B1) or P implants were injected iv with 0.4 ml of a potent anti-rat inhibin serum (anti I alpha, prepared in sheep against rat inhibin alpha (1-26)-Tyr27 coupled to human alpha-globulins) or normal sheep serum at 1700 to 1830 h on day 29 and were killed at 0900 h on day 30. Animals which received the inhibin antiserum showed significantly (P less than 0.001) elevated serum FSH levels (22.9 +/- 1.9 ng/ml [E2 + B1] and 17.1 +/- 0.6 ng/ml [E2 + P]) compared to those which received normal serum (4.4 +/- 0.1 [E2 + B1] and 4.2 +/- 0.1 [E2 + P]). Serum LH was undetectable (less than 0.6 ng/ml) in all groups. Free glycoprotein alpha-subunit was also increased (P less than 0.001) by antiserum to inhibin in E2 + B1-treated rats but was significantly suppressed by P after injection of either normal serum or anti I alpha. Total pituitary RNA was extracted and hybridized to cDNA probes for rat FSH beta, LH beta, and the common alpha-subunit by Northern blot analysis; RNA levels were normalized with beta-actin or cyclophilin probes. As expected, in rats which received normal serum, FSH beta mRNA levels were about 4-fold higher after treatment with E2 + P implants than after treatment with E2 + B1 implants. However, injection with anti-inhibin serum resulted in a striking elevation of FSH beta mRNA levels: 13-fold in animals treated with E2 + B1 implants and 5-fold in animals treated with E2 + P implants. There were no significant differences in levels of LH beta or alpha-subunit mRNAs between rats which received anti-inhibin or normal serum although there was a 30-40% decrease in alpha mRNA after P treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
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↗
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↗
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↗
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↗
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↗
Specific roles of activin/inhibin in human erythropoiesis in vitro.
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Activins↗
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↗
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↗
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↗
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↗
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↗