Differing levels of excision repair in human fetal dermis and brain cells

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Gibson, R.E.; D'Ambrosio, S.M.; Ohio State Univ., Columbus

1982-01-01

The levels of DNA excision repair, as measured by unscheduled DNA synthesis (UDS) and the UV-endonuclease sensitive site assay, were compared in cells derived from human fetal brain and dermal tissues. The level of UDS induced following ultraviolet (UV) irradiation was found to be lower (approx. 60%) in the fetal brain cells than in fetal dermal cells. It was determined, using the UV-endonuclease sensitive site assay to confirm the UDS observation, that 50% of the dimers induced by UV in fetal dermal cells were repaired in 8 h. while only 15% were removed in the fetal brain cells during the same period of time. Even after 24 h. only 44% of the dimers induced by UV in the fetal brain cells were repaired, while 65% were removed in the dermal cells. These data suggest that cultured human fetal brain cells exhibit lower levels of excision repair compared to cultured human fetal dermal cells. (author)

Characterization of the fetal blood transcriptome and proteome in maternal anti-fetal rejection: evidence of a distinct and novel type of human fetal systemic inflammatory response.

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Lee, Joonho; Romero, Roberto; Chaiworapongsa, Tinnakorn; Dong, Zhong; Tarca, Adi L; Xu, Yi; Chiang, Po Jen; Kusanovic, Juan Pedro; Hassan, Sonia S; Yeo, Lami; Yoon, Bo Hyun; Than, Nandor Gabor; Kim, Chong Jai

2013-10-01

The human fetus is able to mount a systemic inflammatory response when exposed to microorganisms. This stereotypic response has been termed the 'fetal inflammatory response syndrome' (FIRS), defined as an elevation of fetal plasma interleukin-6 (IL-6). FIRS is frequently observed in patients whose preterm deliveries are associated with intra-amniotic infection, acute inflammatory lesions of the placenta, and a high rate of neonatal morbidity. Recently, a novel form of fetal systemic inflammation, characterized by an elevation of fetal plasma CXCL10, has been identified in patients with placental lesions consistent with 'maternal anti-fetal rejection'. These lesions include chronic chorioamnionitis, plasma cell deciduitis, and villitis of unknown etiology. In addition, positivity for human leukocyte antigen (HLA) panel-reactive antibodies (PRA) in maternal sera can also be used to increase the index of suspicion for maternal anti-fetal rejection. The purpose of this study was to determine (i) the frequency of pathologic lesions consistent with maternal anti-fetal rejection in term and spontaneous preterm births; (ii) the fetal serum concentration of CXCL10 in patients with and without evidence of maternal anti-fetal rejection; and (iii) the fetal blood transcriptome and proteome in cases with a fetal inflammatory response associated with maternal anti-fetal rejection. Maternal and fetal sera were obtained from normal term (n = 150) and spontaneous preterm births (n = 150). A fetal inflammatory response associated with maternal anti-fetal rejection was diagnosed when the patients met two or more of the following criteria: (i) presence of chronic placental inflammation; (ii) ≥80% of maternal HLA class I PRA positivity; and (iii) fetal serum CXCL10 concentration >75th percentile. Maternal HLA PRA was analyzed by flow cytometry. The concentrations of fetal CXCL10 and IL-6 were determined by ELISA. Transcriptome analysis was undertaken after the extraction of total RNA

Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad.

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Andrew J Childs

Full Text Available The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA. Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8-9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may

Retinoic Acid Signalling and the Control of Meiotic Entry in the Human Fetal Gonad

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Kinnell, Hazel L.; Anderson, Richard A.; Saunders, Philippa T. K.

2011-01-01

The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA). Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8–9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may be important in

Distinct functional programming of human fetal and adult monocytes.

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Krow-Lucal, Elisabeth R; Kim, Charles C; Burt, Trevor D; McCune, Joseph M

2014-03-20

Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.

Anti-inflammatory Elafin in human fetal membranes.

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Stalberg, Cecilia; Noda, Nathalia; Polettini, Jossimara; Jacobsson, Bo; Menon, Ramkumar

2017-02-01

Elafin is a low molecular weight protein with antileukoproteinase, anti-inflammatory, antibacterial and immunomodulating properties. The profile of Elafin in fetal membranes is not well characterized. This study determined the changes in Elafin expression and concentration in human fetal membrane from patients with preterm prelabor rupture of membranes (PPROM) and in vitro in response to intra-amniotic polymicrobial pathogens. Elafin messenger RNA (mRNA) expressions were studied in fetal membranes from PPROM, normal term as well as in normal term not in labor membranes in an organ explant system treated (24 h) with lipopolysaccharide (LPS), using quantitative reverse transcription-polymerase chain reaction (RT-PCR). Enzyme-linked immunosorbent assay (ELISA) measured Elafin concentrations in culture supernatants from tissues treated with LPS and polybacterial combinations of heat-inactivated Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Gardnerella vaginalis (GV). Elafin mRNA expression in fetal membranes from women with PPROM was significantly higher compared to women who delivered at term after normal pregnancy (5.09±3.50 vs. 11.71±2.21; Pmembranes showed a significantly increased Elafin m-RNA expression (Pmembranes also showed no changes in Elafin protein concentrations compared to untreated controls. Higher Elafin expression in PPROM fetal membranes suggests a host response to an inflammatory pathology. However, lack of Elafin response to LPS and polymicrobial treatment is indicative of the minimal anti-inflammatory impact of this molecule in fetal membranes.

Human fetal anatomy: MR imaging.

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Weinreb, J C; Lowe, T; Cohen, J M; Kutler, M

1985-12-01

Twenty-four pregnant women carrying 26 fetuses (two sets of twins) were imaged with magnetic resonance (MR) imaging at 0.35 T following sonographic evaluation. Each study was retrospectively evaluated to determine which of 33 normal fetal structures were visible on the images and which imaging parameters were most useful for depicting fetal anatomy. Fetal motion degraded fetal images in all but two cases, both with oligohydramnios and in the third trimester of gestation. Nevertheless, many fetal structures were identifiable, particularly in the third trimester. Visualization of fetal anatomy improved with intravenous maternal sedation in five cases. Relatively T1-weighted images occasionally offered the advantage of less image degradation owing to fetal motion and improved contrast between different fetal structures. More T2 weighting was believed to be advantageous in one case for outlining the fetal head and in one case for delineation of the brain. In many cases, structures were similarly identifiable (though with different signal intensities) regardless of the parameters selected. The authors conclude that MR imaging of many fetal structures is currently unsatisfactory and is probably of limited value, particularly in the first and second trimesters. However, the relative frequency and detail with which the fetal head and liver can be depicted indicate that these may be areas for further investigation, and the potential utility of imaging fetal fat warrants further investigation.

Myocardial bridges of the coronary arteries in the human fetal heart.

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Cakmak, Yusuf Ozgür; Cavdar, Safiye; Yalin, Aymelek; Yener, Nuran; Ozdogmus, Omer

2010-09-01

During the last century, many investigators reported on myocardial bridges in the adult human heart. In the present study, 39 human fetal hearts (the mean gestastional age was 30 weeks) were studied for myocardial bridging, and the results were correlated with adult data. Among the 39 (27 male and 12 female) fetal hearts studied, 26 bridges were observed on 18 fetal hearts (46.2%). Ten of the bridges had one myocardial bridge, whereas double myocardial bridges were observed in eight fetal hearts. The most frequent myocardial bridges were observed on the left anterior descending artery (LAD), which had 13 bridges (50%). Eight (30.7%) myocardial bridges were on the diagonal artery, and on the posterior descending artery there were five (19.3%). Myocardial bridges were not observed on the circumflex artery. The data presented in this study may provide potentially useful information for the preoperative evaluation of the newborn and may have a clinical implication for sudden fetal death.

Histochemical and radioautographic studies of normal human fetal colon

International Nuclear Information System (INIS)

Lev, R.; Orlic, D.; New York Medical Coll., N.Y.

1974-01-01

Twenty fetal and infant colons ranging from 10 weeks in utero to 20 months postpartum, and 12 adult human colons were examined using histochemical techniques in conjunction with in vitro radioautography using Na 2 35 SO 4 as a sulfomucin precursor. Only the sulfated components of mucus in fetal goblet cells was found to differ significantly from adult colonic mucins. In the fetus sulfomucin staining was much weaker than in the adult, and was more intense in the left colon which is the reverse of the adult pattern. Sulfomucin was concentrated in the crypts throughout the fetal colon whereas in the adult right colon it predominated in the surface cells. As in the adult, saponification liberated carboxyl groups, possibly belonging to sialic acid, and vicinal hydroxyl groups from fetal mucins suggesting that this procedure hydrolyses an ester linkage between these 2 reactive groups. During the middle trimester of fetal life the colon possesses villi whose constituent cells display alkaline phosphatase in their surface coat. These and other morphological and histochemical similarities to fetal small intestine suggest that the fetal colon may have a limited capacity to absorb materials contained within swallowed amniotic fluid during this period. (orig.) [de

Comparative cortical bone thickness between the long bones of humans and five common non-human mammal taxa.

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Croker, Sarah L; Reed, Warren; Donlon, Denise

2016-03-01

The task of identifying fragments of long bone shafts as human or non-human is difficult but necessary, for both forensic and archaeological cases, and a fast simple method is particularly useful. Previous literature suggests there may be differences in the thickness of the cortical bone between these two groups, but this has not been tested thoroughly. The aim of this study was not only to test this suggestion, but also to provide data that could be of practical assistance for future comparisons. The major limb bones (humerus, radius, femur and tibia) of 50 Caucasoid adult skeletons of known age and sex were radiographed, along with corresponding skeletal elements from sheep, pigs, cattle, large dogs and kangaroos. Measurements were taken from the radiographs at five points along the bone shaft, of shaft diameter, cortical bone thickness, and a cortical thickness index (sum of cortices divided by shaft diameter) in both anteroposterior and mediolateral orientations. Each variable for actual cortical bone thickness as well as cortical thickness indices were compared between the human group (split by sex) and each of the non-human groups in turn, using Student's t-tests. Results showed that while significant differences did exist between the human groups and many of the non-human groups, these were not all in the same direction. That is, some variables in the human groups were significantly greater than, and others were significantly less than, the corresponding variable in the non-human groups, depending on the particular non-human group, sex of the human group, or variable under comparison. This was the case for measurements of both actual cortical bone thickness and cortical thickness index. Therefore, for bone shaft fragments for which the skeletal element is unknown, the overlap in cortical bone thickness between different areas of different bones is too great to allow identification using this method alone. However, by providing extensive cortical bone

Fetal functional imaging portrays heterogeneous development of emerging human brain networks

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Andras eJakab

2014-10-01

Full Text Available The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st – 38th gestational weeks (GW with a network-based statistical inference approach. The overall connectivity network, short range and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29. GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW, temporal (peak: 26 GW, frontal (peak: 26.4 GW and parietal expansion (peak: 27.5 GW. We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macroconnectivity.

Fetal functional imaging portrays heterogeneous development of emerging human brain networks.

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Jakab, András; Schwartz, Ernst; Kasprian, Gregor; Gruber, Gerlinde M; Prayer, Daniela; Schöpf, Veronika; Langs, Georg

2014-01-01

The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable morphological abnormalities. After adapting functional magnetic resonance acquisition, motion correction, and nuisance signal reduction procedures of resting-state functional data analysis to fetuses, we extracted neural activity information for major cortical and subcortical structures. Resting fMRI networks were observed for increasing regional functional connectivity from 21st to 38th gestational weeks (GWs) with a network-based statistical inference approach. The overall connectivity network, short range, and interhemispheric connections showed sigmoid expansion curve peaking at the 26-29 GW. In contrast, long-range connections exhibited linear increase with no periods of peaking development. Region-specific increase of functional signal synchrony followed a sequence of occipital (peak: 24.8 GW), temporal (peak: 26 GW), frontal (peak: 26.4 GW), and parietal expansion (peak: 27.5 GW). We successfully adapted functional neuroimaging and image post-processing approaches to correlate macroscopical scale activations in the fetal brain with gestational age. This in vivo study reflects the fact that the mid-fetal period hosts events that cause the architecture of the brain circuitry to mature, which presumably manifests in increasing strength of intra- and interhemispheric functional macro connectivity.

Discovery and Characterization of piRNAs in the Human Fetal Ovary

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Zev Williams

2015-10-01

Full Text Available Piwi-interacting RNAs (piRNAs, a class of 26- to 32-nt non-coding RNAs (ncRNAs, function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference somatic tissues. This revealed abundant piRNAs originating from 150 piRNA-encoding genes, including some exhibiting gender-specific expression, in fetal ovary and adult testis—developmental periods coinciding with mitotic cell divisions expanding fetal germ cells prior to meiotic divisions. The absence of reads mapping uniquely to annotated piRNA genes demonstrated their paucity in fetal testis and adult ovary and absence in somatic tissues. We curated human piRNA-expressing regions and defined their precise borders and observed piRNA-guided cleavage of transcripts antisense to some piRNA-producing genes. This study provides insights into sex-specific mammalian piRNA expression and function and serves as a reference for human piRNA analysis and annotation.

Changes of the glomerular size during the human fetal kidney development

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Daković-Bjelaković Marija

2006-01-01

Full Text Available Introduction. Newborns adaptation on postnatal conditions includes significant morphological and functional renal changes. Every kidney contains a constant number of nephrons, at the end of the nephrogenesis period, which extends from week 8 to 34 of gestation. Mature juxtamedullary nephrons possess higher filtration capacity than primitive superficial nephrons, which have insufficient vascularization. Objective. The objective of the study was to calculate an average glomerular diameter in cortical zones of the kidney during development, to define periods of their most intensive growth, and to record differences of glomerular size between different cortical zones. METHOD A total of 30 human fetal kidneys aged from IV to X lunar months were analyzed. Stereological methods were used for calculating the average glomerular diameter in superficial, intermediate and juxtamedullary zone of the kidney cortex. Results. Glomeruli in the superficial cortical zone had the lowest average diameter. The average glomerular diameter continually increased from IV lunar month (0.057±0.004 mm to X lunar month (0.082±0.004 mm, with highly significant correlation with gestational age (r=0.755; p<0.01. The average glomerular diameter in the intermediate zone increased from 0.081±0.004 mm (IV lunar month to 0.096±0.004 mm (X lunar month with low linear correlation with gestational age (r=0.161. Juxtamedullary glomeruli were the biggest ones. Their average diameter, during the IV LM ranged from 0.093±0.006 mm to 0.101±0.004 mm. In the newborns (X lunar month, juxtamedullary glomeruli had spherical structures with an average diameter of 0.103±0.004 mm, and low negative correlation (r=-0.032 with gestational age. In the IV and V lunar months of gestation, there was significant difference (p<0.01; p<0.05 between the average glomerular diameter in the different zones of the kidney cortex. Conclusion. Superficial glomeruli had the smallest diameter, while

Assessment of fetal activity concentration and fetal dose for selected radionuclides based on animal and human data

International Nuclear Information System (INIS)

Roedler, H.D.

1987-01-01

Biokinetic data of selected radionuclide compounds from investigations in man and animal were taken from literature references with the purpose to provide a basis for a comparative assessment of fetal and adult radiation doses after intake or administration of radionuclides. The following ratios of fetal to adult doses were derived from human data: 0.5 for caesium 137 and total body, 2.3 for iron 59 and liver, 0.06 - 0.3 - 1.1 for iodine 131 and thyroid, and 0.1 - 0.3 for strontium 90 and bone. The ratios of activity concentrations in fetal and adult tissues are of considerable variability - up to three orders of magnitude. Further studies on fetal and adult biokinetics specifically designed for comparative dose assessment are indispensable. 106 refs.; 6 tabs

Programmed Fetal Membrane Senescence and Exosome-Mediated Signaling: A Mechanism Associated With Timing of Human Parturition

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Ramkumar Menon

2017-08-01

Full Text Available Human parturition is an inflammatory process that involves both fetal and maternal compartments. The precise immune cell interactions have not been well delineated in human uterine tissues during parturition, but insights into human labor initiation have been informed by studies in animal models. Unfortunately, the timing of parturition relative to fetal maturation varies among viviparous species—indicative of different phylogenetic clocks and alarms—but what is clear is that important common pathways must converge to control the birth process. Herein, we hypothesize a novel signaling mechanism initiated by human fetal membrane aging and senescence-associated inflammation. Programmed events of fetal membrane aging coincide with fetal growth and organ maturation. Mechanistically, senescence involves in telomere shortening and activation of p38 mitogen-activated signaling kinase resulting in aging-associated phenotypic transition. Senescent tissues release inflammatory signals that are propagated via exosomes to cause functional changes in maternal uterine tissues. In vitro, oxidative stress causes increased release of inflammatory mediators (senescence-associated secretory phenotype and damage-associated molecular pattern markers that can be packaged inside the exosomes. These exosomes traverse through tissues layers, reach maternal tissues to increase overall inflammatory load transitioning them from a quiescent to active state. Animal model studies have shown that fetal exosomes can travel from fetal to the maternal side. Thus, aging fetal membranes and membrane-derived exosomes cargo fetal signals to the uterus and cervix and may trigger parturition. This review highlights a novel hypothesis in human parturition research based on data from ongoing research using human fetal membrane model system.

Immunohistochemical distribution of regulatory peptides in the human fetal adenohypophysis

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Reyes, R; Valladares, F; Gutiérrez, R; González, M; Bello, A R

2008-01-01

We have studied here the cellular distribution of several regulatory peptides in hormone-producing cells of the human pituitary during the fetal period. Immunohistochemistry was used to show the expression of several regulatory peptides, namely Angiotensin-II, Neurotensin and Galanin, at successive gestational stages and their co-localization with hormones in the human fetal adenohypophysis. Somatotrophs, gonadotrophs and thyrotrophs were differentiated earliest. At gestational week 9, Angiotensin-II immunoreactivity was co-localized only with growth hormone immunoreactivity in somatotrophs, one of the first hormone-producing cells to differentiate. This co-localization remained until week 37. Neurotensin immunoreactivity was present in gonadotrophs and thyrotrophs in week 23, after FSH and TSH hormone differentiation. Galanin immunoreactivity was present in all hormone-producing cell types except corticotrophs. The different pro-opiomelanocortin-derived peptides were detected at different stages of gestation and adrenocorticotrophic hormone immunoreaction was the last to be detected. Our results show an interesting relationship between regulatory peptides and hormones during human fetal development, which could imply that these peptides play a regulatory role in the development of pituitary function. PMID:18510508

Mathematical models of human cerebellar development in the fetal period.

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Dudek, Krzysztof; Nowakowska-Kotas, Marta; Kędzia, Alicja

2018-04-01

The evaluation of cerebellar growth in the fetal period forms a part of a widely used examination to identify any features of abnormalities in early stages of human development. It is well known that the development of anatomical structures, including the cerebellum, does not always follow a linear model of growth. The aim of the study was to analyse a variety of mathematical models of human cerebellar development in fetal life to determine their adequacy. The study comprised 101 fetuses (48 males and 53 females) between the 15th and 28th weeks of fetal life. The cerebellum was exposed and measurements of the vermis and hemispheres were performed, together with statistical analyses. The mathematical model parameters of fetal growth were assessed for crown-rump length (CRL) increases, transverse cerebellar diameter and ventrodorsal dimensions of the cerebellar vermis in the transverse plane, and rostrocaudal dimensions of the cerebellar vermis and hemispheres in the frontal plane. A variety of mathematical models were applied, including linear and non-linear functions. Taking into consideration the variance between models and measurements, as well as correlation parameters, the exponential and Gompertz models proved to be the most suitable for modelling cerebellar growth in the second and third trimesters of pregnancy. However, the linear model gave a satisfactory approximation of cerebellar growth, especially in older fetuses. The proposed models of fetal cerebellar growth constructed on the basis of anatomical examination and objective mathematical calculations could be useful in the estimation of fetal development. © 2018 Anatomical Society.

Quaternary structure and spin state of human fetal methemoglobin

International Nuclear Information System (INIS)

Chevion, M.; Navok, T.; Ilan, Y.A.; Czapski, G.

1981-01-01

Using the pulse-radiolysis technique, solutions of fetal human methemoglobin were irradiated in order to reduce a single heme-iron within the protein tetramers. The valence-hybrids thus formed ere reacted wjth oxygen. Kinetics of the reactions were studied. The effects of p and inositol-hexaphosphate (IHP) were examined. The kinetics of the ligation of oxygen to stripped valence-hybrids showed a single-phase behaviour at the pH range 7-9. As the pH was lowered below 6.5, a second slower phase became apparent. This slow phase consisted of approximately 50% at pH 5.8. In the presence of IHP above pH 7.4, the kinetics of oxygen-binding was of a single-phase. As the pH was lowered a transition to a second, slower phase was noticed. Below pH 7 the slower phase was the only detectable one. The analysis of the relative contribution of the faster phase to the total reaction, as a function of the pH, showed a typical sigmoidal transition curve characterized by a pK = 7.2 and a Hill parameter n = 3.06. On this basis it is concluded that stripped, fetal human methemoglobin resides in an R quaternary structure while the presence of IHP stabilizes the T structure at pH below 7.2. The switch between the high spin aquomet- and the low spin hydroxymet-derivatives of adult and fetal human hemoglobins was studied optically in detail. These switches were found to be only slightly affected by IHP, and exhibited very low cooperativity (pK = 8.04; n = 1.1 and pK = 8.10; n = 1.3 for adult methemoglobin when stripped and in the presence of IHP, respectively; pK = 8.18; n = 1.11 and pK = 8.21; n = 1.28 for fetal methemoglobin when stripped and in the presence of IHP, respectively). These findings lead to the conclusion that the transition between quaternary structures in either human or fetal methemoglobins is not coupled to the switch of the spin state of the ferric heme. (author)

Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

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Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

1999-05-01

Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

Mapping directionality specific volume changes using tensor based morphometry: an application to the study of gyrogenesis and lateralization of the human fetal brain.

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Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A; Kim, Kio; Rousseau, Francois; Glenn, Orit A; Barkovich, A James; Studholme, Colin

2012-11-01

Tensor based morphometry (TBM) is a powerful approach to analyze local structural changes in brain anatomy. However, conventional scalar TBM methods do not completely capture all direction specific volume changes required to model complex changes such as those during brain growth. In this paper, we describe novel TBM descriptors for studying direction-specific changes in a subject population which can be used in conjunction with scalar TBM to analyze local patterns in directionality of volume change during brain development. We also extend the methodology to provide a new approach to mapping directional asymmetry in deformation tensors associated with the emergence of structural asymmetry in the developing brain. We illustrate the use of these methods by studying developmental patterns in the human fetal brain, in vivo. Results show that fetal brain development exhibits a distinct spatial pattern of anisotropic growth. The most significant changes in the directionality of growth occur in the cortical plate at major sulci. Our analysis also detected directional growth asymmetry in the peri-Sylvian region and the medial frontal lobe of the fetal brain. Copyright © 2012 Elsevier Inc. All rights reserved.

Liquid-Diet with Alcohol Alters Maternal, Fetal and Placental Weights and the Expression of Molecules Involved in Integrin Signaling in the Fetal Cerebral Cortex

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Ujjwal K. Rout

2010-11-01

Full Text Available Maternal alcohol consumption during pregnancy causes wide range of behavioral and structural deficits in children, commonly known as Fetal Alcohol Syndrome (FAS. Children with FAS may suffer behavioral deficits in the absence of obvious malformations. In rodents, the exposure to alcohol during gestation changes brain structures and weights of offspring. The mechanism of FAS is not completely understood. In the present study, an established rat (Long-Evans model of FAS was used. The litter size and the weights of mothers, fetuses and placentas were examined on gestation days 18 or 20. On gestation day 18, the effects of chronic alcohol on the expression levels of integrin receptor subunits, phospholipase-Cγ and N-cadherin were examined in the fetal cerebral cortices. Presence of alcohol in the liquid-diet reduced the consumption and decreased weights of mothers and fetuses but increased the placental weights. Expression levels of β1 and α3 integrin subunits and phospholipase-Cγ2 were significantly altered in the fetal cerebral cortices of mothers on alcohol containing diet. Results show that alcohol consumption during pregnancy even with protein, mineral and vitamin enriched diet may affect maternal and fetal health, and alter integrin receptor signaling pathways in the fetal cerebral cortex disturbing the development of fetal brains.

Early development of synchrony in cortical activations in the human.

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Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

2016-05-13

Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

Science.gov (United States)

Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

2009-10-01

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

Histomorphometry and cortical robusticity of the adult human femur.

Science.gov (United States)

Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

2018-01-13

Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

The complexity of the calretinin-expressing progenitors in the human cerebral cortex

Directory of Open Access Journals (Sweden)

Nevena V Radonjic

2014-08-01

Full Text Available The complex structure and function of the cerebral cortex critically depend on the balance of excitation and inhibition provided by the pyramidal projection neurons and GABAergic interneurons, respectively. The calretinin-expressing (CalR+ cell is a subtype of GABAergic cortical interneurons that is more prevalent in humans than in rodents. In rodents, CalR+ interneurons originate in the caudal ganglionic eminence (CGE from Gsx2+ progenitors, but in humans it has been suggested that a subpopulation of CalR+ cells can also be generated in the cortical ventricular/subventricular zone (VZ/SVZ. The progenitors for cortically generated CalR+ subpopulation in primates are not yet characterized. Hence, the aim of this study was to identify patterns of expression of the transcription factors (TFs that commit cortical stem cells to the CalR fate, with a focus on Gsx2. First, we studied the expression of Gsx2 and its downstream effectors, Ascl1 and Sp8 in the cortical regions of the fetal human forebrain at midgestation. Next, we established that a subpopulation of cells expressing these TFs are proliferating in the cortical SVZ, and can be co-labeled with CalR. The presence and proliferation of Gsx2+ cells, not only in the ventral telencephalon (GE as previously reported, but also in the cerebral cortex suggests cortical origin of a subpopulation of CalR+ neurons in humans. In vitro treatment of human cortical progenitors with Sonic hedgehog (Shh, an important morphogen in the specification of interneurons, decreased levels of Ascl1 and Sp8 proteins, but did not affect Gsx2 levels. Taken together, our ex-vivo and in vitro results on human fetal brain suggest complex endogenous and exogenous regulation of TFs implied in the specification of different subtypes of CalR+ cortical interneurons.

Cortical surface area and cortical thickness in the precuneus of adult humans.

Science.gov (United States)

Bruner, E; Román, F J; de la Cuétara, J M; Martin-Loeches, M; Colom, R

2015-02-12

The precuneus has received considerable attention in the last decade, because of its cognitive functions, its role as a central node of the brain networks, and its involvement in neurodegenerative processes. Paleoneurological studies suggested that form changes in the deep parietal areas represent a major character associated with the origin of the modern human brain morphology. A recent neuroanatomical survey based on shape analysis suggests that the proportions of the precuneus are also a determinant source of overall brain geometrical differences among adult individuals, influencing the brain spatial organization. Here, we evaluate the variation of cortical thickness and cortical surface area of the precuneus in a sample of adult humans, and their relation with geometry and cognition. Precuneal thickness and surface area are not correlated. There is a marked individual variation. The right precuneus is thinner and larger than the left one, but there are relevant fluctuating asymmetries, with only a modest correlation between the hemispheres. Males have a thicker cortex but differences in cortical area are not significant between sexes. The surface area of the precuneus shows a positive allometry with the brain surface area, although the correlation is modest. The dilation/contraction of the precuneus, described as a major factor of variability within adult humans, is associated with absolute increase/decrease of its surface, but not with variation in thickness. Precuneal thickness, precuneal surface area and precuneal morphology are not correlated with psychological factors such as intelligence, working memory, attention control, and processing speed, stressing further possible roles of this area in supporting default mode functions. Beyond gross morphology, the processes underlying the large phenotypic variation of the precuneus must be further investigated through specific cellular analyses, aimed at considering differences in cellular size, density

Maternal exercise, season and sex modify the human fetal circadian rhythm.

Science.gov (United States)

Sletten, Julie; Cornelissen, Germaine; Assmus, Jørg; Kiserud, Torvid; Albrechtsen, Susanne; Kessler, Jörg

2018-05-13

The knowledge on circadian rhythmicity is rapidly expanding. We aimed to define the longitudinal development of the circadian heart rate rhythm in the human fetus in an unrestricted, out-of-hospital setting, and to examine the effects of maternal physical activity, season and fetal sex. We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Circadian rhythmicity in fetal heart rate and fetal heart rate variation was detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. For the fetal heart rate and fetal heart rate variation, a significant circadian rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings, respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (prhythm diversity was found in male fetuses, during higher maternal physical activity and during the summer season. The dynamic development of the fetal circadian heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Proteolytic processing of anti-Müllerian hormone differs between human fetal testes and adult ovaries

DEFF Research Database (Denmark)

Mamsen, L S; Petersen, T S; Jeppesen, J V

2015-01-01

and specificity of a panel of five novel high-affinity AMH monoclonal antibodies. Two recognize the mature C-terminal form of AMH, whereas three recognize the active pro-mature form of AMH in human tissue. The antibodies were tested on fetal male testicular and mesonephric tissue aged 8-19 weeks post conception...... (pc), fetal male serum aged 16-26 weeks pc and human immature GCs by immunofluorescence, immunohistochemistry, ELISA and western blotting. The active pro-mature forms of AMH were expressed in both Sertoli cells from human fetal testis and human immature GCs. In contrast, the mature C-terminal form...... of AMH was hardly detected in Sertoli cells, but was readily detected in GCs. This particular form was also located to the nucleus in GCs, whereas the other investigated AMH forms remained in the cytoplasm. Interestingly, the distribution of the AMH forms in the fetal serum of boys showed...

Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

Energy Technology Data Exchange (ETDEWEB)

Muczynski, V. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Cravedi, J.P. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Lehraiki, A.; Levacher, C.; Moison, D.; Lecureuil, C.; Messiaen, S. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Perdu, E. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Frydman, R. [Service de Gynécologie-Obstétrique, Hôpital A. Béclère, Université Paris Sud F-92141 Clamart (France); Habert, R. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); and others

2012-05-15

The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

Abnormal fetal cerebral laminar organization in cobblestone complex as seen on post-mortem MRI and DTI

International Nuclear Information System (INIS)

Widjaja, Elysa; Geibprasert, Sasikhan; Blaser, Susan; Rayner, Tammy; Shannon, Patrick

2009-01-01

We report a unique case of cobblestone complex using post-mortem MR and diffusion tensor imaging to assess the laminar organization of the fetal cerebrum. The imaging findings were correlated with autopsy findings. Abnormal cortical development in cobblestone complex resulted in disruption of normal laminar organization of the fetal brain, which was seen as interruption and nodularity of the high-signal T1 cortical band with increased anisotropy and medium diffusivity extending beyond the cortical band into the cerebral mantle on post-mortem MR and diffusion tensor imaging. (orig.)

Abnormal fetal cerebral laminar organization in cobblestone complex as seen on post-mortem MRI and DTI

Energy Technology Data Exchange (ETDEWEB)

Widjaja, Elysa; Geibprasert, Sasikhan; Blaser, Susan; Rayner, Tammy [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Shannon, Patrick [University of Toronto, Department of Pathology, Mount Sinai Hospital, Toronto (Canada)

2009-08-15

We report a unique case of cobblestone complex using post-mortem MR and diffusion tensor imaging to assess the laminar organization of the fetal cerebrum. The imaging findings were correlated with autopsy findings. Abnormal cortical development in cobblestone complex resulted in disruption of normal laminar organization of the fetal brain, which was seen as interruption and nodularity of the high-signal T1 cortical band with increased anisotropy and medium diffusivity extending beyond the cortical band into the cerebral mantle on post-mortem MR and diffusion tensor imaging. (orig.)

A radiographic study of the human fetal spine

International Nuclear Information System (INIS)

Bagnall, K.M.; Harris, P.F.; Jones, P.R.M.

1979-01-01

Regression equations are presented which describe the growth in length of the various regions of the vertebral column in the human fetus. From 8 weeks on the thoracic is always the longest region and the sacral the shortest, while the lumbar region is longer than the cervical. From the regression equations predictions of fetal vertebral length can be made from fetal age: this should be useful in obstetric practice when diagnostic ultrasound techniques are being employed for the diagnosis of growth disorders and skeletal abnormalities. A different development pattern emerges when average 'vertebral units' for each region are compared. The lumbar vertebrae are always the largest with the thoracic, cervical and sacral vertebrae being progressively smaller. (author)

Syllabic discrimination in premature human infants prior to complete formation of cortical layers

OpenAIRE

Mahmoudzadeh, Mahdi; Dehaene-Lambertz, Ghislaine; Fournier, Marc; Kongolo, Guy; Goudjil, Sabrina; Dubois, Jessica; Grebe, Reinhard; Wallois, Fabrice

2013-01-01

The ontogeny of linguistic functions in the human brain remains elusive. Although some auditory capacities are described before term, whether and how such immature cortical circuits might process speech are unknown. Here we used functional optical imaging to evaluate the cerebral responses to syllables at the earliest age at which cortical responses to external stimuli can be recorded in humans (28- to 32-wk gestational age). At this age, the cortical organization in layers is not completed. ...

Cortico-Cortical Receptive Field Estimates in Human Visual Cortex

Directory of Open Access Journals (Sweden)

Koen V Haak

2012-05-01

Full Text Available Human visual cortex comprises many visual areas that contain a map of the visual field (Wandell et al 2007, Neuron 56, 366–383. These visual field maps can be identified readily in individual subjects with functional magnetic resonance imaging (fMRI during experimental sessions that last less than an hour (Wandell and Winawer 2011, Vis Res 718–737. Hence, visual field mapping with fMRI has been, and still is, a heavily used technique to examine the organisation of both normal and abnormal human visual cortex (Haak et al 2011, ACNR, 11(3, 20–21. However, visual field mapping cannot reveal every aspect of human visual cortex organisation. For example, the information processed within a visual field map arrives from somewhere and is sent to somewhere, and visual field mapping does not derive these input/output relationships. Here, we describe a new, model-based analysis for estimating the dependence between signals in distinct cortical regions using functional magnetic resonance imaging (fMRI data. Just as a stimulus-referred receptive field predicts the neural response as a function of the stimulus contrast, the neural-referred receptive field predicts the neural response as a function of responses elsewhere in the nervous system. When applied to two cortical regions, this function can be called the cortico-cortical receptive field (CCRF. We model the CCRF as a Gaussian-weighted region on the cortical surface and apply the model to data from both stimulus-driven and resting-state experimental conditions in visual cortex.

ABSORPTION-SPECTRA OF HUMAN FETAL AND ADULT OXYHEMOGLOBIN, DE-OXYHEMOGLOBIN, CARBOXYHEMOGLOBIN, AND METHEMOGLOBIN

NARCIS (Netherlands)

ZIJLSTRA, WG; MEEUWSENVANDERROEST, WP

We determined the millimolar absorptivities of the four clinically relevant derivatives of fetal and adult human hemoglobin in the visible and near-infrared spectral range (450-1000 nm). As expected, spectral absorption curves of similar shape were found, but the small differences between fetal and

Cellular and Molecular Effect of MEHP Involving LXRα in Human Fetal Testis and Ovary

OpenAIRE

Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N’Tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

2012-01-01

Background Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Methodology/Principal Findings Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10−4M...

Normal anatomy and MR findings of fetal main organs at MR imaging

International Nuclear Information System (INIS)

Xia Liming; Zou Mingli; Feng Dingyi; Hu Junwu; Qi Jianpin; Wang Chengyuan

2005-01-01

Objective: To investigate normal anatomy and MR findings of fetal main organs. Methods: Forty-seven fetus underwented fast MR imaging, SSFSE sequence was used, the normal anatomy and MR findings of fetal main organs was observed in different gestational age. The organs included: brain, lungs, heart, liver, spleen, gastrointestinal tract, urinary collecting systems, bladder, bones, spine, and subcutaneous fat. Results: Results of MR in 47 fetus showed that the main organs had developed by 20-week-old fetus, about 20 weeks gestation, cerebral cortical surface was smooth, no cortical gyri and sulci, then cortical gyri and sulci developed slowly. The lungs, trachea, bronchus, gastrointestinal tract, renal collecting system and bladder showed high signal intensity; the heart, great vessels, liver, spleen, bones and muscles appeared hypointense; the kidneys appeared isointense, the spine had developed and subcutaneous fat was seen in 20-week-old fetus, the subcutaneous fat increased with fetus maturating. Conclusion: Normal anatomy and MR findings of fetal main organs were clearly showed by fast MR imaging, and they are different from the newborns. (authors)

Altered Decorin and Smad Expression in Human Fetal Membranes in PPROM1

Science.gov (United States)

Horgan, Casie E.; Roumimper, Hailey; Tucker, Richard; Lechner, Beatrice E.

2014-01-01

ABSTRACT Humans with Ehlers-Danlos syndrome, a subtype of which is caused by abnormal decorin expression, are at increased risk of preterm birth due to preterm premature rupture of fetal membranes (PPROM). In the mouse model, the absence of decorin leads to fetal membrane abnormalities, preterm birth, and dysregulation of decorin's downstream pathway components, including the transcription factor p-Smad-2. However, the role of decorin and p-Smad-2 in idiopathic human PPROM is unknown. Fetal membranes from 20–25 pregnancies per group were obtained as a cross-sectional sample of births at one institution between January 2010 and December 2012. The groups were term, preterm without PPROM, and preterm with PPROM. Immunohistochemical analysis of fetal membranes was performed for decorin and p-Smad-2 using localization and quantification assessment. Decorin expression is developmentally regulated in fetal membranes and is decreased in preterm birth with PPROM compared to preterm birth without PPROM. In preterm with PPROM samples, the presence of infection is associated with significant decorin downregulation compared to preterm with PPROM samples without infection. The preterm with PPROM group exhibited decreased p-Smad-2 staining compared to both the term controls and the preterm-without-PPROM group. Our findings suggest that dysregulation of decorin and its downstream pathway component p-Smad-2 occurs in fetal membranes during the second trimester in pathological pregnancies, thus supporting a role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes. These findings may lead to the discovery of new targets for the diagnosis and treatment of PPROM. PMID:25232019

High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain.

Science.gov (United States)

Zhou, Ting; Tan, Lei; Cederquist, Gustav Y; Fan, Yujie; Hartley, Brigham J; Mukherjee, Suranjit; Tomishima, Mark; Brennand, Kristen J; Zhang, Qisheng; Schwartz, Robert E; Evans, Todd; Studer, Lorenz; Chen, Shuibing

2017-08-03

Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus1

Science.gov (United States)

Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A.; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M.; Sandman, Curt A.

2009-01-01

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks’ GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks’ GA, females however, presented with a mature FHR startle response by 31 weeks’ GA. The results indicate that there are different rates of maturation in the male and female fetus that may have implications for sex-specific programming influences. PMID:19726143

Chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch

International Nuclear Information System (INIS)

Melis, M.; Demopulos, G.; Najfeld, V.; Zhang, J.W.; Brice, M.; Papayannopoulou, T.; Stamatoyannopoulos, G.

1987-01-01

Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control γ-to-β switching, the authors analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome -- i.e., chromosome 11 -- is sufficient for expression of human fetal globin and the subsequent γ-to-β switch. The results suggest that the γ-to-β switch is controlled either cis to the β-globin locus of by a trans-acting mechanism, the genes of which reside on human chromosome 11

Expanding the spectrum of human ganglionic eminence region anomalies on fetal magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Righini, Andrea; Parazzini, Cecilia; Izzo, Giana [Children' s Hospital ' ' V. Buzzi' ' , Department of Radiology and Neuroradiology, Milan (Italy); Cesaretti, Claudia [Children' s Hospital ' ' V. Buzzi' ' , Department of Radiology and Neuroradiology, Milan (Italy); Ospedale Maggiore Policlinico, Medical Genetics Unit, Fondazione I.R.C.C.S. Ca' Granda, Milan (Italy); Conte, Giorgio [Children' s Hospital ' ' V. Buzzi' ' , Department of Radiology and Neuroradiology, Milan (Italy); University of Milan, Department of Health Sciences, Milan (Italy); Frassoni, Carolina; Inverardi, Francesca [Fondazione I.R.C.C.S. Istituto Neurologico ' ' C. Besta' ' , Clinical Epileptology and Experimental Neurophysiology Unit, Milan (Italy); Bulfamante, Gaetano; Avagliano, Laura [San Paolo Hospital, Division of Human Pathology, Milan (Italy); Rustico, Mariangela [Children' s Hospital ' ' V. Buzzi' ' , Department of Obstetrics and Gynaecology, Prenatal Diagnosis, Milan (Italy)

2016-03-15

Ganglionic eminence (GE) is a transient fetal brain structure that harvests a significant amount of precursors of cortical GABA-ergic interneurons. Prenatal magnetic resonance (MR) imaging features of GE anomalies (i.e., cavitations) have already been reported associated with severe micro-lissencephaly. The purpose of this report was to illustrate the MR imaging features of GE anomalies in conditions other than severe micro-lissencephalies. Among all the fetuses submitted to prenatal MR imaging at our center from 2005 to 2014, we collected eight cases with GE anomalies and only limited associated brain anomalies. The median gestational age at the time of MR imaging was 21 weeks ranging from 19 to 29 weeks. Two senior pediatric neuroradiologists categorized the anomalies of the GE region in two groups: group one showing cavitation in the GE region and group two showing enlarged GE region. For each fetal case, associated cranial anomalies were also reported. Five out of the eight cases were included in group one and three in group two. Besides the GE region abnormality, all eight cases had additional intracranial anomalies, such as mild partial callosal agenesis, vermian hypoplasia and rotation, cerebellar hypoplasia, ventriculomegaly, enlarged subarachnoid spaces, molar tooth malformation. Ultrasound generally detected most of the associated intracranial anomalies, prompting the MR investigation; on the contrary in none of the cases, GE anomalies had been detected by ultrasound. Our observation expands the spectrum of human GE anomalies, demonstrating that these may take place also without associated severe micro-lissencephalies. (orig.)

Expanding the spectrum of human ganglionic eminence region anomalies on fetal magnetic resonance imaging

International Nuclear Information System (INIS)

Righini, Andrea; Parazzini, Cecilia; Izzo, Giana; Cesaretti, Claudia; Conte, Giorgio; Frassoni, Carolina; Inverardi, Francesca; Bulfamante, Gaetano; Avagliano, Laura; Rustico, Mariangela

2016-01-01

Ganglionic eminence (GE) is a transient fetal brain structure that harvests a significant amount of precursors of cortical GABA-ergic interneurons. Prenatal magnetic resonance (MR) imaging features of GE anomalies (i.e., cavitations) have already been reported associated with severe micro-lissencephaly. The purpose of this report was to illustrate the MR imaging features of GE anomalies in conditions other than severe micro-lissencephalies. Among all the fetuses submitted to prenatal MR imaging at our center from 2005 to 2014, we collected eight cases with GE anomalies and only limited associated brain anomalies. The median gestational age at the time of MR imaging was 21 weeks ranging from 19 to 29 weeks. Two senior pediatric neuroradiologists categorized the anomalies of the GE region in two groups: group one showing cavitation in the GE region and group two showing enlarged GE region. For each fetal case, associated cranial anomalies were also reported. Five out of the eight cases were included in group one and three in group two. Besides the GE region abnormality, all eight cases had additional intracranial anomalies, such as mild partial callosal agenesis, vermian hypoplasia and rotation, cerebellar hypoplasia, ventriculomegaly, enlarged subarachnoid spaces, molar tooth malformation. Ultrasound generally detected most of the associated intracranial anomalies, prompting the MR investigation; on the contrary in none of the cases, GE anomalies had been detected by ultrasound. Our observation expands the spectrum of human GE anomalies, demonstrating that these may take place also without associated severe micro-lissencephalies. (orig.)

IL-27 induces a pro-inflammatory response in human fetal membranes mediating preterm birth.

Science.gov (United States)

Yin, Nanlin; Wang, Hanbing; Zhang, Hua; Ge, Huisheng; Tan, Bing; Yuan, Yu; Luo, Xiaofang; Olson, David M; Baker, Philip N; Qi, Hongbo

2017-09-01

Inflammation at the maternal-fetal interface has been shown to be involved in the pathogenesis of preterm birth. Interleukin 27 (IL-27), a heterodimeric cytokine, is known to mediate an inflammatory response in some pregnancy complications. In this study, we aimed to determine whether IL-27 could induce an inflammatory reaction at the maternal-fetal interface that would mediate the onset of preterm birth. We found elevated expression of IL-27 in human peripheral serum and elevated expression of its specific receptor (wsx-1) on fetal membranes in cases of preterm birth. Moreover, the release of inflammatory markers (CXCL10, IFN-γ, MCP-1, IL-6, IL-1β and TNF-α), especially CXCL10, was markedly augmented upon stimulation of IL-27 in the fetal membranes. Additionally, IL-27 and IFN-γ cooperated to amplify the expression of CXCL10 in the fetal membranes. Moreover, the production of CXCL10 was increased in IL-27-treated fetal membrane through JNK, PI3K or Erk signaling pathways. Finally, MMP2 and MMP9 were activated by IL-27 in human fetal membranes, which may be related to the onset of preterm premature rupture of membranes (pPROM). In conclusion, for the first time, we reported that the aberrant expression of IL-27 could mediate an excessive inflammatory response in fetal membranes through the JNK, PI3K or Erk signaling pathways, which contributes to preterm birth. Copyright © 2017 Elsevier B.V. All rights reserved.

Prediction for human intelligence using morphometric characteristics of cortical surface: partial least square analysis.

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Yang, J-J; Yoon, U; Yun, H J; Im, K; Choi, Y Y; Lee, K H; Park, H; Hough, M G; Lee, J-M

2013-08-29

A number of imaging studies have reported neuroanatomical correlates of human intelligence with various morphological characteristics of the cerebral cortex. However, it is not yet clear whether these morphological properties of the cerebral cortex account for human intelligence. We assumed that the complex structure of the cerebral cortex could be explained effectively considering cortical thickness, surface area, sulcal depth and absolute mean curvature together. In 78 young healthy adults (age range: 17-27, male/female: 39/39), we used the full-scale intelligence quotient (FSIQ) and the cortical measurements calculated in native space from each subject to determine how much combining various cortical measures explained human intelligence. Since each cortical measure is thought to be not independent but highly inter-related, we applied partial least square (PLS) regression, which is one of the most promising multivariate analysis approaches, to overcome multicollinearity among cortical measures. Our results showed that 30% of FSIQ was explained by the first latent variable extracted from PLS regression analysis. Although it is difficult to relate the first derived latent variable with specific anatomy, we found that cortical thickness measures had a substantial impact on the PLS model supporting the most significant factor accounting for FSIQ. Our results presented here strongly suggest that the new predictor combining different morphometric properties of complex cortical structure is well suited for predicting human intelligence. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Dynamic expression of calretinin in embryonic and early fetal human cortex

Directory of Open Access Journals (Sweden)

Miriam eGonzalez-Gomez

2014-06-01

Full Text Available Calretinin (CR is one of the earliest neurochemical markers in human corticogenesis. In embryos from Carnegie stages (CS 17 to 23, calbindin (CB and CR stain opposite poles of the incipient cortex suggesting early regionalization: CB marks the neuroepithelium of the medial boundary of the cortex with the choroid plexus (cortical hem. By contrast, CR is confined to the subventricular zone (SVZ of the lateral and caudal ganglionic eminences at the pallial-subpallial boundary (PSB, or antihem, from where CR+/Tbr1- neurons migrate toward piriform cortex and amygdala as a component of the lateral cortical stream. At CS 19, columns of CR+ cells arise in the rostral cortex, and contribute at CS 20 to the monolayer of horizontal Tbr1+/CR+ and GAD+ cells in the preplate. At CS 21, the pioneer cortical plate appears as a radial aggregation of CR+/Tbr1+ neurons, which cover the entire future neocortex and extend the first corticofugal axons. CR expression in early human corticogenesis is thus not restricted to interneurons, but is also present in the first excitatory projection neurons of the cortex. At CS 21/22, the cortical plate is established following a lateral to medial gradient, when Tbr1+/CR- neurons settle within the pioneer cortical plate, and thus separate superficial and deep pioneer neurons. CR+ pioneer neurons disappear shortly after the formation of the cortical plate. Reelin+ Cajal-Retzius cells begin to express CR around CS21 (7/8 PCW. At CS 21-23, the CR+ SVZ at the PSB is the source of CR+ interneurons migrating into the cortical SVZ. In turn, CB+ interneurons migrate from the subpallium into the intermediate zone following the fibers of the internal capsule. Early CR+ and CB+ interneurons thus have different origins and migratory routes. CR+ cell populations in the embryonic telencephalon take part in a complex sequence of events not analyzed so far in other mammalian species, which may represent a distinctive trait of the initial steps

Probing region-specific microstructure of human cortical areas using high angular and spatial resolution diffusion MRI.

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Aggarwal, Manisha; Nauen, David W; Troncoso, Juan C; Mori, Susumu

2015-01-15

Regional heterogeneity in cortical cyto- and myeloarchitecture forms the structural basis of mapping of cortical areas in the human brain. In this study, we investigate the potential of diffusion MRI to probe the microstructure of cortical gray matter and its region-specific heterogeneity across cortical areas in the fixed human brain. High angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 92-μm and 30 diffusion-encoding directions were acquired using a 3D diffusion-weighted gradient-and-spin-echo sequence, from prefrontal (Brodmann area 9), primary motor (area 4), primary somatosensory (area 3b), and primary visual (area 17) cortical specimens (n=3 each) from three human subjects. Further, the diffusion MR findings in these cortical areas were compared with histological silver impregnation of the same specimens, in order to investigate the underlying architectonic features that constitute the microstructural basis of diffusion-driven contrasts in cortical gray matter. Our data reveal distinct and region-specific diffusion MR contrasts across the studied areas, allowing delineation of intracortical bands of tangential fibers in specific layers-layer I, layer VI, and the inner and outer bands of Baillarger. The findings of this work demonstrate unique sensitivity of diffusion MRI to differentiate region-specific cortical microstructure in the human brain, and will be useful for myeloarchitectonic mapping of cortical areas as well as to achieve an understanding of the basis of diffusion NMR contrasts in cortical gray matter. Copyright © 2014 Elsevier Inc. All rights reserved.

Fetal magnetic resonance imaging and human genetics

International Nuclear Information System (INIS)

Hengstschlaeger, Markus

2006-01-01

The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data

Fetal magnetic resonance imaging and human genetics

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Hengstschlaeger, Markus [Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)]. E-mail: markus.hengstschlaeger@meduniwien.ac.at

2006-02-15

The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data.

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

Science.gov (United States)

Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

2015-01-01

Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

BMP signaling in the human fetal ovary is developmentally regulated and promotes primordial germ cell apoptosis.

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Childs, Andrew J; Kinnell, Hazel L; Collins, Craig S; Hogg, Kirsten; Bayne, Rosemary A L; Green, Samira J; McNeilly, Alan S; Anderson, Richard A

2010-08-01

Primordial germ cells (PGCs) are the embryonic precursors of gametes in the adult organism, and their development, differentiation, and survival are regulated by a combination of growth factors collectively known as the germ cell niche. Although many candidate niche components have been identified through studies on mouse PGCs, the growth factor composition of the human PGC niche has not been studied extensively. Here we report a detailed analysis of the expression of components of the bone morphogenetic protein (BMP) signaling apparatus in the human fetal ovary, from postmigratory PGC proliferation to the onset of primordial follicle formation. We find developmentally regulated and reciprocal patterns of expression of BMP2 and BMP4 and identify germ cells to be the exclusive targets of ovarian BMP signaling. By establishing long-term cultures of human fetal ovaries in which PGCs are retained within their physiological niche, we find that BMP4 negatively regulates postmigratory PGC numbers in the human fetal ovary by promoting PGC apoptosis. Finally, we report expression of both muscle segment homeobox (MSX)1 and MSX2 in the human fetal ovary and reveal a selective upregulation of MSX2 expression in human fetal ovary in response to BMP4, suggesting this gene may act as a downstream effector of BMP-induced apoptosis in the ovary, as in other systems. These data reveal for the first time growth factor regulation of human PGC development in a physiologically relevant context and have significant implications for the development of cultures systems for the in vitro maturation of germ cells, and their derivation from pluripotent stem cells.

Interactions between thalamic and cortical rhythms during semantic memory recall in human

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Slotnick, Scott D.; Moo, Lauren R.; Kraut, Michael A.; Lesser, Ronald P.; Hart, John, Jr.

2002-04-01

Human scalp electroencephalographic rhythms, indicative of cortical population synchrony, have long been posited to reflect cognitive processing. Although numerous studies employing simultaneous thalamic and cortical electrode recording in nonhuman animals have explored the role of the thalamus in the modulation of cortical rhythms, direct evidence for thalamocortical modulation in human has not, to our knowledge, been obtained. We simultaneously recorded from thalamic and scalp electrodes in one human during performance of a cognitive task and found a spatially widespread, phase-locked, low-frequency rhythm (7-8 Hz) power decrease at thalamus and scalp during semantic memory recall. This low-frequency rhythm power decrease was followed by a spatially specific, phase-locked, fast-rhythm (21-34 Hz) power increase at thalamus and occipital scalp. Such a pattern of thalamocortical activity reflects a plausible neural mechanism underlying semantic memory recall that may underlie other cognitive processes as well.

Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

Science.gov (United States)

Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2016-08-01

Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Higher cortical modulation of pain perception in the human brain: Psychological determinant.

Science.gov (United States)

Chen, Andrew Cn

2009-10-01

Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.

Comparison of the biological features between human fetal hepatocyte and immortalized L-02 hepatocyte in vitro

International Nuclear Information System (INIS)

Kong Weiwei; Teng Gaojun

2004-01-01

Objective: To evaluate the feasibilities of the potential donors in liver cell transplantation using the human fetal hepatocytes and immortalized L-02 hepatocytes by comparing their biological features. Methods: Human fetal hepatocytes were isolated from aborted fetal livers (gestational ages from 14 w to 24 w) by an improved two-stage perfusion method and cultured in a conditioned medium without any growth factors. α-fetal protein (AFP) and albumin (ALB) were detected by radioimmunoassay (RIA) and cytokeratin-19 (CK-19 ) was identified by cellular immunochemistry study. Immortalized L-02 hepatocytes were cultured in the same condition and the characteristic proteins were detected by the same methods. Results: The viability of human fetal hepatocytes was approximately 95% using the perfusion method, and the maximum survival time of the cultured hepatocytes was 3 weeks. The expression of AFP, ALB, and CK19 was detected at the same time, especially during Day 3 to Day 7 in the culture. By comparison, the proliferation ability of L-02 hepatocyte was greater, although with a lower level of ALB secretion. The expression of AFP and CK19 was not detected. Furthermore, during the long culture, L-02 hepatocytes may undergo a morphologic change and fail to express ALB. Conclusion: Human fetal hepatocyte may be a practical donor for hepatocyte transplantation with its high-level protein expression and potential bi-differentiation ability. In view of the absent expression of ALB and the morphologic change in culture, although with better proliferation, L-02 hepatocyte seems not useful for hepatocyte transplantation

Immortalization of Human Fetal Hepatocyte by Ectopic Expression of Human Telomerase Reverse Transcriptase, Human Papilloma Virus (E7) and Simian Virus 40 Large T (SV40 T) Antigen Towards Bioartificial Liver Support.

Science.gov (United States)

Giri, Shibashish; Bader, Augustinus

2014-09-01

Generation of genetically stable and non-tumoric immortalization cell line from primary cells would be enormously useful for research and therapeutic purposes, but progress towards this goal has so far been limited. It is now universal acceptance that immortalization of human fetal hepatocytes based on recent advances of telomerase biology and oncogene, lead to unlimited population doubling could be the possible source for bioartificial liver device. Immortalization of human fetal hepatocytes cell line by ectopic expression of human telomerase reverse transcriptase (hTERT), human papilloma virus gene (E7) and simian virus 40 large T (SV40 T) antigens is main goal of present study. We used an inducible system containing human telomerase and E7, both of which are cloned into responder constructs controlled by doxycycline transactivator. We characterized the immortalized human fetal hepatocyte cells by analysis of green fluorescent cells (GFP) positive cells using flow cytometry (FACs) cell sorting and morphology, proliferative rate and antigen expression by immunohistochemical analysis. In addition to we analysized lactate formation, glucose consumption, albumin secretion and urea production of immortalized human fetal hepatocyte cells. After 25 attempts for transfection of adult primary hepatocytes by human telomerase and E7 to immortalize them, none of the transfection systems resulted in the production of a stable, proliferating cell line. Although the transfection efficiency was more than 70% on the first day, the vast majority of the transfected hepatocytes lost their signal within the first 5-7 days. The remaining transfected hepatocytes persisted for 2-4 weeks and divided one or two times without forming a clone. After 10 attempts of transfection human fetal hepatocytes using the same transfection system, we obtained one stable human fetal hepatocytes cell line which was able albumin secretion urea production and glucose consumption. We established a

K -shell decomposition reveals hierarchical cortical organization of the human brain

International Nuclear Information System (INIS)

Lahav, Nir; Ksherim, Baruch; Havlin, Shlomo; Ben-Simon, Eti; Maron-Katz, Adi; Cohen, Reuven

2016-01-01

In recent years numerous attempts to understand the human brain were undertaken from a network point of view. A network framework takes into account the relationships between the different parts of the system and enables to examine how global and complex functions might emerge from network topology. Previous work revealed that the human brain features ‘small world’ characteristics and that cortical hubs tend to interconnect among themselves. However, in order to fully understand the topological structure of hubs, and how their profile reflect the brain’s global functional organization, one needs to go beyond the properties of a specific hub and examine the various structural layers that make up the network. To address this topic further, we applied an analysis known in statistical physics and network theory as k-shell decomposition analysis. The analysis was applied on a human cortical network, derived from MRI/DSI data of six participants. Such analysis enables us to portray a detailed account of cortical connectivity focusing on different neighborhoods of inter-connected layers across the cortex. Our findings reveal that the human cortex is highly connected and efficient, and unlike the internet network contains no isolated nodes. The cortical network is comprised of a nucleus alongside shells of increasing connectivity that formed one connected giant component, revealing the human brain’s global functional organization. All these components were further categorized into three hierarchies in accordance with their connectivity profile, with each hierarchy reflecting different functional roles. Such a model may explain an efficient flow of information from the lowest hierarchy to the highest one, with each step enabling increased data integration. At the top, the highest hierarchy (the nucleus) serves as a global interconnected collective and demonstrates high correlation with consciousness related regions, suggesting that the nucleus might serve as a

Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues

International Nuclear Information System (INIS)

Prody, C.A.; Zevin-Sonkin, D.; Gnatt, A.; Goldberg, O.; Soreq, H.

1987-01-01

To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase and Torpedo electric organ true acetylcholinesterase. Using these probes, the authors isolated several cDNA clones from λgt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A) + RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These finding demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species

Fetal abdominal magnetic resonance imaging

International Nuclear Information System (INIS)

Brugger, Peter C.; Prayer, Daniela

2006-01-01

This review deals with the in vivo magnetic resonance imaging (MRI) appearance of the human fetal abdomen. Imaging findings are correlated with current knowledge of human fetal anatomy and physiology, which are crucial to understand and interpret fetal abdominal MRI scans. As fetal MRI covers a period of more than 20 weeks, which is characterized not only by organ growth, but also by changes and maturation of organ function, a different MR appearance of the fetal abdomen results. This not only applies to the fetal intestines, but also to the fetal liver, spleen, and adrenal glands. Choosing the appropriate sequences, various aspects of age-related and organ-specific function can be visualized with fetal MRI, as these are mirrored by changes in signal intensities. Knowledge of normal development is essential to delineate normal from pathological findings in the respective developmental stages

Fetal abdominal magnetic resonance imaging

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Brugger, Peter C. [Center of Anatomy and Cell Biology, Integrative Morphology Group, Medical University of Vienna, Waehringerstrasse 13, 1090 Vienna (Austria)]. E-mail: peter.brugger@meduniwien.ac.at; Prayer, Daniela [Department of Radiology, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna (Austria)

2006-02-15

This review deals with the in vivo magnetic resonance imaging (MRI) appearance of the human fetal abdomen. Imaging findings are correlated with current knowledge of human fetal anatomy and physiology, which are crucial to understand and interpret fetal abdominal MRI scans. As fetal MRI covers a period of more than 20 weeks, which is characterized not only by organ growth, but also by changes and maturation of organ function, a different MR appearance of the fetal abdomen results. This not only applies to the fetal intestines, but also to the fetal liver, spleen, and adrenal glands. Choosing the appropriate sequences, various aspects of age-related and organ-specific function can be visualized with fetal MRI, as these are mirrored by changes in signal intensities. Knowledge of normal development is essential to delineate normal from pathological findings in the respective developmental stages.

Human oocyte cryopreservation and the fate of cortical granules.

Science.gov (United States)

Ghetler, Yehudith; Skutelsky, Ehud; Ben Nun, Isaac; Ben Dor, Liah; Amihai, Dina; Shalgi, Ruth

2006-07-01

To examine the effect of the commonly used oocyte cryopreservation protocol on the cortical granules (CGs) of human immature germinal vesicle (GV) and mature metaphase II (MII) oocytes. Laboratory study. IVF unit. Unfertilized, intracytoplasmic sperm injected (ICSI) oocytes, and immature oocytes were cryopreserved using a slow freezing-rapid thawing program with 1,2-propanediol (PROH) as a cryoprotectant. Cortical granule exocytosis (CGE) was assessed by either confocal microscopy or transmission electron microscopy (TEM). The survival rates of frozen-thawed oocytes (mature and immature) were significantly lower compared with zygotes. Both mature and immature oocytes exhibited increased fluorescence after cryopreservation, indicating the occurrence of CGE. Mere exposure of oocytes to cryoprotectants induced CGE of 70% the value of control zygotes. The TEM revealed a drastic reduction in the amount of CGs at the cortex of frozen-thawed GV and MII oocytes, as well as appearance of vesicles in the ooplasm. The commonly used PROH freezing protocol for human oocytes resulted in extensive CGE. This finding explains why ICSI is needed to achieve fertilization of frozen-thawed human oocytes.

Spatiotemporal distribution of PAX6 and MEIS2 expression and total cell numbers in the ganglionic eminence in the early developing human forebrain

DEFF Research Database (Denmark)

Larsen, Karen B; Lutterodt, Melissa C; Laursen, Henning

2010-01-01

The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in nuclei of radial glia cells in the neocortical proliferative...... in the same time window. We demonstrate by in situ hybridization and immunohistochemistry that the two homeobox genes are expressed during early fetal brain development in humans. PAX6 mRNA and protein were located in the proliferative zones of the neocortex and in single cells in the cortical preplate at 7...... in the proliferative zones of the human fetal neocortex and a higher expression of MEIS2 than PAX6 was observed in these areas at 9 fetal weeks. Further, MEIS2 was expressed at a very high level in the developing ganglionic eminence and at a more moderate level in the cortical plate....

Recording human cortical population spikes non-invasively--An EEG tutorial.

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Waterstraat, Gunnar; Fedele, Tommaso; Burghoff, Martin; Scheer, Hans-Jürgen; Curio, Gabriel

2015-07-30

Non-invasively recorded somatosensory high-frequency oscillations (sHFOs) evoked by electric nerve stimulation are markers of human cortical population spikes. Previously, their analysis was based on massive averaging of EEG responses. Advanced neurotechnology and optimized off-line analysis can enhance the signal-to-noise ratio of sHFOs, eventually enabling single-trial analysis. The rationale for developing dedicated low-noise EEG technology for sHFOs is unfolded. Detailed recording procedures and tailored analysis principles are explained step-by-step. Source codes in Matlab and Python are provided as supplementary material online. Combining synergistic hardware and analysis improvements, evoked sHFOs at around 600 Hz ('σ-bursts') can be studied in single-trials. Additionally, optimized spatial filters increase the signal-to-noise ratio of components at about 1 kHz ('κ-bursts') enabling their detection in non-invasive surface EEG. sHFOs offer a unique possibility to record evoked human cortical population spikes non-invasively. The experimental approaches and algorithms presented here enable also non-specialized EEG laboratories to combine measurements of conventional low-frequency EEG with the analysis of concomitant cortical population spike responses. Copyright © 2014 Elsevier B.V. All rights reserved.

DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light

International Nuclear Information System (INIS)

Ben-Ishai, R.; Sharon, R.; Rothman, M.; Miskin, R.

1984-01-01

We have tested human fetal fibroblasts for development associated changes in DNA repair by utilizing nucleoid sedimentation as an assay for excision repair. Among skin fibroblasts the rate of excision repair was significantly higher in non-fetal cells than in fibroblasts derived from an 8 week fetus; this was evident by a delay in both the relaxation and the restoration of DNA supercoiling in nucleoids after irradiation. Skin fibroblasts derived at 12 week gestation were more repair proficient than those derived at 8 week gestation. However, they exhibited a somewhat lower rate of repair than non-fetal cells. The same fetal and non-fetal cells were also tested for induction of the protease plasminogen activator (PA) after u.v. irradiation. Enhancement of PA was higher in skin fibroblasts derived at 8 week than in those derived at 12 week gestation and was absent in non-fetal skin fibroblasts. These results are consistent with our previous findings that in human cells u.v. light-induced PA synthesis is correlated with reduced DNA repair capacity. Excision repair and PA inducibility were found to depend on tissue of origin in addition to gestational stage, as shown for skin and lung fibroblasts from the same 12 week fetus. Lung compared to skin fibroblasts exhibited lower repair rates and produced higher levels of PA after irradiation. The sedimentation velocity of nucleoids, prepared from unirradiated fibroblasts, in neutral sucrose gradients with or without ethidium bromide, indicated the presence of DNA strand breaks in fetal cells. It is proposed that reduced DNA repair in fetal cells may result from alterations in DNA supercoiling, and that persistent DNA strand breaks enhance transcription of PA gene(s)

Fetal MRI and ultrasound of congenital CNS anomalies

International Nuclear Information System (INIS)

Pogledic, I.; Reith, W.; Meyberg-Solomayer, G.

2013-01-01

In the last decade the newest technologies, fetal magnetic resonance imaging (MRI) and 3D ultrasound, have given an insight into the minute structures of the fetal brain. However, without knowledge of the basic developmental processes the imaging is futile. Knowledge of fetal neuroanatomy corresponding to the gestational week is necessary in order to recognize pathological structures. Furthermore, a modern neuroradiologist should be acquainted with the three steps in the formation of the cerebral cortex: proliferation, migration and differentiation of neurons in order to be in a position to suspect that there is a pathology and start recognizing and discovering the abnormalities. The fetal MRI has become an important complementary method to ultrasound especially in cortical malformations when confirmation of the prenatal diagnosis is needed and additional pathologies need to be diagnosed. In this manner these two methods help in parental counseling and treatment planning. (orig.) [de

Recent advances in the prenatal interrogation of the human fetal genome.

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Hui, Lisa; Bianchi, Diana W

2013-02-01

The amount of genetic and genomic information obtainable from the human fetus during pregnancy is accelerating at an unprecedented rate. Two themes have dominated recent technological advances in prenatal diagnosis: interrogation of the fetal genome in increasingly high resolution and the development of non-invasive methods of fetal testing using cell-free DNA in maternal plasma. These two areas of advancement have now converged with several recent reports of non-invasive assessment of the entire fetal genome from maternal blood. However, technological progress is outpacing the ability of the healthcare providers and patients to incorporate these new tests into existing clinical care, and further complicates many of the economic and ethical dilemmas in prenatal diagnosis. This review summarizes recent work in this field and discusses the integration of these new technologies into the clinic and society. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mapping human brain networks with cortico-cortical evoked potentials

Science.gov (United States)

Keller, Corey J.; Honey, Christopher J.; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D.

2014-01-01

The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. PMID:25180306

Nonlinear dynamics of cortical responses to color in the human cVEP.

Science.gov (United States)

Nunez, Valerie; Shapley, Robert M; Gordon, James

2017-09-01

The main finding of this paper is that the human visual cortex responds in a very nonlinear manner to the color contrast of pure color patterns. We examined human cortical responses to color checkerboard patterns at many color contrasts, measuring the chromatic visual evoked potential (cVEP) with a dense electrode array. Cortical topography of the cVEPs showed that they were localized near the posterior electrode at position Oz, indicating that the primary cortex (V1) was the major source of responses. The choice of fine spatial patterns as stimuli caused the cVEP response to be driven by double-opponent neurons in V1. The cVEP waveform revealed nonlinear color signal processing in the V1 cortex. The cVEP time-to-peak decreased and the waveform's shape was markedly narrower with increasing cone contrast. Comparison of the linear dynamics of retinal and lateral geniculate nucleus responses with the nonlinear dynamics of the cortical cVEP indicated that the nonlinear dynamics originated in the V1 cortex. The nature of the nonlinearity is a kind of automatic gain control that adjusts cortical dynamics to be faster when color contrast is greater.

Cortical Network Dynamics of Perceptual Decision-Making in the Human Brain

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Markus eSiegel

2011-02-01

Full Text Available Goal-directed behavior requires the flexible transformation of sensory evidence about our environment into motor actions. Studies of perceptual decision-making have shown that this transformation is distributed across several widely separated brain regions. Yet, little is known about how decision-making emerges from the dynamic interactions among these regions. Here, we review a series of studies, in which we characterized the cortical network interactions underlying a perceptual decision process in the human brain. We used magnetoencephalography (MEG to measure the large-scale cortical population dynamics underlying each of the sub-processes involved in this decision: the encoding of sensory evidence and action plan, the mapping between the two, and the attentional selection of task-relevant evidence. We found that these sub-processes are mediated by neuronal oscillations within specific frequency ranges. Localized gamma-band oscillations in sensory and motor cortices reflect the encoding of the sensory evidence and motor plan. Large-scale oscillations across widespread cortical networks mediate the integrative processes connecting these local networks: Gamma- and beta-band oscillations across frontal, parietal and sensory cortices serve the selection of relevant sensory evidence and its flexible mapping onto action plans. In sum, our results suggest that perceptual decisions are mediated by oscillatory interactions within overlapping local and large-scale cortical networks.

Human cortical areas involved in perception of surface glossiness.

Science.gov (United States)

Wada, Atsushi; Sakano, Yuichi; Ando, Hiroshi

2014-09-01

Glossiness is the visual appearance of an object's surface as defined by its surface reflectance properties. Despite its ecological importance, little is known about the neural substrates underlying its perception. In this study, we performed the first human neuroimaging experiments that directly investigated where the processing of glossiness resides in the visual cortex. First, we investigated the cortical regions that were more activated by observing high glossiness compared with low glossiness, where the effects of simple luminance and luminance contrast were dissociated by controlling the illumination conditions (Experiment 1). As cortical regions that may be related to the processing of glossiness, V2, V3, hV4, VO-1, VO-2, collateral sulcus (CoS), LO-1, and V3A/B were identified, which also showed significant correlation with the perceived level of glossiness. This result is consistent with the recent monkey studies that identified selective neural response to glossiness in the ventral visual pathway, except for V3A/B in the dorsal visual pathway, whose involvement in the processing of glossiness could be specific to the human visual system. Second, we investigated the cortical regions that were modulated by selective attention to glossiness (Experiment 2). The visual areas that showed higher activation to attention to glossiness than that to either form or orientation were identified as right hV4, right VO-2, and right V3A/B, which were commonly identified in Experiment 1. The results indicate that these commonly identified visual areas in the human visual cortex may play important roles in glossiness perception. Copyright © 2014. Published by Elsevier Inc.

3H-cyclosporine internalization and secretion by human fetal pancreatic islets

International Nuclear Information System (INIS)

Formby, B.; Walker, L.; Peterson, C.M.

1988-01-01

Human fetal pancreatic islets were isolated from 16- to 20-week-old fetuses by a collagenase technique and cultured 48 hr in RPMI 1640 containing 10% human adult serum and unlabeled 0 to 5 micrograms cyclosporine A (CsA)/ml. Insulin secretory capacity of human fetal islets was expressed as a fractional stimulatory ratio FSR = F2/F1 of the fractional secretion rates during two successive 1 hr static incubations first with 2 mM glucose (F1) to stabilize secretion followed by maximal stimulus, i.e., 25 mM glucose plus 10 mM L-leucine and 10 mM L-arginine (F2). Unlabeled CsA at the above concentrations had no significant effects on the insulin secretory capacity expressed by FSR-values. Studies of net uptake of 3H-CsA by islets cultured for varying periods up to 40 hr and expressed as picomole 3H-CsA per picomole islet insulin content demonstrated that uptake rate was slow and did not reach isotopic equilibrium over the 40 hr of culture. When isolated fetal islets were cultured for 48 hr in the presence of 3H-CsA and varying concentrations of unlabeled CsA it was found during two successive 1 hr static incubations that fetal islets secrete insulin concomitantly with 3H-CsA following maximal stimulus for secretion. An optimal secretory molar ratio of 3H-CsA to insulin of 4.0 +/- 1.3 (n = 7) was found after islets were cultured 48 hr in the presence of a saturating 2.128 micrograms 3H-CsA per milliliter culture medium. In three successive 30-min static incubations of 3H-CsA loaded islets, first with low glucose, followed by high glucose plus L-arginine and L-leucine, and finally with high glucose plus L-arginine and L-leucine and 10 mM theophylline, the proportional fractional secretion rates of insulin and 3H-CsA were of the same magnitude

Lens artifacts in human fetal eyes - the challenge of interpreting the histomorphology of human fetal lenses.

Science.gov (United States)

Herwig, Martina C; Müller, Annette M; Klarmann-Schulz, Ute; Holz, Frank G; Loeffler, Karin U

2014-01-01

Evaluation of the lens, including cataractous changes, is often of paramount importance in the classification of fetal syndromes or forensic questions. On histology, the crystalline lens is - especially in fetal and infant eyes - an organ susceptible to numerous artifacts. Thus, the aim of our study was to study various factors (including fixatives) that might have an impact on lens histomorphology. Twenty eyes from ten fetuses (formalin fixation: n = 10, glutaraldehyde fixation: n = 10), matched for gestational age and abortion (spontaneous vs. induced), were investigated macroscopically and by light microscopy. Sections were stained with routine hematoxylin & eosin (H&E), and periodic acid schiff (PAS). The age of the fetal eyes ranged from 15 to 36 weeks of gestation. Lens artifacts were analyzed and compared to fetal and adult lenses with definitive cataractous changes. In addition, 34 eyes from 27 fetuses with trisomy 21 were investigated for lens changes. All lenses showed artifacts of varying extent, in particular globules, vacuoles, clefts, anterior/posterior capsular separation, subcapsular proteinaceous material, fragmentation of the lens capsule/epithelium, and a posterior umbilication. Glutaraldehyde-fixed lenses displayed less artifacts compared to those fixed in formalin. Slight differences in the appearance of artifacts were found dependent on the fixative (formaldehyde vs glutaraldehyde) and the kind of abortion (iatrogenous vs spontaneous). The gestational age did not have a significant influence on the type and extent of lens artifacts. The lenses from fetuses with trisomy 21 displayed similar lens artifacts with no specific findings. Alterations in fetal lens morphology are extremely frequent and variable. These artifacts have to be carefully taken into account when interpreting post-mortem findings. Thus, the postmortem diagnosis of a fetal cataract should be made with great caution, and should include, in adherence to our proposed

Transforming growth factor-β (TGF-β) signaling in healthy human fetal skin: a descriptive study.

Science.gov (United States)

Walraven, M; Beelen, R H J; Ulrich, M M W

2015-05-01

TGF-β plays an important role in growth and development but is also involved in scarring and fibrosis. Differences for this growth factor are known between scarless fetal wound healing and adult wound healing. Nonetheless, most of the data in this area are from animal studies or in vitro studies and, thus, information about the human situation is incomplete and scarce. The aim of this study was to compare the canonical TGF-β signaling in unwounded human fetal and adult skin. Q-PCR, immunohistochemistry, Western Blot and Luminex assays were used to determine gene expression, protein levels and protein localization of components of this pathway in healthy skin. All components of the canonical TGF-β pathway were present in unwounded fetal skin. Compared to adult skin, fetal skin had differential concentrations of the TGF-β isoforms, had high levels of phosphorylated receptor-Smads, especially in the epidermis, and had low expression of several fibrosis-associated target genes. Further, the results indicated that the processes of receptor endocytosis might also differ between fetal and adult skin. This descriptive study showed that there are differences in gene expression, protein concentrations and protein localization for most components of the canonical TGF-β pathway between fetal and adult skin. The findings of this study can be a starting point for further research into the role of TGF-β signaling in scarless healing. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Long chain poly-unsaturated fatty acids attenuate the IL-1?-induced pro-inflammatory response in human fetal intestinal epithelial cells

OpenAIRE

Wijendran, Vasuki; Brenna, JT; Wang, Dong Hao; Zhu, Weishu; Meng, Di; Ganguli, Kriston; Kothapalli, Kumar SD; Requena, Pilar; Innis, Sheila; Walker, WA

2015-01-01

Background Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture. Methods Human fetal IEC in culture were derived from a healthy fetal small intestine (H4) or resected small intestine of a neonate wit...

Fetal Microchimerism in Cancer Protection and Promotion: Current Understanding in Dogs and the Implications for Human Health.

Science.gov (United States)

Bryan, Jeffrey N

2015-05-01

Fetal microchimerism is the co-existence of small numbers of cells from genetically distinct individuals living within a mother's body following pregnancy. During pregnancy, bi-directional exchange of cells occurs resulting in maternal microchimerism and even sibling microchimerism in offspring. The presence of fetal microchimerism has been identified with lower frequency in patients with cancers such as breast and lymphoma and with higher frequency in patients with colon cancer and autoimmune diseases. Microchimeric cells have been identified in healing and healed tissues as well as normal and tumor tissues. This has led to the hypothesis that fetal microchimerism may play a protective role in some cancers and may provoke other cancers or autoimmune disease. The long periods of risk for these diseases make it a challenge to prospectively study this phenomenon in human populations. Dogs get similar cancers as humans, share our homes and environmental exposures, and live compressed life-spans, allowing easier prospective study of disease development. This review describes the current state of understanding of fetal microchimerism in humans and dogs and highlights the similarities of the common cancers mammary carcinoma, lymphoma, and colon cancer between the two species. Study of fetal microchimerism in dogs might hold the key to characterization of the type and function of microchimeric cells and their role in health and disease. Such an understanding could then be applied to preventing and treating disease in humans.

KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas

NARCIS (Netherlands)

Roost, Matthias S; van Iperen, Liesbeth; Ariyurek, Yavuz; Buermans, Henk P; Arindrarto, Wibowo; Devalla, Harsha D; Passier, Robert; Mummery, Christine L; Carlotti, Françoise; de Koning, Eelco J P; van Zwet, Erik W; Goeman, Jelle J; Chuva de Sousa Lopes, Susana M

2015-01-01

Differentiated derivatives of human pluripotent stem cells in culture are generally phenotypically immature compared to their adult counterparts. Their identity is often difficult to determine with certainty because little is known about their human fetal equivalents in vivo. Cellular identity and

An RNA gene expressed during cortical development evolved rapidly in humans

DEFF Research Database (Denmark)

Pollard, Katherine S; Salama, Sofie R; Lambert, Nelle

2006-01-01

in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other...

Using modern human cortical bone distribution to test the systemic robusticity hypothesis.

Science.gov (United States)

Baab, Karen L; Copes, Lynn E; Ward, Devin L; Wells, Nora; Grine, Frederick E

2018-06-01

The systemic robusticity hypothesis links the thickness of cortical bone in both the cranium and limb bones. This hypothesis posits that thick cortical bone is in part a systemic response to circulating hormones, such as growth hormone and thyroid hormone, possibly related to physical activity or cold climates. Although this hypothesis has gained popular traction, only rarely has robusticity of the cranium and postcranial skeleton been considered jointly. We acquired computed tomographic scans from associated crania, femora and humeri from single individuals representing 11 populations in Africa and North America (n = 228). Cortical thickness in the parietal, frontal and occipital bones and cortical bone area in limb bone diaphyses were analyzed using correlation, multiple regression and general linear models to test the hypothesis. Absolute thickness values from the crania were not correlated with cortical bone area of the femur or humerus, which is at odds with the systemic robusticity hypothesis. However, measures of cortical bone scaled by total vault thickness and limb cross-sectional area were positively correlated between the cranium and postcranium. When accounting for a range of potential confounding variables, including sex, age and body mass, variation in relative postcranial cortical bone area explained ∼20% of variation in the proportion of cortical cranial bone thickness. While these findings provide limited support for the systemic robusticity hypothesis, cranial cortical thickness did not track climate or physical activity across populations. Thus, some of the variation in cranial cortical bone thickness in modern humans is attributable to systemic effects, but the driving force behind this effect remains obscure. Moreover, neither absolute nor proportional measures of cranial cortical bone thickness are positively correlated with total cranial bone thickness, complicating the extrapolation of these findings to extinct species where only cranial

Effect of placental factors on growth and function of the human fetal adrenal in vitro.

Science.gov (United States)

Riopel, L; Branchaud, C L; Goodyer, C G; Zweig, M; Lipowski, L; Adkar, V; Lefebvre, Y

1989-11-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: 1) maximal response to PM was 2-5 times greater; 2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; 3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

Effect of placental factors on growth and function of the human fetal adrenal in vitro

Energy Technology Data Exchange (ETDEWEB)

Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. (McGill Univ.-Montreal Children' s Hospital Research Institute, Quebec (Canada))

1989-11-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

Effect of placental factors on growth and function of the human fetal adrenal in vitro

International Nuclear Information System (INIS)

Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y.

1989-01-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland

A Case of Alloimmune Thrombocytopenia, Hemorrhagic Anemia-Induced Fetal Hydrops, Maternal Mirror Syndrome, and Human Chorionic Gonadotropin–Induced Thyrotoxicosis

Directory of Open Access Journals (Sweden)

Venu Jain

2013-05-01

Full Text Available Fetal/neonatal alloimmune thrombocytopenia (FNAIT can be a cause of severe fetal thrombocytopenia, with the common presentation being intracranial hemorrhage in the fetus, usually in the third trimester. A very unusual case of fetal anemia progressed to hydrops. This was further complicated by maternal Mirror syndrome and human chorionic gonadotropin–induced thyrotoxicosis. Without knowledge of etiology, and possibly due to associated cardiac dysfunction, fetal transfusion resulted in fetal demise. Subsequent testing revealed FNAIT as the cause of severe hemorrhagic anemia. In cases with fetal anemia without presence of red blood cell antibodies, FNAIT must be ruled out as a cause prior to performing fetal transfusion. Fetal heart may adapt differently to acute hemorrhagic anemia compared with a more subacute hemolytic anemia.

The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction.

Science.gov (United States)

Makropoulos, Antonios; Robinson, Emma C; Schuh, Andreas; Wright, Robert; Fitzgibbon, Sean; Bozek, Jelena; Counsell, Serena J; Steinweg, Johannes; Vecchiato, Katy; Passerat-Palmbach, Jonathan; Lenz, Gregor; Mortari, Filippo; Tenev, Tencho; Duff, Eugene P; Bastiani, Matteo; Cordero-Grande, Lucilio; Hughes, Emer; Tusor, Nora; Tournier, Jacques-Donald; Hutter, Jana; Price, Anthony N; Teixeira, Rui Pedro A G; Murgasova, Maria; Victor, Suresh; Kelly, Christopher; Rutherford, Mary A; Smith, Stephen M; Edwards, A David; Hajnal, Joseph V; Jenkinson, Mark; Rueckert, Daniel

2018-06-01

The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Induced pluripotent stem (iPS) cells from human fetal stem cells.

Science.gov (United States)

Guillot, Pascale V

2016-02-01

Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, focusing in particular on stem cells derived from human amniotic fluid, and the development of chemical reprogramming. We next address the advantages and disadvantages of deriving pluripotent cells from fetal tissues and the potential clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Permeability of human placenta and fetal membranes to thyrotropin-stimulating hormone in vitro.

Science.gov (United States)

Bajoria, R; Fisk, N M

1998-05-01

We determined the placental transfer of TSH in an in vitro model of dually perfused isolated lobule in 28 human term placentas by adding varying concentrations (5-60 microIU mL(-1)) of TSH as a single bolus dose to the closed maternal circulation. Transmembrane transfer of TSH was also studied by adding 45 microIU mL(-1) to the maternal or fetal compartment of a dual chamber of fetal membranes in culture. Passage of freely diffusible markers creatinine and antipyrine were also studied in this model. TSH concentration was measured by third generation chemiluminescence assay with a sensitivity of 10 mIU mL(-1). In the perfusion experiments, at physiologic concentrations the slow decline of TSH in the maternal circulation was associated with a small linear increase in fetal levels to 0.11 +/- 0.04% of initial dose at 2 h. The placental transfer rate was 0.08 microIU min(-1). Increasing maternal concentrations of TSH were associated with proportional increases in transfer rate (y = 0.002x; R2 = 0.99) and placental uptake (y = 0.01x; R2 = 0.97). The placental permeability of TSH was 2.4 x 10(-4) mL min(-1) g(-1) and was proportional to its coefficients of diffusion in water and molecular size. The transmembrane transfer and permeability of TSH was comparable to those of the placenta. We conclude that TSH crosses the human term placenta and fetal membranes sparingly.

Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

Science.gov (United States)

Muczynski, Vincent; Lecureuil, Charlotte; Messiaen, Sébastien; Guerquin, Marie-Justine; N'tumba-Byn, Thierry; Moison, Delphine; Hodroj, Wassim; Benjelloun, Hinde; Baijer, Jan; Livera, Gabriel; Frydman, René; Benachi, Alexandra; Habert, René; Rouiller-Fabre, Virginie

2012-01-01

Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR) superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro. Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4)M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array) and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro. We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary.

Directory of Open Access Journals (Sweden)

Vincent Muczynski

Full Text Available Phthalates have been shown to have reprotoxic effects in rodents and human during fetal life. Previous studies indicate that some members of the nuclear receptor (NR superfamilly potentially mediate phthalate effects. This study aimed to assess if expression of these nuclear receptors are modulated in the response to MEHP exposure on the human fetal gonads in vitro.Testes and ovaries from 7 to 12 gestational weeks human fetuses were exposed to 10(-4M MEHP for 72 h in vitro. Transcriptional level of NRs and of downstream genes was then investigated using TLDA (TaqMan Low Density Array and qPCR approaches. To determine whether somatic or germ cells of the testis are involved in the response to MEHP exposure, we developed a highly efficient cytometric germ cell sorting approach. In vitro exposure of fetal testes and ovaries to MEHP up-regulated the expression of LXRα, SREBP members and of downstream genes involved in the lipid and cholesterol synthesis in the whole gonad. In sorted testicular cells, this effect is only observable in somatic cells but not in the gonocytes. Moreover, the germ cell loss induced by MEHP exposure, that we previously described, is restricted to the male gonad as oogonia density is not affected in vitro.We evidenced for the first time that phthalate increases the levels of mRNA for LXRα, and SREBP members potentially deregulating lipids/cholesterol synthesis in human fetal gonads. Interestingly, this novel effect is observable in both male and female whereas the germ cell apoptosis is restricted to the male gonad. Furthermore, we presented here a novel and potentially very useful flow cytometric cell sorting method to analyse molecular changes in germ cells versus somatic cells.

Epicardial excitation pattern as observed in the isolated revived and perfused fetal human heart

NARCIS (Netherlands)

Durrer, D.; Büller, J.; Graaff, P.; Lo, G.I.; Meijler, F.L.

1961-01-01

The resuscitated fetal human heart can be used as an experimental tooI for the investigation of the excitatory process in the human heart. During perfusion the configuration of the epicardial electrocardiograms does not change appreciably. For accurate recording permitting a detailed analysis, the

The origin of fetal sterols in second-trimester amniotic fluid : endogenous synthesis or maternal-fetal transport?

NARCIS (Netherlands)

Baardman, Maria E.; Erwich, Jan Jaap H. M.; Berger, Rolf M. F.; Hofstra, Robert M. W.; Kerstjens-Frederikse, Wilhelmina S.; Luetjohann, Dieter; Plosch, Torsten; Lutjohann, D.

OBJECTIVE: Cholesterol is crucial for fetal development. To gain more insight into the origin of the fetal cholesterol pool in early human pregnancy, we determined cholesterol and its precursors in the amniotic fluid of uncomplicated, singleton human pregnancies. STUDY DESIGN: Total sterols were

The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts.

Science.gov (United States)

Schultz, Francisca; Hasan, Alveera; Alvarez-Laviada, Anita; Miragoli, Michele; Bhogal, Navneet; Wells, Sarah; Poulet, Claire; Chambers, Jenny; Williamson, Catherine; Gorelik, Julia

2016-01-01

Bile acids are elevated in the blood of women with intrahepatic cholestasis of pregnancy (ICP) and this may lead to fetal arrhythmia, fetal hypoxia and potentially fetal death in utero. The bile acid taurocholic acid (TC) causes abnormal calcium dynamics and contraction in neonatal rat cardiomyocytes. Ursodeoxycholic acid (UDCA), a drug clinically used to treat ICP, prevents adverse effects of TC. During development, the fetus is in a state of relative hypoxia. Although this is essential for the development of the heart and vasculature, resident fibroblasts can transiently differentiate into myofibroblasts and form gap junctions with cardiomyocytes in vitro, resulting in cardiomyocyte depolarization. We expanded on previously published work using an in vitro hypoxia model to investigate the differentiation of human fetal fibroblasts into myofibroblasts. Recent evidence shows that potassium channels are involved in maintaining the membrane potential of ventricular fibroblasts and that ATP-dependent potassium (KATP) channel subunits are expressed in cultured fibroblasts. KATP channels are a valuable target as they are thought to have a cardioprotective role during ischaemic and hypoxic conditions. We investigated whether UDCA could modulate fibroblast membrane potential. We established the isolation and culture of human fetal cardiomyocytes and fibroblasts to investigate the effect of hypoxia, TC and UDCA on human fetal cardiac cells. UDCA hyperpolarized myofibroblasts and prevented TC-induced depolarisation, possibly through the activation of KATP channels that are expressed in cultured fibroblasts. Also, similar to the rat model, UDCA can counteract TC-induced calcium abnormalities in human fetal cultures of cardiomyocytes and myofibroblasts. Under normoxic conditions, we found a higher number of myofibroblasts in cultures derived from human fetal hearts compared to cells isolated from neonatal rat hearts, indicating a possible increased number of myofibroblasts

Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2

DEFF Research Database (Denmark)

Jensen, Charlotte Harken; Teisner, Børge; Højrup, Peter

1993-01-01

Fetal antigen 1 was purified from second trimester human amniotic fluid by immunospecific affinity chromatography followed by reversed-phase chromatography. Fetal antigen 1 is a single chain glycoprotein with a M(r) of 32-38 kDa. The amino acid composition revealed a high content of cysteines......, prolines and amino acids (aa) with acidic side-chains indicating that fetal antigen 1 is a compactly folded, strongly hydrophilic molecule. The N-terminal amino acid sequence (37 aa) revealed no homology to other known protein sequences, implying that fetal antigen 1 is a 'novel' human protein. When the aa...... sequence was back-translated into the appropriate degenerate sequence of nucleic acids, fetal antigen 1 could be partially aligned to a 'human adrenal-specific mRNA, pG2'. The indirect immunoperoxidase technique demonstrated fetal antigen 1 in fetal hepatocytes, glandular cells of fetal pancreas...

Organizing Principles of Human Cortical Development--Thickness and Area from 4 to 30 Years: Insights from Comparative Primate Neuroanatomy.

Science.gov (United States)

Amlien, Inge K; Fjell, Anders M; Tamnes, Christian K; Grydeland, Håkon; Krogsrud, Stine K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

2016-01-01

The human cerebral cortex undergoes a protracted, regionally heterogeneous development well into young adulthood. Cortical areas that expand the most during human development correspond to those that differ most markedly when the brains of macaque monkeys and humans are compared. However, it remains unclear to what extent this relationship derives from allometric scaling laws that apply to primate brains in general, or represents unique evolutionary adaptations. Furthermore, it is unknown whether the relationship only applies to surface area (SA), or also holds for cortical thickness (CT). In 331 participants aged 4 to 30, we calculated age functions of SA and CT, and examined the correspondence of human cortical development with macaque to human expansion, and with expansion across nonhuman primates. CT followed a linear negative age function from 4 to 30 years, while SA showed positive age functions until 12 years with little further development. Differential cortical expansion across primates was related to regional maturation of SA and CT, with age trajectories differing between high- and low-expanding cortical regions. This relationship adhered to allometric scaling laws rather than representing uniquely macaque-human differences: regional correspondence with human development was as large for expansion across nonhuman primates as between humans and macaque. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Amniotic oxytocin and vasopressin in relation to human fetal development and labour

NARCIS (Netherlands)

Oosterbaan, H. P.; Swaab, D. F.

1989-01-01

Previous experiments in rats revealed increased amniotic oxytocin (OXT) levels in the course of normal development and increased vasopressin (AVP) levels in retarded fetal growth. In order to see whether similar changes would also occur in human, OXT and AVP levels were determined in amniotic fluid,

A developmental stage-specific switch from DAZL to BOLL occurs during fetal oogenesis in humans, but not mice.

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Jing He

Full Text Available The Deleted in Azoospermia gene family encodes three germ cell-specific RNA-binding proteins (DAZ, DAZL and BOLL that are essential for gametogenesis in diverse species. Targeted disruption of Boll in mice causes male-specific spermiogenic defects, but females are apparently fertile. Overexpression of human BOLL promotes the derivation of germ cell-like cells from genetically female (XX, but not male (XY human ES cells however, suggesting a functional role for BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed during oogenesis in mammals also remains unclear. We have therefore investigated the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate that BOLL protein is expressed in the germ cells of the human fetal ovary, at a later developmental stage than, and almost mutually-exclusive to, the expression of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial follicles form, revealing BOLL expression to be restricted to a narrow window during fetal oogenesis. By quantifying the extent of co-expression of DAZL and BOLL with markers of meiosis, we show that this window likely corresponds to the later stages of meiotic prophase I. Finally, we demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl. These data reveal significant similarities and differences between the expression of BOLL homologues during oogenesis in humans and mice, and raise questions as to the validity of the Boll(-/- mouse as a model for understanding BOLL function during human oogenesis.

Fetal MRI and ultrasound of congenital CNS anomalies; Fetales MRT und Ultraschall der angeborenen ZNS-Fehlbildungen

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Pogledic, I.; Reith, W. [Universitaetsklinikum des Saarlandes, Homburg/Saar, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany); Meyberg-Solomayer, G. [Universitaetsklinikum des Saarlandes, Homburg/Saar, Klinik fuer Frauenheilkunde, Geburtsheilkunde und Reproduktionsmedizin, Homburg/Saar (Germany)

2013-02-15

In the last decade the newest technologies, fetal magnetic resonance imaging (MRI) and 3D ultrasound, have given an insight into the minute structures of the fetal brain. However, without knowledge of the basic developmental processes the imaging is futile. Knowledge of fetal neuroanatomy corresponding to the gestational week is necessary in order to recognize pathological structures. Furthermore, a modern neuroradiologist should be acquainted with the three steps in the formation of the cerebral cortex: proliferation, migration and differentiation of neurons in order to be in a position to suspect that there is a pathology and start recognizing and discovering the abnormalities. The fetal MRI has become an important complementary method to ultrasound especially in cortical malformations when confirmation of the prenatal diagnosis is needed and additional pathologies need to be diagnosed. In this manner these two methods help in parental counseling and treatment planning. (orig.) [German] Dank neuer Technologien (z. B. fetale MRT, 3-D-Sonographie) ist es moeglich, kleinste Hirnstrukturen darzustellen. Ohne Kenntnisse der grundlegenden Entwicklungsprozesse des Gehirns waere die Bildgebung jedoch sinnlos. Um pathologische Veraenderungen zu erkennen, ist es notwendig, den Stand der fetalen Neuroanatomie in der entsprechenden Schwangerschaftswoche zu kennen. Heutzutage sollte sich ein Neuroradiologe mit den 3 Schritten der kortikalen Entwicklung - Proliferation, Migration und Differenzierung der Neuronen - vertraut machen. Nur dann wird er in der Lage sein, pathologische Veraenderungen in Betracht zu ziehen, bzw. diese zu erkennen. Die fetale MRT ist besonders wichtig, ergaenzend zur zerebralen Sonographie, zur Diagnosebestaetigung bei kortikalen Veraenderungen und Nachweis weiterer Pathologien. In dieser Kombination ermoeglichen diese Methoden eine adaequate Beratung der Eltern und Planung der Behandlung. (orig.)

Ex vivo culture of human fetal gonads: manipulation of meiosis signalling by retinoic acid treatment disrupts testis development.

Science.gov (United States)

Jørgensen, A; Nielsen, J E; Perlman, S; Lundvall, L; Mitchell, R T; Juul, A; Rajpert-De Meyts, E

2015-10-01

What are the effects of experimentally manipulating meiosis signalling by addition of retinoic acid (RA) in cultured human fetal gonads? RA-treatment accelerated meiotic entry in cultured fetal ovary samples, while addition of RA resulted in a dysgenetic gonadal phenotype in fetal testis cultures. One of the first manifestations of sex differentiation is the initiation of meiosis in fetal ovaries. In contrast, meiotic entry is actively prevented in the fetal testis at this developmental time-point. It has previously been shown that RA-treatment mediates initiation of meiosis in human fetal ovary ex vivo. This was a controlled ex vivo study of human fetal gonads treated with RA in 'hanging-drop' tissue cultures. The applied experimental set-up preserves germ cell-somatic niche interactions and the investigated outcomes included tissue integrity and morphology, cell proliferation and survival and the expression of markers of meiosis and sex differentiation. Tissue from 24 first trimester human fetuses was included in this study, all from elective terminations at gestational week (GW) 7-12. Gonads were cultured for 2 weeks with and without addition of 1 µM RA. Samples were subsequently formalin-fixed and investigated by immunohistochemistry and cell counting. Proteins investigated and quantified included; octamer-binding transcription factor 4 (OCT4), transcription factor AP-2 gamma (AP2γ) (embryonic germ cell markers), SRY (sex determining region Y)-box 9 (SOX9), anti-Müllerian hormone (AMH) (immature Sertoli cell markers), COUP transcription factor 2 (COUP-TFII) (marker of interstitial cells), forkhead box L2 (FOXL2) (granulosa cell marker), H2A histone family, member X (γH2AX) (meiosis marker), doublesex and mab-3 related transcription factor 1 (DMRT1) (meiosis regulator), cleaved poly ADP ribose polymerase (PARP), cleaved Caspase 3 (apoptosis markers) and Ki-67 antigen (Ki-67) (proliferation marker). Also, proliferation was determined using a 5'-bromo-2

Analysis of the volumetric relationship among human ocular, orbital and fronto-occipital cortical morphology

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Masters, Michael; Bruner, Emiliano; Queer, Sarah; Traynor, Sarah; Senjem, Jess

2015-01-01

Recent research on the visual system has focused on investigating the relationship among eye (ocular), orbital, and visual cortical anatomy in humans. This issue is relevant in evolutionary and medical fields. In terms of evolution, only in modern humans and Neandertals are the orbits positioned beneath the frontal lobes, with consequent structural constraints. In terms of medicine, such constraints can be associated with minor deformation of the eye, vision defects, and patterns of integration among these features, and in association with the frontal lobes, are important to consider in reconstructive surgery. Further study is therefore necessary to establish how these variables are related, and to what extent ocular size is associated with orbital and cerebral cortical volumes. Relationships among these anatomical components were investigated using magnetic resonance images from a large sample of 83 individuals, which also included each subject’s body height, age, sex, and uncorrected visual acuity score. Occipital and frontal gyri volumes were calculated using two different cortical parcellation tools in order to provide a better understanding of how the eye and orbit vary in relation to visual cortical gyri, and frontal cortical gyri which are not directly related to visual processing. Results indicated that ocular and orbital volumes were weakly correlated, and that eye volume explains only a small proportion of the variance in orbital volume. Ocular and orbital volumes were also found to be equally and, in most cases, more highly correlated with five frontal lobe gyri than with occipital lobe gyri associated with V1, V2, and V3 of the visual cortex. Additionally, after accounting for age and sex variation, the relationship between ocular and total visual cortical volume was no longer statistically significant, but remained significantly related to total frontal lobe volume. The relationship between orbital and visual cortical volumes remained significant for

Analysis of the volumetric relationship among human ocular, orbital and fronto-occipital cortical morphology.

Science.gov (United States)

Masters, Michael; Bruner, Emiliano; Queer, Sarah; Traynor, Sarah; Senjem, Jess

2015-10-01

Recent research on the visual system has focused on investigating the relationship among eye (ocular), orbital, and visual cortical anatomy in humans. This issue is relevant in evolutionary and medical fields. In terms of evolution, only in modern humans and Neandertals are the orbits positioned beneath the frontal lobes, with consequent structural constraints. In terms of medicine, such constraints can be associated with minor deformation of the eye, vision defects, and patterns of integration among these features, and in association with the frontal lobes, are important to consider in reconstructive surgery. Further study is therefore necessary to establish how these variables are related, and to what extent ocular size is associated with orbital and cerebral cortical volumes. Relationships among these anatomical components were investigated using magnetic resonance images from a large sample of 83 individuals, which also included each subject's body height, age, sex, and uncorrected visual acuity score. Occipital and frontal gyri volumes were calculated using two different cortical parcellation tools in order to provide a better understanding of how the eye and orbit vary in relation to visual cortical gyri, and frontal cortical gyri which are not directly related to visual processing. Results indicated that ocular and orbital volumes were weakly correlated, and that eye volume explains only a small proportion of the variance in orbital volume. Ocular and orbital volumes were also found to be equally and, in most cases, more highly correlated with five frontal lobe gyri than with occipital lobe gyri associated with V1, V2, and V3 of the visual cortex. Additionally, after accounting for age and sex variation, the relationship between ocular and total visual cortical volume was no longer statistically significant, but remained significantly related to total frontal lobe volume. The relationship between orbital and visual cortical volumes remained significant for a

Evidence for cortical structural plasticity in humans after a day of waking and sleep deprivation.

Science.gov (United States)

Elvsåshagen, Torbjørn; Zak, Nathalia; Norbom, Linn B; Pedersen, Per Ø; Quraishi, Sophia H; Bjørnerud, Atle; Alnæs, Dag; Doan, Nhat Trung; Malt, Ulrik F; Groote, Inge R; Westlye, Lars T

2017-08-01

Sleep is an evolutionarily conserved process required for human health and functioning. Insufficient sleep causes impairments across cognitive domains, and sleep deprivation can have rapid antidepressive effects in mood disorders. However, the neurobiological effects of waking and sleep are not well understood. Recently, animal studies indicated that waking and sleep are associated with substantial cortical structural plasticity. Here, we hypothesized that structural plasticity can be observed after a day of waking and sleep deprivation in the human cerebral cortex. To test this hypothesis, 61 healthy adult males underwent structural magnetic resonance imaging (MRI) at three time points: in the morning after a regular night's sleep, the evening of the same day, and the next morning, either after total sleep deprivation (N=41) or a night of sleep (N=20). We found significantly increased right prefrontal cortical thickness from morning to evening across all participants. In addition, pairwise comparisons in the deprived group between the two morning scans showed significant thinning of mainly bilateral medial parietal cortices after 23h of sleep deprivation, including the precuneus and posterior cingulate cortex. However, there were no significant group (sleep vs. sleep deprived group) by time interactions and we can therefore not rule out that other mechanisms than sleep deprivation per se underlie the bilateral medial parietal cortical thinning observed in the deprived group. Nonetheless, these cortices are thought to subserve wakefulness, are among the brain regions with highest metabolic rate during wake, and are considered some of the most sensitive cortical regions to a variety of insults. Furthermore, greater thinning within the left medial parietal cluster was associated with increased sleepiness after sleep deprivation. Together, these findings add to a growing body of data showing rapid structural plasticity within the human cerebral cortex detectable with

Typing of human fetal organs for the histocompatibility antigens A, B and DR.

Science.gov (United States)

Tuch, B E; Doran, T J; Messel, N; Turtle, J R

1985-01-01

In the transplantation of human fetal pancreatic explants into diabetic man, the importance of matching the histocompatibility antigens of donor and recipient to decrease the chances of rejection is unknown. Before this question can be answered human fetuses must be tissue typed. We have shown that lymphocytes harvested from fetal liver, thymus, bone marrow and spleen can be successfully HLA DR typed in 64% and A and B typed in 57% of 58 fetuses aged 15 wk or more. Typing should ideally be carried out on unseparated T and B cells. Best results were achieved if all four of the above organs were available and more than one million viable cells were able to be harvested for typing. Whilst the DR antigens could be typed from all tissues, the A and B antigens could be typed, with few exceptions only from thymus, spleen and bone marrow. The efficacy of matching the histocompatibility antigens of recipient and donor fetuses, especially the DR antigens can now be tested in the human diabetic being transplanted with pancreatic explants.

Platelet-rich plasma can replace fetal bovine serum in human meniscus cell cultures

NARCIS (Netherlands)

Gonzales, V.K.; Mulder, E.L.W. de; Boer, T. den; Hannink, G.; Tienen, T.G. van; Heerde, W.L. van; Buma, P.

2013-01-01

Concerns over fetal bovine serum (FBS) limit the clinical application of cultured tissue-engineered constructs. Therefore, we investigated if platelet-rich plasma (PRP) can fully replace FBS for meniscus tissue engineering purposes. Human PRP and platelet-poor plasma (PPP) were isolated from three

Fetal cardiology

International Nuclear Information System (INIS)

Meijboom, E.J.; Rijsterborgh, N.; Bom, N.

1986-01-01

Doppler echocardiography makes it possible to diagnose congenital heart disease in early pregnancy. It allows us to study the anatomical configuration of the fetal heart, and additionally, to evaluate the physiological conditions of the fetus. Evaluation of the direction, velocity, wave form pattern, and quantification of blood flow at the various sites in the fetal heart helps us to assess the characteristics of the fetal circulation and condition of the fetal heart. In order to use this technique in pathological situations, an initial study of the developing normal human fetal circulation was necessary. The authors studied 34 uncomplicated pregnancies by serial Doppler echocardiography. The studies were performed every 4 weeks from 16-weeks gestation to term. The pulsed Doppler sector scanner provided cardiac cross-sectional images, mitral and tricuspid blood velocities were obtained from apical four-chamber views. Angle corrected maximal and mean temporal velocities were calculated by digitizing the Doppler frequency shift recording on a graphic tablet computed with a minicomputer. The angle between the Doppler interrogation beam and the direction of blood flow was kept as small as possible in order to minimize the error

Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

Science.gov (United States)

Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

2010-01-01

Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be

STEREOLOGICAL STUDIES ON FETAL VASCULAR DEVELOPMENT IN HUMAN PLACENTAL VILLI

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Terry M Mayhew

2011-05-01

Full Text Available In human pregnancy, fetal well-being depends on the development of placental villi and the creation and maintenance of fetal microvessels within them. The aim of this study was to define stereological measures of the growth, capillarization and maturation of villi and of fetoplacental angiogenesis and capillary remodelling. Placentas were collected at 12-41 weeks of gestation and assigned to six age groups spanning equal age ranges. Tissue samples were randomised for position and orientation. Overall growth of peripheral (intermediate and terminal villi and their capillaries was evaluated using total volumes, surface areas and lengths. Measures of villous capillarization comprised capillary volume, surface and length densities and capillary:villus surface and length ratios. Size and shape remodelling of villi and capillaries was assessed using mean cross-sectional areas, perimeters and shape coefficients (perimeter2/area. Group comparisons were drawn by analysis of variance. Villous and capillary volumes, surfaces and lengths increased significantly throughout gestation. Villous maturation involved phasic (capillary:villus surface and length ratios or progressive (volume, surface and length densities increases in indices of villous capillarization. It also involved isomorphic thinning (cross-sectional areas and perimeters declined but shape coefficients did not alter. In contrast, growth of capillaries did not involve changes in luminal areas or perimeters. The results show that villous growth and fetal angiogenesis involve increases in overall length rather than calibre and that villous differentiation involves increased capillarization. Although they do not distinguish between increases in the lengths versus numbers of capillary segments, other studies have shown that capillaries switch from branching to non-branching angiogenesis during gestation. Combined with maintenance of capillary calibres, these processes will contribute to the reduced

Fetal MRI demonstrates glioependymal cyst in a case of sonographic unilateral ventriculomegaly

International Nuclear Information System (INIS)

Muehler, Matthias R.; Hartmann, Christian; Werner, Walter; Meyer, Oliver; Bollmann, Rainer; Klingebiel, Randolf

2007-01-01

We report a fetus of 28 weeks' gestation in which ultrasonography demonstrated unilateral ventriculomegaly and microcephaly. Fetal MRI demonstrated a simple, left paramedian occipital cyst with rarefaction of the corpus callosum and thinning of the adjacent cortical mantle. Ischaemia was suggested as the underlying pathogenesis, but autopsy after termination of pregnancy revealed a glioependymal cyst. This case highlights consideration of the rare diagnosis of glioependymal cyst when a cystic lesion associated with cerebral malformations, particularly dysgenesis of the corpus callosum, is demonstrated and fetal MRI suggests an ischaemic origin. (orig.)

Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

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Carmen eRey-Santano

2011-09-01

Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

Central vagal sensory and motor connections: human embryonic and fetal development.

Science.gov (United States)

Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

2004-07-30

The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

MR imaging methods for assessing fetal brain development.

Science.gov (United States)

Rutherford, Mary; Jiang, Shuzhou; Allsop, Joanna; Perkins, Lucinda; Srinivasan, Latha; Hayat, Tayyib; Kumar, Sailesh; Hajnal, Jo

2008-05-01

Fetal magnetic resonance imaging provides an ideal tool for investigating growth and development of the brain in vivo. Current imaging methods have been hampered by fetal motion but recent advances in image acquisition can produce high signal to noise, high resolution 3-dimensional datasets suitable for objective quantification by state of the art post acquisition computer programs. Continuing development of imaging techniques will allow a unique insight into the developing brain, more specifically process of cell migration, axonal pathway formation, and cortical maturation. Accurate quantification of these developmental processes in the normal fetus will allow us to identify subtle deviations from normal during the second and third trimester of pregnancy either in the compromised fetus or in infants born prematurely.

The Zagreb Collection of human brains: a unique, versatile, but underexploited resource for the neuroscience community.

Science.gov (United States)

Judaš, Miloš; Šimić, Goran; Petanjek, Zdravko; Jovanov-Milošević, Nataša; Pletikos, Mihovil; Vasung, Lana; Vukšić, Mario; Kostović, Ivica

2011-05-01

The Zagreb Collection of developing and adult human brains was founded in 1974 by Ivica Kostović and consists of 1,278 developing and adult human brains, including 610 fetal, 317 children, and 359 adult brains. It is one of the largest collections of developing human brains. The collection serves as a key resource for many focused research projects and has led to several seminal contributions on mammalian cortical development, such as the discovery of the transient fetal subplate zone and of early bilaminar synaptogenesis in the embryonic and fetal human cerebral cortex, and the first description of growing afferent pathways in the human fetal telencephalon. The Zagreb Collection also serves as a core resource for ever-growing networks of international collaboration and represents the starting point for many young investigators who now pursue independent research careers at leading international institutions. The Zagreb Collection, however, remains underexploited owing to a lack of adequate funding in Croatia. Funding could establish an online catalog of the collection and modern virtual microscopy scanning methods to make the collection internationally more accessible. © 2011 New York Academy of Sciences.

Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

DEFF Research Database (Denmark)

Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue

2017-01-01

SCOPE: Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal...... steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours....... The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA...

A Brief Account of the Discovery of the Fetal/Placental Unit for Estrogen Production in Equine and Human Pregnancies: Relation to Human Medicine.

Science.gov (United States)

Raeside, James I

2017-09-01

The role of steroids in human medicine is well recognized, but the major contributions made by the large domestic animals as a source of material in the discovery, isolation, and determination of the structure of the steroid hormones is less well appreciated. After a brief reminder of the early efforts to obtain a reliable source of steroids for clinical use, the narrative here is to outline one example where success was ultimately achieved for estrogen replacement therapy. Whereas knowledge of the high concentrations of estrogens in urine of pregnant women and mares dates from the late 1920s, it was not until the 1940s that the latter was shown to be a practical source. Initially, the placenta was held to be responsible, but the involvement of the fetus in each case was eventually established. The remarkable enlargement of the human fetal adrenal glands and the fetal gonads in the horse, with characteristic features of steroid secreting tissues, suggested their participation. Ultimately, it was 16-hydroxylation by the fetal liver that resulted in estriol being the major estrogen type, by far, in late human pregnancy. In the mare, the pattern of estrogen production reflected that of the growth and later regression of the fetal gonads. The characteristic production ring-B, unsaturated estrogens in the mare is derived from an alternative pathway involving retention of the additional double bond in the biosynthesis of equilin.

Automatic segmentation of human cortical layer-complexes and architectural areas using diffusion MRI and its validation

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Matteo Bastiani

2016-11-01

Full Text Available Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high resolution diffusion MRI data. Several groups of adjacent layers could be distinguished in human primary motor and premotor cortex. We then used the signature of diffusion MRI signals along cortical depth as a criterion to detect area boundaries and find borders at which the signature changes abruptly. We validate our clustering results by histological analysis of the same tissue. These results confirm earlier studies which show that diffusion MRI can probe layer-specific intracortical fiber organization and, moreover, suggests that it contains enough information to automatically classify architecturally distinct cortical areas. We discuss the strengths and weaknesses of the automatic clustering approach and its appeal for MR-based cortical histology.

Neuroimaging in human MDMA (Ecstasy) users: A cortical model

Science.gov (United States)

Cowan, Ronald L; Roberts, Deanne M; Joers, James M

2009-01-01

MDMA (3,4 methylenedioxymethamphetamine) has been used by millions of people worldwide as a recreational drug. MDMA and Ecstasy are often used synonymously but it is important to note that the purity of Ecstasy sold as MDMA is not certain. MDMA use is of public health concern, not so much because MDMA produces a common or severe dependence syndrome, but rather because rodent and non-human primate studies have indicated that MDMA (when administered at certain dosages and intervals) can cause long-lasting reductions in markers of brain serotonin (5-HT) that appear specific to fine diameter axons arising largely from the dorsal raphe nucleus (DR). Given the popularity of MDMA, the potential for the drug to produce long-lasting or permanent 5-HT axon damage or loss, and the widespread role of 5-HT function in the brain, there is a great need for a better understanding of brain function in human users of this drug. To this end, neuropsychological, neuroendocrine, and neuroimaging studies have all suggested that human MDMA users may have long-lasting changes in brain function consistent with 5-HT toxicity. Data from animal models leads to testable hypotheses regarding MDMA effects on the human brain. Because neuropsychological and neuroimaging findings have focused on the neocortex, a cortical model is developed to provide context for designing and interpreting neuroimaging studies in MDMA users. Aspects of the model are supported by the available neuroimaging data but there are controversial findings in some areas and most findings have not been replicated across different laboratories and using different modalities. This paper reviews existing findings in the context of a cortical model and suggests directions for future research. PMID:18991874

In an in-vitro model using human fetal membranes, 17-α hydroxyprogesterone caproate is not an optimal progestogen for inhibition of fetal membrane weakening.

Science.gov (United States)

Kumar, Deepak; Moore, Robert M; Mercer, Brian M; Mansour, Joseph M; Mesiano, Sam; Schatz, Frederick; Lockwood, Charles J; Moore, John J

2017-12-01

The progestogen 17-α hydroxyprogesterone caproate (17-OHPC) is 1 of only 2 agents recommended for clinical use in the prevention of spontaneous preterm delivery, and studies of its efficacy have been conflicting. We have developed an in-vitro model to study the fetal membrane weakening process that leads to rupture in preterm premature rupture of the fetal membranes (pPROM). Inflammation/infection associated with tumor necrosis factor-α (TNF-α) induction and decidual bleeding/abruption associated thrombin release are leading causes of preterm premature rupture of the fetal membranes. Both agents (TNF-α and thrombin) cause fetal membrane weakening in the model system. Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical intermediate for both TNF-α and thrombin-induced fetal membrane weakening. In a previous report, we demonstrated that 3 progestogens, progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone acetate (MPA), each inhibit both TNF-α- and thrombin-induced fetal membrane weakening at 2 distinct points of the fetal membrane weakening pathway. Each block both the production of and the downstream action of the critical intermediate granulocyte-macrophage colony-stimulating factor. The objective of the study was to characterize the inhibitory effects of 17-OHPC on TNF-α- and thrombin-induced fetal membrane weakening in vitro. Full-thickness human fetal membrane fragments from uncomplicated term repeat cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured with/without 17-alpha hydroxyprogesterone caproate (10 -9 to 10 -7 M). After 24 hours, medium (supernatant) was removed and replaced with/without the addition of tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte-macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture, medium from the maternal side compartment of the model was assayed for granulocyte-macrophage colony

Transport and biodistribution of dendrimers across human fetal membranes: implications for intravaginal administration of dendrimer-drug conjugates.

Science.gov (United States)

Menjoge, Anupa R; Navath, Raghavendra S; Asad, Abbas; Kannan, Sujatha; Kim, Chong J; Romero, Roberto; Kannan, Rangaramanujam M

2010-06-01

Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly (amidoamine)) dendrimers, across human fetal membrane (using a side by side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size approximately 400 Da) and fluorophore-tagged G(4)-PAMAM dendrimers (approximately 16 kDa). The fluorophore-tagged G(4)-PAMAM dendrimers were synthesized and characterized using (1)H NMR, MALDI TOF MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a 5 h period, the dendrimer transport across all the three membranes was less than dendrimer (5.8 x 10(-8) cm(2)/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5-4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother

Higher cortical modulation of pain perception in the human brain: Psychological determinant

OpenAIRE

Chen, Andrew Cn

2009-01-01

Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed d...

Births and deaths including fetal deaths

Data.gov (United States)

U.S. Department of Health & Human Services — Access to a variety of United States birth and death files including fetal deaths: Birth Files, 1968-2009; 1995-2005; Fetal death file, 1982-2005; Mortality files,...

Hypothesis-driven methods to augment human cognition by optimizing cortical oscillations

Directory of Open Access Journals (Sweden)

Jörn M. Horschig

2014-06-01

Full Text Available Cortical oscillations have been shown to represent fundamental functions of a working brain, e.g. communication, stimulus binding, error monitoring, and inhibition, and are directly linked to behavior. Recent studies intervening with these oscillations have demonstrated effective modulation of both the oscillations and behavior. In this review, we collect evidence in favor of how hypothesis-driven methods can be used to augment cognition by optimizing cortical oscillations. We elaborate their potential usefulness for three target groups: healthy elderly, patients with attention deficit/hyperactivity disorder, and healthy young adults. We discuss the relevance of neuronal oscillations in each group and show how each of them can benefit from the manipulation of functionally-related oscillations. Further, we describe methods for manipulation of neuronal oscillations including direct brain stimulation as well as indirect task alterations. We also discuss practical considerations about the proposed techniques. In conclusion, we propose that insights from neuroscience should guide techniques to augment human cognition, which in turn can provide a better understanding of how the human brain works.

Cortical control of gait in healthy humans: an fMRI study

International Nuclear Information System (INIS)

ChiHong, Wang; YauYau, Wai; BoCheng, Kuo; Yei-Yu, Yeh; JiunJie Wang

2008-01-01

This study examined the cortical control of gait in healthy humans using functional magnetic resonance imaging (fMRI). Two block-designed fMRI sessions were conducted during motor imagery of a locomotor-related task. Subjects watched a video clip that showed an actor standing and walking in an egocentric perspective. In a control session, additional fMRI images were collected when participants observed a video clip of the clutch movement of a right hand. In keeping with previous studies using SPECT and NIRS, we detected activation in many motor-related areas including supplementary motor area, bilateral precentral gyrus, left dorsal premotor cortex, and cingulate motor area. Smaller additional activations were observed in the bilateral precuneus, left thalamus, and part of right putamen. Based on these findings, we propose a novel paradigm to study the cortical control of gait in healthy humans using fMRI. Specifically, the task used in this study - involving both mirror neurons and mental imagery - provides a new feasible model to be used in functional neuroimaging studies in this area of research. (author)

Distribution of 131I-labeled recombinant human erythropoietin in maternal and fetal organs following intravenous administration in pregnant rats

International Nuclear Information System (INIS)

Yilmaz, O.; Lambrecht, F.Y.; Durkan, K.; Gokmen, N.; Erbayraktar, S.

2007-01-01

The aim of the present study was to demonstrate the possible transplacental transmission of 131 I labeled recombinant human erythropoietin ( 131 I-rh-EPO) in pregnant rats and its distribution through maternal and fetal organs. Six Wistar Albino Rats in their pregnancy of 18 days were used 131 I labeled recombinant human erythropoietin (specific activity = 2.4 μCi/IU) was injected into the tail vein of rats. After 30 minutes labeled erythropoietin infusion maternal stomach, kidney, lung, liver, brain and heart as well as fetus were removed. Then, the same organs were removed from each fetus. Measuring weight of maternal and fetal organs as well as placenta were followed by radioactivity count via Cd(Te) detector. 131 I labeled recombinant human erythropoietin was found to be able to pass rat placenta and its distribution order in fetal organs was similar to those of maternal organs. Besides, as measurements were performed closer to cornu uteri, uptakes were decreasing in every fetus and its corresponding placenta. (author)

Radiation absorbed dose to the human fetal thyroid

International Nuclear Information System (INIS)

Watson, E.E.

1992-01-01

The embryo/fetus is recognized to be particularly susceptible to damage from exposure to radiation. Many advisory groups have studied available information concerning radiation doses and radiation effects with the goal of reducing the risk to the embryo/fetus. Of particular interest are radioactive isotopes of iodine. Radioiodine taken into the body of a pregnant woman presents a possible hazard for the embryo/fetus. The fetal thyroid begins to concentrate iodine at about 13 weeks after conception and continues to do so throughout gestation. At term, the organic iodine concentration in the fetal blood is about 75% of that in the mother's blood. This paper presents a review the models that have been proposed for the calculation of the dose to the fetal thyroid from radioisotopes of iodine taken into the body of the pregnant woman as sodium iodide. A somewhat different model has been proposed, and estimates of the radiation dose to the fetal thyroid calculated from this model are given for each month of pregnancy from 123 I , 124 I , 125 I , and 131 I

Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

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Agneta Månsson-Broberg

2016-04-01

Full Text Available The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.

A synergy-based hand control is encoded in human motor cortical areas

Science.gov (United States)

Leo, Andrea; Handjaras, Giacomo; Bianchi, Matteo; Marino, Hamal; Gabiccini, Marco; Guidi, Andrea; Scilingo, Enzo Pasquale; Pietrini, Pietro; Bicchi, Antonio; Santello, Marco; Ricciardi, Emiliano

2016-01-01

How the human brain controls hand movements to carry out different tasks is still debated. The concept of synergy has been proposed to indicate functional modules that may simplify the control of hand postures by simultaneously recruiting sets of muscles and joints. However, whether and to what extent synergic hand postures are encoded as such at a cortical level remains unknown. Here, we combined kinematic, electromyography, and brain activity measures obtained by functional magnetic resonance imaging while subjects performed a variety of movements towards virtual objects. Hand postural information, encoded through kinematic synergies, were represented in cortical areas devoted to hand motor control and successfully discriminated individual grasping movements, significantly outperforming alternative somatotopic or muscle-based models. Importantly, hand postural synergies were predicted by neural activation patterns within primary motor cortex. These findings support a novel cortical organization for hand movement control and open potential applications for brain-computer interfaces and neuroprostheses. DOI: http://dx.doi.org/10.7554/eLife.13420.001 PMID:26880543

Human fetal growth is constrained below optimal for perinatal survival

NARCIS (Netherlands)

Vasak, B.; Koenen, S. V.; Koster, M. P. H.; Hukkelhoven, C. W. P. M.; Franx, A.; Hanson, M. A.; Visser, GHA

ObjectiveThe use of fetal growth charts assumes that the optimal size at birth is at the 50(th) birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for

Fetal Mesenchymal Stromal Cells Differentiating towards Chondrocytes Acquire a Gene Expression Profile Resembling Human Growth Plate Cartilage

NARCIS (Netherlands)

van Gool, S.A.; Emons, J.A.M.; Leijten, Jeroen Christianus Hermanus; Decker, E.; Sticht, C.; van Houwelingen, J.C.; Goeman, J.J.; Kleijburg, C.; Scherjon, S.; Gretz, N.; Wit, J.M.; Rappold, G.; Post, Janine Nicole; Karperien, Hermanus Bernardus Johannes

2012-01-01

Abstract We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether

Cortical Thought Theory: A Working Model of the Human Gestalt Mechanism.

Science.gov (United States)

1985-07-01

2. The Artificial Inteligence Perspective • -° 2.1 Introduction: Chapter Overview This chapter addresses the development of a...6 . . 2. The Artificial Intelligence Perspective ... .......... 9 2.1 Introduction: Chapter Overview .... ........... 9 2.2 The Problem 9...new unified theory of human brain function called Cortical Thought Theory (CTT). The analysis integrates the disciplines of Artificial Intelligence

125I-human epidermal growth factor specific binding to placentas and fetal membranes from varoius pregnancy states

International Nuclear Information System (INIS)

Hofmann, G.E.; Siddiqi, T.A.; Rao, Ch. V.; Carman, F.R.

1988-01-01

Specific binding of 125 I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class A/B diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more 125 I-hEGF than did fetal membranes (P 125 I-hEGF binding to fetal membranes from the various pregnancy states (P 125 I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P 125 I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P 125 I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P 125 I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P<0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone. (author)

Optimal staining methods for delineation of cortical areas and neuron counts in human brains.

Science.gov (United States)

Uylings, H B; Zilles, K; Rajkowska, G

1999-04-01

For cytoarchitectonic delineation of cortical areas in human brain, the Gallyas staining for somata with its sharp contrast between cell bodies and neuropil is preferable to the classical Nissl staining, the more so when an image analysis system is used. This Gallyas staining, however, does not appear to be appropriate for counting neuron numbers in pertinent brain areas, due to the lack of distinct cytological features between small neurons and glial cells. For cell counting Nissl is preferable. In an optimal design for cell counting at least both the Gallyas and the Nissl staining must be applied, the former staining for cytoarchitectural delineaton of cortical areas and the latter for counting the number of neurons in the pertinent cortical areas. Copyright 1999 Academic Press.

Fetal and perinatal outcomes in type 1 diabetes pregnancy: a randomized study comparing insulin aspart with human insulin in 322 subjects

DEFF Research Database (Denmark)

Hod, Moshe; Damm, Peter; Kaaja, Risto

2008-01-01

The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy.......The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy....

The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias

International Nuclear Information System (INIS)

Amson, R.; Przedborski, S.; Telerman, A.; Sigaux, F.; Flandrin, G.; Givol, D.

1989-01-01

The authors measured the human pim-1 protooncogene (PIM) expression during fetal development and in hematopoietic malignancies. The data indicate that during human fetal hematopoiesis the 33-kDa pim product, p33pim, is highly expressed in the liver and the spleen. In contrast, a the adult stage it is only slightly expressed in circulating granulocytes. Out of 70 hematopoietic malignancies analyzed, 51 patients and 19 cell lines, p33pim was overexpressed in ∼ 30% of the samples, particularly in myeloid and lymphoid acute leukemias. This overexpression was unrelated to any stage of cellular differentiation and was not due to gene rearrangement or amplification. These results imply a physiological role of the pim-1 protooncogene during hematopoietic development and a deregulation in various leukemias

Groupwise connectivity-based parcellation of the whole human cortical surface using watershed-driven dimension reduction.

Science.gov (United States)

Lefranc, Sandrine; Roca, Pauline; Perrot, Matthieu; Poupon, Cyril; Le Bihan, Denis; Mangin, Jean-François; Rivière, Denis

2016-05-01

Segregating the human cortex into distinct areas based on structural connectivity criteria is of widespread interest in neuroscience. This paper presents a groupwise connectivity-based parcellation framework for the whole cortical surface using a new high quality diffusion dataset of 79 healthy subjects. Our approach performs gyrus by gyrus to parcellate the whole human cortex. The main originality of the method is to compress for each gyrus the connectivity profiles used for the clustering without any anatomical prior information. This step takes into account the interindividual cortical and connectivity variability. To this end, we consider intersubject high density connectivity areas extracted using a surface-based watershed algorithm. A wide validation study has led to a fully automatic pipeline which is robust to variations in data preprocessing (tracking type, cortical mesh characteristics and boundaries of initial gyri), data characteristics (including number of subjects), and the main algorithmic parameters. A remarkable reproducibility is achieved in parcellation results for the whole cortex, leading to clear and stable cortical patterns. This reproducibility has been tested across non-overlapping subgroups and the validation is presented mainly on the pre- and postcentral gyri. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Early Cerebral Hemodynamic, Metabolic, and Histological Changes in Hypoxic-Ischemic Fetal Lambs during Postnatal Life.

Science.gov (United States)

Rey-Santano, Carmen; Mielgo, Victoria E; Gastiasoro, Elena; Murgia, Xabier; Lafuente, Hector; Ruiz-Del-Yerro, Estibaliz; Valls-I-Soler, Adolf; Hilario, Enrique; Alvarez, Francisco J

2011-01-01

The hemodynamic, metabolic, and biochemical changes produced during the transition from fetal to neonatal life may be aggravated if an episode of asphyxia occurs during fetal life. The aim of the study was to examine regional cerebral blood flow (RCBF), histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress in the first hours of postnatal life following severe fetal asphyxia. Eighteen chronically instrumented newborn lambs were randomly assigned to either a control group or the hypoxic-ischemic (HI) group, in which case fetal asphyxia was induced just before delivery. All the animals were maintained on intermittent positive pressure ventilation for 3 h after delivery. During the HI insult, the injured group developed acidosis, hypoxia, hypercapnia, lactic acidosis, and tachycardia (relative to the control group), without hypotension. The intermittent positive pressure ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilatory support, there continued to be an increased RCBF in inner regions among the HI group, but no significant differences were detected in cortical flow compared to the control group. Also, the magnitude of the increase in TUNEL positive cells (apoptosis) and antioxidant enzymes, and decrease of ATP reserves was significantly greater in the brain regions where the RCBF was not higher. In conclusion, our findings identify early metabolic, histological, and hemodynamic changes involved in brain damage in premature asphyxiated lambs. Such changes have been described in human neonates, so our model could be useful to test the safety and the effectiveness of different neuroprotective or ventilation strategies applied in the first hours after fetal HI injury.

Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth.

Directory of Open Access Journals (Sweden)

Stacy Zamudio

2010-01-01

Full Text Available The most well known reproductive consequence of residence at high altitude (HA >2700 m is reduction in fetal growth. Reduced fetoplacental oxygenation is an underlying cause of pregnancy pathologies, including intrauterine growth restriction and preeclampsia, which are more common at HA. Therefore, altitude is a natural experimental model to study the etiology of pregnancy pathophysiologies. We have shown that the proximate cause of decreased fetal growth is not reduced oxygen availability, delivery, or consumption. We therefore asked whether glucose, the primary substrate for fetal growth, might be decreased and/or whether altered fetoplacental glucose metabolism might account for reduced fetal growth at HA.Doppler and ultrasound were used to measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were collected at elective cesarean delivery and analyzed for glucose, lactate and insulin. Maternal delivery and fetal uptakes for oxygen and glucose were calculated.The maternal arterial - venous glucose concentration difference was greater at HA. However, umbilical venous and arterial glucose concentrations were markedly decreased, resulting in lower glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but strongly correlated with glucose delivery, highlighting the relevance of glucose concentration to fetal uptake. At altitude, fetal lactate levels were increased, insulin concentrations decreased, and the expression of GLUT1 glucose transporter protein in the placental basal membrane was reduced.Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that

/sup 125/I-human epidermal growth factor specific binding to placentas and fetal membranes from varoius pregnancy states

Energy Technology Data Exchange (ETDEWEB)

Hofmann, G.E.; Siddiqi, T.A.; Rao, Ch. V.; Carman, F.R.

1988-01-01

Specific binding of /sup 125/I-human epidermal growth factor (hEGF) to homogenates of term human placentas and fetal membranes from normal and appropriate for gestational age (N = 20), intrauterine growth retarded (N = 9), twin (N = 11), White class AB diabetic (N = 12), and large for gestational age (N = 13) pregnancies was measured. In all pregnancy states, placentas bound approximately four times more /sup 125/I-hEGF than did fetal membranes (P<0.0001). There was no significant differnce in /sup 125/I-hEGF binding to fetal membranes from the various pregnancy states (P<0.05). /sup 125/I-hEGF specific binding to placentas from intrauterine growth retarded or twin pregnancies was significantly greater compared with placentas from normal and appropriate for gestational age pregnancies (P<0.05). The binding to placentas from pregnancies complicated by White class AB diabetes or large for gestational age infants, on the other hand, was not significantly different from that to placentas from normal and appropriate for gestational age pregnancies. /sup 125/I-hEGF specific binding did not differ between placentas from intrauterine growth retarded or twin pregnancies (P<0.05). Placental and fetal membrane /sup 125/I-hEGF binding did not vary with fetal sex, maternal race, placental weight, or gestational age between 37 to 42 weeks (P<0.05). Placental but not fetal membrane /sup 125/I-hEGF binding increased with increasing infant weight when appropriate for gestational age and large for gestational age infants were included (P<0.05, r = 0.38, N = 32) but not for intrauterine growth retarded, appropriate for gestational age, or large for gestational age infants alone.

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

Science.gov (United States)

Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

2003-11-15

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

101 labeled brain images and a consistent human cortical labeling protocol

Directory of Open Access Journals (Sweden)

Arno eKlein

2012-12-01

Full Text Available We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The Desikan-Killiany-Tourville (DKT protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://www.mindboggle.info/data/ website.

101 Labeled Brain Images and a Consistent Human Cortical Labeling Protocol

Science.gov (United States)

Klein, Arno; Tourville, Jason

2012-01-01

We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The “Desikan–Killiany–Tourville” (DKT) protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://mindboggle.info/data website. PMID:23227001

Spatial Mapping of Structural and Connectional Imaging Data for the Developing Human Brain with Diffusion Tensor Imaging

Science.gov (United States)

Ouyang, Austin; Jeon, Tina; Sunkin, Susan M.; Pletikos, Mihovil; Sedmak, Goran; Sestan, Nenad; Lein, Ed S.; Huang, Hao

2014-01-01

During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain. PMID:25448302

Spatial mapping of structural and connectional imaging data for the developing human brain with diffusion tensor imaging.

Science.gov (United States)

Ouyang, Austin; Jeon, Tina; Sunkin, Susan M; Pletikos, Mihovil; Sedmak, Goran; Sestan, Nenad; Lein, Ed S; Huang, Hao

2015-02-01

During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain. Copyright © 2014 Elsevier Inc. All rights reserved.

GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth

Directory of Open Access Journals (Sweden)

Emily F. Winterbottom

2015-06-01

Full Text Available Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.

Increased oxidative stress in human fetal membranes overlying the cervix from term non-labouring and post labour deliveries.

Science.gov (United States)

Chai, M; Barker, G; Menon, R; Lappas, M

2012-08-01

Enzymatic breakdown of the collagen-rich extracellular matrix (ECM) that connects the amnion and chorion layers of the fetal membranes is one of the key events leading to rupture of membranes. Oxidant stress caused by increased formation of reactive oxygen species and/or reduced antioxidant capacity may predispose to membrane rupture, a major cause of preterm birth. The aim of this study was to determine the effect of human labour and supracervical (SC) apposition on antioxidant enzymes and 8-isoprostane (a marker of lipid peroxidation). To determine the effect of human labour on oxidative stress status, fetal membranes from the SC site (SCS) were collected from women at term Caesarean section (no labour), and from the site of membrane rupture (SOR) after spontaneous labour onset and delivery (post labour). To determine the effect of SC apposition on oxidative stress status, amnion was collected from the SCS and a distal site (DS) in women at term Caesarean section in the absence of labour. The release of 8-isoprostane was significantly higher in amnion from the SCS compared to DS, and in fetal membranes from the SOR compared to the SCS. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were lower in amnion from the SC compared to DS. SOD gene expression and enzyme activity were lower in fetal membranes after labour. There was no difference in expression or activity in catalase, GPx and glutathione reductase (GSR) between no labour and post labour fetal membranes. In primary amnion cells, SOD supplementation significantly augmented IL-1β induced MMP-9 expression and activity. In summary, non-labouring SC fetal membranes are characterised by reduced antioxidant enzyme activity when compared to distal membranes, and, as such, may be more susceptible to oxidative damage and thus membrane rupture. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cortical networks for encoding near and far space in the non-human primate.

Science.gov (United States)

Cléry, Justine; Guipponi, Olivier; Odouard, Soline; Wardak, Claire; Ben Hamed, Suliann

2018-04-19

While extra-personal space is often erroneously considered as a unique entity, early neuropsychological studies report a dissociation between near and far space processing both in humans and in monkeys. Here, we use functional MRI in a naturalistic 3D environment to describe the non-human primate near and far space cortical networks. We describe the co-occurrence of two extended functional networks respectively dedicated to near and far space processing. Specifically, far space processing involves occipital, temporal, parietal, posterior cingulate as well as orbitofrontal regions not activated by near space, possibly subserving the processing of the shape and identity of objects. In contrast, near space processing involves temporal, parietal, prefrontal and premotor regions not activated by far space, possibly subserving the preparation of an arm/hand mediated action in this proximal space. Interestingly, this network also involves somatosensory regions, suggesting a cross-modal anticipation of touch by a nearby object. Last, we also describe cortical regions that process both far and near space with a preference for one or the other. This suggests a continuous encoding of relative distance to the body, in the form of a far-to-near gradient. We propose that these cortical gradients in space representation subserve the physically delineable peripersonal spaces described in numerous psychology and psychophysics studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Influence of mesh density, cortical thickness and material properties on human rib fracture prediction.

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Li, Zuoping; Kindig, Matthew W; Subit, Damien; Kent, Richard W

2010-11-01

The purpose of this paper was to investigate the sensitivity of the structural responses and bone fractures of the ribs to mesh density, cortical thickness, and material properties so as to provide guidelines for the development of finite element (FE) thorax models used in impact biomechanics. Subject-specific FE models of the second, fourth, sixth and tenth ribs were developed to reproduce dynamic failure experiments. Sensitivity studies were then conducted to quantify the effects of variations in mesh density, cortical thickness, and material parameters on the model-predicted reaction force-displacement relationship, cortical strains, and bone fracture locations for all four ribs. Overall, it was demonstrated that rib FE models consisting of 2000-3000 trabecular hexahedral elements (weighted element length 2-3mm) and associated quadrilateral cortical shell elements with variable thickness more closely predicted the rib structural responses and bone fracture force-failure displacement relationships observed in the experiments (except the fracture locations), compared to models with constant cortical thickness. Further increases in mesh density increased computational cost but did not markedly improve model predictions. A ±30% change in the major material parameters of cortical bone lead to a -16.7 to 33.3% change in fracture displacement and -22.5 to +19.1% change in the fracture force. The results in this study suggest that human rib structural responses can be modeled in an accurate and computationally efficient way using (a) a coarse mesh of 2000-3000 solid elements, (b) cortical shells elements with variable thickness distribution and (c) a rate-dependent elastic-plastic material model. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

Epigenetic regulation and fetal programming.

Science.gov (United States)

Gicquel, Christine; El-Osta, Assam; Le Bouc, Yves

2008-02-01

Fetal programming encompasses the role of developmental plasticity in response to environmental and nutritional signals during early life and its potential adverse consequences (risk of cardiovascular, metabolic and behavioural diseases) in later life. The first studies in this field highlighted an association between poor fetal growth and chronic adult diseases. However, environmental signals during early life may lead to adverse long-term effects independently of obvious effects on fetal growth. Adverse long-term effects reflect a mismatch between early (fetal and neonatal) environmental conditions and the conditions that the individual will confront later in life. The mechanisms underlying this risk remain unclear. However, experimental data in rodents and recent observations in humans suggest that epigenetic changes in regulatory genes and growth-related genes play a significant role in fetal programming. Improvements in our understanding of the biochemical and molecular mechanisms at play in fetal programming would make it possible to identify biomarkers for detecting infants at high risk of adult-onset diseases. Such improvements should also lead to the development of preventive and therapeutic strategies.

Human-Specific Cortical Synaptic Connections and Their Plasticity: Is That What Makes Us Human?

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Joana Lourenço

2017-01-01

Full Text Available One outstanding difference between Homo sapiens and other mammals is the ability to perform highly complex cognitive tasks and behaviors, such as language, abstract thinking, and cultural diversity. How is this accomplished? According to one prominent theory, cognitive complexity is proportional to the repetition of specific computational modules over a large surface expansion of the cerebral cortex (neocortex. However, the human neocortex was shown to also possess unique features at the cellular and synaptic levels, raising the possibility that expanding the computational module is not the only mechanism underlying complex thinking. In a study published in PLOS Biology, Szegedi and colleagues analyzed a specific cortical circuit from live postoperative human tissue, showing that human-specific, very powerful excitatory connections between principal pyramidal neurons and inhibitory neurons are highly plastic. This suggests that exclusive plasticity of specific microcircuits might be considered among the mechanisms endowing the human neocortex with the ability to perform highly complex cognitive tasks.

Human cerebral cortices: signal variation on diffusion-weighted MR imaging

Energy Technology Data Exchange (ETDEWEB)

Asao, Chiaki [Kumamoto Regional Medical Center, Department of Radiology, Kumamoto (Japan); National Hospital Organization Kumamoto Medical Center, Department of Radiology, Kumamoto (Japan); Hirai, Toshinori; Yamashita, Yasuyuki [Kumamoto University Graduate School of Medical Sciences, Department of Diagnostic Radiology, Kumamoto (Japan); Yoshimatsu, Shunji [National Hospital Organization Kumamoto Medical Center, Department of Radiology, Kumamoto (Japan); Matsukawa, Tetsuya; Imuta, Masanori [Kumamoto Regional Medical Center, Department of Radiology, Kumamoto (Japan); Sagara, Katsuro [Kumamoto Regional Medical Center, Department of Internal Medicine, Kumamoto (Japan)

2008-03-15

We have often encountered high signal intensity (SI) of the cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity on DW images has not been investigated systematically. The purpose of our study was to determine whether there is regional signal variation in the brain cortices of neurologically healthy adults on DW-MR images. The SI of the cerebral cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes were analyzed by visually assessment of the differences in appearance among the cortices on apparent diffusion coefficient (ADC) maps. Increased SI was frequently seen in the cingulate gyrus and insula regardless of patient age. There were no significant gender- or laterality-related differences. The CNR was significantly higher in the cingulate gyrus and insula than in the other cortices (p <.01), and significant differences existed among the cortical regions (p <.001). There were no apparent ADC differences among the cortices on ADC maps. Regional signal variation of the brain cortices was observed on DW-MR images of healthy subjects, and the cingulate gyrus and insula frequently manifested high SI. These findings may help in the recognition of cortical signal abnormalities as visualized on DW-MR images. (orig.)

Human cerebral cortices: signal variation on diffusion-weighted MR imaging

International Nuclear Information System (INIS)

Asao, Chiaki; Hirai, Toshinori; Yamashita, Yasuyuki; Yoshimatsu, Shunji; Matsukawa, Tetsuya; Imuta, Masanori; Sagara, Katsuro

2008-01-01

We have often encountered high signal intensity (SI) of the cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity on DW images has not been investigated systematically. The purpose of our study was to determine whether there is regional signal variation in the brain cortices of neurologically healthy adults on DW-MR images. The SI of the cerebral cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes were analyzed by visually assessment of the differences in appearance among the cortices on apparent diffusion coefficient (ADC) maps. Increased SI was frequently seen in the cingulate gyrus and insula regardless of patient age. There were no significant gender- or laterality-related differences. The CNR was significantly higher in the cingulate gyrus and insula than in the other cortices (p <.01), and significant differences existed among the cortical regions (p <.001). There were no apparent ADC differences among the cortices on ADC maps. Regional signal variation of the brain cortices was observed on DW-MR images of healthy subjects, and the cingulate gyrus and insula frequently manifested high SI. These findings may help in the recognition of cortical signal abnormalities as visualized on DW-MR images. (orig.)

Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

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Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

2015-12-01

Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

Isolation and characterization of neural stem cells from human fetal striatum

International Nuclear Information System (INIS)

Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

2005-01-01

This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

Extensive cochleotopic mapping of human auditory cortical fields obtained with phase-encoding FMRI.

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Ella Striem-Amit

Full Text Available The primary sensory cortices are characterized by a topographical mapping of basic sensory features which is considered to deteriorate in higher-order areas in favor of complex sensory features. Recently, however, retinotopic maps were also discovered in the higher-order visual, parietal and prefrontal cortices. The discovery of these maps enabled the distinction between visual regions, clarified their function and hierarchical processing. Could such extension of topographical mapping to high-order processing regions apply to the auditory modality as well? This question has been studied previously in animal models but only sporadically in humans, whose anatomical and functional organization may differ from that of animals (e.g. unique verbal functions and Heschl's gyrus curvature. Here we applied fMRI spectral analysis to investigate the cochleotopic organization of the human cerebral cortex. We found multiple mirror-symmetric novel cochleotopic maps covering most of the core and high-order human auditory cortex, including regions considered non-cochleotopic, stretching all the way to the superior temporal sulcus. These maps suggest that topographical mapping persists well beyond the auditory core and belt, and that the mirror-symmetry of topographical preferences may be a fundamental principle across sensory modalities.

Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development.

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Keith M Godfrey

Full Text Available Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001 and at age 4 years (r = 0.16, P = 0.02. In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02. This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04. We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fat.

Mapping auditory core, lateral belt, and parabelt cortices in the human superior temporal gyrus

DEFF Research Database (Denmark)

Sweet, Robert A; Dorph-Petersen, Karl-Anton; Lewis, David A

2005-01-01

The goal of the present study was to determine whether the architectonic criteria used to identify the core, lateral belt, and parabelt auditory cortices in macaque monkeys (Macaca fascicularis) could be used to identify homologous regions in humans (Homo sapiens). Current evidence indicates...

The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Integration of Animal and Human Evidence for PFOA Effects on Fetal Growth

Science.gov (United States)

Koustas, Erica; Sutton, Patrice; Johnson, Paula I.; Atchley, Dylan S.; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

2014-01-01

Background: The Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making. Objective: Our aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question “Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?” Methods: We developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as “high,” “moderate,” or “low”; b) rate the strength of the human and nonhuman evidence separately as “sufficient,” “limited,” “moderate,” or “evidence of lack of toxicity”; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion. Results: We identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as “moderate” quality and “sufficient” strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is “known to be toxic” to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. Conclusion: We concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health. Citation: Lam J, Koustas E, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health

Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

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Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

2017-09-01

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also

Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators.

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Lim, R; Barker, G; Lappas, M

2015-04-01

In non-gestational tissues, the activation of adenosine monophosphate (AMP)-activated kinase (AMPK) is associated with potent anti-inflammatory actions. Infection and/or inflammation, by stimulating pro-inflammatory cytokines and matrix metalloproteinase (MMP)-9, play a central role in the rupture of fetal membranes. However, no studies have examined the role of AMPK in human labour. Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and after preterm pre-labour rupture of membranes (PPROM). AMPK activity was assessed by Western blotting of phosphorylated AMPK expression. To determine the effect of AMPK activators on pro-inflammatory cytokines, fetal membranes were pre-treated with AMPK activators then stimulated with bacterial products LPS and flagellin or viral dsDNA analogue poly(I:C). Primary amnion cells were used to determine the effect of AMPK activators on IL-1β-stimulated MMP-9 expression. AMPK activity was decreased with term labour. There was no effect of preterm labour. AMPK activity was also decreased in preterm fetal membranes, in the absence of labour, with PROM compared to intact membranes. AMPK activators AICAR, phenformin and A769662 significantly decreased IL-6 and IL-8 stimulated by LPS, flagellin and poly(I:C). Primary amnion cells treated with AMPK activators significantly decreased IL-1β-induced MMP-9 expression. The decrease in AMPK activity in fetal membranes after spontaneous term labour and PPROM indicates an anti-inflammatory role for AMPK in human labour and delivery. The use of AMPK activators as possible therapeutics for threatened preterm labour would be an exciting future avenue of research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reduced cell number in the neocortical part of the human fetal brain in Down syndrome

DEFF Research Database (Denmark)

Larsen, K.B.; Laursen, H.; Graem, N.

2008-01-01

Mental retardation is seen in all individuals with Down syndrome (DS) and different brain abnormalities are reported. The aim of this study was to investigate if mental retardation at least in part is a result of a lower cell number in the neocortical part of the human fetal forebrain. We therefore...

Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

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Nitsche, Michael A; Grundey, Jessica; Liebetanz, David; Lang, Nicolas; Tergau, Frithjof; Paulus, Walter

2004-11-01

Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

Cortical thickness development of human primary visual cortex related to the age of blindness onset.

Science.gov (United States)

Li, Qiaojun; Song, Ming; Xu, Jiayuan; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

2017-08-01

Blindness primarily induces structural alteration in the primary visual cortex (V1). Some studies have found that the early blind subjects had a thicker V1 compared to sighted controls, whereas late blind subjects showed no significant differences in the V1. This implies that the age of blindness onset may exert significant effects on the development of cortical thickness of the V1. However, no previous research used a trajectory of the age of blindness onset-related changes to investigate these effects. Here we explored this issue by mapping the cortical thickness trajectory of the V1 against the age of blindness onset using data from 99 blind individuals whose age of blindness onset ranged from birth to 34 years. We found that the cortical thickness of the V1 could be fitted well with a quadratic curve in both the left (F = 11.59, P = 3 × 10 -5 ) and right hemispheres (F = 6.54, P = 2 × 10 -3 ). Specifically, the cortical thickness of the V1 thinned rapidly during childhood and adolescence and did not change significantly thereafter. This trend was not observed in the primary auditory cortex (A1), primary motor cortex (M1), or primary somatosensory cortex (S1). These results provide evidence that an onset of blindness before adulthood significantly affects the cortical thickness of the V1 and suggest a critical period for cortical development of the human V1.

Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

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DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

2016-01-01

Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodermal activity and fetal heart rate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include: within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physiological processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship. We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

Human fetal liver stromal cells that overexpress bFGF support growth and maintenance of human embryonic stem cells.

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Jiafei Xi

Full Text Available In guiding hES cell technology toward the clinic, one key issue to be addressed is to culture and maintain hES cells much more safely and economically in large scale. In order to avoid using mouse embryonic fibroblasts (MEFs we isolated human fetal liver stromal cells (hFLSCs from 14 weeks human fetal liver as new human feeder cells. hFLSCs feeders could maintain hES cells for 15 passages (about 100 days. Basic fibroblast growth factor (bFGF is known to play an important role in promoting self-renewal of human embryonic stem (hES cells. So, we established transgenic hFLSCs that stably express bFGF by lentiviral vectors. These transgenic human feeder cells--bFGF-hFLSCs maintained the properties of H9 hES cells without supplementing with any exogenous growth factors. H9 hES cells culturing under these conditions maintained all hES cell features after prolonged culture, including the developmental potential to differentiate into representative tissues of all three embryonic germ layers, unlimited and undifferentiated proliferative ability, and maintenance of normal karyotype. Our results demonstrated that bFGF-hFLSCs feeder cells were central to establishing the signaling network among bFGF, insulin-like growth factor 2 (IGF-2, and transforming growth factor β (TGF-β, thereby providing the framework in which hES cells were instructed to self-renew or to differentiate. We also found that the conditioned medium of bFGF-hFLSCs could maintain the H9 hES cells under feeder-free conditions without supplementing with bFGF. Taken together, bFGF-hFLSCs had great potential as feeders for maintaining pluripotent hES cell lines more safely and economically.

Recognizing different tissues in human fetal femur cartilage by label-free Raman microspectroscopy

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Kunstar, Aliz; Leijten, Jeroen; van Leuveren, Stefan; Hilderink, Janneke; Otto, Cees; van Blitterswijk, Clemens A.; Karperien, Marcel; van Apeldoorn, Aart A.

2012-11-01

Traditionally, the composition of bone and cartilage is determined by standard histological methods. We used Raman microscopy, which provides a molecular "fingerprint" of the investigated sample, to detect differences between the zones in human fetal femur cartilage without the need for additional staining or labeling. Raman area scans were made from the (pre)articular cartilage, resting, proliferative, and hypertrophic zones of growth plate and endochondral bone within human fetal femora. Multivariate data analysis was performed on Raman spectral datasets to construct cluster images with corresponding cluster averages. Cluster analysis resulted in detection of individual chondrocyte spectra that could be separated from cartilage extracellular matrix (ECM) spectra and was verified by comparing cluster images with intensity-based Raman images for the deoxyribonucleic acid/ribonucleic acid (DNA/RNA) band. Specific dendrograms were created using Ward's clustering method, and principal component analysis (PCA) was performed with the separated and averaged Raman spectra of cells and ECM of all measured zones. Overall (dis)similarities between measured zones were effectively visualized on the dendrograms and main spectral differences were revealed by PCA allowing for label-free detection of individual cartilaginous zones and for label-free evaluation of proper cartilaginous matrix formation for future tissue engineering and clinical purposes.

Low vascularization of the nephrogenic zone of the fetal kidney suggests a major role for hypoxia in human nephrogenesis.

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Gerosa, C; Fanni, D; Faa, A; Van Eyken, P; Ravarino, A; Fanos, V; Faa, G

2017-09-01

CD31 reactivity is generally utilized as a marker of endothelial cells. CD31 immunoreactivity in the developing human kidney revealed that fetal glomerular capillary endothelial cells change their immunohistochemical phenotype during maturation. The aim of this study was to analyze CD31 reactivity in the fetal human kidney in the different stages of intrauterine development: We observed different distribution of CD31-reactive vascular progenitors in the different areas of the developing kidney. In particular, the nephrogenic zone and the renal capsule were characterized by a scarcity of CD31-reactive cells at all gestational ages. These data suggest the hypothesis that nephrogenesis does not need high oxygen levels and confirms a major role of hypoxia in nephrogenesis.

21 CFR 864.7455 - Fetal hemoglobin assay.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal hemoglobin...

Human occipital cortices differentially exert saccadic suppression: intracranial recording in children

Science.gov (United States)

Uematsu, Mitsugu; Matsuzaki, Naoyuki; Brown, Erik C.; Kojima, Katsuaki; Asano, Eishi

2013-01-01

By repeating saccades unconsciously, humans explore the surrounding world every day. Saccades inevitably move external visual images across the retina at high velocity; nonetheless, healthy humans don’t perceive transient blurring of the visual scene during saccades. This perceptual stability is referred to as saccadic suppression. Functional suppression is believed to take place transiently in the visual systems, but it remains unknown how commonly or differentially the human occipital lobe activities are suppressed at the large-scale cortical network level. We determined the spatial-temporal dynamics of intracranially-recorded gamma activity at 80–150 Hz around spontaneous saccades under no-task conditions during wakefulness and those in darkness during REM sleep. Regardless of wakefulness or REM sleep, a small degree of attenuation of gamma activity was noted in the occipital regions during saccades, most extensively in the polar and least in the medial portions. Longer saccades were associated with more intense gamma-attenuation. Gamma-attenuation was subsequently followed by gamma-augmentation most extensively involving the medial and least involving the polar occipital region. Such gamma-augmentation was more intense during wakefulness and temporally locked to the offset of saccades. The polarities of initial peaks of perisaccadic event-related potentials (ERPs) were frequently positive in the medial and negative in the polar occipital regions. The present study, for the first time, provided the electrophysiological evidence that human occipital cortices differentially exert peri-saccadic modulation. Transiently suppressed sensitivity of the primary visual cortex in the polar region may be an important neural basis for saccadic suppression. Presence of occipital gamma-attenuation even during REM sleep suggests that saccadic suppression might be exerted even without external visual inputs. The primary visual cortex in the medial region, compared to the

Anatomical relationships between testis and epididymis during the fetal period in humans (10-36 weeks postconception)

NARCIS (Netherlands)

Favorito, LA; Sampaio, FJB

1998-01-01

Objective: To determine the anatomy of the epididymis and its relationship with the testis during the fetal period in normal individuals. Methods: We studied bilaterally 146 testes and epididymides taken from 73 normal fresh human fetuses ranging in age from 10 to 36 weeks postconception. The

Effects of environmental Bisphenol A exposures on germ cell development and Leydig cell function in the human fetal testis.

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Soria Eladak

Full Text Available Using an organotypic culture system termed human Fetal Testis Assay (hFeTA we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models.Using the hFeTA system, first trimester testes were cultured for 3 days with 0.01 to 10 μM BPA. For xenografts, adult castrate male nude mice were injected with hCG and grafted with first trimester testes. Host mice received 10 μM BPA (~ 500 μg/kg/day in their drinking water for 5 weeks. Plasma levels of total and unconjugated BPA were 0.10 μM and 0.038 μM respectively. Mice grafted with second trimester testes received 0.5 and 50 μg/kg/day BPA by oral gavage for 5 weeks.With first trimester human testes, using the hFeTA model, 10 μM BPA increased germ cell apoptosis. In xenografts, germ cell density was also reduced by BPA exposure. Importantly, BPA exposure significantly decreased the percentage of germ cells expressing the pluripotency marker AP-2γ, whilst the percentage of those expressing the pre-spermatogonial marker MAGE-A4 significantly increased. BPA exposure did not affect hCG-stimulated androgen production in first and second trimester xenografts as evaluated by both plasma testosterone level and seminal vesicle weight in host mice.Exposure to BPA at environmentally relevant concentrations impairs germ cell development in first trimester human fetal testis, whilst gonadotrophin-stimulated testosterone production was unaffected in both first and second trimester testis. Studies using first trimester human fetal testis demonstrate the complementarity of the FeTA and xenograft models for determining the respective short-term and long term effects of environmental exposures.

Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?

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Burnouf, Thierry; Strunk, Dirk; Koh, Mickey B C; Schallmoser, Katharina

2016-01-01

The essential physiological role of platelets in wound healing and tissue repair builds the rationale for the use of human platelet derivatives in regenerative medicine. Abundant growth factors and cytokines stored in platelet granules can be naturally released by thrombin activation and clotting or artificially by freeze/thaw-mediated platelet lysis, sonication or chemical treatment. Human platelet lysate prepared by the various release strategies has been established as a suitable alternative to fetal bovine serum as culture medium supplement, enabling efficient propagation of human cells under animal serum-free conditions for a multiplicity of applications in advanced somatic cell therapy and tissue engineering. The rapidly increasing number of studies using platelet derived products for inducing human cell proliferation and differentiation has also uncovered a considerable variability of human platelet lysate preparations which limits comparability of results. The main variations discussed herein encompass aspects of donor selection, preparation of the starting material, the possibility for pooling in plasma or additive solution, the implementation of pathogen inactivation and consideration of ABO blood groups, all of which can influence applicability. This review outlines the current knowledge about human platelet lysate as a powerful additive for human cell propagation and highlights its role as a prevailing supplement for human cell culture capable to replace animal serum in a growing spectrum of applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Navigation Guide - evidence-based medicine meets environmental health: integration of animal and human evidence for PFOA effects on fetal growth.

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Lam, Juleen; Koustas, Erica; Sutton, Patrice; Johnson, Paula I; Atchley, Dylan S; Sen, Saunak; Robinson, Karen A; Axelrad, Daniel A; Woodruff, Tracey J

2014-10-01

The Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making. Our aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question "Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?" We developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as "high," "moderate," or "low"; b) rate the strength of the human and nonhuman evidence separately as "sufficient," "limited," "moderate," or "evidence of lack of toxicity"; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion. We identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as "moderate" quality and "sufficient" strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is "known to be toxic" to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. We concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health.

On the homogeneity and heterogeneity of cortical thickness profiles in Homo sapiens sapiens.

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Koten, Jan Willem; Schüppen, André; Morozova, Maria; Lehofer, Agnes; Koschutnig, Karl; Wood, Guilherme

2017-12-20

Cortical thickness has been investigated since the beginning of the 20th century, but we do not know how similar the cortical thickness profiles among humans are. In this study, the local similarity of cortical thickness profiles was investigated using sliding window methods. Here, we show that approximately 5% of the cortical thickness profiles are similarly expressed among humans while 45% of the cortical thickness profiles show a high level of heterogeneity. Therefore, heterogeneity is the rule, not the exception. Cortical thickness profiles of somatosensory homunculi and the anterior insula are consistent among humans, while the cortical thickness profiles of the motor homunculus are more variable. Cortical thickness profiles of homunculi that code for muscle position and skin stimulation are highly similar among humans despite large differences in sex, education, and age. This finding suggests that the structure of these cortices remains well preserved over a lifetime. Our observations possibly relativize opinions on cortical plasticity.

Aging and Fracture of Human Cortical Bone and Tooth Dentin

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Ager, Joel; Koester, Kurt J.; Ager III, Joel W.; Ritchie, Robert O.

2008-05-07

Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force, e.g., the stress intensity, as a function of crack extension ("R-curve approach"). Here this methodology is used to study of the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

Towards a new era in fetal medicine in the Nordic countries

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Sitras, Vasilis; Brodszki, Jana; Carlsson, Ylva

2016-01-01

Fetal medicine is a subspecialty of obstetrics investigating the development, growth and disease of the human fetus. The advances in fetal imaging (ultrasonography, MRI) and molecular diagnostic techniques, together with the possibility of intervention in utero, make fetal medicine an important, ...

Lifespan anxiety is reflected in human amygdala cortical connectivity

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He, Ye; Xu, Ting; Zhang, Wei

2016-01-01

Abstract The amygdala plays a pivotal role in processing anxiety and connects to large‐scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting‐state functional MRI data from 280 healthy adults (18–83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network‐specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network‐specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety–connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety–connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety–gender interactions on its iFC with amygdala. Together with findings from additional vertex‐wise analysis, these data clearly indicated that both low‐level sensory networks and high‐level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders. Hum Brain Mapp 37:1178–1193, 2016. © 2015 The Authors Human Brain Mapping

Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary.

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Fowler, Paul A; Anderson, Richard A; Saunders, Philippa T; Kinnell, Hazel; Mason, J Ian; Evans, Dean B; Bhattacharya, Siladitya; Flannigan, Samantha; Franks, Stephen; Monteiro, Ana; O'Shaughnessy, Peter J

2011-06-01

Ovarian primordial follicle formation is critical for subsequent human female fertility. It is likely that steroid, and especially estrogen, signaling is required for this process, but details of the pathways involved are currently lacking. The aim was to identify and characterize key members of the steroid-signaling pathway expressed in the second trimester human fetal ovary. We conducted an observational study of the female fetus, quantifying and localizing steroid-signaling pathway members. The study was conducted at the Universities of Aberdeen, Edinburgh, and Glasgow. Ovaries were collected from 43 morphologically normal human female fetuses from women undergoing elective termination of second trimester pregnancies. We measured mRNA transcript levels and immunolocalized key steroidogenic enzymes and steroid receptors, including those encoded by ESR2, AR, and CYP19A1. Levels of mRNA encoding the steroidogenic apparatus and steroid receptors increased across the second trimester. CYP19A1 transcript increased 4.7-fold during this period with intense immunostaining for CYP19A detected in pregranulosa cells around primordial follicles and somatic cells around oocyte nests. ESR2 was localized primarily to germ cells, but androgen receptor was exclusively expressed in somatic cells. CYP17A1 and HSD3B2 were also localized to oocytes, whereas CYP11A1 was detected in oocytes and some pregranulosa cells. The human fetal ovary expresses the machinery to produce and detect multiple steroid signaling pathways, including estrogenic signaling, with the oocyte acting as a key component. This study provides a step-change in our understanding of local dynamics of steroid hormone signaling during the key period of human primordial follicle formation.

Common cortical responses evoked by appearance, disappearance and change of the human face

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Kida Tetsuo

2009-04-01

Full Text Available Abstract Background To segregate luminance-related, face-related and non-specific components involved in spatio-temporal dynamics of cortical activations to a face stimulus, we recorded cortical responses to face appearance (Onset, disappearance (Offset, and change (Change using magnetoencephalography. Results Activity in and around the primary visual cortex (V1/V2 showed luminance-dependent behavior. Any of the three events evoked activity in the middle occipital gyrus (MOG at 150 ms and temporo-parietal junction (TPJ at 250 ms after the onset of each event. Onset and Change activated the fusiform gyrus (FG, while Offset did not. This FG activation showed a triphasic waveform, consistent with results of intracranial recordings in humans. Conclusion Analysis employed in this study successfully segregated four different elements involved in the spatio-temporal dynamics of cortical activations in response to a face stimulus. The results show the responses of MOG and TPJ to be associated with non-specific processes, such as the detection of abrupt changes or exogenous attention. Activity in FG corresponds to a face-specific response recorded by intracranial studies, and that in V1/V2 is related to a change in luminance.

High vulnerability of the developing fetal brain to ionizing radiation and hyperthermia

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Kameyama, Yoshiro

1989-01-01

The developing brain is one of the fetal structures most susceptible to environmental teratogenic insults, because of its long-lasting sensitive period extending from the beginning of embryonic organogenesis to the postnatal infantile period, the great vulnerability of undifferentiated neural cells to a wide range of environmental agents, and the lack of further reproductive capacity of neurons. Among the environmental agents which affect the developing brain, ionizing radiation and hyperthermia are regarded as the most important physical agents. The most prevalent disorders of the brain produced are histogenetic ones such as a deficit of cortical neurons, disorganized cortical architecture, and poor dendritic arborization of the cortical neurons. In this review, emphasis is given to a review of studies on the critical development stage for the induction of histogenetic disorders of the cerebral cortex and on the high vulnerability of developing neuronal cells to the two physical environmental agents mentioned. (author) 59 refs

An anatomical and functional topography of human auditory cortical areas

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Michelle eMoerel

2014-07-01

Full Text Available While advances in magnetic resonance imaging (MRI throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla. Importantly, we illustrate that - whereas a group-based approach to analyze functional (tonotopic maps is appropriate to highlight the main tonotopic axis - the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e. myelination as well as of functional properties (e.g. broadness of frequency tuning is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions.

Fetal hyperglycemia changes human preadipocyte function in adult life

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Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line

2017-01-01

Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal...... acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease....

MSCs can be differentially isolated from maternal, middle and fetal segments of the human umbilical cord.

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Lim, Jezamine; Razi, Zainul Rashid Mohamad; Law, Jiaxian; Nawi, Azmawati Mohammed; Idrus, Ruszymah Binti Haji; Ng, Min Hwei

2016-12-01

Human Wharton's jelly-derived mesenchymal stromal cells (hWJMSCs) are possibly the most suitable allogeneic cell source for stromal cell therapy and tissue engineering applications because of their hypo-immunogenic and non-tumorigenic properties, easy availability and minimal ethical concerns. Furthermore, hWJMSCs possess unique properties of both adult mesenchymal stromal cells and embryonic stromal cells. The human umbilical cord (UC) is approximately 50-60 cm long and the existing studies in the literature have not provided information on which segment of the UC was studied. In this study, hWJMSCs derived from three anatomical segments of the UC are compared. Three segments of the whole UC, each 3 cm in length, were identified anatomically as the maternal, middle and fetal segments. The hWJMSCs from the different segments were analyzed via trypan blue exclusion assay to determine the growth kinetics and cell viability, flow cytometry for immunophenotyping and immunofluorescence and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of stromal cell transcriptional factors. Furthermore, the trilineage differentiation potential (osteogenic, adipogenic and chondrogenic) of these cells was also assessed. hWJMSCs isolated from the maternal and fetal segments displayed greater viability and possessed a significantly higher proliferation rate compared with cells from the middle segment. Immunophenotyping revealed that hWJMSCs derived from all three segments expressed the MSC markers CD105, CD73, CD90, CD44, CD13 and CD29, as well as HLA-ABC and HLA-DR, but were negative for hematopoietic markers CD14, CD34 and CD45. Analysis of the embryonic markers showed that all three segments expressed Nanog and Oct 3/4, but only the maternal and fetal segments expressed SSEA 4 and TRA-160. Cells from all three segments were able to differentiate into chondrogenic, osteogenic and adipogenic lineages with the middle segments showing much lower differentiation

Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

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Linn S Strandberg

Full Text Available Congenital heart block (CHB is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation. Using human fetal hearts (20-22 wks gestation, our immunoprecipitation (IP, Western blot analysis and immunofluorescence (IF staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I. Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN cells.Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

Rab11 family expression in the human placenta: Localization at the maternal-fetal interface

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Artemiuk, Patrycja A.; Hanscom, Sara R.; Lindsay, Andrew J.; Wuebbolt, Danielle; Breathnach, Fionnuala M.; Tully, Elizabeth C.; Khan, Amir R.; McCaffrey, Mary W.

2017-01-01

Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting. The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. These findings encouraged us to further analyse the localization of these Rabs and their common effector protein, the Rab Coupling Protein (RCP), by immunofluorescence microscopy and to extend this work to normal human placental tissue. The placenta is a highly active exchange interface, facilitating transfer between mother and fetus during pregnancy. As Rab11 proteins are closely involved in transcytosis we hypothesized that the placenta would be an interesting human tissue model system for Rab investigation. By immunofluorescence microscopy, Rab11a, Rab11c(Rab25), Rab14 as well as their common FIP effector RCP showed prominent expression in the placental cell lines. We also identified the expression of these proteins in human placental lysates by Western blot analysis. Further, via fluorescent immunohistochemistry, we noted abundant localization of these proteins within key functional areas of primary human placental tissues, namely the outer syncytial layer of placental villous tissue and the endothelia of fetal blood vessels. Overall these findings highlight the expression of the Rab11 family within the human

The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin.

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Stelnicki, E J; Kömüves, L G; Holmes, D; Clavin, W; Harrison, M R; Adzick, N S; Largman, C

1997-10-01

In order to identify homeobox genes which may regulate skin development and possibly mediate scarless fetal wound healing we have screened amplified human fetal skin cDNAs by polymerase chain reaction (PCR) using degenerate oligonucleotide primers designed against highly conserved regions within the homeobox. We identified three non-HOX homeobox genes, MSX-1, MSX-2, and MOX-1, which were differentially expressed in fetal and adult human skin. MSX-1 and MSX-2 were detected in the epidermis, hair follicles, and fibroblasts of the developing fetal skin by in situ hybridization. In contrast, MSX-1 and MSX-2 expression in adult skin was confined to epithelially derived structures. Immunohistochemical analysis of these two genes suggested that their respective homeoproteins may be differentially regulated. While Msx-1 was detected in the cell nucleus of both fetal and adult skin; Msx-2 was detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in adult epidermis. MOX-1 was expressed in a pattern similar to MSX early in gestation but then was restricted exclusively to follicular cells in the innermost layer of the outer root sheath by 21 weeks of development. Furthermore, MOX-1 expression was completely absent in adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in skin development.

Fetal injury induced by Ca-DTPA in dogs

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Taylor, G.N.; Mays, C.W.

1978-01-01

The chelating agent Ca-DTPA, used to remove plutonium from the body, has produced fetal deaths and deformities in mice and rats. Damage is caused by depletion of essential trace elements, particularly zinc and manganese. It is suggested that a relationship may exist between the daily amount of Ca-DTPA,per kg body weight needed,to produce fetal toxicity and the daily intake of dietary zinc per kg body weight, and that this relationship could be used to predict fetal toxicity thresholds in various species. Results of a study on beagles are presented. Ca-DTPA treatment at the dose levels used in human therapy did not produce any symptoms in the pregnant dams but the fetuses showed depressed birth weight, abnormal hair colour due to pigmentary deficiency, brain damage and neutropenia. Extrapolation from dogs to humans predicts a toxic fetal dose less that one sixth of the daily dosage presently used for an adult woman, and emphasizes the hazards of Ca-DTPA therapy during pregnancy. (author)

Model cortical association fields account for the time course and dependence on target complexity of human contour perception.

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Vadas Gintautas

2011-10-01

Full Text Available Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas distributed among groups of randomly rotated fragments (clutter. The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms, followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least [Formula: see text] ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas.

Vision first? The development of primary visual cortical networks is more rapid than the development of primary motor networks in humans.

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Patricia Gervan

Full Text Available The development of cortical functions and the capacity of the mature brain to learn are largely determined by the establishment and maintenance of neocortical networks. Here we address the human development of long-range connectivity in primary visual and motor cortices, using well-established behavioral measures--a Contour Integration test and a Finger-tapping task--that have been shown to be related to these specific primary areas, and the long-range neural connectivity within those. Possible confounding factors, such as different task requirements (complexity, cognitive load are eliminated by using these tasks in a learning paradigm. We find that there is a temporal lag between the developmental timing of primary sensory vs. motor areas with an advantage of visual development; we also confirm that human development is very slow in both cases, and that there is a retained capacity for practice induced plastic changes in adults. This pattern of results seems to point to human-specific development of the "canonical circuits" of primary sensory and motor cortices, probably reflecting the ecological requirements of human life.

The use of small interfering RNAs to inhibit adipocyte differentiation in human preadipocytes and fetal-femur-derived mesenchymal cells

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Xu, Y.; Mirmalek-Sani, S.-H.; Yang, X.; Zhang, J.; Oreffo, R.O.C.

2006-01-01

RNA interference (RNAi) has been used in functional genomics and offers innovative approaches in the development of novel therapeutics. Human mesenchymal stem cells offer a unique cell source for tissue engineering/regeneration strategies. The current study examined the potential of small interfering RNAs (siRNA) against human peroxisome proliferator activated receptor gamma (PPARγ) to suppress adipocyte differentiation (adipogenesis) in human preadipocytes and fetal-femur-derived mesenchymal cells. Adipogenesis was investigated using cellular and biochemical analysis. Transient transfection with PPARγ-siRNA using a liposomal-based strategy resulted in a significant inhibition of adipogenesis in human preadipocytes and fetal-femur-derived mesenchymal cells, compared to controls (cell, liposomal and negative siRNA). The inhibitory effect of PPARγ-siRNA was supported by testing human PPARγ mRNA and adipogenic associated genes using reverse transcription polymerase chain reaction (RT-PCR) to adiponectin receptor 1 and 2 as well as examination of fatty acid binding protein 3 (FABP 3 ) expression, an adipocyte-specific marker. The current studies indicate that PPARγ-siRNA is a useful tool to study adipogenesis in human cells, with potential applications both therapeutic and in the elucidation of mesenchymal cell differentiation in the modulation of cell differentiation in human mesenchymal cells

Developmental changes in human dopamine neurotransmission: cortical receptors and terminators

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Rothmond Debora A

2012-02-01

Full Text Available Abstract Background Dopamine is integral to cognition, learning and memory, and dysfunctions of the frontal cortical dopamine system have been implicated in several developmental neuropsychiatric disorders. The dorsolateral prefrontal cortex (DLPFC is critical for working memory which does not fully mature until the third decade of life. Few studies have reported on the normal development of the dopamine system in human DLPFC during postnatal life. We assessed pre- and postsynaptic components of the dopamine system including tyrosine hydroxylase, the dopamine receptors (D1, D2 short and D2 long isoforms, D4, D5, catechol-O-methyltransferase, and monoamine oxidase (A and B in the developing human DLPFC (6 weeks -50 years. Results Gene expression was first analysed by microarray and then by quantitative real-time PCR. Protein expression was analysed by western blot. Protein levels for tyrosine hydroxylase peaked during the first year of life (p O-methyltransferase (p = 0.024 were significantly higher in neonates and infants as was catechol-O-methyltransferase protein (32 kDa, p = 0.027. In contrast, dopamine D1 receptor mRNA correlated positively with age (p = 0.002 and dopamine D1 receptor protein expression increased throughout development (p Conclusions We find distinct developmental changes in key components of the dopamine system in DLPFC over postnatal life. Those genes that are highly expressed during the first year of postnatal life may influence and orchestrate the early development of cortical neural circuitry while genes portraying a pattern of increasing expression with age may indicate a role in DLPFC maturation and attainment of adult levels of cognitive function.

Malnutrition during fetal life, fetal programming and implications for farm aninals productivity

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Nielsen, Mette Olaf; Khanal, Prabhat; Johnsen, Lærke

Some 20 years ago, observations from human epidemiological research revolutionized the scientific view of the importance of fetal life development for body functions in postnatal life. Until then, it was believed that the genome received from the parents at conception in mammals would define the ...

Development of the penis during the human fetal period (13 to 36 weeks after conception).

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Gallo, Carla B M; Costa, Waldemar S; Furriel, Angelica; Bastos, Ana L; Sampaio, Francisco J B

2013-11-01

We analyzed the development of the area of the penis and erectile structures (corpora cavernosa and corpus spongiosum) and the thickness of the tunica albuginea during the fetal period (13 to 36 weeks after conception) in humans to establish normative patterns of growth. We studied 56 male human fetuses at 13 to 36 weeks after conception. We used histochemical and morphometric techniques to analyze the parameters of total penile area, area of corpora cavernosa, area of corpus spongiosum, and thickness of tunica albuginea in the dorsal and ventral regions using ImageJ software (National Institutes of Health, Bethesda, Maryland). Between 13 and 36 weeks after conception the area of the penis varies from 0.95 to 24.25 mm2. The area of the corpora cavernosa varies from 0.28 to 9.12 mm2, and the area of the corpus spongiosum varies from 0.14 to 3.99 mm2. The thickness of the tunica albuginea varies from 0.029 to 0.296 mm in the dorsal region and from 0.014 to 0.113 mm in the ventral region of the corpora cavernosa. We found a strong correlation between the total penile area, corpora cavernosa and corpus spongiosum with fetal age (weeks following conception). The growth rate was more intense during the second trimester (13 to 24 weeks of gestation) compared to the third trimester (25 to 36 weeks). Tunica albuginea thickness also was strongly correlated with fetal age and this structure was thicker in the dorsal vs ventral region. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Assessment of cortical dysfunction in human strabismic amblyopia using magnetoencephalography (MEG)

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Anderson, S.J.; Holliday, I.E.; Harding, G.F.A.

1999-01-01

The aim of this study was to use the technique of magnetoencephalography (MEG) to determine the effects of strabismic amblyopia on the processing of spatial information within the occipital cortex of humans. We recorded evoked magnetic responses to the onset of a chromatic (red/green) sinusoidal grating of periodicity 0.5-4.0 c deg -1 using a 19-channel SQUID-based neuromagnetometer. Evoked responses were recorded monocularly on six amblyopes and six normally-sighted controls, the stimuli being positioned near the fovea in the lower right visual field of each observer. For comparison, the spatial contrast sensitivity function (CSF) for the detection of chromatic gratings was measured for one amblyope and one control using a two alternate forced-choice psychophysical procedure. We chose red/green sinusoids as our stimuli because they evoke strong magnetic responses from the occipital cortex in adult humans (Fylan, Holliday, Singh, Anderson and Harding. (1997). Neuroimage, 6, 47-57). Magnetic field strength was plotted as a function of stimulus spatial frequency for each eye of each subject. Interocular differences were only evident within the amblyopic group: for stimuli of 1-2 c deg -1 , the evoked responses had significantly longer latencies and reduced amplitudes through the amblyopic eye (P<0.05). Importantly, the extent of the deficit was uncorrelated with either Snellen acuity or contrast sensitivity. Localization of the evoked responses was performed using a single equivalent current dipole model. Source localizations, for both normal and amblyopic subjects, were consistent with neural activity at the occipital pole near the V1/V2 border. We conclude that MEG is sensitive to the deficit in cortical processing associated with human amblyopia, and can be used to make quantitative neurophysiological measurements. The nature of the cortical deficit is discussed. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

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Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

2017-01-01

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

Is there a place for human fetal-derived stem cells for cell replacement therapy in Huntington's disease?

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Precious, Sophie V; Zietlow, Rike; Dunnett, Stephen B; Kelly, Claire M; Rosser, Anne E

2017-06-01

Huntington's disease (HD) is a neurodegenerative disease that offers an excellent paradigm for cell replacement therapy because of the associated relatively focal cell loss in the striatum. The predominant cells lost in this condition are striatal medium spiny neurons (MSNs). Transplantation of developing MSNs taken from the fetal brain has provided proof of concept that donor MSNs can survive, integrate and bring about a degree of functional recovery in both pre-clinical studies and in a limited number of clinical trials. The scarcity of human fetal tissue, and the logistics of coordinating collection and dissection of tissue with neurosurgical procedures makes the use of fetal tissue for this purpose both complex and limiting. Alternative donor cell sources which are expandable in culture prior to transplantation are currently being sought. Two potential donor cell sources which have received most attention recently are embryonic stem (ES) cells and adult induced pluripotent stem (iPS) cells, both of which can be directed to MSN-like fates, although achieving a genuine MSN fate has proven to be difficult. All potential donor sources have challenges in terms of their clinical application for regenerative medicine, and thus it is important to continue exploring a wide variety of expandable cells. In this review we discuss two less well-reported potential donor cell sources; embryonic germ (EG) cells and fetal neural precursors (FNPs), both are which are fetal-derived and have some properties that could make them useful for regenerative medicine applications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cortical basis of communication: local computation, coordination, attention.

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Alexandre, Frederic

2009-03-01

Human communication emerges from cortical processing, known to be implemented on a regular repetitive neuronal substratum. The supposed genericity of cortical processing has elicited a series of modeling works in computational neuroscience that underline the information flows driven by the cortical circuitry. In the minimalist framework underlying the current theories for the embodiment of cognition, such a generic cortical processing is exploited for the coordination of poles of representation, as is reported in this paper for the case of visual attention. Interestingly, this case emphasizes how abstract internal referents are built to conform to memory requirements. This paper proposes that these referents are the basis for communication in humans, which is firstly a coordination and an attentional procedure with regard to their congeners.

The Anti-Inflammatory Effects of Lipoxygenase and Cyclo-Oxygenase Inhibitors in Inflammation-Induced Human Fetal Glia Cells and the Aβ Degradation Capacity of Human Fetal Astrocytes in an Ex vivo Assay

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Rea Pihlaja

2017-05-01

Full Text Available Chronic inflammation is a common phenomenon present in the background of multiple neurodegenerative diseases, including Alzheimer's disease (AD. The arachidonic acid pathway overproduces proinflammatory eicosanoids during these states and glial cells in the brain gradually lose their vital functions of protecting and supporting neurons. In this study, the role of different key enzymes of the eicosanoid pathway mediating inflammatory responses was examined in vitro and ex vivo using human fetal glial cells. Astrocytes and microglia were exposed to proinflammatory agents i.e., cytokines interleukin 1-β (IL-1β and tumor necrosis factor (TNF-α. ELISA assays were used to examine the effects of inhibitors of key enzymes in the eicosanoid pathway. Inhibitors for 5-lipoxygenase (5-LOX and cyclo-oxygenase 2 (COX-2 in both cell types and 5-, 12-, and 15-LOX-inhibitor in astrocytes reduced significantly IL-6 secretion, compared to exposed glial cells without inhibitors. The cytokine antibody array showed that especially treatments with 5, -12, and -15 LOX inhibitor in astrocytes, 5-LOX inhibitor in microglia and COX-2 inhibitor in both glial cell types significantly reduced the expression of multiple proinflammatory cytokines. Furthermore, human fetal astrocytes and microglia were cultured on top of AD-affected and control human brain sections for 30 h. According to the immunochemical evaluation of the level of total Aβ, astrocytes were very efficient at degrading Aβ from AD-affected brain sections ex vivo; simultaneously added enzyme inhibitors did not increase their Aβ degradation capabilities. Microglia were not able to reduce the level of total Aβ during the 30 h incubation time.

Magnetic resonance angiography of fetal vasculature at 3.0 T

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Krishnamurthy, Uday; Jella, Pavan K.; Mody, Swati S.; Yadav, Brijesh K.; Hendershot, Kelly; Hernandez-Andrade, Edgar; Yeo, Lami; Cabrera, Maria D.; Haacke, Ewart M.; Hassan, Sonia S.; Romero, Roberto

2016-01-01

Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non-contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possible to visualize fetal vascular networks in late pregnancy. PMID:27189488

Magnetic resonance angiography of fetal vasculature at 3.0 T

International Nuclear Information System (INIS)

Neelavalli, Jaladhar; Krishnamurthy, Uday; Yadav, Brijesh K.; Haacke, Ewart M.; Jella, Pavan K.; Hendershot, Kelly; Cabrera, Maria D.; Mody, Swati S.; Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto

2016-01-01

Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non-contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possible to visualize fetal vascular networks in late pregnancy. (orig.)

Magnetic resonance angiography of fetal vasculature at 3.0 T

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Neelavalli, Jaladhar; Krishnamurthy, Uday; Yadav, Brijesh K.; Haacke, Ewart M. [Wayne State University School of Medicine, Department of Radiology, Detroit, MI (United States); Wayne State University, Department of Biomedical Engineering, Detroit, MI (United States); Jella, Pavan K.; Hendershot, Kelly; Cabrera, Maria D. [Wayne State University School of Medicine, Department of Radiology, Detroit, MI (United States); Mody, Swati S. [Wayne State University School of Medicine, Department of Radiology, Detroit, MI (United States); Children' s Hospital of Michigan, Department of Radiology, Detroit, MI (United States); Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S. [Wayne State University, Department of Obstetrics and Gynecology, Detroit, MI (United States); Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI (United States); Romero, Roberto [Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI (United States); University of Michigan, Department of Obstetrics and Gynecology, Ann Arbor, MI (United States); Michigan State University, Department of Epidemiology and Biostatistics, East Lansing, MI (United States); Wayne State University, Center for Molecular Medicine and Genetics, Detroit, MI (United States)

2016-12-15

Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non-contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possible to visualize fetal vascular networks in late pregnancy. (orig.)

Analysis of gene expression in fetal and adult cells infected with rubella virus

International Nuclear Information System (INIS)

Adamo, Maria Pilar; Zapata, Marta; Frey, Teryl K.

2008-01-01

Congenital infection with rubella virus (RUB) leads to persistent infection and congenital defects and we showed previously that primary human fetal fibroblasts did not undergo apoptosis when infected with RUB, which could promote fetal virus persistence [Adamo, P., Asis, L., Silveyra, P., Cuffini, C., Pedranti, M., Zapata, M., 2004. Rubella virus does not induce apoptosis in primary human embryo fibroblasts cultures: a possible way of viral persistence in congenital infection. Viral Immunol. 17, 87-100]. To extend this observation, gene chip analysis was performed on a line of primary human fetal fibroblasts (10 weeks gestation) and a line of human adult lung fibroblasts (which underwent apoptosis in response to RUB infection) to compare gene expression in infected and uninfected cells. A total of 632 and 516 genes were upregulated or downregulated in the infected fetal and adult cells respectively in comparison to uninfected cells, however only 52 genes were regulated in both cell types. Although the regulated genes were different, across functional gene categories the patterns of gene regulation were similar. In general, regulation of pro- and anti-apoptotic genes following infection appeared to favor apoptosis in the adult cells and lack of apoptosis in the fetal cells, however there was a greater relative expression of anti-apoptotic genes and reduced expression of pro-apoptotic genes in uninfected fetal cells versus uninfected adult cells and thus the lack of apoptosis in fetal cells following RUB infection was also due to the prevailing background of gene expression that is antagonistic to apoptosis. In support of this hypothesis, it was found that of a battery of five chemicals known to induce apoptosis, two induced apoptosis in the adult cells, but not in fetal cells, and two induced apoptosis more rapidly in the adult cells than in fetal cells (the fifth did not induce apoptosis in either). A robust interferon-stimulated gene response was induced

Fetal echocardiography

International Nuclear Information System (INIS)

Chaubal, Nitin G.; Chaubal, Jyoti

2009-01-01

USG performed with a high-end machine, using a good cine-loop facility is extremely helpful in the diagnosis of fetal cardiac anomalies. In fetal echocardiography, the four-chamber view and the outflow-tract view are used to diagnose cardiac anomalies. The most important objective during a targeted anomaly scan is to identify those cases that need a dedicated fetal echocardiogram. Associated truncal and chromosomal anomalies need to be identified. This review shows how fetal echocardiography, apart from identifying structural defects in the fetal heart, can be used to look at rhythm abnormalities and other functional aspects of the fetal heart

Edentulation alters material properties of cortical bone in the human craniofacial skeleton: functional implications for craniofacial structure in primate evolution

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Dechow, Paul C.; Wang, Qian; Peterson, Jill

2011-01-01

Skeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from fifteen edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, while these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area-specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which

Progesterone promotes maternal–fetal tolerance by reducing human maternal T‐cell polyfunctionality and inducing a specific cytokine profile

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Eldershaw, Suzy A.; Inman, Charlotte F.; Coomarasamy, Aravinthan; Moss, Paul A. H.; Kilby, Mark D.

2015-01-01

Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4+ and CD8+ T cells, with reductions not only in potentially deleterious IFN‐γ and TNF‐α production but also in IL‐10 and IL‐5. Conversely, production of IL‐4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL‐4. This was accompanied by reduced T‐cell proliferation. Using fetal and viral antigen‐specific CD8+ T‐cell clones, we confirmed that this as a direct, nonantigen‐specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4+ and CD8+ T cells responded to progesterone in a dose‐dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal–fetal interface. This characterization of how progesterone modulates T‐cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. PMID:26249148

Growth-inhibitory effect of TGF-B on human fetal adrenal cells in primary monolayer culture.

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Riopel, L; Branchaud, C L; Goodyer, C G; Adkar, V; Lefebvre, Y

1989-08-01

We examined the effects of transforming-growth factor-B (TGF-B) on growth ([3H]-thymidine uptake) and function (dehydroepiandrosterone sulfate [DHAS] and cortisol production) of human fetal zone adrenal cells. Results indicate that TGF-B significantly inhibits, in a dose-related manner, both basal and epidermal growth factor (EGF)-stimulated cell growth: IC50 = 0.1-0.25 ng/ml. EGF is ineffective in overcoming the inhibitory effect of TGF-B, suggesting a noncompetitive antagonism between the two factors. Also, the inhibitory effect of TGF-B is additive to that of adrenocorticotropic hormone (ACTH). On the other hand, TGF-B (1 ng/ml) does not significantly change basal or ACTH-stimulated DHAS or cortisol secretion. We conclude that, unlike its effect on other steroid-producing cells, TGF-B inhibits growth of fetal zone cells and does not appear to have a significant inhibitory effect on steroidogenesis.

Fetal magnetic resonance: technique applications and normal fetal anatomy

International Nuclear Information System (INIS)

Martin, C.; Darnell, A.; Duran, C.; Mellado, F.; Corona, M

2003-01-01

Ultrasonography is the preferred diagnostic imaging technique for intrauterine fetal examination. Nevertheless, circumstances sometimes dictate the use of other techniques in order to analyze fetal structures. The advent of ultra rapid magnetic resonance (MR) sequencing has led to the possibility of doing MR fetal studies, since images are obtained in an extradordiarily short time and are not affected by either maternal or fetal movements. It does not employ ionizing radiations, it provides high-contrast images and it can obtain such images in any plane of space without being influenced by either the child bearer's physical characteristics of fetal position. MR provides good quality images of most fetal organs. It is extremely useful in analysing distinct structures, as well as permitting an evaluation of cervical structures, lungs, diaphragms, intra-abdominal and retroperitoneal structures, and fetal extremities. It can also provide useful information regarding the placenta,umbilical cord, amniotic fluid and uterus. The objective of this work is to describe MR technique as applied to intrauterine fetal examination, and to illustrate normal fetal anatomy as manifested by MR and its applications. (Author) 42 refs

Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons.

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Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew Cn; Swindale, Nicholas V; Murphy, Timothy H

2017-02-04

Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps.

Research ethics in Canada: experience of a group operating a human embryo and fetal tissue bank.

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Milos, N; Bamforth, S; Bagnall, K

1999-04-01

A Canadian research group is establishing a human embryo and fetal tissue bank. Its purpose is to provide researchers with frozen or fixed tissue specimens for use in protein and gene expression studies. Several legal and ethical issues have arisen, including questions about consent, use of these rare tissues, cost recovery, and profit-making. These issues are discussed here in light of the present lack of legislation in Canada. We make recommendations in these areas, and suggest that the bank's operations could legally fall under the jurisdiction of the Human Tissue Gift Act.

Human herpesvirus 6A induces apoptosis of primary human fetal astrocytes via both caspase-dependent and -independent pathways

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Gu Bin

2011-12-01

Full Text Available Abstract Background Human herpesvirus 6 (HHV-6 is a T-lymphtropic and neurotropic virus that can infect various types of cells. Sequential studies reported that apoptosis of glia and neurons induced by HHV-6 might act a potential trigger for some central nervous system (CNS diseases. HHV-6 is involved in the pathogenesis of encephalitis, multiple sclerosis (MS and fatigue syndrome. However, the mechanisms responsible for the apoptosis of infected CNS cells induced by HHV-6 are poorly understood. In this study, we investigated the cell death processes of primary human fetal astrocytes (PHFAs during productive HHV-6A infection and the underlying mechanisms. Results HHV-6A can cause productive infection in primary human fetal astrocytes. Annexin V-PI staining and electron microscopic analysis indicated that HHV-6A was an inducer of apoptosis. The cell death was associated with activation of caspase-3 and cleavage of poly (ADP-ribose polymerase (PARP, which is known to be an important substrate for activated caspase-3. Caspase-8 and -9 were also significantly activated in HHV-6A-infected cells. Moreover, HHV-6A infection led to Bax up-regulation and Bcl-2 down-regulation. HHV-6A infection increased the release of Smac/Diablo, AIF and cytochrome c from mitochondria to cytosol, which induced apoptosis via the caspase-dependent and -independent pathways. In addition, we also found that anti-apoptotic factors such as IAPs and NF-κB decreased in HHV-6A infected PHFAs. Conclusion This is the first demonstration of caspase-dependent and -independent apoptosis in HHV-6A-infected glial cells. These findings would be helpful in understanding the mechanisms of CNS diseases caused by HHV-6.

Analysis of fetal movements by Doppler actocardiogram and fetal B-mode imaging.

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Maeda, K; Tatsumura, M; Utsu, M

1999-12-01

We have presented that fetal surveillance may be enhanced by use of the fetal actocardiogram and by computerized processing of fetal motion as well as fetal B-mode ultrasound imaging. Ultrasonic Doppler fetal actogram is a sensitive and objective method for detecting and recording fetal movements. Computer processing of the actograph output signals enables powerful, detailed, and convenient analysis of fetal physiologic phenomena. The actocardiogram is a useful measurement tool not only in fetal behavioral studies but also in evaluation of fetal well-being. It reduces false-positive, nonreactive NST and false-positive sinusoidal FHR pattern. It is a valuable tool to predict fetal distress. The results of intrapartum fetal monitoring are further improved by the antepartum application of the actocardiogram. Quantified fetal motion analysis is a useful, objective evaluation of the embryo and fetus. This method allows monitoring of changes in fetal movement, as well as frequency, amplitude, and duration. Furthermore, quantification of fetal motion enables evaluation of fetal behavior states and how these states relate to other measurements, such as changes in FHR. Numeric analysis of both fetal actogram and fetal motion from B-mode images is a promising application in the correlation of fetal activity or behavior with other fetal physiologic measurements.

Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

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Vesterinen, Hanna M; Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J

2017-01-01

Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

International Nuclear Information System (INIS)

Kurokawa, Yuko; Sekiguchi, Fumiko; Kubo, Satoko; Yamasaki, Yoshiko; Matsuda, Sachi; Okamoto, Yukari; Sekimoto, Teruki; Fukatsu, Anna; Nishikawa, Hiroyuki; Kume, Toshiaki; Fukushima, Nobuyuki; Akaike, Akinori; Kawabata, Atsufumi

2011-01-01

Highlights: ► Hydrogen sulfide causes NMDA receptor-independent neurotoxicity in mouse fetal cortical neurons. ► Activation of ERK mediates the toxicity of hydrogen sulfide. ► Apoptotic mechanisms are involved in the hydrogen-induced cell death. -- Abstract: Hydrogen sulfide (H 2 S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H 2 S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H 2 S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.

How Tough is Human Cortical Bone? In-Situ Measurements on Realistically Short Cracks

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Ritchie, Robert O; Koester, K. J.; Ager III, J. W.; Ritchie, R.O.

2008-05-10

Bone is more difficult to break than to split. Although this is well known, and many studies exist on the behavior of long cracks in bone, there is a need for data on the orientation-dependent crack-growth resistance behavior of human cortical bone which accurately assesses its toughness at appropriate size-scales. Here we use in-situ mechanical testing in the scanning electron microscope and x-ray computed tomography to examine how physiologically-pertinent short (<600 mu m) cracks propagate in both the transverse and longitudinal orientations in cortical bone, using both crack-deflection/twist mechanics and nonlinear-elastic fracture mechanics to determine crack-resistance curves. We find that after only 500 mu m of cracking, the driving force for crack propagation was more than five times higher in the transverse (breaking) direction than in the longitudinal (splitting) direction due to major crack deflections/twists principally at cement sheathes. Indeed, our results show that the true transverse toughness of cortical bone is far higher than previously reported. However, the toughness in the longitudinal orientation, where cracks tend to follow the cement lines, is quite low at these small crack sizes; it is only when cracks become several millimeters in length that bridging mechanisms can develop leading to the (larger-crack) toughnesses generally quoted for bone.

Intrapartum fetal heart rate profiles with and without fetal asphyxia.

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Low, J A; Pancham, S R; Worthington, D N

1977-04-01

Fetal heart rate profiles for periods up to 12 hours prior to delivery have been reviewed in 515 patients with a fetus at risk. Mechanisms other than fetal asphyxia will cause fetal heart rate decelerations, and fetal asphyxia may in some instances develop in the absence of total or late decelerations. However, an increasing incidence of total decelerations and late decelerations and particularly a marked pattern of total decelerations and late decelerations are of value in the prediction of fetal asphyxia. Fetal heart rate deceleration patterns can predict the probability of fetal asphyxia at the time of initial intervention, while a progression of fetal heart rate deceleration patterns in the individual fetus can be of assistance in the subsequent scheduling of serial acid-base assessments during labor.

Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

Science.gov (United States)

Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

2014-05-01

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

A Mechanistic Link from GABA to Cortical Architecture and Perception.

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Kolasinski, James; Logan, John P; Hinson, Emily L; Manners, Daniel; Divanbeighi Zand, Amir P; Makin, Tamar R; Emir, Uzay E; Stagg, Charlotte J

2017-06-05

Understanding both the organization of the human cortex and its relation to the performance of distinct functions is fundamental in neuroscience. The primary sensory cortices display topographic organization, whereby receptive fields follow a characteristic pattern, from tonotopy to retinotopy to somatotopy [1]. GABAergic signaling is vital to the maintenance of cortical receptive fields [2]; however, it is unclear how this fine-grain inhibition relates to measurable patterns of perception [3, 4]. Based on perceptual changes following perturbation of the GABAergic system, it is conceivable that the resting level of cortical GABAergic tone directly relates to the spatial specificity of activation in response to a given input [5-7]. The specificity of cortical activation can be considered in terms of cortical tuning: greater cortical tuning yields more localized recruitment of cortical territory in response to a given input. We applied a combination of fMRI, MR spectroscopy, and psychophysics to substantiate the link between the cortical neurochemical milieu, the tuning of cortical activity, and variability in perceptual acuity, using human somatosensory cortex as a model. We provide data that explain human perceptual acuity in terms of both the underlying cellular and metabolic processes. Specifically, higher concentrations of sensorimotor GABA are associated with more selective cortical tuning, which in turn is associated with enhanced perception. These results show anatomical and neurochemical specificity and are replicated in an independent cohort. The mechanistic link from neurochemistry to perception provides a vital step in understanding population variability in sensory behavior, informing metabolic therapeutic interventions to restore perceptual abilities clinically. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Influence of the fetal bovine serum proteins on the growth of human osteoblast cells on graphene

Czech Academy of Sciences Publication Activity Database

Kalbáčová, M.; Brož, A.; Kalbáč, Martin

100A, č. 11 (2012), s. 3001-3007 ISSN 1549-3296 R&D Projects: GA AV ČR IAA400400911; GA AV ČR KAN200100801; GA ČR GAP204/10/1677; GA ČR(CZ) GAP208/12/1062; GA MŠk ME09060 Institutional support: RVO:61388955 Keywords : human osteoblast * graphene * fetal bovine serum Subject RIV: CG - Electrochemistry Impact factor: 2.834, year: 2012

Human cortical activity related to unilateral movements. A high resolution EEG study.

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Urbano, A; Babiloni, C; Onorati, P; Babiloni, F

1996-12-20

In the present study a modern high resolution electroencephalography (EEG) technique was used to investigate the dynamic functional topography of human cortical activity related to simple unilateral internally triggered finger movements. The sensorimotor area (M1-S1) contralateral to the movement as well as the supplementary motor area (SMA) and to a lesser extent the ipsilateral M1-S1 were active during the preparation and execution of these movements. These findings suggest that both hemispheres may cooperate in both planning and production of simple unilateral volitional acts.

Sex-specific differences in fetal germ cell apoptosis induced by ionizing radiation

International Nuclear Information System (INIS)

Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G.; Bakalska, M.; Frydman, R.; Frydman, R.; Frydman, R.

2009-01-01

Background: We have previously shown that male human fetal germ cells are highly radiosensitive and that their death depends on p53 activation. Male germ cell apoptosis was initiated with doses as low as 0.1 Gy and was prevented by pifithrin α, a p53 inhibitor. In this study, we investigated the radiosensitivity of early female and male fetal proliferating germ cells. Methods and results: Both male and female fetal germ cells displayed a similar number of γH2AX foci in response to ionizing radiation (IR). In organ culture of human fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin α did not affect oogonia apoptosis following irradiation. IR induced apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during oogonial proliferation. Germ cell survival in testes from p53 knockout or p63 knockout mice exposed to IR was better than wild-type, whereas female germ cell survival was unaffected by p53 or p63 knockout. Conclusions: These findings show that pre-meiotic male and female fetal germ cells behave differently in response to a genotoxic stress-irradiation with oogonia being less sensitive and undergoing p53-independent apoptosis. (authors)

Sex-specific differences in fetal germ cell apoptosis induced by ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [CEA, DSV/DRR/SEGG/LDRG, Laboratory of Differentiation and Radiobiology of the Gonads, Unit of Gametogenesis and Genotoxicity, F-92265 Fontenay aux Roses (France); Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [Univ. Paris 7-Denis Diderot, UFR of Biology, UMR-S 566, F-92265 Fontenay aux Roses (France); Guerquin, M.J.; Duquenne, C.; Coffigny, H.; Rouiller-Fabre, V.; Lambrot, R.; Habert, R.; Livera, G. [INSERM, U566, F-92265 Fontenay aux Roses (France); Bakalska, M. [Institute of Experimental Morphology and Anthropology, Bulgarian Academy of Sciences, Sofia (Bulgaria); Frydman, R. [Univ Paris-Sud, Clamart F-92140 (France); Frydman, R. [AP-HP, Service de Gynecologie-Obstetrique et Medecine de la Reproduction, Hopital Antoine Beclere, Clamart F-92141 (France); Frydman, R. [INSERM, U782, Clamart F-92140 (France)

2009-07-01

Background: We have previously shown that male human fetal germ cells are highly radiosensitive and that their death depends on p53 activation. Male germ cell apoptosis was initiated with doses as low as 0.1 Gy and was prevented by pifithrin {alpha}, a p53 inhibitor. In this study, we investigated the radiosensitivity of early female and male fetal proliferating germ cells. Methods and results: Both male and female fetal germ cells displayed a similar number of {gamma}H2AX foci in response to ionizing radiation (IR). In organ culture of human fetal ovaries, the germ cells underwent apoptosis only when exposed to high doses of IR (1.5 Gy and above). Accumulation of p53 was detected in irradiated male human fetal germ cells but not in female ones. Inhibition of p53 with pifithrin {alpha} did not affect oogonia apoptosis following irradiation. IR induced apoptosis similarly in mouse fetal ovaries in organ culture and in vivo during oogonial proliferation. Germ cell survival in testes from p53 knockout or p63 knockout mice exposed to IR was better than wild-type, whereas female germ cell survival was unaffected by p53 or p63 knockout. Conclusions: These findings show that pre-meiotic male and female fetal germ cells behave differently in response to a genotoxic stress-irradiation with oogonia being less sensitive and undergoing p53-independent apoptosis. (authors)

The maturation of cortical sleep rhythms and networks over early development

OpenAIRE

Chu, Catherine Jean; Leahy, J.; Pathmanathan, Jay Sriram; Kramer, M.A.; Cash, Sydney S.

2014-01-01

Objective: Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. Methods: We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. ...

The effect of fetal sex on customized fetal growth charts.

Science.gov (United States)

Rizzo, Giuseppe; Prefumo, Federico; Ferrazzi, Enrico; Zanardini, Cristina; Di Martino, Daniela; Boito, Simona; Aiello, Elisa; Ghi, Tullio

2016-12-01

To evaluate the effect of fetal sex on singleton pregnancy growth charts customized for parental characteristics, race, and parity Methods: In a multicentric cross-sectional study, 8070 ultrasonographic examinations from low-risk singleton pregnancies between 16 and 40 weeks of gestation were considered. The fetal measurements obtained were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Quantile regression was used to examine the impact of fetal sex across the biometric percentiles of the fetal measurements considered together with parents' height, weight, parity, and race. Fetal gender resulted to be a significant covariate for BDP, HC, and AC with higher values for male fetuses (p ≤ 0.0009). Minimal differences were found among sexes for FL. Parity, maternal race, paternal height and maternal height, and weight resulted significantly related to the fetal biometric parameters considered independently from fetal gender. In this study, we constructed customized biometric growth charts for fetal sex, parental, and obstetrical characteristics using quantile regression. The use of gender-specific charts offers the advantage to define individualized normal ranges of fetal biometric parameters at each specific centile. This approach may improve the antenatal identification of abnormal fetal growth.

The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Human Evidence for PFOA Effects on Fetal Growth

Science.gov (United States)

Sutton, Patrice; Atchley, Dylan S.; Koustas, Erica; Lam, Juleen; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

2014-01-01

Background: The Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method. Objective: We applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans. Methods: We applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence. Results: We identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a –18.9 g (95% CI: –29.8, –7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a “moderate” quality rating to the overall body of human evidence. Conclusion: On the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is “sufficient” human evidence that developmental exposure to PFOA reduces fetal growth. Citation: Johnson PI, Sutton P, Atchley DS, Koustas E, Lam J, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth. Environ Health Perspect 122:1028–1039; http://dx.doi.org/10.1289/ehp.1307893 PMID:24968388

Vitamin D: Effects on human reproduction, pregnancy, and fetal well-being.

Science.gov (United States)

Heyden, E L; Wimalawansa, S J

2018-06-01

Pregnancy places exceptional demands on vitamin D and calcium availability; thus, their deficiencies during pregnancy threaten the woman and her fetus. Globally, vitamin D and other micronutrient deficiencies are common during pregnancy, especially in developing countries where pregnant women have less access to nutritional supplements. Vitamin D deficiency has been reported to be as high as 40% among pregnant women. As a pregnancy progresses, the requirements for vitamin D increase and thus, can worsen preexisting hypovitaminosis D. Consequently, hypovitaminosis D is increasingly associated with a higher incidence of fetal miscarriage, preeclampsia, gestational diabetes, bacterial vaginosis, and impaired fetal and childhood growth and development. This review explores the recent advances in the understanding of vitamin D and the pivotal role it plays in human reproduction, with an emphasis on pregnancy and its outcomes. Given the seriousness of the issue, there is a pressing need for clinicians to become aware of the risks associated with not identifying and correcting vitamin D deficiency. Identifying and correcting vitamin D deficiency, including safe exposure to sunlight, is particularly relevant for those who seek assistance with fertility issues or prenatal counseling, and those in the beginning of their pregnancy. The data point to a significant protective effects of vitamin D during pregnancy when the 25(OH)D serum level exceeds 30 ng/mL before pregnancy and during the first trimester and, sufficient levels are maintained throughout the pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study.

Science.gov (United States)

Seed, Mike; van Amerom, Joshua F P; Yoo, Shi-Joon; Al Nafisi, Bahiyah; Grosse-Wortmann, Lars; Jaeggi, Edgar; Jansz, Michael S; Macgowan, Christopher K

2012-11-26

We present the first phase contrast (PC) cardiovascular magnetic resonance (CMR) measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG). A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30-39 weeks). Flow was measured in the major fetal vessels and indexed to the fetal weight. There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96). Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO) 540 ± 101, main pulmonary artery (MPA) 327 ± 68, ascending aorta (AAo) 198 ± 38, superior vena cava (SVC) 147 ± 46, ductus arteriosus (DA) 220 ± 39,pulmonary blood flow (PBF) 106 ± 59,descending aorta (DAo) 273 ± 85, umbilical vein (UV) 160 ± 62, foramen ovale (FO)107 ± 54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60 ± 4, AAo37 ± 4, SVC 28 ± 7, DA 41 ± 8, PBF 19 ± 10, DAo50 ± 12, UV 30 ± 9, FO 21 ± 12. This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.

Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study

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Seed Mike

2012-11-01

Full Text Available Abstract Background We present the first phase contrast (PC cardiovascular magnetic resonance (CMR measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG. Methods A validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30–39 weeks. Flow was measured in the major fetal vessels and indexed to the fetal weight. Results There was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96. Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO 540±101, main pulmonary artery (MPA 327±68, ascending aorta (AAo 198±38, superior vena cava (SVC 147±46, ductus arteriosus (DA 220±39,pulmonary blood flow (PBF 106±59,descending aorta (DAo 273±85, umbilical vein (UV 160±62, foramen ovale (FO107±54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60±4, AAo37±4, SVC 28±7, DA 41±8, PBF 19±10, DAo50±12, UV 30±9, FO 21±12. Conclusion This study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.

Progesterone promotes maternal-fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile.

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Lissauer, David; Eldershaw, Suzy A; Inman, Charlotte F; Coomarasamy, Aravinthan; Moss, Paul A H; Kilby, Mark D

2015-10-01

Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4(+) and CD8(+) T cells, with reductions not only in potentially deleterious IFN-γ and TNF-α production but also in IL-10 and IL-5. Conversely, production of IL-4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL-4. This was accompanied by reduced T-cell proliferation. Using fetal and viral antigen-specific CD8(+) T-cell clones, we confirmed that this as a direct, nonantigen-specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4(+) and CD8(+) T cells responded to progesterone in a dose-dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal-fetal interface. This characterization of how progesterone modulates T-cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fetal MRI; Fetales MRT

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Blondin, D. [Inst. fuer Diagn. Radiologie, Uniklinikum Duesseldorf (Germany); Turowski, B. [Inst. fuer Diagn. Radiologie, Neuroradiologie, Uniklinikum Duesseldorf (Germany); Schaper, J. [Inst. fuer Diagn. Radiologie, Kinderradiologie, Uniklinikum Duesseldorf (Germany)

2007-02-15

Ultrasonography is the method of choice for prenatal malformation screening, but it does not always provide sufficient information for correct diagnosis or adequate abnormality evaluation. Fetal MRI is increasingly being used to complete sonographic findings. It was initially used for evaluation of cerebral abnormalities but is increasingly being applied to other fetal areas. In vivo investigation of fetal brain maturation has been enhanced by MRI. An adequate analysis of fetal chest and abdomen can be achieved with fast T2-, T1-weighted and diffusion-weighted imaging (DWI). The advantages include the great field of view and the excellent soft tissue contrast. This allows correct diagnosis of congenital diaphragmatic hernia and evaluation of the consequences on pulmonary growth. Other pulmonary malformations, such as cystic adenomatoid malformation, sequestration and brochogenic cysts, can also be easily identified. Renal position can be quickly determined using DWI sequences and renal agenesia can be easily diagnosed with only one sequence. Prenatal MRI is virtually as effective as postnatal examination, dispenses with transport of a potentially very ill newborn, and provides logistic advantages. Therefore, prenatal MRI is useful for adequate postnatal treatment of newborns with malformations. (orig.)

Wound healing in a fetal, adult, and scar tissue model: a comparative study

NARCIS (Netherlands)

Coolen, N.A.; Schouten, K.C.; Boekema, B.K.; Middelkoop, E.; Ulrich, M.

2010-01-01

Early gestation fetal wounds heal without scar formation. Understanding the mechanism of this scarless healing may lead to new therapeutic strategies for improving adult wound healing. The aims of this study were to develop a human fetal wound model in which fetal healing can be studied and to

Magnetic resonance angiography of fetal vasculature at 3.0 T

OpenAIRE

Neelavalli, Jaladhar; Krishnamurthy, Uday; Jella, Pavan K.; Mody, Swati S.; Yadav, Brijesh K.; Hendershot, Kelly; Hernandez-Andrade, Edgar; Yeo, Lami; Cabrera, Maria D.; Haacke, Ewart M.; Hassan, Sonia S.; Romero, Roberto

2016-01-01

Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non-contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possibl...

Evaluation of human platelet lysate versus fetal bovine serum for culture of mesenchymal stromal cells.

Science.gov (United States)

Hemeda, Hatim; Giebel, Bernd; Wagner, Wolfgang

2014-02-01

Culture media for therapeutic cell preparations-such as mesenchymal stromal cells (MSCs)-usually comprise serum additives. Traditionally, fetal bovine serum is supplemented in basic research and in most clinical trials. Within the past years, many laboratories adapted their culture conditions to human platelet lysate (hPL), which further stimulates proliferation and expansion of MSCs. Particularly with regard to clinical application, human alternatives for fetal bovine serum are clearly to be preferred. hPL is generated from human platelet units by disruption of the platelet membrane, which is commonly performed by repeated freeze and thaw cycles. Such culture supplements are notoriously ill-defined, and many parameters contribute to batch-to-batch variation in hPL such as different amounts of plasma, a broad range of growth factors and donor-specific effects. The plasma components of hPL necessitate addition of anticoagulants such as heparins to prevent gelatinization of hPL medium, and their concentration must be standardized. Labels for description of hPL-such as "xenogen-free," "animal-free" and "serum free"-are not used consistently in the literature and may be misleading if not critically assessed. Further analysis of the precise composition of relevant growth factors, attachment factors, microRNAs and exosomes will pave the way for optimized and defined culture conditions. The use of hPL has several advantages and disadvantages: they must be taken into account because the choice of cell culture additive has major impact on cell preparations. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: independence from CD4 and major chemokine receptors.

Science.gov (United States)

Sabri, F; Tresoldi, E; Di Stefano, M; Polo, S; Monaco, M C; Verani, A; Fiore, J R; Lusso, P; Major, E; Chiodi, F; Scarlatti, G

1999-11-25

Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-1 isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1beta, RANTES, MIP-1beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-1 isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages. Copyright 1999 Academic Press.

Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.

Directory of Open Access Journals (Sweden)

Isabelle Sahut-Barnola

2010-06-01

Full Text Available Carney complex (CNC is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD, a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1alpha of the cAMP-dependent protein kinase (PKA have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO. AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD.

Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

Science.gov (United States)

Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

2016-01-01

Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The significance of crack-resistance curves to the mixed-mode fracture toughness of human cortical bone

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Zimmermann, Elizabeth A.; Launey, Maximilien E.; Ritchie, Robert O.

2010-03-25

The majority of fracture mechanics studies on the toughness of bone have been performed under tensile loading. However, it has recently been shown that the toughness of human cortical bone in the transverse (breaking) orientation is actually much lower in shear (mode II) than in tension (mode I); a fact that is physiologically relevant as in vivo bone is invariably loaded multiaxially. Since bone is a material that derives its fracture resistance primarily during crack growth through extrinsic toughening mechanisms, such as crack deflection and bridging, evaluation of its toughness is best achieved through measurements of the crack-resistance or R-curve, which describes the fracture toughness as a function of crack extension. Accordingly, in this study, we attempt to measure for the first time the R-curve fracture toughness of human cortical bone under physiologically relevant mixed-mode loading conditions. We show that the resulting mixed-mode (mode I + II) toughness depends strongly on the crack trajectory and is the result of the competition between the paths of maximum mechanical driving force and 'weakest' microstructural resistance.

Human Chorionic Gonadotropin Has Anti-Inflammatory Effects at the Maternal-Fetal Interface and Prevents Endotoxin-Induced Preterm Birth, but Causes Dystocia and Fetal Compromise in Mice1

Science.gov (United States)

Furcron, Amy-Eunice; Romero, Roberto; Mial, Tara N.; Balancio, Amapola; Panaitescu, Bogdan; Hassan, Sonia S.; Sahi, Aashna; Nord, Claire; Gomez-Lopez, Nardhy

2016-01-01

Human chorionic gonadotropin (hCG) is implicated in the maintenance of uterine quiescence by down-regulating myometrial gap junctions during pregnancy, and it was considered as a strategy to prevent preterm birth after the occurrence of preterm labor. However, the effect of hCG on innate and adaptive immune cells implicated in parturition is poorly understood. Herein, we investigated the immune effects of hCG at the maternal-fetal interface during late gestation, and whether this hormone can safely prevent endotoxin-induced preterm birth. Using immunophenotyping, we demonstrated that hCG has immune effects at the maternal-fetal interface (decidual tissues) by: 1) increasing the proportion of regulatory T cells; 2) reducing the proportion of macrophages and neutrophils; 3) inducing an M1 → M2 macrophage polarization; and 4) increasing the proportion of T helper 17 cells. Next, ELISAs were used to determine whether the local immune changes were associated with systemic concentrations of progesterone, estradiol, and/or cytokines (IFNgamma, IL1beta, IL2, IL4, IL5, IL6, IL10, IL12p70, KC/GRO, and TNFalpha). Plasma concentrations of IL1beta, but not progesterone, estradiol, or any other cytokine, were increased following hCG administration. Pretreatment with hCG prevented endotoxin-induced preterm birth by 44%, proving the effectiveness of this hormone as an anti-inflammatory agent. However, hCG administration alone caused dystocia and fetal compromise, as proven by Doppler ultrasound. These results provide insight into the mechanisms whereby hCG induces an anti-inflammatory microenvironment at the maternal-fetal interface during late gestation, and demonstrate its effectiveness in preventing preterm labor/birth. However, the deleterious effects of this hormone on mothers and fetuses warrant caution. PMID:27146032

Spatial interactions reveal inhibitory cortical networks in human amblyopia.

Science.gov (United States)

Wong, Erwin H; Levi, Dennis M; McGraw, Paul V

2005-10-01

Humans with amblyopia have a well-documented loss of sensitivity for first-order, or luminance defined, visual information. Recent studies show that they also display a specific loss of sensitivity for second-order, or contrast defined, visual information; a type of image structure encoded by neurons found predominantly in visual area A18/V2. In the present study, we investigate whether amblyopia disrupts the normal architecture of spatial interactions in V2 by determining the contrast detection threshold of a second-order target in the presence of second-order flanking stimuli. Adjacent flanks facilitated second-order detectability in normal observers. However, in marked contrast, they suppressed detection in each eye of the majority of amblyopic observers. Furthermore, strabismic observers with no loss of visual acuity show a similar pattern of detection suppression. We speculate that amblyopia results in predominantly inhibitory cortical interactions between second-order neurons.

Oxidative and nonoxidative metabolism of polycyclic aromatic hydrocarbons in rabbit and chicken aortas and in human fetal smooth-muscle cells

International Nuclear Information System (INIS)

Bond, J.A.; Kocan, R.M.; Benditt, E.P.; Juchau, M.R.

1980-01-01

A description of the various enzyme systems in aortas of rabbits and chickens and in human fetal smooth muscle cells in culture which are responsible overall for the metabolism of F, 12-dimethylbenz(a)anthracene and benzo(a)pyrene-4, 5-oxide are provided

A transcriptome-wide screen for mRNAs enriched in fetal Leydig cells: CRHR1 agonism stimulates rat and mouse fetal testis steroidogenesis.

Directory of Open Access Journals (Sweden)

Erin N McDowell

Full Text Available Fetal testis steroidogenesis plays an important role in the reproductive development of the male fetus. While regulators of certain aspects of steroidogenesis are known, the initial driver of steroidogenesis in the human and rodent fetal testis is unclear. Through comparative analysis of rodent fetal testis microarray datasets, 54 candidate fetal Leydig cell-specific genes were identified. Fetal mouse testis interstitial expression of a subset of these genes with unknown expression (Crhr1, Gramd1b, Itih5, Vgll3, and Vsnl1 was verified by whole-mount in situ hybridization. Among the candidate fetal Leydig cell-specific factors, three receptors (CRHR1, PRLR, and PROKR2 were tested for a steroidogenic function using ex vivo fetal testes treated with receptor agonists (CRH, PRL, and PROK2. While PRL and PROK2 had no effect, CRH, at low (approximately 1 to 10 nM concentration, increased expression of the steroidogenic genes Cyp11a1, Cyp17a1, Scarb1, and Star in GD15 mouse and GD17 rat testes, and in conjunction, testosterone production was increased. Exposure of GD15 fetal mouse testis to a specific CRHR1 antagonist blunted the CRH-induced steroidogenic gene expression and testosterone responses. Similar to ex vivo rodent fetal testes, ≥ 10 nM CRH exposure of MA-10 Leydig cells increased steroidogenic pathway mRNA and progesterone levels, showing CRH can enhance steroidogenesis by directly targeting Leydig cells. Crh mRNA expression was observed in rodent fetal hypothalamus, and CRH peptide was detected in rodent amniotic fluid. Together, these data provide a resource for discovering factors controlling fetal Leydig cell biology and suggest that CRHR1 activation by CRH stimulates rat and mouse fetal Leydig cell steroidogenesis in vivo.

Spatial integration and cortical dynamics.

Science.gov (United States)

Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

1996-01-23

Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells within each cortical area over distances of 6-8 mm. The relationship between horizontal connections and cortical functional architecture suggests a role in visual segmentation and spatial integration. The distribution of lateral interactions within striate cortex was visualized with optical recording, and their functional consequences were explored by using comparable stimuli in human psychophysical experiments and in recordings from alert monkeys. They may represent the substrate for perceptual phenomena such as illusory contours, surface fill-in, and contour saliency. The dynamic nature of receptive field properties and cortical architecture has been seen over time scales ranging from seconds to months. One can induce a remapping of the topography of visual cortex by making focal binocular retinal lesions. Shorter-term plasticity of cortical receptive fields was observed following brief periods of visual stimulation. The mechanisms involved entailed, for the short-term changes, altering the effectiveness of existing cortical connections, and for the long-term changes, sprouting of axon collaterals and synaptogenesis. The mutability of cortical function implies a continual process of calibration and normalization of the perception of visual attributes that is dependent on sensory experience throughout adulthood and might further represent the mechanism of perceptual learning.

SLC9B1 methylation predicts fetal intolerance of labor.

Science.gov (United States)

Knight, Anna K; Conneely, Karen N; Kilaru, Varun; Cobb, Dawayland; Payne, Jennifer L; Meilman, Samantha; Corwin, Elizabeth J; Kaminsky, Zachary A; Dunlop, Anne L; Smith, Alicia K

2018-01-01

Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24-32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses. We focused on 57 women aged 18-36 (mean 25.4), who had DNA methylation data available from their second prenatal visit. DNA methylation patterns at CpG sites across the genome were interrogated for associations with fetal intolerance of labor. Four CpG sites (P value intolerance of labor. DNA methylation and gene expression were negatively associated when examined longitudinally during pregnancy using a linear mixed-effects model. Positive predictive values of methylation of these four sites ranged from 0.80 to 0.89, while negative predictive values ranged from 0.91 to 0.92. The four CpG sites were also associated with fetal intolerance of labor in an independent cohort (the Johns Hopkins Prospective PPD cohort). Therefore, fetal intolerance of labor could be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation. Fetal intolerance of labor may be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation by assessing DNA methylation patterns of SLC9B1. The identification of pregnant women at elevated risk for fetal intolerance of labor may allow for the development of targeted treatments or management plans.

Magnetic resonance angiography of fetal vasculature at 3.0 T.

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Neelavalli, Jaladhar; Krishnamurthy, Uday; Jella, Pavan K; Mody, Swati S; Yadav, Brijesh K; Hendershot, Kelly; Hernandez-Andrade, Edgar; Yeo, Lami; Cabrera, Maria D; Haacke, Ewart M; Hassan, Sonia S; Romero, Roberto

2016-12-01

Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non-contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possible to visualize fetal vascular networks in late pregnancy. • 3D-visualization of fetal vasculature is feasible using non-contrast MRA at 3.0 T. • Visualization of placental vasculature is also possible with this method. • Fetal MRA can serve as a vascular localizer for quantitative MRI studies. • This method can be extended to 1.5 T.

Markers of Pluripotency in Human Amniotic Epithelial Cells and Their Differentiation to Progenitor of Cortical Neurons

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García-Castro, Irma Lydia; García-López, Guadalupe; Ávila-González, Daniela; Flores-Herrera, Héctor; Molina-Hernández, Anayansi; Portillo, Wendy; Ramón-Gallegos, Eva; Díaz, Néstor Fabián

2015-01-01

Human pluripotent stem cells (hPSC) have promise for regenerative medicine due to their auto-renovation and differentiation capacities. Nevertheless, there are several ethical and methodological issues about these cells that have not been resolved. Human amniotic epithelial cells (hAEC) have been proposed as source of pluripotent stem cells. Several groups have studied hAEC but have reported inconsistencies about their pluripotency properties. The aim of the present study was the in vitro characterization of hAEC collected from a Mexican population in order to identify transcription factors involved in the pluripotency circuitry and to determine their epigenetic state. Finally, we evaluated if these cells differentiate to cortical progenitors. We analyzed qualitatively and quantitatively the expression of the transcription factors of pluripotency (OCT4, SOX2, NANOG, KLF4 and REX1) by RT-PCR and RT-qPCR in hAEC. Also, we determined the presence of OCT4, SOX2, NANOG, SSEA3, SSEA4, TRA-1-60, E-cadherin, KLF4, TFE3 as well as the proliferation and epigenetic state by immunocytochemistry of the cells. Finally, hAEC were differentiated towards cortical progenitors using a protocol of two stages. Here we show that hAEC, obtained from a Mexican population and cultured in vitro (P0-P3), maintained the expression of several markers strongly involved in pluripotency maintenance (OCT4, SOX2, NANOG, TFE3, KLF4, SSEA3, SSEA4, TRA-1-60 and E-cadherin). Finally, when hAEC were treated with growth factors and small molecules, they expressed markers characteristic of cortical progenitors (TBR2, OTX2, NeuN and β-III-tubulin). Our results demonstrated that hAEC express naïve pluripotent markers (KLF4, REX1 and TFE3) as well as the cortical neuron phenotype after differentiation. This highlights the need for further investigation of hAEC as a possible source of hPSC. PMID:26720151

Fetal alcohol exposure and development of the integument

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Longhurst WD

2016-05-01

Full Text Available William D Longhurst,1 Jordan Ernst,2 Larry Burd3 1Center for Emergency Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA; 2University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA; 3Department of Pediatrics, North Dakota Fetal Alcohol Syndrome Center, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA Background: The physiology of fetal alcohol exposure changes across gestation. Early in pregnancy placental, fetal, and amniotic fluid concentrations of alcohol exposure are equivalent. Beginning in mid-pregnancy, the maturing fetal epidermis adds keratins which decrease permeability resulting in development of a barrier between fetal circulation and the amniotic fluid. Barrier function development is essential for viability in late pregnancy and in the extra-uterine environment. In this paper we provide a selected review of the effects of barrier function on fetal alcohol exposure. Methods: We utilized a search of PubMed and Google for all years in all languages for MeSH on Demand terms: alcohol drinking, amnion, amniotic fluid, epidermis, ethanol, female, fetal development, fetus, humans, keratins, permeability, and pregnancy. We also reviewed the reference lists of relevant papers and hand-searched reference lists of textbooks for additional references. Results: By 30 gestational weeks, development of barrier function alters the pathophysiology of ethanol dispersion between the fetus and amniotic fluid. Firstly, increases in the effectiveness of barrier function decreases the rate of diffusion of alcohol from fetal circulation across fetal skin into the amniotic fluid. This reduces the volume of alcohol entering the amniotic fluid. Secondly, barrier function increases the duration of fetal exposure by decreasing the rate of alcohol diffusion from amniotic fluid back into fetal circulation. Ethanol is then transported into

Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome.

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Bertolaccini, Maria Laura; Contento, Gregorio; Lennen, Ross; Sanna, Giovanni; Blower, Philip J; Ma, Michelle T; Sunassee, Kavitha; Girardi, Guillermina

2016-12-01

Placental ischemic disease and adverse pregnancy outcomes are frequently observed in patients with antiphospholipid syndrome (APS). Despite the administration of conventional antithrombotic treatment a significant number of women continue to experience adverse pregnancy outcomes, with uncertain prevention and management. Efforts to develop effective pharmacological strategies for refractory obstetric APS cases will be of significant clinical benefit for both mothers and fetuses. Although the antimalarial drug, hydroxychloroquine (HCQ) is increasingly used to treat pregnant women with APS, little is known about its efficacy and mechanism of action of HCQ. Because complement activation plays a crucial and causative role in placental ischemia and abnormal fetal brain development in APS we hypothesised that HCQ prevents these pregnancy complications through inhibition of complement activation. Using a mouse model of obstetric APS that closely resembles the clinical condition, we found that HCQ prevented fetal death and the placental metabolic changes -measured by proton magnetic resonance spectroscopy in APS-mice. Using 111 In labelled antiphospholipid antibodies (aPL) we identified the placenta and the fetal brain as the main organ targets in APS-mice. Using this same method, we found that HCQ does not inhibit aPL binding to tissues as was previously suggested from in vitro studies. While HCQ did not affect aPL binding to fetal brain it prevented fetal brain abnormal cortical development. HCQ prevented complement activation in vivo and in vitro. Complement C5a levels in serum samples from APS patients and APS-mice were lower after treatment with HCQ while the antibodies titres remained unchanged. HCQ prevented not only placental insufficiency but also abnormal fetal brain development in APS. By inhibiting complement activation, HCQ might also be an effective antithrombotic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal exposure to hurricane destruction and fetal mortality.

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Zahran, Sammy; Breunig, Ian M; Link, Bruce G; Snodgrass, Jeffrey G; Weiler, Stephan; Mielke, Howard W

2014-08-01

The majority of research documenting the public health impacts of natural disasters focuses on the well-being of adults and their living children. Negative effects may also occur in the unborn, exposed to disaster stressors when critical organ systems are developing and when the consequences of exposure are large. We exploit spatial and temporal variation in hurricane behaviour as a quasi-experimental design to assess whether fetal death is dose-responsive in the extent of hurricane damage. Data on births and fetal deaths are merged with Parish-level housing wreckage data. Fetal outcomes are regressed on housing wreckage adjusting for the maternal, fetal, placental and other risk factors. The average causal effect of maternal exposure to hurricane destruction is captured by difference-in-differences analyses. The adjusted odds of fetal death are 1.40 (1.07-1.83) and 2.37 (1.684-3.327) times higher in parishes suffering 10-50% and >50% wreckage to housing stock, respectively. For every 1% increase in the destruction of housing stock, we observe a 1.7% (1.1-2.4%) increase in fetal death. Of the 410 officially recorded fetal deaths in these parishes, between 117 and 205 may be attributable to hurricane destruction and postdisaster disorder. The estimated fetal death toll is 17.4-30.6% of the human death toll. The destruction caused by Hurricanes Katrina and Rita imposed significant measurable losses in terms of fetal death. Postdisaster migratory dynamics suggest that the reported effects of maternal exposure to hurricane destruction on fetal death may be conservative. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Medical use of fetal cells and tissue: ethical aspects].

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Wolff, H P

1992-04-01

After considering the moral status of the living and of the dead human fetus, the article examines various ethical arguments connected with the use of fetal remains following elective abortion: financial or humanitarian incentives for the termination of pregnancy, conflicts of interest between mother and user, authority over fetal remains and modality of donation and utilization of the fetus. To prevent improper use of fetal remains it is recommended: to separate completely the decisions relating to abortion (first) and to the subsequent use of fetal tissues (second); to obtain explicit informed consent from the mother, making it impossible for her to direct any specific use of the fetal tissues; to base decisions on the method and timing of an abortion on the mother's health care needs alone; to exclude those involved in the process of abortion from any use of the fetus; to protect the anonymity of donor and recipient through an intermediary (tissue bank).

Fetal plasma erythropoietin concentration in severe growth retardation.

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Snijders, R J; Abbas, A; Melby, O; Ireland, R M; Nicolaides, K H

1993-02-01

The aim of this study was to determine whether hypoxemia induces an increase in plasma erythropoietin concentration in human fetal life and, if so, whether this response stimulates fetal erythropoiesis. The plasma erythropoietin concentration in blood samples from 33 small-for-gestational-age fetuses at 26 to 38 weeks' gestation was measured. Measurements were compared with the reference range for gestation, and associations with PO2, pH, and erythroblast and erythrocyte counts were examined. The mean plasma erythropoietin concentration in the small-for-gestational-age fetuses was significantly increased, and the degree of increase was significantly associated both with fetal acidemia and, more strongly, with fetal erythroblastosis. Erythropoietin production in response to tissue hypoxia occurs from at least 26 weeks' gestation with measurable physiologic effects on erythropoiesis. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.

Variation in ovarian follicle density during human fetal development.

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Geber, Selmo; Megale, Rodrigo; Vale, Fabiene; Lanna, Ana Maria Arruda; Cabral, Antônio Carlos Vieira

2012-09-01

To obtain a precise estimate of ovarian follicle density and variation in the number of follicles at several gestational ages during human fetal development. Twelve necropsied ovaries from 9 fetuses (gestational age: 24 to 36 weeks) and 3 neonates (who died within the first hours of life) were studied. Ovaries were fixed with 4 % formaldehyde and embedded in paraffin. Serial, 7 mm thick sections of the ovaries were cut and evaluated at every 50 cuts. Follicles were counted in 10 regions (each measuring 625 μm(2)) of the ovarian cortex and the number of follicles per mm³ was calculated. The number of follicles per 0.25 mm² ranged from 10.9 (± 4.8) in a neonate to 34.7 (± 10.6) also in a neonate. Among fetuses, follicle density was lowest at 36 weeks of gestation (11.1 ± 6.2) and highest at 26 weeks (32 ± 8.9). The total number of follicles ranged from 500,000 at the age of 22 weeks to > 1,000,000 at the age of 39 weeks. Our results show a peak in the number of follicles during intrauterine life at approximately 26 weeks, followed by a rapid reduction in this number before birth, providing a step forward towards the understanding of primordial follicular assembly in humans and, ultimately, the identification of the determinants of reproductive capacity.

Assisted Reproduction Causes Reduced Fetal Growth Associated with Downregulation of Paternally Expressed Imprinted Genes That Enhance Fetal Growth in Mice.

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Li, Bo; Chen, Shuqiang; Tang, Na; Xiao, Xifeng; Huang, Jianlei; Jiang, Feng; Huang, Xiuying; Sun, Fangzhen; Wang, Xiaohong

2016-02-01

Alteration of intrauterine growth trajectory is linked to metabolic diseases in adulthood. In mammalian and, specifically, human species, pregnancies through assisted reproductive technology (ART) are associated with changes in intrauterine growth trajectory. However, it is still unclear how ART alters intrauterine growth trajectory, especially reduced fetal growth in early to midgestation. In this study, using a mouse model, it was found that ART procedures reduce fetal and placental growth at Embryonic Day 10.5. Furthermore, ART leads to decreased methylation levels at H19, KvDMR1, and Snrpn imprinting control regions in the placentae, instead of fetuses. Furthermore, in the placenta, ART downregulated a majority of parentally expressed imprinted genes, which enhance fetal growth, whereas it upregulated a majority of maternally expressed genes which repress fetal growth. Additionally, the expression of genes that regulate placental development was also affected by ART. ART also downregulated a majority of placental nutrient transporters. Disruption of genomic imprinting and abnormal expression of developmentally and functionally relevant genes in placenta may influence the placental development and function, which affect fetal growth and reprogramming. © 2016 by the Society for the Study of Reproduction, Inc.

Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

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DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

2015-01-01

Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24...

Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes.

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Baxter, Melissa; Withey, Sarah; Harrison, Sean; Segeritz, Charis-Patricia; Zhang, Fang; Atkinson-Dell, Rebecca; Rowe, Cliff; Gerrard, Dave T; Sison-Young, Rowena; Jenkins, Roz; Henry, Joanne; Berry, Andrew A; Mohamet, Lisa; Best, Marie; Fenwick, Stephen W; Malik, Hassan; Kitteringham, Neil R; Goldring, Chris E; Piper Hanley, Karen; Vallier, Ludovic; Hanley, Neil A

2015-03-01

Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Characterization of energy and neurotransmitter metabolism in cortical glutamatergic neurons derived from human induced pluripotent stem cells: A novel approach to study metabolism in human neurons.

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Aldana, Blanca I; Zhang, Yu; Lihme, Maria Fog; Bak, Lasse K; Nielsen, Jørgen E; Holst, Bjørn; Hyttel, Poul; Freude, Kristine K; Waagepetersen, Helle S

2017-06-01

Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U- 13 C]glucose, [U- 13 C]glutamate or [U- 13 C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography. Additionally, we evaluated mitochondrial function using real-time assessment of oxygen consumption via the Seahorse XF e 96 Analyzer. Moreover, in order to validate the hiPSC-derived neurons as a model system, a metabolic profiling was performed in parallel in primary neuronal cultures of mouse cerebral cortex and cerebellum. These serve as well-established models of GABAergic and glutamatergic neurons, respectively. The hiPSC-derived neurons were previously characterized as being forebrain-specific cortical glutamatergic neurons. However, a comparable preparation of predominantly mouse cortical glutamatergic neurons is not available. We found a higher glycolytic capacity in hiPSC-derived neurons compared to mouse neurons and a substantial oxidative metabolism through the mitochondrial tricarboxylic acid (TCA) cycle. This finding is supported by the extracellular acidification and oxygen consumption rates measured in the cultured human neurons. [U- 13 C]Glutamate and [U- 13 C]glutamine were found to be efficient energy substrates for the neuronal cultures originating from both mice and humans. Interestingly, isotopic labeling in metabolites from [U- 13 C]glutamate was higher than that from [U- 13 C]glutamine. Although the metabolic profile of hiPSC-derived neurons in vitro was

Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection

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Kummer, Lawrence W.; Lanthier, Paula; Kim, In-Jeong; Kuki, Atsuo; Thomas, Stephen J.

2018-01-01

Zika virus (ZIKV) infection during human pregnancy may cause diverse and serious congenital defects in the developing fetus. Previous efforts to generate animal models of human ZIKV infection and clinical symptoms often involved manipulating mice to impair their Type I interferon (IFN) signaling, thereby allowing enhanced infection and vertical transmission of virus to the embryo. Here, we show that even pregnant mice competent to generate Type I IFN responses that can limit ZIKV infection nonetheless develop profound placental pathology and high frequency of fetal demise. We consistently found that maternal ZIKV exposure led to placental pathology and that ZIKV RNA levels measured in maternal, placental or embryonic tissues were not predictive of the pathological effects seen in the embryos. Placental pathology included trophoblast hyperplasia in the labyrinth, trophoblast giant cell necrosis in the junctional zone, and loss of embryonic vessels. Our findings suggest that, in this context of limited infection, placental pathology rather than embryonic/fetal viral infection may be a stronger contributor to adverse pregnancy outcomes in mice. Our finding demonstrates that in immunocompetent mice, direct viral infection of the embryo is not essential for fetal demise. Our immunologically unmanipulated pregnancy mouse model provides a consistent and easily measurable congenital abnormality readout to assess fetal outcome, and may serve as an additional model to test prophylactic and therapeutic interventions to protect the fetus during pregnancy, and for studying the mechanisms of ZIKV congenital immunopathogenesis. PMID:29634758

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

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Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose.

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Grażyna E Sroga

Full Text Available To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs at the levels that corresponded to approx. 25-30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation or ribose (ribosylation. Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women. More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples. Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar

Primary cortical folding in the human newborn: an early marker of later functional development

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Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Ha-Vinh Leuchter, R.; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Hüppi, P. S.

2008-01-01

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26–36 weeks of gestational age), and defined early ‘endophenotypes’ of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants’ outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB). PMID:18587151

Epigenetic regulation during fetal femur development: DNA methylation matters.

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María C de Andrés

Full Text Available Epigenetic modifications are heritable changes in gene expression without changes in DNA sequence. DNA methylation has been implicated in the control of several cellular processes including differentiation, gene regulation, development, genomic imprinting and X-chromosome inactivation. Methylated cytosine residues at CpG dinucleotides are commonly associated with gene repression; conversely, strategic loss of methylation during development could lead to activation of lineage-specific genes. Evidence is emerging that bone development and growth are programmed; although, interestingly, bone is constantly remodelled throughout life. Using human embryonic stem cells, human fetal bone cells (HFBCs, adult chondrocytes and STRO-1(+ marrow stromal cells from human bone marrow, we have examined a spectrum of developmental stages of femur development and the role of DNA methylation therein. Using pyrosequencing methodology we analysed the status of methylation of genes implicated in bone biology; furthermore, we correlated these methylation levels with gene expression levels using qRT-PCR and protein distribution during fetal development evaluated using immunohistochemistry. We found that during fetal femur development DNA methylation inversely correlates with expression of genes including iNOS (NOS2 and COL9A1, but not catabolic genes including MMP13 and IL1B. Furthermore, significant demethylation was evident in the osteocalcin promoter between the fetal and adult developmental stages. Increased TET1 expression and decreased expression of DNA (cytosine-5--methyltransferase 1 (DNMT1 in adult chondrocytes compared to HFBCs could contribute to the loss of methylation observed during fetal development. HFBC multipotency confirms these cells to be an ideal developmental system for investigation of DNA methylation regulation. In conclusion, these findings demonstrate the role of epigenetic regulation, specifically DNA methylation, in bone development

Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles.

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Lai, Ruenn Chai; Arslan, Fatih; Tan, Soon Sim; Tan, Betty; Choo, Andre; Lee, May May; Chen, Tian Sheng; Teh, Bao Ju; Eng, John Kun Long; Sidik, Harwin; Tanavde, Vivek; Hwang, Wei Sek; Lee, Chuen Neng; El Oakley, Reida Menshawe; Pasterkamp, Gerard; de Kleijn, Dominique P V; Tan, Kok Hian; Lim, Sai Kiang

2010-06-01

The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives. Here we derived five MSC cultures from limb, kidney and liver tissues of three first trimester aborted fetuses and like our previously described hESC-derived MSCs; they were highly expandable and had similar telomerase activities. Each line has the potential to generate at least 10(16-19) cells or 10(7-10) doses of cardioprotective secretion for a pig model of MI/R injury. Unlike previously described fetal MSCs, they did not express pluripotency-associated markers such as Oct4, Nanog or Tra1-60. They displayed a typical MSC surface antigen profile and differentiated into adipocytes, osteocytes and chondrocytes in vitro. Global gene expression analysis by microarray and qRT-PCR revealed a typical MSC gene expression profile that was highly correlated among the five fetal MSC cultures and with that of hESC-MSCs (r(2)>0.90). Like hESC-MSCs, they produced secretion that was cardioprotective in a mouse model of MI/R injury. HPLC analysis of the secretion revealed the presence of a population of microparticles with a hydrodynamic radius of 50-65 nm. This purified population of microparticles was cardioprotective at approximately 1/10 dosage of the crude secretion. (c) 2009 Elsevier Ltd. All rights reserved.

The uptake of tritium-labelled carnitine by monolayer cultures of human fetal muscle and its potential as a label in cytotoxicity studies

International Nuclear Information System (INIS)

Cambridge, G.; Stern, C.M.M.

1981-01-01

As a novel approach to the investigation of immune responses directed against muscle antigens in inflammatory muscle disease, the use of tritium-labelled carnitine as a selective marker for myotubes in monolayer cultures was investigated. Tritium-labelled carnitine was incubated either with monolayer cultures of human fetal muscle or with syngeneic monolayer cultures of human fetal fibroblasts. The rate of uptake and loss of tritium-labelled carnitine by muscle cultures was compared with that shown by fibroblast cultures; values for the ratio Ksub(m)/Vsub(max) were 3.1 for muscle cultures and 0.46 for fibroblast cultures. Freeze-dried radioautographs of muscle monolayers, previously incubated with tritium-labelled carnitine confirmed the specific intra-tubular localization of the label. Fetal muscle monolayers, previously incubated with tritium-labelled carnitine, were used as targets in long-term cytotoxicity experiments into lymphocyte-mediated myotoxicity. Peripheral blood lymphocytes from patients with inflammatory muscle disease were shown to be myotoxic, but lymphocytes from normal individuals or those with non-inflammatory muscle disease were not. Carnitine-based measures of myotoxicity closely followed the clinical activity of the disease in one patient and the test shows considerable potential as a means of assessing myotube killing by lymphocytes on a per-cell basis. (author)

Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

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Erica L. McGrath

2017-03-01

Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

Science.gov (United States)

McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

2017-03-14

Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Average fetal depth in utero: data for estimation of fetal absorbed radiation dose

International Nuclear Information System (INIS)

Ragozzino, M.W.; Breckle, R.; Hill, L.M.; Gray, J.E.

1986-01-01

To estimate fetal absorbed dose from radiographic examinations, the depth from the anterior maternal surface to the midline of the fetal skull and abdomen was measured by ultrasound in 97 pregnant women. The relationships between fetal depth, fetal presentation, and maternal parameters of height, weight, anteroposterior (AP) thickness, gestational age, placental location, and bladder volume were analyzed. Maternal AP thickness (MAP) can be estimated from gestational age, maternal height, and maternal weight. Fetal midskull and abdominal depths were nearly equal. Fetal depth normalized to MAP was independent or nearly independent of maternal parameters and fetal presentation. These data enable a reasonable estimation of absorbed dose to fetal brain, abdomen, and whole body

Is cortical bone hip? What determines cortical bone properties?

Science.gov (United States)

Epstein, Sol

2007-07-01

Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal

The human cerebral cortex is neither one nor many: Neuronal distribution reveals two quantitatively different zones in the grey matter, three in the white matter, and explains local variations in cortical folding

Directory of Open Access Journals (Sweden)

Pedro F. M. Ribeiro

2013-09-01

Full Text Available The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital that differ in how neurons distributed across their grey matter volume and in three zones (prefrontal, occipital, and non-occipital that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non

MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13

OpenAIRE

Sankaran, Vijay G.; Menne, Tobias F.; Šćepanović, Danilo; Vergilio, Jo-Anne; Ji, Peng; Kim, Jinkuk; Thiru, Prathapan; Orkin, Stuart H.; Lander, Eric S.; Lodish, Harvey F.

2011-01-01

Many human aneuploidy syndromes have unique phenotypic consequences, but in most instances it is unclear whether these phenotypes are attributable to alterations in the dosage of specific genes. In human trisomy 13, there is delayed switching and persistence of fetal hemoglobin (HbF) and elevation of embryonic hemoglobin in newborns. Using partial trisomy cases, we mapped this trait to chromosomal band 13q14; by examining the genes in this region, two microRNAs, miR-15a and -16-1, appear as t...

Fetal behavioral teratology.

Science.gov (United States)

Visser, Gerard H A; Mulder, Eduard J H; Tessa Ververs, F F

2010-10-01

Ultrasound studies of fetal motor behavior provide direct – in vivo – insight in the functioning of the motor component of the fetal central nervous system. In this article, studies are reviewed showing changes in the first timetable of appearance of fetal movements, changes in quality and/or quantity of movements and disturbances in the development of fetal behavioral states in case of endogenous malfunctions, maternal diseases and exogenous behavioral teratogens.

Donor-Specific Anti-HLA Antibodies in Huntington's Disease Recipients of Human Fetal Striatal Grafts.

Science.gov (United States)

Porfirio, Berardino; Paganini, Marco; Mazzanti, Benedetta; Bagnoli, Silvia; Bucciantini, Sandra; Ghelli, Elena; Nacmias, Benedetta; Putignano, Anna Laura; Rombolà, Giovanni; Saccardi, Riccardo; Lombardini, Letizia; Di Lorenzo, Nicola; Vannelli, Gabriella B; Gallina, Pasquale

2015-01-01

Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid organ transplants, hence the minor impact on the efficacy of the transplant. How much prophylactic immune protection is required for neural allotransplantation is also debated. High-sensitive anti-HLA antibody screening in this field has never been reported. Sixteen patients with Huntington's disease underwent human fetal striatal transplantation in the frame of an open-label observational trial, which is being carried out at Florence University. All patients had both brain hemispheres grafted in two separate robotic-stereotactic procedures. The trial started in February 2006 with the first graft to the first patient (R1). R16 was given his second graft on March 2011. All patients received triple immunosuppressive treatment. Pre- and posttransplant sera were analyzed for the presence of anti-HLA antibodies using the multiplexed microsphere-based suspension array Luminex xMAP technology. Median follow-up was 38.5 months (range 13-85). Six patients developed anti-HLA antibodies, which turned out to be donor specific. Alloimmunization occurred in a time window of 0-49 months after the first neurosurgical procedure. The immunogenic determinants were non-self-epitopes from mismatched HLA antigens. These determinants were both public epitopes shared by two or more HLA molecules and private epitopes unique to individual HLA molecules. One patient had non-donor-specific anti-HLA antibodies in her pretransplant serum sample, possibly due to previous sensitization events. Although the clinical significance of donor-specific antibodies is far from being established, particularly in the setting of neuronal transplantation, these findings underline the need of careful pre- and posttransplant immunogenetic evaluation of patients with intracerebral grafts.

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

NARCIS (Netherlands)

Ganguli, K.; Collado, M.C.; Rautava, J.; Lu, L.; Satokari, R.M.; Ossowski, von I.; Reunanen, J.; Vos, de W.M.; Palva, A.; Isolauri, E.; Salminen, S.; Walker, W.A.; Rautava, S.

2015-01-01

BACKGROUND: Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human

Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

Science.gov (United States)

Thakor, Avnesh S; Allison, Beth J; Niu, Youguo; Botting, Kimberley J; Serón-Ferré, Maria; Herrera, Emilio A; Giussani, Dino A

2015-08-01

Experimental studies in animal models supporting protective effects on the fetus of melatonin in adverse pregnancy have prompted clinical trials in human pregnancy complicated by fetal growth restriction. However, the effects of melatonin on the fetal defense to acute hypoxia, such as that which may occur during labor, remain unknown. This translational study tested the hypothesis, in vivo, that melatonin modulates the fetal cardiometabolic defense responses to acute hypoxia in chronically instrumented late gestation fetal sheep via alterations in fetal nitric oxide (NO) bioavailability. Under anesthesia, 6 fetal sheep at 0.85 gestation were instrumented with vascular catheters and a Transonic flow probe around a femoral artery. Five days later, fetuses were exposed to acute hypoxia with or without melatonin treatment. Fetal blood was taken to determine blood gas and metabolic status and plasma catecholamine concentrations. Hypoxia during melatonin treatment was repeated during in vivo NO blockade with the NO clamp. This technique permits blockade of de novo synthesis of NO while compensating for the tonic production of the gas, thereby maintaining basal cardiovascular function. Melatonin suppressed the redistribution of blood flow away from peripheral circulations and the glycemic and plasma catecholamine responses to acute hypoxia. These are important components of the fetal brain sparing response to acute hypoxia. The effects of melatonin involved NO-dependent mechanisms as the responses were reverted by fetal treatment with the NO clamp. Melatonin modulates the in vivo fetal cardiometabolic responses to acute hypoxia by increasing NO bioavailability. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Histological features of layers and sublayers in cortical visual areas V1 and V2 of chimpanzees, macaque monkeys, and humans

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Balaram P

2014-09-01

Full Text Available Pooja Balaram, Nicole A Young, Jon H Kaas Department of Psychology, Vanderbilt University, Nashville, TN, USA Abstract: The layers and sublayers of primary visual cortex, or V1, in primates are easily distinguishable compared to those in other cortical areas, and are especially distinct in anthropoid primates – monkeys, apes, and humans – where they also vary in histological appearance. This variation in primate-specific specialization has led to a longstanding confusion over the identity of layer 4 and its proposed sublayers in V1. As the application of different histological markers relate to the issue of defining and identifying layers and sublayers, we applied four traditional and four more recent histological markers to brain sections of V1 and adjoining secondary visual cortex (V2 in macaque monkeys, chimpanzees, and humans in order to compare identifiable layers and sublayers in both cortical areas across these species. The use of Nissl, neuronal nuclear antigen (NeuN, Gallyas myelin, cytochrome oxidase (CO, acetylcholinesterase (AChE, nonphosphorylated neurofilament H (SMI-32, parvalbumin (PV, and vesicular glutamate transporter 2 (VGLUT2 preparations support the conclusion that the most popular scheme of V1 lamination, that of Brodmann, misidentifies sublayers of layer 3 (3Bβ and 3C as sublayers of layer 4 (4A and 4B, and that the specialized sublayer of layer 3 in monkeys, 3Bβ, is not present in humans. These differences in interpretation are important as they relate to the proposed functions of layer 4 in primate species, where layer 4 of V1 is a layer that receives and processes information from the visual thalamus, and layer 3 is a layer that transforms and distributes information to other cortical areas. Keywords: area 17, area 18, cortical layers, histology, immunohistochemistry

The Navigation Guide - evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth.

Science.gov (United States)

Johnson, Paula I; Sutton, Patrice; Atchley, Dylan S; Koustas, Erica; Lam, Juleen; Sen, Saunak; Robinson, Karen A; Axelrad, Daniel A; Woodruff, Tracey J

2014-10-01

The Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method. We applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans. We applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence. We identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a -18.9 g (95% CI: -29.8, -7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a "moderate" quality rating to the overall body of human evidence. On the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is "sufficient" human evidence that developmental exposure to PFOA reduces fetal growth.

Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries.

Science.gov (United States)

Tegeder, Irmgard

2016-12-01

Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].

Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile X syndrome and autism spectrum disorder

Directory of Open Access Journals (Sweden)

Lindsay M Oberman

2010-06-01

Full Text Available Fragile X Syndrome (FXS is the most common heritable cause of intellectual disability. In vitro electrophysiologic data from mouse models of FXS suggest that loss of Fragile X Mental Retardation Protein (FMRP affects intracortical excitability and synaptic plasticity. Specifically, the cortex appears hyperexcitable, and use-dependent long-term potentiation (LTP and long-term depression (LTD of synaptic strength are abnormal. Though animal models provide important information, FXS and other neurodevelopmental disorders are human diseases and as such translational research to evaluate cortical excitability and plasticity must be applied in the human. Transcranial magnetic stimulation (TMS paradigms have recently been developed to noninvasively investigate cortical excitability using paired-pulse stimulation, as well as LTP- and LTD-like synaptic plasticity in response to theta burst stimulation (TBS in vivo in the human. TBS applied on consecutive days can be used to measure metaplasticity (the ability of the synapse to undergo a second plastic change following a recent induction of plasticity. The current study investigated intracortical inhibition, plasticity and metaplasticity in full mutation females with FXS, participants with autism spectrum disorders (ASD, and neurotypical controls. Results suggest that intracortical inhibition is normal in participants with FXS, while plasticity and metaplasticity appear abnormal. ASD participants showed abnormalities in plasticity and metaplasticity, as well as heterogeneity in intracortical inhibition. Our findings highlight the utility of noninvasive neurophysiological measures to translate insights from animal models to humans with neurodevelopmental disorders, and thus provide direct confirmation of cortical dysfunction in patients with FXS and ASD.

Fetal echocardiography

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... page: //medlineplus.gov/ency/article/007340.htm Fetal echocardiography To use the sharing features on this page, please enable JavaScript. Fetal echocardiography is a test that uses sound waves ( ultrasound ) ...

Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

Energy Technology Data Exchange (ETDEWEB)

Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland and Diagnostic Imaging Center, Kuopio University Hospital, P.O. Box 100, Kuopio FI-70029 (Finland); Malo, M. K. H., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Liukkonen, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211 (Finland); Karjalainen, J. P., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Bone Index Finland Ltd., P.O. Box 1188, Kuopio FI-70211 (Finland)

2016-05-15

Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated

Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

International Nuclear Information System (INIS)

Eneh, C. T. M.; Töyräs, J.; Jurvelin, J. S.; Malo, M. K. H.; Liukkonen, J.; Karjalainen, J. P.

2016-01-01

Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R"2 ≥ 0.493, p < 0.01 and R"2 ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated in vivo

Fetal electrocardiogram (ECG) for fetal monitoring during labour.

Science.gov (United States)

Neilson, James P

2015-12-21

Hypoxaemia during labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably the relation of the PR to RR intervals, and elevation or depression of the ST segment. Technical systems have therefore been developed to monitor the fetal ECG during labour as an adjunct to continuous electronic fetal heart rate monitoring with the aim of improving fetal outcome and minimising unnecessary obstetric interference. To compare the effects of analysis of fetal ECG waveforms during labour with alternative methods of fetal monitoring. The Cochrane Pregnancy and Childbirth Group's Trials Register (latest search 23 September 2015) and reference lists of retrieved studies. Randomised trials comparing fetal ECG waveform analysis with alternative methods of fetal monitoring during labour. One review author independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. One review author assessed the quality of the evidence using the GRADE approach. Seven trials (27,403 women) were included: six trials of ST waveform analysis (26,446 women) and one trial of PR interval analysis (957 women). The trials were generally at low risk of bias for most domains and the quality of evidence for ST waveform analysis trials was graded moderate to high. In comparison to continuous electronic fetal heart rate monitoring alone, the use of adjunctive ST waveform analysis made no obvious difference to primary outcomes: births by caesarean section (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.96 to 1.08; six trials, 26,446 women; high quality evidence); the number of babies with severe metabolic acidosis at birth (cord arterial pH less than 7.05 and base deficit greater than 12 mmol/L) (average RR 0.72, 95% CI 0.43 to 1.20; six trials, 25,682 babies; moderate quality evidence); or babies with neonatal encephalopathy (RR 0.61, 95% CI 0.30 to 1.22; six trials, 26,410 babies; high quality evidence). There were, however, on average

Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.

Science.gov (United States)

Szabo, Linda; Morey, Robert; Palpant, Nathan J; Wang, Peter L; Afari, Nastaran; Jiang, Chuan; Parast, Mana M; Murry, Charles E; Laurent, Louise C; Salzman, Julia

2015-06-16

The pervasive expression of circular RNA is a recently discovered feature of gene expression in highly diverged eukaryotes, but the functions of most circular RNAs are still unknown. Computational methods to discover and quantify circular RNA are essential. Moreover, discovering biological contexts where circular RNAs are regulated will shed light on potential functional roles they may play. We present a new algorithm that increases the sensitivity and specificity of circular RNA detection by discovering and quantifying circular and linear RNA splicing events at both annotated and un-annotated exon boundaries, including intergenic regions of the genome, with high statistical confidence. Unlike approaches that rely on read count and exon homology to determine confidence in prediction of circular RNA expression, our algorithm uses a statistical approach. Using our algorithm, we unveiled striking induction of general and tissue-specific circular RNAs, including in the heart and lung, during human fetal development. We discover regions of the human fetal brain, such as the frontal cortex, with marked enrichment for genes where circular RNA isoforms are dominant. The vast majority of circular RNA production occurs at major spliceosome splice sites; however, we find the first examples of developmentally induced circular RNAs processed by the minor spliceosome, and an enriched propensity of minor spliceosome donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, these results suggest a potentially significant role for circular RNA in human development.

Telomere length and fetal programming: A review of recent scientific advances.

Science.gov (United States)

Whiteman, Valerie E; Goswami, Anjali; Salihu, Hamisu M

2017-05-01

We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication. Our results showed that socio-demographic factors like age, sex, genetic inheritance, and acquired disease impact telomere length. Further, we found several maternal characteristics to be associated with fetal telomere length shortening, and these include maternal chemical exposure (eg, tobacco smoke), maternal stress during pregnancy, maternal nutritional and sleeping disorders during pregnancy as well as maternal disease status. Due to paucity of data, our review could not synthesize evidence directly linking fetal phenotypes to telomere length shortening. Although the research summarized in this review shows some association between determinants of intrauterine programming and fetal telomere length, there is still significant work that needs to be done to delineate the direct relationship of telomere attrition with specific fetal phenotypes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

DEFF Research Database (Denmark)

Tornehave, D; Jensen, Charlotte Harken; Teisner, B

1996-01-01

Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Drosophila homeotic...... proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine...... tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...

Pulmonary Hypoplasia Caused by Fetal Ascites in Congenital Cytomegalovirus Infection Despite Fetal Therapy

Directory of Open Access Journals (Sweden)

Kazumichi Fujioka

2017-11-01

Full Text Available We report two cases of pulmonary hypoplasia due to fetal ascites in symptomatic congenital cytomegalovirus (CMV infections despite fetal therapy. The patients died soon after birth. The pathogenesis of pulmonary hypoplasia in our cases might be thoracic compression due to massive fetal ascites as a result of liver insufficiency. Despite aggressive fetal treatment, including multiple immunoglobulin administration, which was supposed to diminish the pathogenic effects of CMV either by neutralization or immunomodulatory effects, the fetal ascites was uncontrollable. To prevent development of pulmonary hypoplasia in symptomatic congenital CMV infections, further fetal intervention to reduce ascites should be considered.

Fetal scalp pH testing

Science.gov (United States)

Fetal scalp blood; Scalp pH testing; Fetal blood testing - scalp; Fetal distress - fetal scalp testing; Labor - fetal scalp testing ... a baby. In these cases, testing the scalp pH can help the doctor decide whether the fetus ...

The double cortical line: a sign of osteopenia

International Nuclear Information System (INIS)

Lamb, C.R.

1990-01-01

The double cortical line is a radiographic sign of osteopenia which results from intracortical resorption of bone. This sign is frequently seen in humans with osteopenia but has received minimal attention in the veterinary literature. This report describes the double cortical line in cases of senile osteopenia, nutritional secondary hyperparathyroidism, suspected renal secondary hyperparathyroidism and in the acetabulum following triple pelvic osteotomy for hip dysplasia

The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

DEFF Research Database (Denmark)

Groppa, Sergiu; Schlaak, Boris H; Münchau, Alexander

2012-01-01

In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1......(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI......) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over...

[Incidence of fetal macrosomia: maternal and fetal morbidity].

Science.gov (United States)

Rodríguez-Rojas, R R; Cantú-Esquivel, M G; Benavides-de la Garza, L; Benavides-de Anda, L

1996-06-01

The macrosomia is an obstetric eventuality associated to high maternal-fetal morbidity-mortality. This assay was planned in order to know the incidence of macrosomia in our institution, the relation between vaginal and abdominal deliveries and the fetal-maternal morbidity we reviewed 3590 records and we found 5.6% incidence of macrosomia in the global obstetric population. There was 58% of vaginal deliveries, 68% of the newborn were male. The main complications were in the C. sections, 2 laceration of the hysterectomy, and 2 peroperative atonias. In the vaginal deliveries, the lacerations of III and IV grade were 9 of each grade. The main fetal complications were 5 slight to severe asphyxia and 4 shoulder dystocias. This assay concludes that the macrosomia in our service is similar to the already published ones, a 42% were C. section and the maternal-fetal morbidity was low.

The use of non-invasive fetal electrocardiography in diagnosing second-degree fetal atrioventricular block.

Science.gov (United States)

Lakhno, Igor; Behar, Joachim A; Oster, Julien; Shulgin, Vyacheslav; Ostras, Oleksii; Andreotti, Fernando

2017-01-01

Complete atrioventricular block in fetuses is known to be mostly associated with autoimmune disease and can be irreversible if no steroids treatment is provided. Conventional methods used in clinical practice for diagnosing fetal arrhythmia are limited since they do not reflect the primary electrophysiological conduction processes that take place in the myocardium. The non-invasive fetal electrocardiogram has the potential to better support fetal arrhythmias diagnosis through the continuous analysis of the beat to beat variation of the fetal heart rate and morphological analysis of the PQRST complex. We present two retrospective case reports on which atrioventricular block diagnosis could have been supported by the non-invasive fetal electrocardiogram. The two cases comprised a 22-year-old pregnant woman with the gestational age of 31 weeks and a 25-year-old pregnant woman with the gestational age of 41 weeks. Both women were admitted to the Department of Maternal and Fetal Medicine at the Kyiv and Kharkiv municipal perinatal clinics. Patients were observed using standard fetal monitoring methods as well as the non-invasive fetal electrocardiogram. The non-invasive fetal electrocardiographic recordings were analyzed retrospectively, where it is possible to identify the presence of the atrioventricular block. This study demonstrates, for the first time, the feasibility of the non-invasive fetal electrocardiogram as a supplementary method to diagnose of the fetal atrioventricular block. Combined with current fetal monitoring techniques, non-invasive fetal electrocardiography could support clinical decisions.

Fetal magnetic resonance imaging: methods and techniques; Fetale Magnetresonanztomographie: Methoden und Technik

Energy Technology Data Exchange (ETDEWEB)

Brugger, P.C. [Zentrum fuer Anatomie und Zellbiologie, Medizinische Universitaet Wien (Austria). Arbeitsgruppe Integrative Morphologie; Stuhr, F.; Lindner, C.; Prayer, D. [Medizinische Universitaet Wien (Austria). Klinik fuer Radiodiagnostik

2006-02-15

Since the introduction of fetal magnetic resonance imaging (MRI) into prenatal diagnostics, advances in coil technology and development of ultrafast sequences have further enhanced this technique. At present numerous sequences are available to visualize the whole fetus with high resolution and image quality, even in late stages of pregnancy. Taking into consideration the special circumstances of examination and adjusting sequence parameters to gestational age, fetal anatomy can be accurately depicted. The variety of sequences also allows further characterization of fetal tissues and pathologies. Fetal MRI not only supplies additional information to routine ultrasound studies, but also reveals fetal morphology and pathology in a way hitherto not possible. (orig.) [German] Seit Einfuehrung der fetalen Magnetresonanztomographie (MRT) in die praenatale Diagnostik wurde das Verfahren durch neue Spulentechniken und die Entwicklung ultraschneller Sequenzen kontinuierlich weiter entwickelt. Gegenwaertig steht eine Vielzahl von Sequenzen zur Verfuegung, die es erlauben, mit hoher Bildqualitaet und raeumlicher Aufloesung selbst in fortgeschrittenen Schwangerschaftsstadien den gesamten Feten darzustellen. Unter Beruecksichtigung der speziellen Untersuchungsbedingungen und des Schwangerschaftsalters kann so die fetale Anatomie genau abgebildet werden. Die Vielfalt an Sequenzen und deren gezielter Einsatz ermoeglichen es weiter, fetale Gewebe und Pathologien naeher zu charakterisierten. Auf diese Weise liefert die fetale MRT nicht nur Zusatzinformationen zur Routineultraschalluntersuchung, sie gibt auch Aufschluss ueber bestimmte fetale Morphologien und Pathologien, die bisher nicht darstellbar waren. (orig.)

Post-adolescent developmental changes in cortical complexity

OpenAIRE

Sandu, Anca-Larisa; Izard, Edouard; Specht, Karsten; Beneventi, Harald; Lundervold, Arvid; Ystad, Martin

2014-01-01

Background: Post-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval. Methods: Magnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 1...

Supplements in human islet culture: human serum albumin is inferior to fetal bovine serum.

Science.gov (United States)

Avgoustiniatos, Efstathios S; Scott, William E; Suszynski, Thomas M; Schuurman, Henk-Jan; Nelson, Rebecca A; Rozak, Phillip R; Mueller, Kate R; Balamurugan, A N; Ansite, Jeffrey D; Fraga, Daniel W; Friberg, Andrew S; Wildey, Gina M; Tanaka, Tomohiro; Lyons, Connor A; Sutherland, David E R; Hering, Bernhard J; Papas, Klearchos K

2012-01-01

Culture of human islets before clinical transplantation or distribution for research purposes is standard practice. At the time the Edmonton protocol was introduced, clinical islet manufacturing did not include culture, and human serum albumin (HSA), instead of fetal bovine serum (FBS), was used during other steps of the process to avoid the introduction of xenogeneic material. When culture was subsequently introduced, HSA was also used for medium supplementation instead of FBS, which was typically used for research islet culture. The use of HSA as culture supplement was not evaluated before this implementation. We performed a retrospective analysis of 103 high-purity islet preparations (76 research preparations, all with FBS culture supplementation, and 27 clinical preparations, all with HSA supplementation) for oxygen consumption rate per DNA content (OCR/DNA; a measure of viability) and diabetes reversal rate in diabetic nude mice (a measure of potency). After 2-day culture, research preparations exhibited an average OCR/DNA 51% higher (p < 0.001) and an average diabetes reversal rate 54% higher (p < 0.05) than clinical preparations, despite 87% of the research islet preparations having been derived from research-grade pancreata that are considered of lower quality. In a prospective paired study on islets from eight research preparations, OCR/DNA was, on average, 27% higher with FBS supplementation than that with HSA supplementation (p < 0.05). We conclude that the quality of clinical islet preparations can be improved when culture is performed in media supplemented with serum instead of albumin.

Computed tomography evaluation of human mandibles with regard to layer thickness and bone density of the cortical bone

International Nuclear Information System (INIS)

Markwardt, Jutta; Meissner, H.; Weber, A.; Reitemeier, B.; Laniado, M.

2013-01-01

Application of function-restoring individual implants for the bridging of defects in mandibles with continuity separation requires a stable fixation with special use of the cortical bone stumps. Five section planes each of 100 computed tomographies of poly-traumatized patients' jaws were used for measuring the thickness of the cortical layer and the bone density of the mandible. The CT scans of 28 female and 72 male candidates aged between 12 and 86 years with different dentition of the mandible were available. The computed tomographic evaluations of human mandibles regarding the layer thickness of the cortical bone showed that the edge of the mandible in the area of the horizontal branch possesses the biggest layer thickness of the whole of the lower jaws. The highest medians of the cortical bone layer thickness were found in the area of the molars and premolars at the lower edge of the lower jaws in 6-o'clock position, in the area of the molars in the vestibular cranial 10-o'clock position and in the chin region lingual-caudal in the 4-o'clock position. The measurement of the bone density showed the highest values in the 8-o'clock position (vestibular-caudal) in the molar region in both males and females. The average values available of the bone density and the layer thickness of the cortical bone in the various regions of the lower jaw, taking into consideration age, gender and dentition, are an important aid in practice for determining a safe fixation point for implants in the area of the surface layer of the mandible by means of screws or similar fixation elements. (orig.)

Functional and structural microanatomy of the fetal sciatic nerve.

Science.gov (United States)

Creze, Maud; Zaitouna, Mazen; Krystel, Nyangoh Timoh; Diallo, Djibril; Lebacle, Cédric; Bellin, Marie-France; Ducreux, Denis; Benoit, Gérard; Bessede, Thomas

2017-10-01

The ultrastructure of a nerve has implications for surgical nerve repair. The aim of our study was to characterize the fascicular versus fibrillar anatomy and the autonomic versus somatic nature of the fetal sciatic nerve (SN). Immunohistochemistry for vesicular acetylcholine transporter, tyrosine hydroxylase, and peripheral myelin protein 22 was performed to identify cholinergic, adrenergic, and somatic axons, respectively, in the human fetal SN. Two-dimensional (2D) analysis and 3D reconstructions were performed. The fetal SN is composed of one-third stromal tissue and two-thirds neural tissue. Autonomic fibers are predominant over somatic fibers within the neural tissue. The distribution of somatic fibers is initially random, but then become topographically organized after intra- and interfascicular rearrangements have occurred within the nerve. The fetal model presents limitations but enables illustration of the nature of the nerve fibers and the 3D fascicular anatomy of the SN. Muscle Nerve 56: 787-796, 2017. © 2017 Wiley Periodicals, Inc.

Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury

DEFF Research Database (Denmark)

Fordham, Robert P; Yui, Shiro; Hannan, Nicholas R F

2013-01-01

Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can...... be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate...... in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region...

Observation of the human fetal corpses with maxillofacial malformations. 1. CT and MRI examinations of the fetal cleft lip and/or palate

International Nuclear Information System (INIS)

Saito, Chikara; Nakano, Yoko; Shigematsu, Shiro

1999-01-01

Of the various types of congenital malformations, the cleft lip and/or palate is one of the most frequent. Observation of human fetal corpses exhibiting cleft lip and palate is very important to research on its onset of its mechanism and development. In recent years, some of researchers have performed clinical studies on prenatal diagnosis and surgical treatment for the entirety. However, there have hardly been any reports on detailed observations of the maxillofacial structure of a fetus with cleft lip and palate. We seized an opportunity of observing the maxillofacial structure of fetuses with cleft lip and/or palate using three-dimensional CT (3D-CT) and MR imaging as non-disjunctive methods. In the present study, nine fetal corpses having cleft lip and/or palate were examined. The results were as follows: CT and MRI were useful for non-invasive observation of the maxillofacial structure, including soft tissues. Because the osseous tissues of young fetus tissue is not fully mature, observation of bone structures was slightly difficult. When corpses were immersed in formalin for a long time, osseous tissue was decalcified, thus making it difficult to obtain clear images. We could observe the details of the maxillofacial structures such as the alveolar process, the hard palate, the maxillary sinus, the nasal cavity, the nasal bone, and the vomer, in some of the cases. 3D-CT and MR findings observed in the fetuses with cleft lip and/or palate should provide some basement of the imaging diagnosis of congenital disorder. (author))

Observation of the human fetal corpses with maxillofacial malformations. 1. CT and MRI examinations of the fetal cleft lip and/or palate

Energy Technology Data Exchange (ETDEWEB)

Saito, Chikara; Nakano, Yoko; Shigematsu, Shiro [Tokyo Dental Coll., Chiba (Japan)] (and others)

1999-06-01

Of the various types of congenital malformations, the cleft lip and/or palate is one of the most frequent. Observation of human fetal corpses exhibiting cleft lip and palate is very important to research on its onset of its mechanism and development. In recent years, some of researchers have performed clinical studies on prenatal diagnosis and surgical treatment for the entirey. However, there have hardly been any reports on detailed observations of the maxillofacial structure of a fetus with cleft lip and palate. We seized an opportunity of observing the maxillofacial structure of fetuses with cleft lip and/or palate using three-dimensional CT (3D-CT) and MR imaging as non-disjunctive methods. In the present study, nine fetal corpses having cleft lip and/or palate were examined. The results were as follows: CT and MRI were useful for non-invasive observation of the maxillofacial structure, including soft tissues. Because the osseous tissues of young fetus tissue is not fully mature, observation of bone structures was slightly difficult. When corpses were immersed in formalin for a long time, osseous tissue was decalcified, thus making it difficult to obtain clear images. We could observe the details of the maxillofacial structures such as the alveolar process, the hard palate, the maxillary sinus, the nasal cavity, the nasal bone, and the vomer, in some of the cases. 3D-CT and MR findings observed in the fetuses with cleft lip and/or palate should provide some basement of the imaging diagnosis of congenital disorder. (author)

Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys

Energy Technology Data Exchange (ETDEWEB)

Patterson, Tucker A. [Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Twaddle, Nathan C. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Roegge, Cindy S. [Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Callicott, Ralph J. [U.S. Food and Drug Administration and Priority One Services Corp, Jefferson, AR 72079 (United States); Fisher, Jeffrey W. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States)

2013-02-15

Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (> 90%) in amounts consistent with aggregate exposure at levels below 1 μg/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100 μg/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) were attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. - Highlights: ► Maternal, placental, and fetal Phase II metabolism attenuate fetal exposure to BPA. ► Serum AUC for aglycone BPA in fetal monkeys is less than half of that in the dam. ► BPA profiles in monkey fetus rule out selective deconjugation and accumulation. ► BPA levels in monkey placenta are similar to other metabolically active tissues. ► Some published human cord blood data for BPA are inconsistent with these measurements.

Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques.

Science.gov (United States)

Magnani, Diogo M; Rogers, Thomas F; Maness, Nicholas J; Grubaugh, Nathan D; Beutler, Nathan; Bailey, Varian K; Gonzalez-Nieto, Lucas; Gutman, Martin J; Pedreño-Lopez, Núria; Kwal, Jaclyn M; Ricciardi, Michael J; Myers, Tereance A; Julander, Justin G; Bohm, Rudolf P; Gilbert, Margaret H; Schiro, Faith; Aye, Pyone P; Blair, Robert V; Martins, Mauricio A; Falkenstein, Kathrine P; Kaur, Amitinder; Curry, Christine L; Kallas, Esper G; Desrosiers, Ronald C; Goldschmidt-Clermont, Pascal J; Whitehead, Stephen S; Andersen, Kristian G; Bonaldo, Myrna C; Lackner, Andrew A; Panganiban, Antonito T; Burton, Dennis R; Watkins, David I

2018-04-24

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

A novel cortical target to enhance hand motor output in humans with spinal cord injury.

Science.gov (United States)

Long, Jinyi; Federico, Paolo; Perez, Monica A

2017-06-01

A main goal of rehabilitation strategies in humans with spinal cord injury is to strengthen transmission in spared neural networks. Although neuromodulatory strategies have targeted different sites within the central nervous system to restore motor function following spinal cord injury, the role of cortical targets remain poorly understood. Here, we use 180 pairs of transcranial magnetic stimulation for ∼30 min over the hand representation of the motor cortex at an interstimulus interval mimicking the rhythmicity of descending late indirect (I) waves in corticospinal neurons (4.3 ms; I-wave protocol) or at an interstimulus interval in-between I-waves (3.5 ms; control protocol) on separate days in a randomized order. Late I-waves are thought to arise from trans-synaptic cortical inputs and have a crucial role in the recruitment of spinal motor neurons following spinal cord injury. Motor evoked potentials elicited by transcranial magnetic stimulation, paired-pulse intracortical inhibition, spinal motor neuron excitability (F-waves), index finger abduction force and electromyographic activity as well as a hand dexterity task were measured before and after both protocols in 15 individuals with chronic incomplete cervical spinal cord injury and 17 uninjured participants. We found that motor evoked potentials size increased in spinal cord injury and uninjured participants after the I-wave but not the control protocol for ∼30 to 60 min after the stimulation. Intracortical inhibition decreased and F-wave amplitude and persistence increased after the I-wave but not the control protocol, suggesting that cortical and subcortical networks contributed to changes in corticospinal excitability. Importantly, hand motor output and hand dexterity increased in individuals with spinal cord injury after the I-wave protocol. These results provide the first evidence that late synaptic input to corticospinal neurons may represent a novel therapeutic target for improving motor function

Maternal and fetal mechanisms of B cell regulation during pregnancy: human Chorionic Gonadotropin stimulates B cells to produce IL-10 while alpha-fetoprotein drives them into apoptosis

Directory of Open Access Journals (Sweden)

Franziska Fettke

2016-12-01

Full Text Available Maternal immune tolerance towards the fetus is an essential requisite for pregnancy. While T cell functions are well documented, little is known about the participation of B cells. We have previously suggested that IL-10 producing B cells are involved in pregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblasts positively regulate the generation of IL-10 producing B cells. We next studied the participation of hormones produced by the placenta as well as the fetal protein alpha-fetoprotein (AFP in B cell modulation. Human Chorionic Gonadotropin (hCG, but not progesterone, estrogen or a combination of both, was able to promote changes in B cell phenotype and boost their IL-10 production, which was abolished after blocking hCG. The hCG-induced B cell phenotype was not associated with augmented galactosylation, sialylation or fucosylation of IgG subclasses in their Fc. In vitro, hCG induced the synthesis of asymmetrically glycosylated antibodies in their Fab region. Interestingly, AFP had dual effects depending on the concentration. At concentrations corresponding to maternal serum levels, it did not modify the phenotype or IL-10 secretion of B cells. At fetal concentrations, however, AFP was able to drive B cells into apoptosis, which may indicate a protective mechanism to avoid maternal B cells to reach the fetus.Our data suggests that the fetus secrete factors that promote a pregnancy-friendly B cell phenotype, unraveling interesting aspects of B cell function and modulation by pregnancy hormones and fetal proteins.

Canonical cortical circuits: current evidence and theoretical implications

Directory of Open Access Journals (Sweden)

Capone F

2016-04-01

contexts. The fourth section (Extending the concept of canonical circuit to economic decisions circuits reviews the experiments conducted in humans by using transcranial magnetic stimulation to demonstrate the validity of the canonical cortical circuit model. The fifth section (Extending the concept of canonical circuit to economic decisions circuits explores the hypothesis that also complex human behaviors such as economic decision-making could also be explained in terms of canonical cortical circuit. The final section (Conclusion provides a critical point of view, evidencing the limits of the available data and tracking directions for future research.Keywords: canonical cortical circuit, cortex, cortical layers, cortical physiology

Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

Science.gov (United States)

Taylor, C A; Overstreet, J W; Samuels, S J; Boyers, S P; Canfield, R E; O'Connor, J F; Hanson, F W; Lasley, B L

1992-06-01

To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

Data from three prospective longitudinal human cohorts of prenatal marijuana exposure and offspring outcomes from the fetal period through young adulthood

Directory of Open Access Journals (Sweden)

Gabrielle L. McLemore

2016-12-01

Full Text Available This article includes data from three prospective longitudinal human cohorts of prenatal marijuana exposure (PME and offspring outcomes from the fetal period through young adulthood. The table herein contains an overview of the major adverse effects associated with PME from the following human cohorts: (1 The Ottawa Prenatal Prospective Study (OPPS; (2 The Maternal Health Practices and Child Development Study (MHPCD; and (3 The Generation R Study (Gen R. In the OPPS, fetal gestational age was measured and age-appropriate standardized neuropsychological instruments were used to assess neonatal responses, and infant–child and adolescent–young adult cognitive and behavioral skills. In the MHPCD, birth length and weight, neonatal body length, and infant–child sleep, cognition, and behavioral parameters were measured. In the Gen R, birth weight and growth were measured, as were infant–child attention and aggression. The data in this article are in support of our report entitled “Prenatal Cannabis Exposure - The "First Hit" to the Endocannabinoid System” (K.A. Richardson, A.K. Hester, G.L. McLemore, 2016 [13].

Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

Science.gov (United States)

Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

2013-01-01

Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5th centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. 14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR. PMID:24204949

Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype.

Directory of Open Access Journals (Sweden)

Mark Robert Dilworth

Full Text Available Fetal growth restriction (FGR is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th centile of customised growth charts. Sildenafil citrate (SC, Viagra™, a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8% in P0 mice following maternal SC treatment (0.4 mg/ml via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056. Additionally, 75% of the P0 fetal weights were below the 5(th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.

Cortical depth dependent population receptive field attraction by spatial attention in human V1.

Science.gov (United States)

Klein, Barrie P; Fracasso, Alessio; van Dijk, Jelle A; Paffen, Chris L E; Te Pas, Susan F; Dumoulin, Serge O

2018-04-27

Visual spatial attention concentrates neural resources at the attended location. Recently, we demonstrated that voluntary spatial attention attracts population receptive fields (pRFs) toward its location throughout the visual hierarchy. Theoretically, both a feed forward or feedback mechanism could underlie pRF attraction in a given cortical area. Here, we use sub-millimeter ultra-high field functional MRI to measure pRF attraction across cortical depth and assess the contribution of feed forward and feedback signals to pRF attraction. In line with previous findings, we find consistent attraction of pRFs with voluntary spatial attention in V1. When assessed as a function of cortical depth, we find pRF attraction in every cortical portion (deep, center and superficial), although the attraction is strongest in deep cortical portions (near the gray-white matter boundary). Following the organization of feed forward and feedback processing across V1, we speculate that a mixture of feed forward and feedback processing underlies pRF attraction in V1. Specifically, we propose that feedback processing contributes to the pRF attraction in deep cortical portions. Copyright © 2018. Published by Elsevier Inc.

Computational fluid dynamics (CFD) study on the fetal aortic coarctation

Science.gov (United States)

Zhou, Yue; Zhang, Yutao; Wang, Jingying

2018-03-01

Blood flows in normal and coarctate fetal aortas are simulated by the CFD technique using T-rex grids. The three-dimensional (3-D) digital model of the fetal arota is reconstructed by the computer-aided design (CAD) software based on two-dimensional (2-D) ultrasono tomographic images. Simulation results displays the development and enhancement of the secondary flow structure in the coarctate fetal arota. As the diameter narrow ratio rises greater than 45%, the pressure and wall shear stress (WSS) of the aorta arch increase exponentially, which is consistent with the conventional clinical concept. The present study also demonstrates that CFD is a very promising assistant technique to investigate human cardiovascular diseases.

Evaluation of Fetal Intestinal Cell Growth and Antimicrobial Biofunctionalities of Donor Human Milk After Preparative Processes.

Science.gov (United States)

Kanaprach, Pasinee; Pongsakul, Nutkridta; Apiwattanakul, Nopporn; Muanprasat, Chatchai; Supapannachart, Sarayut; Nuntnarumit, Pracha; Chutipongtanate, Somchai

2018-04-01

Donor human milk is considered the next best nutrition following mother's own milk to prevent neonatal infection and necrotizing enterocolitis in preterm infants who are admitted at neonatal intensive care unit. However, donor milk biofunctionalities after preparative processes have rarely been documented. To evaluate biofunctionalities preserved in donor milk after preparative processes by cell-based assays. Ten pools of donor milk were produced from 40 independent specimens. After preparative processes, including bacterial elimination methods (holder pasteurization and cold-sterilization microfiltration) and storage conditions (-20°C freezing storage and lyophilization) with varied duration of storage (0, 3, and 6, months), donor milk biofunctionalities were examined by fetal intestinal cell growth and antimicrobial assays. At baseline, raw donor milk exhibited 193.1% ± 12.3% of fetal intestinal cell growth and 42.4% ± 11.8% of antimicrobial activities against Escherichia coli. After bacteria eliminating processes, growth promoting activity was better preserved in pasteurized donor milk than microfiltrated donor milk (169.5% ± 14.3% versus 146.0% ± 11.8%, respectively; p pasteurized donor milk was further examined for the effects of storage conditions at 3 and 6 months. Freezing storage, but not lyophilization, could preserve higher growth-promoting activity during 6 months of storage (163.0% ± 9.4% versus 72.8% ± 6.2%, respectively; p < 0.005). Nonetheless, antimicrobial activity was lost at 6 months, regardless of the storage methods. This study revealed that fetal intestinal cell growth and antimicrobial assays could be applied to measure donor milk biofunctionalities and support the utilization of donor milk within 3 months after preparative processes.

Yeast-2-Hybrid data file showing progranulin interactions in human fetal brain and bone marrow libraries

Directory of Open Access Journals (Sweden)

Irmgard Tegeder

2016-12-01

Full Text Available Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech. This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].

Complex Trajectories of Brain Development in the Healthy Human Fetus.

Science.gov (United States)

Andescavage, Nickie N; du Plessis, Adre; McCarter, Robert; Serag, Ahmed; Evangelou, Iordanis; Vezina, Gilbert; Robertson, Richard; Limperopoulos, Catherine

2017-11-01

This study characterizes global and hemispheric brain growth in healthy human fetuses during the second half of pregnancy using three-dimensional MRI techniques. We studied 166 healthy fetuses that underwent MRI between 18 and 39 completed weeks gestation. We created three-dimensional high-resolution reconstructions of the brain and calculated volumes for left and right cortical gray matter (CGM), fetal white matter (FWM), deep subcortical structures (DSS), and the cerebellum. We calculated the rate of growth for each tissue class according to gestational age and described patterns of hemispheric growth. Each brain region demonstrated major increases in volume during the second half of gestation, the most pronounced being the cerebellum (34-fold), followed by FWM (22-fold), CGM (21-fold), and DSS (10-fold). The left cerebellar hemisphere, CGM, and DSS had larger volumes early in gestation, but these equalized by term. It has been increasingly recognized that brain asymmetry evolves throughout the human life span. Advanced quantitative MRI provides noninvasive measurements of early structural asymmetry between the left and right fetal brain that may inform functional and behavioral laterality differences seen in children and young adulthood. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Fetal MSCs

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. Derived from extra embryonic tissues (amniotic fluid, placenta, cord blood, Wharton's Jelly) and fetal tissues (aborted fetuses). Derived from extra embryonic tissues (amniotic fluid, placenta, cord blood, Wharton's Jelly) and fetal tissues (aborted fetuses). In comparison ...

Fetal and neo-natal maxillary ontogeny in extant humans and the utility of prenatal maxillary morphology in predicting ancestral affiliation

Science.gov (United States)

Nicholas, Christina L.

2016-01-01

Objectives The midface of extant H. sapiens is known to undergo shape changes through fetal and neo-natal ontogeny; however, little work has been done to quantify these shape changes. Further, while midfacial traits which vary in frequency between populations of extant humans are presumed to develop prenatally, patterns of population-specific variation maxillary shape across ontogeny are not well documented. Only one study of fetal ontogeny which included specific discussion of the midface has taken a 3D geometric morphometric approach, and that study was limited to one population (Japanese). The present research project seeks to augment our understanding of fetal maxillary growth patterns, most especially in terms of intraspecific variation. Materials and Methods Three-dimensional coordinate landmark data were collected on the right maxillae of 102 fetal and neo-natal individuals from three groups (Euro-American, African-American, “Mixed Ancestry”). Results Shape changes were seen mainly in the lateral wall of the piriform aperture, the anterior nasal spine, and the subnasal alveolar region. The greatest difference across age groups (2nd Trimester, 3rd Trimester, Neonates) was between the second and third trimester. Euro-Americans and African-Americans clustered by population and differences in midfacial morphology related to ancestry could be discerned as early as the second trimester (p=0.002), indicating that population variation in maxillary morphology appears very early in ontogeny. Discussion The midface is a critical region of the skull for assessing ancestry and these results indicate that maxillary morphology may be useful for estimating ancestry for prenatal individuals as young as the second trimester. PMID:27412693

Effects of Exposure to Acetaminophen and Ibuprofen on Fetal Germ Cell Development in Both Sexes in Rodent and Human Using Multiple Experimental Systems

DEFF Research Database (Denmark)

Hurtado-Gonzalez, Pablo; Anderson, Richard A; Macdonald, Joni

2018-01-01

/ovaries using in vitro and xenograft approaches. METHODS: Gonocyte (TFAP2C+) number was reduced relative to controls in first-trimester human fetal testes exposed in vitro to acetaminophen (-28%) or ibuprofen (-22%) and also in ovaries exposed to acetaminophen (-43%) or ibuprofen (-49%). Acetaminophen exposure...

Anti-correlated cortical networks of intrinsic connectivity in the rat brain.

Science.gov (United States)

Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

Maternal Therapy with Ad.VEGF-A165 Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.

Science.gov (United States)

Swanson, Anna M; Rossi, Carlo A; Ofir, Keren; Mehta, Vedanta; Boyd, Michael; Barker, Hannah; Ledwozyw, Agata; Vaughan, Owen; Martin, John; Zachary, Ian; Sebire, Neil; Peebles, Donald M; David, Anna L

2016-12-01

In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-conceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A 165 or Ad.LacZ (1 × 10 10 vp) was applied at mid-gestation via laparotomy, delivered externally to the uterine circulation with thermosensitive gel. At short-term (3-8 days post surgery) or at term gestation, pups were weighed, and tissues were sampled for vector spread analysis, VEGF expression, and its downstream effects. Fetal weight at term was increased (88.01 ± 13.36 g; n = 26) in Ad.VEGF-A 165 -treated animals compared with Ad.LacZ-treated animals (85.52 ± 13.00 g; n = 19; p = 0.028). The brain, liver, and lung weight and crown rump length were significantly larger in short-term analyses, as well as VEGF expression in transduced tissues. At term, molecular analyses confirmed the presence of VEGF transgene in target tissues but not in fetal samples. Tissue histology analysis and blood biochemistry/hematological examination were comparable with controls. Uterine artery relaxation in Ad.VEGF-A 165 -treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A 165 increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.

Cloning of a novel cell type from human fetal liver expressing cytoplasmic CD3 delta and epsilon but not membrane CD3

NARCIS (Netherlands)

Hori, T.; de Waal Malefyt, R.; Duncan, B. W.; Harrison, M. R.; Roncarolo, M. G.; Spits, H.

1991-01-01

Seventeen-week human fetal liver cells cultured with a feeder cell mixture of irradiated PBL, irradiated JY cells (an EBV-transformed B cell line) and PHA contained a subpopulation of CD3- cells in addition to a major population of T cells with the mature phenotype. After 12 days in culture, CD3-

Effects of cytokine-suppressive anti-inflammatory drugs on inflammatory activation in ex vivo human and ovine fetal membranes.

Science.gov (United States)

Stinson, Lisa F; Ireland, Demelza J; Kemp, Matthew W; Payne, Matthew S; Stock, Sarah J; Newnham, John P; Keelan, Jeffrey A

2014-03-01

Intrauterine infection and inflammation are responsible for the majority of early (PTBs). Anti-inflammatory agents, delivered intra-amniotically together with antibiotics, may be an effective strategy for preventing PTB. In this study, the effects of four cytokine-suppressive anti-inflammatory drugs (CSAIDs: N-acetyl cysteine (NAC), SB239063, TPCA-1 and NEMO binding domain inhibitor (NBDI)) were assessed on human and ovine gestational membrane inflammation. Full-thickness membranes were collected from healthy, term, human placentas delivered by Caesarean section (n=5). Using a Transwell model, they were stimulated ex vivo with γ-irradiation-killed Escherichia coli applied to the amniotic face. Membranes from near-term, ovine placentas were stimulated in utero with lipopolysaccharide, Ureaplasma parvum or saline control and subjected to explant culture. The effects of treatment with CSAIDs or vehicle (1% DMSO) on accumulation of PGE2 and cytokines (human interleukin 6 (IL6), IL10 and TNFα; ovine IL8 (oIL8)) were assessed in conditioned media at various time points (3-20  h). In human membranes, the IKKβ inhibitor TPCA-1 (7  μM) and p38 MAPK inhibitor SB239063 (20  μM) administered to the amniotic compartment were the most effective in inhibiting accumulation of cytokines and PGE2 in the fetal compartment. NAC (10  mM) inhibited accumulation of PGE2 and IL10 only; NBDI (10  μM) had no significant effect. In addition to the fetal compartment, SB239063 also exerted consistent and significant inhibitory effects in the maternal compartment. TPCA-1 and SB239063 suppressed oIL8 production, while all CSAIDs tested suppressed ovine PGE2 production. These results support the further investigation of intra-amniotically delivered CSAIDs for the prevention of inflammation-mediated PTB.

Fetal tachycardia : diagnosis and treatment

NARCIS (Netherlands)

Oudijk, Martijn Alexander

2003-01-01

Part I: Fetal tachyarrhythmias Diagnosis Fetal tachycardia is a serious condition warranting specialized evaluation. In chapter 2, methods of diagnosis of fetal tachycardia are described, including doppler and M-mode echocardiography and fetal magnetocardiography. The study presented in chapter 3

Fetal short time variation during labor: a non-invasive alternative to fetal scalp pH measurements?

Science.gov (United States)

Schiermeier, Sven; Reinhard, Joscha; Hatzmann, Hendrike; Zimmermann, Ralf C; Westhof, Gregor

2009-01-01

To determine whether short time variation (STV) of fetal heart beat correlates with scalp pH measurements during labor. From 1279 deliveries, 197 women had at least one fetal scalp pH measurement. Using the CTG-Player, STVs were calculated from the electronically saved cardiotocography (CTG) traces and related to the fetal scalp pH measurements. There was no correlation between STV and fetal scalp pH measurements (r=-0.0592). Fetal STV is an important parameter with high sensitivity for antenatal fetal acidosis. This study shows that STV calculations do not correlate with fetal scalp pH measurements during labor, hence are not helpful in identifying fetal acidosis.

Ethanol-induced transcriptional activation of programmed cell death 4 (Pdcd4 is mediated by GSK-3β signaling in rat cortical neuroblasts.

Directory of Open Access Journals (Sweden)

Amanjot Kaur Riar

Full Text Available Ingestion of ethanol (ETOH during pregnancy induces grave abnormalities in developing fetal brain. We have previously reported that ETOH induces programmed cell death 4 (PDCD4, a critical regulator of cell growth, in cultured fetal cerebral cortical neurons (PCNs and in the cerebral cortex in vivo and affect protein synthesis as observed in Fetal Alcohol Spectrum Disorder (FASD. However, the mechanism which activates PDCD4 in neuronal systems is unclear and understanding this regulation may provide a counteractive strategy to correct the protein synthesis associated developmental changes seen in FASD. The present study investigates the molecular mechanism by which ethanol regulates PDCD4 in cortical neuroblasts, the immediate precursor of neurons. ETOH treatment significantly increased PDCD4 protein and transcript expression in spontaneously immortalized rat brain neuroblasts. Since PDCD4 is regulated at both the post-translational and post-transcriptional level, we assessed ETOH's effect on PDCD4 protein and mRNA stability. Chase experiments demonstrated that ETOH does not significantly impact either PDCD4 protein or mRNA stabilization. PDCD4 promoter-reporter assays confirmed that PDCD4 is transcriptionally regulated by ETOH in neuroblasts. Given a critical role of glycogen synthase kinase 3β (GSK-3β signaling in regulating protein synthesis and neurotoxic mechanisms, we investigated the involvement of GSK-3β and showed that multifunctional GSK-3β was significantly activated in response to ETOH in neuroblasts. In addition, we found that ETOH-induced activation of PDCD4 was inhibited by pharmacologic blockade of GSK-3β using inhibitors, lithium chloride (LiCl and SB-216763 or siRNA mediated silencing of GSK-3β. These results suggest that ethanol transcriptionally upregulates PDCD4 by enhancing GSK-3β signaling in cortical neuroblasts. Further, we demonstrate that canonical Wnt-3a/GSK-3β signaling is involved in regulating PDCD4 protein

Restoring cortical control of functional movement in a human with quadriplegia.

Science.gov (United States)

Bouton, Chad E; Shaikhouni, Ammar; Annetta, Nicholas V; Bockbrader, Marcia A; Friedenberg, David A; Nielson, Dylan M; Sharma, Gaurav; Sederberg, Per B; Glenn, Bradley C; Mysiw, W Jerry; Morgan, Austin G; Deogaonkar, Milind; Rezai, Ali R

2016-05-12

Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic 'neural bypass' to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements. In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles. Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant's forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5-C6) to the seventh cervical to first thoracic (C7-T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology

The relationship between maternal and fetal vitamin D, insulin resistance, and fetal growth.

LENUS (Irish Health Repository)

Walsh, Jennifer M

2013-05-01

Evidence for a role of vitamin D in maintaining normal glucose homeostasis is inconclusive. We sought to clarify the relationship between maternal and fetal insulin resistance and vitamin D status. This is a prospective cohort study of 60 caucasian pregnant women. Concentrations of 25-hydroxyvitamin D (25-OHD), glucose, insulin, and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width, a marker of fetal adiposity. At delivery birth weight was recorded and fetal 25-OHD, glucose, C-peptide, and leptin measured in cord blood. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA) equation. We found that those with lower 25-OHD in early pregnancy had higher HOMA indices at 28 weeks, (r = -.32, P = .02). No significant relationship existed between maternal or fetal leptin and 25-OHD, or between maternal or fetal 25-OHD and fetal anthropometry or birth weight. The incidence of vitamin D deficiency was high at each time point (15%-45%). These findings lend support to routine antenatal supplementation with vitamin D in at risk populations.

Fetal Echocardiography and Indications

Directory of Open Access Journals (Sweden)

Melih Atahan Güven

2008-09-01

Full Text Available Congenital heart diseases are encountered in 0.8% of live births and are among the most frequently diagnosed malformations. At least half of these anomalies end up with death or require surgical interventions and are responsible for 30% of the perinatal mortality. Fetal echocardiography is the sum of knowledge, skill and orientation rather than knowing the embryologic details of the fetal heart. The purpose of fetal echocardiography is to document the presence of normal fetal cardiac anatomy and rhythm in high risk group and to define the anomaly and arrhythmia if present. A certain sequence should be followed during the evaluation of fetal heart. Sequential segmental analysis (SSA and basic definition terminology made it possible to determine a lot of complex cardiac anomalies during prenatal period. By the end of 1970’s, Shinebourne started using sequential segmental analysis for fetal cardiac evaluation and today, prenatal diagnosis of congenital heart disease is possible without any confusion. In this manner, whole fetal heart can be evaluated as the relation of three segments (atria, ventricles and the great arteries with each other, irrelevant of complexity of a possible cardiac anomaly. Presence of increased nuchal thickness during early gestation and abnormal four-chamber-view during ultrasonography by the obstetrician presents a clear indication for fetal echocardiography,however, one should keep in mind that 80-90% of the babies born with a congenital heart disease do not have a familial or maternal risk factor. In addition, it should be remembered that expectant mothers with diabetes mellitus pose an indication for fetal echocardiography.

Value of amniocentesis versus fetal tissue for cytogenetic analysis in cases of fetal demise.

Science.gov (United States)

Bryant Borders, Ann E; Greenberg, Jessica; Plaga, Stacey; Shepard-Hinton, Megan; Yates, Carin; Elias, Sherman; Shulman, Lee P

2009-01-01

Use of fetal tissue for cytogenetic analysis in cases of second- and third-trimester fetal demise frequently results in unacceptably high failure rates. We reviewed our ongoing use of amniocentesis prior to uterine evacuation to determine if this provided a better source of cells for cytogenetic analysis. We compared cytogenetic results using fetal tissues obtained following uterine evacuation to our ongoing use of amniotic fluid cell obtained by transabdominal amniocentesis prior to uterine evacuation from 2003 to 2008. In 49 of the 63 cases evaluated by fetal tissue biopsies performed after uterine evacuation, a karyotypic analysis was obtained (77.8%). Among the 38 cases evaluated by amniocentesis, an amniotic fluid sample and fetal cytogenetic results were obtained in all 38 (100%) cases. Our findings indicate that amniocentesis is a more reliable source of cytogenetic information than fetal tissue in cases of second- and third-trimester fetal demise.

The World Health Organization fetal growth charts: concept, findings, interpretation, and application.

Science.gov (United States)

Kiserud, Torvid; Benachi, Alexandra; Hecher, Kurt; Perez, Rogelio González; Carvalho, José; Piaggio, Gilda; Platt, Lawrence D

2018-02-01

weight was strongest on the lowest percentiles and smallest on the highest percentiles for estimated fetal weight. (3) When adjustment was made for maternal covariates, there was still a significant effect of country as covariate that indicated that ethnic, cultural, and geographic variation play a role. (4) Variation between populations was not restricted to fetal size because there were also differences in growth trajectories. (5) The wide physiologic ranges, as illustrated by the 5th-95th percentile for estimated fetal weight being 2205-3538 g at 37 weeks gestation, signify that human fetal growth under optimized maternal conditions is not uniform. Rather, it has a remarkable variation that largely is unexplained by commonly known factors. We suggest this variation could be part of our common biologic strategy that makes human evolution extremely successful. The World Health Organization fetal growth charts are intended to be used internationally based on low-risk pregnancies from populations in Africa, Asia, Europe, and South America. We consider it prudent to test and monitor whether the growth charts' performance meets the local needs, because refinements are possible by a change in cut-offs or customization for fetal sex, maternal factors, and populations. In the same line, the study finding of variations emphasizes the need for carefully adjusted growth charts that reflect optimal local growth when public health issues are addressed. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical implications from monitoring fetal activity.

Science.gov (United States)

Rayburn, W F

1982-12-15

The monitoring of fetal motion in high-risk pregnancies has been shown to be worthwhile in predicting fetal distress and impending fetal death. The maternal recording of perceived fetal activity is an inexpensive surveillance technique which is most useful when there is chronic uteroplacental insufficiency or when a stillbirth may be expected. The presence of an active, vigorous fetus is reassuring, but documented fetal inactivity required a reassessment of the underlying antepartum complication and further fetal evaluation with real-time ultrasonography, fetal heart rate testing, and biochemical testing. Fetal distress from such acute changes as abruptio placentae or umbilical cord compression may not be predicted by monitoring fetal motion. Although not used for routine clinical investigation, electromechanical devices such as tocodynamometry have provided much insight into fetal behavioral patterns at many stages of pregnancy and in pregnancies with an antepartum complication.

Creation of an in vitro microenvironment to enhance human fetal synovium-derived stem cell chondrogenesis.

Science.gov (United States)

Li, Jingting; He, Fan; Pei, Ming

2011-09-01

Our aim was to assess the feasibility of the sequential application of extracellular matrix (ECM) and low oxygen to enhance chondrogenesis in human fetal synovium-derived stem cells (hfSDSCs). Human fetal synovial fibroblasts (hfSFs) were characterized and found to include hfSDSCs, as evidenced by their multi-differentiation capacity and the surface phenotype markers typical of mesenchymal stem cells. Passage-7 hfSFs were plated on either conventional plastic flasks (P) or ECM deposited by hfSFs (E) for one passage. Passage-8 hfSFs were then reseeded for an additional passage on either P or E. The pellets from expanded hfSFs were incubated in a serum-free chondrogenic medium supplemented with 10 ng/ml transforming growth factor-β3 under either normoxia (21% O(2); 21) or hypoxia (5% O(2); 5) for 14 days. Pellets were collected for evaluation of the treatments (EE21, EE5, EP21, EP5, PE21, PE5, PP21, and PP5) on expanded hfSF chondrogenesis by using histology, immunostaining, biochemistry, and real-time polymerase chain reaction. Our data suggest that, compared with seeding on conventional plastic flasks, hfSFs expanded on ECM exhibit a lower expression of senescence-associated β-galactosidase and an enhanced level of stage-specific embryonic antigen-4. ECM-expanded hfSFs also show increased cell numbers and an enhanced chondrogenic potential. Low oxygen (5% O(2)) during pellet culture enhances hfSF chondrogenesis. Thus, we demonstrate, for the first time, the presence of stem cells in hfSFs, and that modulation of the in vitro microenvironment can enhance hfSDSC chondrogenesis. hfSDSCs might represent a promising cell source for cartilage tissue engineering and regeneration.

A high density of human communication-associated genes in chromosome 7q31-q36: differential expression in human and non-human primate cortices.

Science.gov (United States)

Schneider, E; Jensen, L R; Farcas, R; Kondova, I; Bontrop, R E; Navarro, B; Fuchs, E; Kuss, A W; Haaf, T

2012-01-01

The human brain is distinguished by its remarkable size, high energy consumption, and cognitive abilities compared to all other mammals and non-human primates. However, little is known about what has accelerated brain evolution in the human lineage. One possible explanation is that the appearance of advanced communication skills and language has been a driving force of human brain development. The phenotypic adaptations in brain structure and function which occurred on the way to modern humans may be associated with specific molecular signatures in today's human genome and/or transcriptome. Genes that have been linked to language, reading, and/or autism spectrum disorders are prime candidates when searching for genes for human-specific communication abilities. The database and genome-wide expression analyses we present here revealed a clustering of such communication-associated genes (COAG) on human chromosomes X and 7, in particular chromosome 7q31-q36. Compared to the rest of the genome, we found a high number of COAG to be differentially expressed in the cortices of humans and non-human primates (chimpanzee, baboon, and/or marmoset). The role of X-linked genes for the development of human-specific cognitive abilities is well known. We now propose that chromosome 7q31-q36 also represents a hot spot for the evolution of human-specific communication abilities. Selective pressure on the T cell receptor beta locus on chromosome 7q34, which plays a pivotal role in the immune system, could have led to rapid dissemination of positive gene variants in hitchhiking COAG. Copyright © 2012 S. Karger AG, Basel.

Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.

Science.gov (United States)

Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan

2014-02-01

Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

Determination of calcium, phosphorus, and the calcium/phosphorus ratio in cortical bone from the human femoral neck by neutron activation analysis

International Nuclear Information System (INIS)

Zaichick, Vladimir; Tzaphlidou, Margaret

2002-01-01

Concentrations of Ca and P as well as the Ca/P ratio were estimated in intact cortical bone samples from the femoral neck of healthy humans, 33 women and 45 men, aged from 15 to 55 yr using instrumental neutron activation analysis. Mean values (M±SD) for the investigated parameters (on dry weight basis) were: 23.0±3.9%, 10.7±2.4% and 2.17±0.31, respectively. No statistically significant differences of the above parameters were observed related either to age or sex. The mean values for Ca, P and Ca/P ratio were within a very wide range of published data and close to their median. The individual variation for the Ca/P ratio in cortical bone from the healthy human femoral neck was lower than those for Ca and P separately. This means that specificity of Ca/P ratio is better than those of Ca and P concentrations are and may be more reliable for diagnosis of bone disorders

Cortical visual impairment

OpenAIRE

Koželj, Urša

2013-01-01

In this thesis we discuss cortical visual impairment, diagnosis that is in the developed world in first place, since 20 percent of children with blindness or low vision are diagnosed with it. The objectives of the thesis are to define cortical visual impairment and the definition of characters suggestive of the cortical visual impairment as well as to search for causes that affect the growing diagnosis of cortical visual impairment. There are a lot of signs of cortical visual impairment. ...

Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.

Science.gov (United States)

Frasch, M G; Müller, T; Wicher, C; Weiss, C; Löhle, M; Schwab, K; Schubert, H; Nathanielsz, P W; Witte, O W; Schwab, M

2007-03-15

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P fetal heart rate depended on fetal weight (P fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.

Intra-cortical excitability in healthy human subjects after tongue training

DEFF Research Database (Denmark)

Baad-Hansen, Lene; Blicher, Jakob; Lapitskaya, Natallia

2009-01-01

Training of specific muscles causes plastic changes in corticomotor pathways which may underlie the effect of various clinical rehabilitation procedures. The paired pulse transcranial magnetic stimulation (ppTMS) technique can be used to assess short interval intra-cortical inhibitory (SICI...... tongue muscles. In tongue motor cortex, bilateral SICI (P training. There were no significant effects of training on single MEPs or SICI/ICF (P > 0.063). The success rate improved during training (P ...) and intra-cortical facilitatory (ICF) networks. This study examined changes in SICI and ICF in tongue motor cortex after tongue training in 11 healthy volunteers using ppTMS. Paired pulse TMS was applied to the 'hot-spot' for the tongue motor cortex and motor-evoked potentials (MEPs) were recorded from...

Pathogenesis of cerebral malformations in human fetuses with meningomyelocele

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Brouwer Oebele F

2008-03-01

Full Text Available Abstract Background Fetal spina bifida aperta (SBA is characterized by a spinal meningomyelocele (MMC and associated with cerebral pathology, such as hydrocephalus and Chiari II malformation. In various animal models, it has been suggested that a loss of ventricular lining (neuroepithelial/ependymal denudation may trigger cerebral pathology. In fetuses with MMC, little is known about neuroepithelial/ependymal denudation and the initiating pathological events. The objective of this study was to investigate whether neuroepithelial/ependymal denudation occurs in human fetuses and neonates with MMC, and if so, whether it is associated with the onset of hydrocephalus. Methods Seven fetuses and 1 neonate (16–40 week gestational age, GA with MMC and 6 fetuses with normal cerebral development (22–41 week GA were included in the study. Identification of fetal MMC and clinical surveillance of fetal head circumference and ventricular width was performed by ultrasound (US. After birth, MMC was confirmed by histology. We characterized hydrocephalus by increased head circumference in association with ventriculomegaly. The median time interval between fetal cerebral ultrasound and fixing tissue for histology was four days. Results At 16 weeks GA, we observed neuroepithelial/ependymal denudation in the aqueduct and telencephalon together with sub-cortical heterotopias in absence of hydrocephalus and/or Chiari II malformation. At 21–34 weeks GA, we observed concurrence of aqueductal neuroepithelial/ependymal denudation and progenitor cell loss with the Chiari II malformation, whereas hydrocephalus was absent. At 37–40 weeks GA, neuroepithelial/ependymal denudation coincided with Chiari II malformation and hydrocephalus. Sub-arachnoidal fibrosis at the convexity was absent in all fetuses but present in the neonate. Conclusion In fetal SBA, neuroepithelial/ependymal denudation in the telencephalon and the aqueduct can occur before Chiari II malformation

Status epilepticus after prolonged umbilical cord occlusion is associated with greater neural injury in [corrected] fetal sheep at term-equivalent.

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Paul P Drury

Full Text Available The majority of pre-clinical studies of hypoxic-ischemic encephalopathy at term-equivalent have focused on either relatively mild insults, or on functional paradigms of cerebral ischemia or hypoxia-ischemia/hypotension. There is surprisingly little information on the responses to single, severe 'physiological' insults. In this study we examined the evolution and pattern of neural injury after prolonged umbilical cord occlusion (UCO. 36 chronically instrumented fetal sheep at 125-129 days gestational age (term = 147 days were subjected to either UCO until mean arterial pressure was < = 8 mmHg (n = 29, or sham occlusion (n = 7. Surviving fetuses were killed after 72 hours for histopathologic assessment with acid-fuchsin thionine. After UCO, 11 fetuses died with intractable hypotension and 5 ewes entered labor and were euthanized. The remaining 13 fetuses showed marked EEG suppression followed by evolving seizures starting at 5.8 (6.8 hours (median (interquartile range. 6 of 13 developed status epilepticus, which was associated with a transient secondary increase in cortical impedance (a measure of cytotoxic edema, p<0.05. All fetuses showed moderate to severe neuronal loss in the hippocampus and the basal ganglia but mild cortical cell loss (p<0.05 vs sham occlusion. Status epilepticus was associated with more severe terminal hypotension (p<0.05 and subsequently, greater neuronal loss (p<0.05. In conclusion, profound UCO in term-equivalent fetal sheep was associated with delayed seizures, secondary cytotoxic edema, and subcortical injury, consistent with the predominant pattern after peripartum sentinel events at term. It is unclear whether status epilepticus exacerbated cortical injury or was simply a reflection of a longer duration of asphyxia.

Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers.

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Gaccioli, Francesca; Aye, Irving L M H; Sovio, Ulla; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-02-01

Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ultrasound screening for fetal growth restriction in the third trimester, but the evidence base is not strong. Implementation of universal ultrasound screening in low-risk women in France failed to reduce the risk of complications among small-for-gestational-age infants but did appear to cause iatrogenic harm to false positives. One strategy to making progress is to improve screening by developing more sensitive and specific tests with the key goal of differentiating between healthy small fetuses and those that are small through fetal growth restriction. As abnormal placentation is thought to be the major cause of fetal growth restriction, one approach is to combine fetal biometry with an indicator of placental dysfunction. In the past, these indicators were generally ultrasonic measurements, such as Doppler flow velocimetry of the uteroplacental circulation. However, another promising approach is to combine ultrasonic suspicion of small-for-gestational-age infant with a blood test indicating placental dysfunction. Thus far, much of the research on maternal serum biomarkers for fetal growth restriction has involved the secondary analysis of tests performed for other indications, such as fetal aneuploidies. An exemplar of this is pregnancy-associated plasma protein A. This blood test is performed primarily to assess the risk of Down syndrome, but women with low first-trimester levels are now serially scanned in later pregnancy due to associations with placental causes of

Cortical representations of communication sounds.

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Heiser, Marc A; Cheung, Steven W

2008-10-01

This review summarizes recent research into cortical processing of vocalizations in animals and humans. There has been a resurgent interest in this topic accompanied by an increased number of studies using animal models with complex vocalizations and new methods in human brain imaging. Recent results from such studies are discussed. Experiments have begun to reveal the bilateral cortical fields involved in communication sound processing and the transformations of neural representations that occur among those fields. Advances have also been made in understanding the neuronal basis of interaction between developmental exposures and behavioral experiences with vocalization perception. Exposure to sounds during the developmental period produces large effects on brain responses, as do a variety of specific trained tasks in adults. Studies have also uncovered a neural link between the motor production of vocalizations and the representation of vocalizations in cortex. Parallel experiments in humans and animals are answering important questions about vocalization processing in the central nervous system. This dual approach promises to reveal microscopic, mesoscopic, and macroscopic principles of large-scale dynamic interactions between brain regions that underlie the complex phenomenon of vocalization perception. Such advances will yield a greater understanding of the causes, consequences, and treatment of disorders related to speech processing.

Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

DEFF Research Database (Denmark)

van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A

2015-01-01

Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons...

Clinical significance of perceptible fetal motion.

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Rayburn, W F

1980-09-15

The monitoring of fetal activity during the last trimester of pregnancy has been proposed to be useful in assessing fetal welfare. The maternal perception of fetal activity was tested among 82 patients using real-time ultrasonography. All perceived fetal movements were visualized on the scanner and involved motion of the lower limbs. Conversely, 82% of all visualized motions of fetal limbs were perceived by the patients. All combined motions of fetal trunk with limbs were preceived by the patients and described as strong movements, whereas clusters of isolated, weak motions of the fetal limbs were less accurately perceived (56% accuracy). The number of fetal movements perceived during the 15-minute test period was significantly (p fetal motion was present (44 of 45 cases) than when it was absent (five of 10 cases). These findings reveal that perceived fetal motion is: (1) reliable; (2) related to the strength of lower limb motion; (3) increased with ruptured amniotic membranes; and (4) reassuring if considered to be active.

Temporal envelope processing in the human auditory cortex: response and interconnections of auditory cortical areas.

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Gourévitch, Boris; Le Bouquin Jeannès, Régine; Faucon, Gérard; Liégeois-Chauvel, Catherine

2008-03-01

Temporal envelope processing in the human auditory cortex has an important role in language analysis. In this paper, depth recordings of local field potentials in response to amplitude modulated white noises were used to design maps of activation in primary, secondary and associative auditory areas and to study the propagation of the cortical activity between them. The comparison of activations between auditory areas was based on a signal-to-noise ratio associated with the response to amplitude modulation (AM). The functional connectivity between cortical areas was quantified by the directed coherence (DCOH) applied to auditory evoked potentials. This study shows the following reproducible results on twenty subjects: (1) the primary auditory cortex (PAC), the secondary cortices (secondary auditory cortex (SAC) and planum temporale (PT)), the insular gyrus, the Brodmann area (BA) 22 and the posterior part of T1 gyrus (T1Post) respond to AM in both hemispheres. (2) A stronger response to AM was observed in SAC and T1Post of the left hemisphere independent of the modulation frequency (MF), and in the left BA22 for MFs 8 and 16Hz, compared to those in the right. (3) The activation and propagation features emphasized at least four different types of temporal processing. (4) A sequential activation of PAC, SAC and BA22 areas was clearly visible at all MFs, while other auditory areas may be more involved in parallel processing upon a stream originating from primary auditory area, which thus acts as a distribution hub. These results suggest that different psychological information is carried by the temporal envelope of sounds relative to the rate of amplitude modulation.

Differential diagnosis between fetal extrarenal pelvis and obstructive uropathy on fetal ultrasonogram

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Han, Byoung Hee; Cho, Jeong Yeon; Cho, Byung Jae; Lee, Kyung Sang [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2003-03-15

To establish the standard guideline for differentiating the extrarenal pelvis from obstructive uropathy on fetal ultrasonogram (US) to avoid unnecessary postnatal follow-up and other additional examinations. From July 2000 to July 2001, Thirty-four kidneys with hydronephrosis diagnosed on fetal ultrasonogram performed during the third trimester of pregnancy were included in this study. Hydronephrosis was defined as the pelvic anteroposterior (AP) diameter being 4 mm or greater before 33 weeks of gestation while 7 mm or greater at or after 33 weeks of gestation. The size of the renal pelvis was measured at intrarenal, intra-extrarenal junctional and extrarenal portions in every kidney on the transverse view of the fetal renal hiluin. Postnatally, all neonates underwent renal ultrasonogram 2 to 8 days after birth, and renal pelvic diameters were measured using the same method as the fetal US in 28 kidneys. We then compared the extrarenal-intrarenal ratio (E/I ratio) of pelvic diameter between fetal and neoatal kidneys. We presumed that the extrarenal pelvis in fetal US was the pelvis showing the normal intrarenal pelvic diameter accompanied by the most dilated exrtarenal pelvic diameter. Follow-up ultrasonograms were measured using the same method as the fetal US in 28 kidneys. We then compared the extrarenal intrarenal ratio (E/I ratio) of pelvic diameter between fetal and neonatal kidneys. We presumed that the extrarenal pelvis on fetal US was the pelvis showing the normal intrarenal pelvic diameter accompanied by the most dilated extrarenal pelvic diameter. Follow-up ultrasonograms were performed in 12 of 17 neonates who had the maximal diameter at extrarenal portion on fetal ultrasonogram. VCUG and IVU were taken in 2 patients with a persistent dilatation of the renal pelvis on follow-up ultrasonograms. On fetal US, 17/34 kidneys showed the extrarenal portion with the most dilatation while in 12/34 kidneys, the intra-extra renal junction portion was the most

Differential diagnosis between fetal extrarenal pelvis and obstructive uropathy on fetal ultrasonogram

International Nuclear Information System (INIS)

Han, Byoung Hee; Cho, Jeong Yeon; Cho, Byung Jae; Lee, Kyung Sang

2003-01-01

To establish the standard guideline for differentiating the extrarenal pelvis from obstructive uropathy on fetal ultrasonogram (US) to avoid unnecessary postnatal follow-up and other additional examinations. From July 2000 to July 2001, Thirty-four kidneys with hydronephrosis diagnosed on fetal ultrasonogram performed during the third trimester of pregnancy were included in this study. Hydronephrosis was defined as the pelvic anteroposterior (AP) diameter being 4 mm or greater before 33 weeks of gestation while 7 mm or greater at or after 33 weeks of gestation. The size of the renal pelvis was measured at intrarenal, intra-extrarenal junctional and extrarenal portions in every kidney on the transverse view of the fetal renal hiluin. Postnatally, all neonates underwent renal ultrasonogram 2 to 8 days after birth, and renal pelvic diameters were measured using the same method as the fetal US in 28 kidneys. We then compared the extrarenal-intrarenal ratio (E/I ratio) of pelvic diameter between fetal and neoatal kidneys. We presumed that the extrarenal pelvis in fetal US was the pelvis showing the normal intrarenal pelvic diameter accompanied by the most dilated exrtarenal pelvic diameter. Follow-up ultrasonograms were measured using the same method as the fetal US in 28 kidneys. We then compared the extrarenal intrarenal ratio (E/I ratio) of pelvic diameter between fetal and neonatal kidneys. We presumed that the extrarenal pelvis on fetal US was the pelvis showing the normal intrarenal pelvic diameter accompanied by the most dilated extrarenal pelvic diameter. Follow-up ultrasonograms were performed in 12 of 17 neonates who had the maximal diameter at extrarenal portion on fetal ultrasonogram. VCUG and IVU were taken in 2 patients with a persistent dilatation of the renal pelvis on follow-up ultrasonograms. On fetal US, 17/34 kidneys showed the extrarenal portion with the most dilatation while in 12/34 kidneys, the intra-extra renal junction portion was the most

Histological features of layers and sublayers in cortical visual areas V1 and V2 of chimpanzees, macaque monkeys, and humans.

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Balaram, Pooja; Young, Nicole A; Kaas, Jon H

2014-09-01

The layers and sublayers of primary visual cortex, or V1, in primates are easily distinguishable compared to those in other cortical areas, and are especially distinct in anthropoid primates - monkeys, apes, and humans - where they also vary in histological appearance. This variation in primate-specific specialization has led to a longstanding confusion over the identity of layer 4 and its proposed sublayers in V1. As the application of different histological markers relate to the issue of defining and identifying layers and sublayers, we applied four traditional and four more recent histological markers to brain sections of V1 and adjoining secondary visual cortex (V2) in macaque monkeys, chimpanzees, and humans in order to compare identifiable layers and sublayers in both cortical areas across these species. The use of Nissl, neuronal nuclear antigen (NeuN), Gallyas myelin, cytochrome oxidase (CO), acetylcholinesterase (AChE), nonphosphorylated neurofilament H (SMI-32), parvalbumin (PV), and vesicular glutamate transporter 2 (VGLUT2) preparations support the conclusion that the most popular scheme of V1 lamination, that of Brodmann, misidentifies sublayers of layer 3 (3Bβ and 3C) as sublayers of layer 4 (4A and 4B), and that the specialized sublayer of layer 3 in monkeys, 3Bβ, is not present in humans. These differences in interpretation are important as they relate to the proposed functions of layer 4 in primate species, where layer 4 of V1 is a layer that receives and processes information from the visual thalamus, and layer 3 is a layer that transforms and distributes information to other cortical areas.

Three-Dimensional Visualization with Large Data Sets: A Simulation of Spreading Cortical Depression in Human Brain

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Ertürk, Korhan Levent; Şengül, Gökhan

2012-01-01

We developed 3D simulation software of human organs/tissues; we developed a database to store the related data, a data management system to manage the created data, and a metadata system for the management of data. This approach provides two benefits: first of all the developed system does not require to keep the patient's/subject's medical images on the system, providing less memory usage. Besides the system also provides 3D simulation and modification options, which will help clinicians to use necessary tools for visualization and modification operations. The developed system is tested in a case study, in which a 3D human brain model is created and simulated from 2D MRI images of a human brain, and we extended the 3D model to include the spreading cortical depression (SCD) wave front, which is an electrical phoneme that is believed to cause the migraine. PMID:23258956

Three-Dimensional Visualization with Large Data Sets: A Simulation of Spreading Cortical Depression in Human Brain

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Korhan Levent Ertürk

2012-01-01

Full Text Available We developed 3D simulation software of human organs/tissues; we developed a database to store the related data, a data management system to manage the created data, and a metadata system for the management of data. This approach provides two benefits: first of all the developed system does not require to keep the patient's/subject's medical images on the system, providing less memory usage. Besides the system also provides 3D simulation and modification options, which will help clinicians to use necessary tools for visualization and modification operations. The developed system is tested in a case study, in which a 3D human brain model is created and simulated from 2D MRI images of a human brain, and we extended the 3D model to include the spreading cortical depression (SCD wave front, which is an electrical phoneme that is believed to cause the migraine.

Pooled human platelet lysate versus fetal bovine serum—investigating the proliferation rate, chromosome stability and angiogenic potential of human adipose tissue-derived stem cells intended for clinical use

DEFF Research Database (Denmark)

Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V

2013-01-01

Because of an increasing focus on the use of adipose-derived stem cells (ASCs) in clinical trials, the culture conditions for these cells are being optimized. We compared the proliferation rates and chromosomal stability of ASCs that had been cultured in Dulbecco's modified Eagle's Medium (DMEM) ......) supplemented with either pooled human platelet lysate (pHPL) or clinical-grade fetal bovine serum (FBS) (DMEM(pHPL) versus DMEM(FBS))....

Development of the Human Placenta and Fetal Heart: Synergic or Independent?

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Graham J. Burton

2018-04-01

Full Text Available The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c. give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12–14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces

Fetal antigen 1 in healthy adults and patients with pituitary disease

DEFF Research Database (Denmark)

Andersen, M; Jensen, Charlotte Harken; Støving, René Klinkby

2001-01-01

Immunohistochemical analysis of the distribution of human fetal antigen 1 (FA1) in adult human tissues has demonstrated a strong association between FA1 and (neuro)endocrine structures. In the anterior pituitary gland FA1 was colocalized with GH, and the present study was performed to evaluate...

THE POSSIBILITIES TO DETERMINE FETAL MATURITY BY ULTRASOUND DIAGNOSTICS

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S. N. Lysenko

2015-01-01

Full Text Available Background: Extragenital disorders in a pregnant patient, as well as complications of pregnancy often necessitate preterm delivery, when the state of the fetus is one of the criteria determining terms and type of delivery. In connection with this, the physician faces the challenge of accurate assessment of fetal maturity. Aim: To identify ultrasound signs of functional fetal maturity. Materials and methods: 120 pregnant patients were assessed at 35 to 40 weeks of gestation. Beyond a standard fetometry, we assessed interhemispheric cerebellar size, the biggest size of the Beclard’s nucleus, the ratio of cortical to medullar substance of fetal adrenal glands (adrenal coefficient, the ration between ultrasound density of lungs, liver and ultrasound density of fetal urine (histogram analysis. Results: Up to 36 weeks of gestation, the interhemispheric cerebellar size was below 52 mm, starting from 37 weeks, above 53 mm and from week 40 on, above 58 mm. All newborns, which had their interhemispheric cerebellar size ≥ 53 mm antenatally, were assessed as being mature at birth (p < 0.05. All newborns, which had Beclard’s nucleus size ≥ 5 mm antenatally, were assessed as being mature at birth (p < 0.05. At 35–35.6 weeks of gestation, mean adrenal coefficients in all cases exceeded 1. Starting with full 36 weeks of gestation onwards, this parameter decreased to 0.94 and showed a steady decrease thereafter. There were no signs of functional immaturity or respiratory distress among newborns with antenatal adrenal coefficient of ≤ 0.99 (p < 0.05. The ratio between ultrasound density of lungs to ultrasound density of bladder contents increases up to 37 weeks of gestation and remains stable up to 40 weeks. The ratio of liver density to the same substrate is non-significantly lower due to lower ultrasound density of the liver itself. The ratio of ultrasound density of the lung to that of the liver up to 36 weeks was at least 1.41 and decreased

Effects of Maternal Obesity on Fetal Programming: Molecular Approaches

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Neri, Caterina; Edlow, Andrea G.

2016-01-01

Maternal obesity has become a worldwide epidemic. Obesity and a high-fat diet have been shown to have deleterious effects on fetal programming, predisposing offspring to adverse cardiometabolic and neurodevelopmental outcomes. Although large epidemiological studies have shown an association between maternal obesity and adverse outcomes for offspring, the underlying mechanisms remain unclear. Molecular approaches have played a key role in elucidating the mechanistic underpinnings of fetal malprogramming in the setting of maternal obesity. These approaches include, among others, characterization of epigenetic modifications, microRNA expression, the gut microbiome, the transcriptome, and evaluation of specific mRNA expression via quantitative reverse transcription polmerase chain reaction (RT-qPCR) in fetuses and offspring of obese females. This work will review the data from animal models and human fluids/cells regarding the effects of maternal obesity on fetal and offspring neurodevelopment and cardiometabolic outcomes, with a particular focus on molecular approaches. PMID:26337113

Critical fluctuations in cortical models near instability

NARCIS (Netherlands)

Aburn, M.J.; Holmes, C.A.; Roberts, J.A.; Boonstra, T.W.; Breakspear, M.

2012-01-01

Computational studies often proceed from the premise that cortical dynamics operate in a linearly stable domain, where fluctuations dissipate quickly and show only short memory. Studies of human electroencephalography (EEG), however, have shown significant autocorrelation at time lags on the scale

Fetal Alcohol Syndrome and Fetal Alcohol Effects in Child Development.

Science.gov (United States)

Pancratz, Diane R.

This literature review defines Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) and considers their causes, diagnoses, prevalence, and educational ramifications. Effects of alcohol during each of the trimesters of pregnancy are summarized. Specific diagnostic characteristics of FAS are listed: (1) growth deficiency, (2) a…

Human fetal antehypophysis in vitro. Immunocytological study and radioimmunoassay of LH and FSH

International Nuclear Information System (INIS)

Li, J.Y.; Begeot, M.; Dubois, P.M.; Claustrat, B.

1977-01-01

Human fetal antehypophysis (16 males, 16 females and 4 unknown sex) were cultivated during several weeks. By immunocytochemistry LH gonadotroph cells were determined with anti-hTSH and anti-pLH serum. The release in vitro of LH and FSH was studied by radioimmunoassay. At the first medium change, the quantity of LH and FSH release was related to the gestational age and sex. A rapid decline of both LH and FSH occured over the 10 first days. There after, a basal release of LH was maintained during several months; the release of FSH was generally maintained at the lower limit of the assay. After 1 month in vitro, the level of LH could not be related to the sex. Release of LH was stimulated by synthetic LRF. A significant increase was observed independently of the sex and age of the fetuses studied [fr

Fetal scalp blood sampling during labor

DEFF Research Database (Denmark)

Chandraharan, Edwin; Wiberg, Nana

2014-01-01

Fetal cardiotocography is characterized by low specificity; therefore, in an attempt to ensure fetal well-being, fetal scalp blood sampling has been recommended by most obstetric societies in the case of a non-reassuring cardiotocography. The scientific agreement on the evidence for using fetal...... scalp blood sampling to decrease the rate of operative delivery for fetal distress is ambiguous. Based on the same studies, a Cochrane review states that fetal scalp blood sampling increases the rate of instrumental delivery while decreasing neonatal acidosis, whereas the National Institute of Health...... and Clinical Excellence guideline considers that fetal scalp blood sampling decreases instrumental delivery without differences in other outcome variables. The fetal scalp is supplied by vessels outside the skull below the level of the cranial vault, which is likely to be compressed during contractions...

Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

Science.gov (United States)

Miner, Jonathan J; Cao, Bin; Govero, Jennifer; Smith, Amber M; Fernandez, Estefania; Cabrera, Omar H; Garber, Charise; Noll, Michelle; Klein, Robyn S; Noguchi, Kevin K; Mysorekar, Indira U; Diamond, Michael S

2016-05-19

Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1(-/-)) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations. Copyright © 2016 Elsevier Inc. All rights reserved.

Revisiting the argument from fetal potential

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Manninen Bertha

2007-05-01

Full Text Available Abstract One of the most famous, and most derided, arguments against the morality of abortion is the argument from potential, which maintains that the fetus' potential to become a person and enjoy the valuable life common to persons, entails that its destruction is prima facie morally impermissible. In this paper, I will revisit and offer a defense of the argument from potential. First, I will criticize the classical arguments proffered against the importance of fetal potential, specifically the arguments put forth by philosophers Peter Singer and David Boonin, by carefully unpacking the claims made in these arguments and illustrating why they are flawed. Secondly, I will maintain that fetal potential is morally relevant when it comes to the morality of abortion, but that it must be accorded a proper place in the argument. This proper place, however, cannot be found until we first answer a very important and complex question: we must first address the issue of personal identity, and when the fetus becomes the type of being who is relevantly identical to a future person. I will illustrate why the question of fetal potential can only be meaningfully addressed after we have first answered the question of personal identity and how it relates to the human fetus.

Intrapartum fetal monitoring by ST-analysis of the fetal ECG

NARCIS (Netherlands)

Westerhuis, M.E.M.H.

2010-01-01

Objective Intrapartum fetal monitoring aims to identify fetuses at risk for neonatal and long-term injury due to asphyxia. To serve this purpose, cardiotocography (CTG) combined with ST-analysis of the fetal electrocardiogram (ECG), which is a relatively new method, may be used. The main aim of this

Ontogenesis of testicular function in humans.

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GaĂŤlle Angenard

2010-01-01

Full Text Available The two major functions of the testis, steroidogenesis and gametogenesis, take place during fetal life. These two functions have been extensively studied in rodents and adult humans. However, their onset during fetal life is poorly documented in humans. In the first part of this work we presented both our experimental data and some data of literature concerning the development of the human fetal testis. In the second part of this article, using the organ culture system we previously developed, we have investigated the regulations or perturbations of fetal testis development both in rodent and human models. Our findings provide important insight into the potential role of exposure to environmental pollutants (physical factors, in particular ionizing radiation, cadmium and endocrine disruptors such as phthalates during fetal testicular development and their potential deleterious effects on male fertility in adulthood. Our results highlight the specificity of the human model compared with rodent models.

Optogenetic stimulation of a meso-scale human cortical model

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Selvaraj, Prashanth; Szeri, Andrew; Sleigh, Jamie; Kirsch, Heidi

2015-03-01

Neurological phenomena like sleep and seizures depend not only on the activity of individual neurons, but on the dynamics of neuron populations as well. Meso-scale models of cortical activity provide a means to study neural dynamics at the level of neuron populations. Additionally, they offer a safe and economical way to test the effects and efficacy of stimulation techniques on the dynamics of the cortex. Here, we use a physiologically relevant meso-scale model of the cortex to study the hypersynchronous activity of neuron populations during epileptic seizures. The model consists of a set of stochastic, highly non-linear partial differential equations. Next, we use optogenetic stimulation to control seizures in a hyperexcited cortex, and to induce seizures in a normally functioning cortex. The high spatial and temporal resolution this method offers makes a strong case for the use of optogenetics in treating meso scale cortical disorders such as epileptic seizures. We use bifurcation analysis to investigate the effect of optogenetic stimulation in the meso scale model, and its efficacy in suppressing the non-linear dynamics of seizures.

Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome

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Hatzirodos, Nicholas; Bayne, Rosemary A.; Irving-Rodgers, Helen F.; Hummitzsch, Katja; Sabatier, Laetitia; Lee, Sam; Bonner, Wendy; Gibson, Mark A.; Rainey, William E.; Carr, Bruce R.; Mason, Helen D.; Reinhardt, Dieter P.; Anderson, Richard A.; Rodgers, Raymond J.

2011-01-01

Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1–3, latent TGF-β binding proteins 1–4, and TGF-β 1–3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life.—Hatzirodos, N., Bayne, R. A., Irving-Rodgers, H. F., Hummitzsch, K., Sabatier, L., Lee, S., Bonner, W., Gibson, M. A., Rainey, W. E., Carr, B. R., Mason, H. D., Reinhardt, D. P., Anderson, R. A., Rodgers, R. J. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. PMID:21411746

Paternal genetic contribution influences fetal vulnerability to maternal alcohol consumption in a rat model of fetal alcohol spectrum disorder.

Directory of Open Access Journals (Sweden)

Laura J Sittig

2010-04-01

Full Text Available Fetal alcohol exposure causes in the offspring a collection of permanent physiological and neuropsychological deficits collectively termed Fetal Alcohol Spectrum Disorder (FASD. The timing and amount of exposure cannot fully explain the substantial variability among affected individuals, pointing to genetic influences that mediate fetal vulnerability. However, the aspects of vulnerability that depend on the mother, the father, or both, are not known.Using the outbred Sprague-Dawley (SD and inbred Brown Norway (BN rat strains as well as their reciprocal crosses, we administered ethanol (E, pair-fed (PF, or control (C diets to the pregnant dams. The dams' plasma levels of free thyroxine (fT4, triiodothyronine (T3, free T3 (fT3, and thyroid stimulating hormone (TSH were measured to elucidate potential differences in maternal thyroid hormonal environment, which affects specific aspects of FASD. We then compared alcohol-exposed, pair fed, and control offspring of each fetal strain on gestational day 21 (G21 to identify maternal and paternal genetic effects on bodyweight and placental weight of male and female fetuses.SD and BN dams exhibited different baseline hypothalamic-pituitary-thyroid function. Moreover, the thyroid function of SD dams was more severely affected by alcohol consumption while that of BN dams was relatively resistant. This novel finding suggests that genetic differences in maternal thyroid function are one source of maternal genetic effects on fetal vulnerability to FASD. The fetal vulnerability to decreased bodyweight after alcohol exposure depended on the genetic contribution of both parents, not only maternal contribution as previously thought. In contrast, the effect of maternal alcohol consumption on placental weight was consistent and not strain-dependent. Interestingly, placental weight in fetuses with different paternal genetic contributions exhibited opposite responses to caloric restriction (pair feeding. In summary

Generation of induced pluripotent stem cells with high efficiency from human embryonic renal cortical cells.

Science.gov (United States)

Yao, Ling; Chen, Ruifang; Wang, Pu; Zhang, Qi; Tang, Hailiang; Sun, Huaping

2016-01-01

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) emerges as a prospective therapeutic angle in regenerative medicine and a tool for drug screening. Although increasing numbers of iPSCs from different sources have been generated, there has been limited progress in yield of iPSC. Here, we show that four Yamanaka factors Oct4, Sox2, Klf4 and c-Myc can convert human embryonic renal cortical cells (hERCCs) to pluripotent stem cells with a roughly 40-fold higher reprogramming efficiency compared with that of adult human dermal fibroblasts. These iPSCs show pluripotency in vitro and in vivo, as evidenced by expression of pluripotency associated genes, differentiation into three embryonic germ layers by teratoma tests, as well as neuronal fate specification by embryoid body formation. Moreover, the four exogenous genes are effectively silenced in these iPSCs. This study highlights the use of hERCCs to generate highly functional human iPSCs which may aid the study of genetic kidney diseases and accelerate the development of cell-based regenerative therapy.

Fetal short time variation during labor: a non-invasive alternative to fetal scalp pH measurements?

OpenAIRE

Schiermeier, Sven; Reinhard, Joscha; Hatzmann, Hendrike; Zimmermann, Ralf C.; Westhof, Gregor

2009-01-01

Objective: To determine whether short time variation (STV) of fetal heart beat correlates with scalp pH measurements during labor. Patients and methods: From 1279 deliveries, 197 women had at least one fetal scalp pH measurement. Using the CTG-Player®, STVs were calculated from the electronically saved cardiotocography (CTG) traces and related to the fetal scalp pH measurements. Results: There was no correlation between STV and fetal scalp pH measurements (r=−0.0592). Conclusions: Fetal ST...

Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping.

Science.gov (United States)

Studholme, Colin

2011-08-15

The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.

Post-adolescent developmental changes in cortical complexity.

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Sandu, Anca-Larisa; Izard, Edouard; Specht, Karsten; Beneventi, Harald; Lundervold, Arvid; Ystad, Martin

2014-11-27

Post-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval. Magnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 14 young adults (mean age 24.24 ± 2.76, 7 women) for measures of brain complexity (fractal dimension--FD), grey matter (GM) volume and surface-area of cortical ribbon. FD was calculated using box-counting and Minkowski-Bouligand methods; FD and GM volume were measured for the whole brain, each hemisphere and lobes: frontal, occipital, parietal and temporal. The results show that the adults have a lower cortical complexity than the adolescents, which was significant for whole brain, left and right hemisphere, frontal and parietal lobes for both genders; and only for males in left temporal lobe. The GM volume was smaller in men than in boys for almost all measurements, and smaller in women than in girls just for right parietal lobe. A significant Pearson correlation was found between FD and GM volume for whole brain and each hemisphere in both genders. The decrease of the GM surface-area was significant in post-adolescence for males, not for females. During post-adolescence there are common changes in cortical complexity in the same regions for both genders, but there are also gender specific changes in some cortical areas. The sex differences from different cortical measurements (FD, GM volume and surface-area of cortical ribbon) could suggest a maturation delay in specific brain regions for each gender in relation to the other and might be explained through the functional role of the corresponding regions reflected in gender difference of developed abilities.

Real-Time Automatic Fetal Brain Extraction in Fetal MRI by Deep Learning

OpenAIRE

Salehi, Seyed Sadegh Mohseni; Hashemi, Seyed Raein; Velasco-Annis, Clemente; Ouaalam, Abdelhakim; Estroff, Judy A.; Erdogmus, Deniz; Warfield, Simon K.; Gholipour, Ali

2017-01-01

Brain segmentation is a fundamental first step in neuroimage analysis. In the case of fetal MRI, it is particularly challenging and important due to the arbitrary orientation of the fetus, organs that surround the fetal head, and intermittent fetal motion. Several promising methods have been proposed but are limited in their performance in challenging cases and in real-time segmentation. We aimed to develop a fully automatic segmentation method that independently segments sections of the feta...

Fetal Eye Movements on Magnetic Resonance Imaging

Science.gov (United States)

Woitek, Ramona; Kasprian, Gregor; Lindner, Christian; Stuhr, Fritz; Weber, Michael; Schöpf, Veronika; Brugger, Peter C.; Asenbaum, Ulrika; Furtner, Julia; Bettelheim, Dieter; Seidl, Rainer; Prayer, Daniela

2013-01-01

Objectives Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. Methods Dynamic SSFP sequences were acquired in 72 singleton fetuses (17–40 GW, three age groups [17–23 GW, 24–32 GW, 33–40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. Results In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3–45%. Conclusions In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations. PMID:24194885

Fetal eye movements on magnetic resonance imaging.

Science.gov (United States)

Woitek, Ramona; Kasprian, Gregor; Lindner, Christian; Stuhr, Fritz; Weber, Michael; Schöpf, Veronika; Brugger, Peter C; Asenbaum, Ulrika; Furtner, Julia; Bettelheim, Dieter; Seidl, Rainer; Prayer, Daniela

2013-01-01

Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. Dynamic SSFP sequences were acquired in 72 singleton fetuses (17-40 GW, three age groups [17-23 GW, 24-32 GW, 33-40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3-45%. In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations.

Evidence for chronically altered cortical serotonin function in human female recreational ecstasy (MDMA) polydrug users

Science.gov (United States)

Di Iorio, Christina R; Watkins, Tristan J; Dietrich, Mary S; Cao, Aize; Blackford, Jennifer U; Rogers, Baxter; Ansari, Mohammed S; Baldwin, Ronald M; Li, Rui; Kessler, Robert M; Salomon, Ronald M; Benningfield, Margaret; Cowan, Ronald L

2012-01-01

Context MDMA (ecstasy) is a popular recreational drug that produces loss of serotonin (5-HT) axons in animal models. Whether MDMA produces chronic reductions in 5-HT signaling in humans remains controversial. Objective To determine if MDMA use is associated with chronic reductions in serotonin signaling in female human cerebral cortex as reflected by increased 5-HT2A receptors. Design Cross sectional case-control study comparing 5-HT2A receptor levels in abstinent female MDMA polydrug users to MDMA-naive females; within-group design assessing the association of lifetime MDMA use and 5-HT2A receptors. Subjects had at least 90 days abstinence from MDMA use as verified by hair sampling. Cortical 5-HT2A receptor levels were assayed with the 5HT2A-specific Positron Emission Tomography (PET) radioligand [18F]setoperone. Setting Academic Medical Center Research Laboratory. Participants Volunteer female MDMA users (N=14) and MDMA-naive controls (N=10). Main exclusion criteria were non-drug-related DSM-IV axis I psychiatric disorders and general medical illness. Main Outcome Measure Cortical 5-HT2A receptor non-displaceable binding potential (5-HT2ABPND). Results MDMA users had increased 5-HT2ABPND in occipital-parietal (19.7%), temporal (20.5%), occipito-temporal-parietal (18.3%), frontal (16.6%), and fronto-parietal (18.5%) regions (pMDMA use associated positively with 5-HT2ABPND in fronto-parietal (β=0.665;p=0.007), occipito-temporal (β=0.798;p=0.002), fronto-limbic (β=0.634;p=0.024), and frontal (β=0.691;p=0.008) regions. In contrast, there were no regions in which MDMA use was inversely associated with receptor levels. There were no statistically significant effects of the duration of MDMA abstinence on 5-HT2ABPND. Conclusions Human recreational MDMA use is associated with long-lasting increases in 5-HT2A receptor density. 5-HT2A receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence. These results suggest that MDMA produces

Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model.

Science.gov (United States)

Kim, Y; Gelehrter, S K; Fifer, C G; Lu, J C; Owens, G E; Berman, D R; Williams, J; Wilkinson, J E; Ives, K A; Xu, Z

2011-04-01

Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. The experiments involved 11 gravid sheep at 102-129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Fetal blood drawing.

Science.gov (United States)

Hobbins, J C; Mahoney, M J

1975-07-19

A small sample of fetal blood suitable for studies of haemoglobin synthesis was obtained from a placental vessel under endoscopic visualisation in 23 of 26 patients in whom the procedure was attempted prior to second-trimester abortion. Fetal blood loss, calculated in 23 cases, was between 0-2 ml. and 2-5 ml., and fetal blood-volume depletion varied from 0-5% to 15%. No short-term ill-effects were demonstrated in mother or fetus in any of 16 patients in whom the injection of aborti-facient was postponed for between 16 and 24 hours after the procedure.

Placenta expresses anti-Müllerian hormone and its receptor: Sex-related difference in fetal membranes.

Science.gov (United States)

Novembri, R; Funghi, L; Voltolini, C; Belmonte, G; Vannuccini, S; Torricelli, M; Petraglia, F

2015-07-01

Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-β superfamily, playing a role in sexual differentiation and recruitment. Since a correlation exists between AMH serum levels in cord blood and fetal sex, the present study aimed to identify mRNA and protein expression of AMH and AMHRII in placenta and fetal membranes according to fetal sex. Placenta and fetal membranes samples (n = 40) were collected from women with singleton uncomplicated pregnancies at term. Identification of AMH protein in placenta and fetal membranes was carried out by immunohistochemistry and AMH and AMHRII protein localization by immunofluorescence, while mRNA expression was assessed by quantitative real-time PCR. AMH and AMHRII mRNAs were expressed by placenta and fetal membranes at term, without any significant difference between males and females. Placental immunostaining showed a syncytial localization of AMH without sex-related differences; while fetal membranes immunostaining was significantly more intense in male than in female fetuses (p membranes. The present study for the first time demonstrated that human placenta and fetal membranes expresses and co-localizes AMH and AMHRII. Although no sex-related difference was found for the mRNA expression both in placenta and fetal membranes, a most intense staining for AMH in male fetal membranes supports AMH as a gender specific hormone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fetal programming of the metabolic syndrome

Directory of Open Access Journals (Sweden)

Aleksandra Marciniak

2017-04-01

Full Text Available Prenatal development is currently recognized as a critical period in the etiology of human diseases. This is particularly so when an unfavorable environment interacts with a genetic predisposition. The fetal programming concept suggests that maternal nutritional imbalance and metabolic disturbances may have a persistent and intergenerational effect on the health of offspring and on the risk of diseases such as obesity, diabetes, and cardiovascular diseases.

Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates.

Directory of Open Access Journals (Sweden)

Wilmon F Grant

2011-02-01

Full Text Available To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD contained equivalent levels of n-3 fatty acids (FA's and higher levels of n-6 FA's than the control diet (CTR, we found significant decreases in docosahexaenoic acid (DHA and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

Applications of brain blood flow imaging in behavioral neurophysiology: cortical field activation hypothesis

International Nuclear Information System (INIS)

Roland, P.E.

1985-01-01

The 133 xenon intracarotid method for rCBF measurements has been a very useful method for functional mapping and functional dissection of the cerebral cortex in humans. With this method it has been shown that different types of cortical information treatment activate different cortical areas and furthermore that sensory and motor functions of the cerebral cortex could be dissected into anatomical and informational subcomponents by behavioral manipulations. The brain organizes its own activity. One of the principles of organization was that the brain could recruit in advance cortical fields that were expected to participate in a certain type of information operation. During brain work in awake human beings the cerebral cortex was activated in fields that, projected on the cerebral surface, most often had a size greater than 3 CM 2 . Such activated fields appeared no matter which type of information processing was going on in the brain: during planning and execution of voluntary movements, during preparation for sensory information processing, and during sensory information processing, as well as during cognitive brain work and retrieval of specific memories. Therefore, it was hypothesized that cortical field activation was the physiological manifestation of normal brain work in awake humans

Applications of brain blood flow imaging in behavioral neurophysiology: cortical field activation hypothesis

Energy Technology Data Exchange (ETDEWEB)

Roland, P.E.

1985-01-01

The /sup 133/xenon intracarotid method for rCBF measurements has been a very useful method for functional mapping and functional dissection of the cerebral cortex in humans. With this method it has been shown that different types of cortical information treatment activate different cortical areas and furthermore that sensory and motor functions of the cerebral cortex could be dissected into anatomical and informational subcomponents by behavioral manipulations. The brain organizes its own activity. One of the principles of organization was that the brain could recruit in advance cortical fields that were expected to participate in a certain type of information operation. During brain work in awake human beings the cerebral cortex was activated in fields that, projected on the cerebral surface, most often had a size greater than 3 CM/sup 2/. Such activated fields appeared no matter which type of information processing was going on in the brain: during planning and execution of voluntary movements, during preparation for sensory information processing, and during sensory information processing, as well as during cognitive brain work and retrieval of specific memories. Therefore, it was hypothesized that cortical field activation was the physiological manifestation of normal brain work in awake humans.

Mutator/hypermutable fetal/juvenile metakaryotic stem cells and human colorectal carcinogenesis.

Directory of Open Access Journals (Sweden)

Lohith G. Kini

2013-10-01

Full Text Available Adult age-specific colorectal cancer incidence rates increase exponentially from maturity, reach a maximum, then decline in extreme old age. Armitage and Doll (1957 postulated that the exponential increase resulted from n mutations occurring throughout adult life in normal cells at risk that initiated the growth of a preneoplastic colony in which subsequent m mutations promoted one of the preneoplastic cells at risk to form a lethal neoplasia. We have reported cytologic evidence that these cells at risk are fetal/juvenile organogenic, then preneoplastic metakaryotic stem cells. Metakaryotic cells display stem-like behaviors of both symmetric and asymmetric nuclear divisions and peculiarities such as bell shaped nuclei and amitotic nuclear fission that distinguish them from embryonic, eukaryotic stem cells. Analyses of mutant colony sizes and numbers in adult lung epithelia supported the inferences that the metakaryotic organogenic stem cells are constitutively mutator/hypermutable and that their contributions to cancer initiation are limited to the fetal/juvenile period. We have amended the two-stage model of Armitage and Doll and incorporated these several inferences in a computer program CancerFit v.5.0. We compared the expectations of the amended model to adult (15-104 yr age-specific colon cancer rates for European American males born 1890-99 and observed remarkable concordance. When estimates of normal colonic fetal/juvenile APC and OAT gene mutation rates (~2-5 x 10-5 per stem cell doubling and preneoplastic colonic gene loss rates (~ 8 x 10-3 were applied, the model was in accordance only for the values of n = 2 and m = 4 or 5.

Fetal and neonatal thyrotoxicosis

Science.gov (United States)

Batra, Chandar Mohan

2013-01-01

Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20th week of pregnancy and reaches its maximum by 30th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

Fetal MRI of pathological brain development; Fetale MRT der pathologischen Hirnentwicklung

Energy Technology Data Exchange (ETDEWEB)

Brugger, P.C. [Medizinische Universitaet Wien (Austria). Arbeitsgruppe Integrative Morphologie, Zentrum fuer Anatomie und Zellbiologie; Prayer, D. [Medizinische Universitaet Wien (Austria). Klinik fuer Radiodiagnostik

2006-02-15

Because of the superior tissue contrast, high spatial resolution, and multiplanar capabilities, fetal magnetic resonance imaging (MRI) can depict fetal brain pathologies with high accuracy. Pathological fetal brain development may result from malformations or acquired conditions. Differentiation of these etiologies is important with respect to managing the actual pregnancy or counseling future pregnancies. As a widened ventricular system is a common hallmark of both maldevelopment and acquired conditions, it may cause problems in the differential diagnosis. Fetal MRI can provide detailed morphological information, which allows refinement of the diagnosis of ventricular enlargement in a large number of cases. Systematic work-up of morphological details that may be recognized on MR images provides an approach for achieving a correct diagnosis in cases of ventricle enlargement. (orig.) [German] Aufgrund des hervorragenden Gewebekontrastes, der hohen raeumlichen Aufloesung und multiplanaren Moeglichkeiten erlaubt die fetale Magnetresonanztomographie (MRT) eine detaillierte Darstellung fetaler Hirnpathologien. Eine pathologische Hirnentwicklung kann sowohl auf Fehlbildungen als auch waehrend der Schwangerschaft erworbenen Stoerungen beruhen. Nachdem die weiteren Konsequenzen fuer die bestehende, aber auch fuer folgende Schwangerschaften zu einem grossen Teil von einer Differenzierung dieser Aetiologien abhaengig sein kann, ist ein Erkennen der jeweiligen Pathologie wesentlich. Die morphologische Praesentation erworbener und fehlbildungsbedingter Veraenderungen auf MR-Bildern ist u. U. sehr aehnlich. Besondere differenzialdiagnostische Probleme bereitet dabei das Vorliegen eines erweiterten Ventrikelsystems, das als Symptom unterschiedlichster Veraenderungen vorliegen kann. Anhand einer systematischen Darstellung mittels MR-erfassbarer morphologischer Details wird eine Anleitung gegeben, bei Bestehen dieses Leitsymptoms zu einer moeglichst genauen Diagnose zu kommen

The maturation of cortical sleep rhythms and networks over early development.

Science.gov (United States)

Chu, C J; Leahy, J; Pathmanathan, J; Kramer, M A; Cash, S S

2014-07-01

Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. We found that the emergence of brain rhythms follows a stereotyped sequence over early development. In general, higher frequencies increase in prominence with striking regional specificity throughout development. The coordination of these rhythmic activities across brain regions follows a general pattern of maturation in which broadly distributed networks of low-frequency oscillations increase in density while networks of high frequency oscillations become sparser and more highly clustered. Our results indicate that a predictable program directs the development of key rhythmic components and physiological brain networks over early development. This work expands our knowledge of normal cortical development. The stereotyped neurophysiological processes observed at the level of rhythms and networks may provide a scaffolding to support critical periods of cognitive growth. Furthermore, these conserved patterns could provide a sensitive biomarker for cortical health across development. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Real-time classification of auditory sentences using evoked cortical activity in humans

Science.gov (United States)

Moses, David A.; Leonard, Matthew K.; Chang, Edward F.

2018-06-01

Objective. Recent research has characterized the anatomical and functional basis of speech perception in the human auditory cortex. These advances have made it possible to decode speech information from activity in brain regions like the superior temporal gyrus, but no published work has demonstrated this ability in real-time, which is necessary for neuroprosthetic brain-computer interfaces. Approach. Here, we introduce a real-time neural speech recognition (rtNSR) software package, which was used to classify spoken input from high-resolution electrocorticography signals in real-time. We tested the system with two human subjects implanted with electrode arrays over the lateral brain surface. Subjects listened to multiple repetitions of ten sentences, and rtNSR classified what was heard in real-time from neural activity patterns using direct sentence-level and HMM-based phoneme-level classification schemes. Main results. We observed single-trial sentence classification accuracies of 90% or higher for each subject with less than 7 minutes of training data, demonstrating the ability of rtNSR to use cortical recordings to perform accurate real-time speech decoding in a limited vocabulary setting. Significance. Further development and testing of the package with different speech paradigms could influence the design of future speech neuroprosthetic applications.

Antithyroid drug-induced fetal goitrous hypothyroidism

DEFF Research Database (Denmark)

Bliddal, Sofie; Rasmussen, Ase Krogh; Sundberg, Karin

2011-01-01

Maternal overtreatment with antithyroid drugs can induce fetal goitrous hypothyroidism. This condition can have a critical effect on pregnancy outcome, as well as on fetal growth and neurological development. The purpose of this Review is to clarify if and how fetal goitrous hypothyroidism can...... be prevented, and how to react when prevention has failed. Understanding the importance of pregnancy-related changes in maternal thyroid status when treating a pregnant woman is crucial to preventing fetal goitrous hypothyroidism. Maternal levels of free T(4) are the most consistent indication of maternal...... and fetal thyroid status. In patients with fetal goitrous hypothyroidism, intra-amniotic levothyroxine injections improve fetal outcome. The best way to avoid maternal overtreatment with antithyroid drugs is to monitor closely the maternal thyroid status, especially estimates of free T(4) levels....

Prenatal cerebellar growth trajectories and the impact of periconceptional maternal and fetal factors

NARCIS (Netherlands)

Koning, I V; Dudink, J; Groenenberg, I A L; Willemsen, S P; Reiss, I K M; Steegers-Theunissen, R P M

2017-01-01

STUDY QUESTION: CAN WE assess human prenatal cerebellar growth from the first until the third trimester of pregnancy and create growth trajectories to investigate associations with periconceptional maternal and fetal characteristics? SUMMARY ANSWER: Prenatal growth trajectories of the human

Histo-blood group antigens in human fetal thymus and in thymomas

DEFF Research Database (Denmark)

Engel, P; Dabelsteen, Erik; Francis, D

1996-01-01

-y, Le-x and sialyl-Le-x) of the ABO-histo-blood group system was investigated in 19 normal fetal thymuses (gestational age 16 to 39 weeks) and in 19 thymomas in order to study possible tumor-associated changes in the glycosylation pattern. The material was investigated by immunochemical stainings...

MR evaluation of fetal demise

International Nuclear Information System (INIS)

Victoria, Teresa; Chauvin, Nancy Anne; Johnson, Ann M.; Kramer, Sandra Sue; Epelman, Monica; Capilla, Elena

2011-01-01

Fetal demise is an uncommon event encountered at MR imaging. When it occurs, recognition by the interpreting radiologist is important to initiate appropriate patient management. To identify MR findings of fetal demise. Following IRB approval, a retrospective search of the radiology fetal MR database was conducted searching the words ''fetal demise'' and ''fetal death.'' Fetuses with obvious maceration or no sonographic confirmation of death were excluded. Eleven cases formed the study group. These were matched randomly to live fetuses of similar gestational age. Images were reviewed independently by three pediatric radiologists. The deceased fetus demonstrates decreased MR soft-tissue contrast and definition of tissue planes, including loss of gray-white matter differentiation in the brain. The signal within the cardiac chambers, when visible, is bright on HASTE sequences from the stagnant blood; the heart is small. Pleural effusions and decreased lung volumes may be seen. Interestingly, the fetal orbits lose their anatomical round shape and become smaller and more elliptical; a dark, irregular rim resembling a mask may be seen. Although fetal demise is uncommonly encountered at MR imaging, radiologists should be aware of such imaging findings so prompt management can be instituted. (orig.)

Isolating the role of elevated Phlda2 in asymmetric late fetal growth restriction in mice

Directory of Open Access Journals (Sweden)

Simon J. Tunster

2014-10-01

Full Text Available Pleckstrin homology-like domain family A member 2 (PHLDA2 is a maternally expressed imprinted gene whose elevated expression has been linked to fetal growth restriction in a number of human studies. In mice, Phlda2 negatively regulates placental growth and limits the accumulation of placental glycogen. We previously reported that a three-copy transgene spanning the Phlda2 locus drove a fetal growth restriction phenotype late in gestation, suggesting a causative role for PHLDA2 in human growth restriction. However, in this mouse model, Phlda2 was overexpressed by fourfold, alongside overexpression of a second imprinted gene, Slc22a18. Here, we genetically isolate the role of Phlda2 in driving late fetal growth restriction in mice. We furthermore show that this Phlda2-driven growth restriction is asymmetrical, with a relative sparing of the brain, followed by rapid catch-up growth after birth, classic features of placental insufficiency. Strikingly, fetal growth restriction showed strain-specific differences, being apparent on the 129S2/SvHsd (129 genetic background and absent on the C57BL6 (BL6 background. A key difference between these two strains is the placenta. Specifically, BL6 placentae possess a more extensive endocrine compartment and substantially greater stores of placental glycogen. Taken together, these data support a direct role for elevated Phlda2 in limiting fetal growth but also suggest that growth restriction only manifests when there is limited placental reserve. These findings should be taken into account in interpreting the results from human studies.

21 CFR 884.2900 - Fetal stethoscope.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal stethoscope. 884.2900 Section 884.2900 Food... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart... conventional stethoscopes. (b) Classification. Class I (general controls). The device is exempt from the...

The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth

NARCIS (Netherlands)

Salavati, Nastaran; Sovio, U.; Mayo, R. Plitman; Charnock-Jones, D. S.; Smith, G. C. S.

Introduction: Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and

Precuneus proportions and cortical folding: A morphometric evaluation on a racially diverse human sample.

Science.gov (United States)

Bruner, Emiliano; Pereira-Pedro, Ana Sofia; Chen, Xu; Rilling, James K

2017-05-01

Recent analyses have suggested that the size and proportions of the precuneus are remarkably variable among adult humans, representing a major source of geometrical difference in midsagittal brain morphology. The same area also represents the main midsagittal brain difference between humans and chimpanzees, being more expanded in our species. Enlargement of the upper parietal surface is a specific feature of Homo sapiens, when compared with other fossil hominids, suggesting the involvement of these cortical areas in recent modern human evolution. Here, we provide a survey on midsagittal brain morphology by investigating whether precuneus size represents the largest component of variance within a larger and racially diverse sample of 265 adult humans. Additionally, we investigate the relationship between precuneus shape variation and folding patterns. Precuneus proportions are confirmed to be a major source of human brain variation even when racial variability is considered. Larger precuneus size is associated with additional precuneal gyri, generally in its anterior district. Spatial variation is most pronounced in the dorsal areas, with no apparent differences between hemispheres, between sexes, or among different racial groups. These dorsal areas integrate somatic and visual information together with the lateral elements of the parietal cortex, representing a crucial node for self-centered mental imagery. The histological basis and functional significance of this intra-specific variation in the upper precuneus remains to be evaluated. Copyright © 2017 Elsevier GmbH. All rights reserved.

Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: Comparison with testing in placental and fetal remains.

Science.gov (United States)

Falcon, M; Pichini, S; Joya, J; Pujadas, M; Sanchez, A; Vall, O; García Algar, O; Luna, A; de la Torre, R; Rotolo, M C; Pellegrini, M

2012-05-10

Drug use by pregnant women in the first trimester of pregnancy and subsequent fetal exposure during early gestation can be assessed only by repetitive/systematic maternal blood/urine analysis or segmental hair analysis. No evidence of any relationship between maternal/fetal exposure during this specific period of gestation has been demonstrated to date in a human model. To clarify drugs toxicokinetics and transplacental passage during early pregnancy, the presence of the most widely used recreational drugs of abuse and metabolites was investigated in the proximal 4cm hair segments of women undergoing voluntary termination of pregnancy (n=280) during the 12th week of gestation and the results were compared to those from placenta and fetal tissue samples in order to verify whether maternal hair testing can reflect fetal exposure and, if so, to what extent. Hair, placenta and fetal remains were analyzed by validated gas chromatography mass spectrometry assays. Eighty one positive hair samples were identified: 60 were positive for cannabis (74.1%), 28 for cocaine (34.6%), 7 for opiates (8.6%), 3 for MDMA (3.7%) and 18.5% were positive for more than one drug. The positive hair test results were confirmed in placenta/fetal tissues in 10 cases out of 60 for cannabis (16. 7%); in 7 out of 28 for cocaine (25%); and none for the 6 opiates positive cases and 3 MDMA cases, respectively. Drugs/metabolites in hair of pregnant women can be used as biomarkers of past drug use (repetitive or sporadic), although the use is not always reflected in fetal/placental tissues. There are several possible hypotheses to explain the results: (1) the use occurred before the start of pregnancy, (2) past sporadic consumption which could be measured in hair but not in fetal and placental remains because of the narrow window of drug detection in placental/fetal tissues; (3) the sensitivity of the analytical methods was not high enough for the detection of the minute amount of drugs of abuse and

Abandonment and reconciliation: addressing political and common law objections to fetal homicide laws.

Science.gov (United States)

Curran, Douglas S

2009-03-01

Fetal homicide laws criminalize killing a fetus largely to the same extent as killing any other human being. Historically, the common law did not generally recognize feticide as a crime, but this was because of the evidentiary "born-alive" rule, not because of the substantive understanding of the term "human being." As medicine and science have advanced, states have become increasingly willing to abandon this evidentiary rule and to criminalize feticide as homicide. Although most states have recognized the crime of fetal homicide, fourteen have not. This is largely the result of two independent obstacles: (judicial) adherence to the born-alive rule and (legislative) concern that fetal homicide laws could erode constitutionally protected reproductive rights. This Note explores a variety of fetal homicide laws that states have adopted, demonstrating that popular opinion has shifted toward recognizing this crime. It then directly confronts the objections that have prevented other states from adopting such laws: it first reviews the literature suggesting that the born-alive rule should be abandoned, as it is an obsolete evidentiary standard; it then argues that constitutionally protected reproductive liberties can be reconciled with, and in fact augmented by, punishing the killing of a fetus as a homicide.

Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

Science.gov (United States)

Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

2016-01-13

Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN

Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select for Different Mesenchymal Stromal Cells.

Science.gov (United States)

Fernandez-Rebollo, Eduardo; Mentrup, Birgit; Ebert, Regina; Franzen, Julia; Abagnale, Giulio; Sieben, Torsten; Ostrowska, Alina; Hoffmann, Per; Roux, Pierre-François; Rath, Björn; Goodhardt, Michele; Lemaitre, Jean-Marc; Bischof, Oliver; Jakob, Franz; Wagner, Wolfgang

2017-07-11

Culture medium of mesenchymal stromal cells (MSCs) is usually supplemented with either human platelet lysate (HPL) or fetal calf serum (FCS). Many studies have demonstrated that proliferation and cellular morphology are affected by these supplements - it is therefore important to determine if they favor outgrowth of different subpopulations and thereby impact on the heterogeneous composition of MSCs. We have isolated and expanded human bone marrow-derived MSCs in parallel with HPL or FCS and demonstrated that HPL significantly increases proliferation and leads to dramatic differences in cellular morphology. Remarkably, global DNA-methylation profiles did not reveal any significant differences. Even at the transcriptomic level, there were only moderate changes in pairwise comparison. Furthermore, the effects on proliferation, cytoskeletal organization, and focal adhesions were reversible by interchanging to opposite culture conditions. These results indicate that cultivation of MSCs with HPL or FCS has no systematic bias for specific cell types.

Characterization of death of human fetal bone marrow CD34+ cells after different dose of γ-irradiation

International Nuclear Information System (INIS)

Xiang Yingsong; Yang Rujun; Tang Gusheng

2001-01-01

Objective: To investigate the characterization of death of the human hematopoietic stem cells after irradiation. Methods: Human fetal bone marrow mononuclear cells were irradiated with different doses of 60 Co γ-rays at different high dose rates. Apoptosis and necrosis of CD34 + cells were analyzed by flow cytometry, following three-color labelling with PE-CD34/FITC-Annexin V/7AAD at different times after irradiation. Results: The death of CD34 + cells after 5 Gy and 8 Gy irradiation showed a continuous process of reproductive death during the first week,and the main death type was apoptosis. A majority of CD34 + cells died of necrosis during the first day after 10 Gy and 12 Gy irradiation, and all of them died within a week. Conclusion: Niches are continuously vacated every day within a week following irradiation and reproductive death of hematopoietic stem cells occurred