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Sample records for human fetal corpses

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

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    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)

  2. A report on the pupae of Desmometopa sp. (Diptera: Milichiidae) recovered from a human corpse in Malaysia.

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    Kumara, T K; Abu Hassan, A; Che Salmah, M R; Bhupinder, S

    2010-04-01

    The pupae of Desmometopa sp. (Diptera: Milichiidae) were collected from a human corpse found indoor in active decay stage together with the larvae of Sarcophagidae, Synthesiomyia nudiseta (Wulp), Chrysomya megacephala (Fabricius) and Chrysomya rufifacies (Macquart). This research note is the first report of the Desmometopa sp. recovered from a human corpse in Malaysia.

  3. First Report of Necrophagous Insects on Human Corpses in Riyadh, Saudi Arabia.

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    Alajmi, R A; AlGhufaili, H; Farrukh, A; Aljohani, H; Mashaly, A M A

    2016-11-01

    Necrophagous species of insects provide useful complementary data to estimate the postmortem interval in forensic cases. Here, for the first time, we report on insect specimens collected from human corpses in Riyadh, Kingdom of Saudi Arabia. During the study, 14 beetle larvae were collected from the outdoor corpse (case report one) and five flies and seven beetles were collected from the indoor corpse (case report two). Sequencing was performed to study the mitochondrial DNA (mtDNA) as the prospective basis of an identification technique. The sequencing focused on a section of the cytochrome oxidase I encoding region of mtDNA. Two beetle species, Dermestes frischii (Kugelann) and Dermestes maculatus (De Geer) (Coleoptera: Dermestidae), and one fly species, Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae), were identified. These results will be instrumental in the implementation of a Saudi database of forensically relevant insects. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. First record of Hermetia illucens (Diptera: Stratiomyidae) on human corpses in Iberian Peninsula.

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    Martínez-Sánchez, Anabel; Magaña, Concepción; Saloña, Marta; Rojo, Santos

    2011-03-20

    This article presents the first record of Hermetia illucens larvae on a human corpse in Spain (the second case report in Europe). Prepupae of H. illucens, and other insects, were recovered from the dead body of a 72-year-old man in an advanced stage of decomposition. The body was located in Reus (NE Spain), in October 1998. This article provides additional biological data on experimental studies and an update on the geographic distribution of this species in the Iberian Peninsula. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Nipah virus infection outbreak with nosocomial and corpse-to-human transmission, Bangladesh.

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    Sazzad, Hossain M S; Hossain, M Jahangir; Gurley, Emily S; Ameen, Kazi M H; Parveen, Shahana; Islam, M Saiful; Faruque, Labib I; Podder, Goutam; Banu, Sultana S; Lo, Michael K; Rollin, Pierre E; Rota, Paul A; Daszak, Peter; Rahman, Mahmudur; Luby, Stephen P

    2013-02-01

    Active Nipah virus encephalitis surveillance identified an encephalitis cluster and sporadic cases in Faridpur, Bangladesh, in January 2010. We identified 16 case-patients; 14 of these patients died. For 1 case-patient, the only known exposure was hugging a deceased patient with a probable case, while another case-patient's exposure involved preparing the same corpse for burial by removing oral secretions and anogenital excreta with a cloth and bare hands. Among 7 persons with confirmed sporadic cases, 6 died, including a physician who had physically examined encephalitis patients without gloves or a mask. Nipah virus-infected patients were more likely than community-based controls to report drinking raw date palm sap and to have had physical contact with an encephalitis patient (29% vs. 4%, matched odds ratio undefined). Efforts to prevent transmission should focus on reducing caregivers' exposure to infected patients' bodily secretions during care and traditional burial practices.

  6. Economic, human and environmental health benefits of replacing formaldehyde in the preservation of corpses.

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    Rocha Ferreira, Jussara; Cardoso Rezende, Lorenna; Barbosa, Abel De Souza; De Carvalho, Phellip; De Lima, Natácia Evangelista; Assis Carvalho, Alexandre

    2017-11-01

    Formaldehyde has been prominent in preserving biological tissues since the nineteenth century. Despite being admittedly harmful to health and to the environment, it is still widely used. The Morphology Department of the University of Brasília - Brazil, applied the rethink, reduce, reuse, recycle and responsibility methodology to their activities in an effort to protect the health of laboratory workers and users, save resources and reduce damage to the environment. Here we evaluate the results obtained a decade after the implementation of this proposal (2005-2015). Formaldehyde was replaced by alcohol and glycerol solutions in corpse conservation. Over five thousand dollars in public funds that would have been destined to buying preserving substances were saved annually, and over a hundred thousand liters of water that would have been contaminated and thrown into the sewage system were spared. The environment used to implement the study was improved and anatomical parts kept for study had their lifespan extended. It is noteworthy that such simple adjustments could cause pronounced changes in laboratory activities. We would avoid contaminating billions of liters of water and it would be possible to save millions if similar practices were implemented in all educational institutions having similar routines. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Andreas Vesalius' corpses.

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    Biesbrouck, Maurits; Steeno, Omer

    2014-01-01

    Judging from his writings, Andreas Vesalius must have had dozens of bodies at his disposal, thirteen of which were definitely from before 1543. They came from cemeteries, places of execution or hospitals. Not only did his students help him obtain the bodies, but also public and judicial authorities. At first, he used the corpses for his own learning purposes, and later to teach his students and to write De humani corporis fabrica, his principal work. Clearly he had an eye for comparative anatomy. He observed anatomical variants and studied foetal anatomy. Occasionally, he would dissect a body to study physiological processes, while the post-mortems on the bodies brought in by the families of the deceased gave him an insight into human pathology. Some of his dissection reports have been preserved.

  8. Psychological Stress In First Year Medical Students In Response To The Dissection Of A Human Corpse

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    Bernhardt, Veronika; Rothkötter, Hermann Josef; Kasten, Erich

    2012-01-01

    the confrontation with corpses. Furthermore, personality tests were shown to be only partly reliable for selecting affected people in advance. With regard to these results capabilities to provide support to the first year medical students should be discussed. PMID:22403597

  9. Psychological stress in first year medical students in response to the dissection of a human corpse.

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    Bernhardt, Veronika; Rothkötter, Hermann Josef; Kasten, Erich

    2012-01-01

    Gross anatomy is one of the most important and time consuming subjects in the first preclinical part of medical school in Germany. In October 2007 186 students started the dissection course at Otto-von-Guericke-University Magdeburg. The objective of this study is to analyze the emotional aspect relating to the gross anatomy course. In order to address this issue, we investigated how medical students experience the first confrontation and the following exposure to the dead bodies and whether there are any differences between various groups (age, gender, experience) of students. The study was carried out with a group of 155 first year medical students (112 female, 43 male, 21.4±2.9 years). Self-composed questionnaires were used to distinguish between concerns related to dissection and individual experiences and anxiety because of deceasing or death. In order to detect the changes of attitudes towards the dissection course, one questionnaire was answered by participants in the beginning of the course and one in the end (n=94, 66 female, 28 male). Additionally, personality traits of the students were analyzed using two scales of the "Freiburger Persönlichkeitsinventar (FPI-R)". The self-composed questionnaires showed high reliability. For some students dissection was emotional stress; about 50% became anxious when coping the first confrontation, however, only 12% to large extent. Concerning the anxiety of dissection of individual body parts it was less for limbs, internal organs and skin and increased for head and genitals. Although hypothesized before, the correlation between age, extraversion, emotionality and the extent of anxiety were small. Almost 90% of the students approve the early beginning of the gross anatomy course. The follow-up study showed a marked decline of anxiety. Our results show that about 50% of the students started the course with emotional stress and about one-tenth of them were very worried about the confrontation with corpses. Furthermore

  10. First donation of human skin obtained from corpse; Primera donacion de piel humana obtenida de cadaver

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    Reyes F, M.L.; Luna Z, D. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)

    2007-07-01

    The first donation of human skin coming from a cadaverous donor was obtained in the State of Mexico. The skin was obtained of a 34 year-old multi organic donor, the extraction of the same was carried out in an operating theatre by medical personnel, supported by personal of the Radio sterilized Tissue Bank (BTR) of the ININ. The skin was transported to the BTR for it processing. (Author)

  11. Radiological assessment of the inferior alveolar artery course in human corpse mandibles

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    Bertl, Kristina [Medical University of Vienna, Division of Oral Surgery, Bernhard Gottlieb School of Dentistry, Vienna (Austria); Malmoe University, Department of Periodontology, Faculty of Odontology, Malmoe (Sweden); Hirtler, Lena [Medical University of Vienna, Center for Anatomy and Cell Biology, Department of Systematic Anatomy, Vienna (Austria); Dobsak, Toni [Medical University of Vienna, Division of Oral Surgery, Bernhard Gottlieb School of Dentistry, Vienna (Austria); Medical University of Vienna, Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Division of Oral Surgery, Vienna (Austria); Austrian Cluster for Tissue Regeneration, Vienna (Austria); Heimel, Patrick [Medical University of Vienna, Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Division of Oral Surgery, Vienna (Austria); Austrian Cluster for Tissue Regeneration, Vienna (Austria); Ludwig Boltzmann Institute for Clinical and Experimental Traumatology, Vienna (Austria); Gahleitner, Andre [Medical University of Vienna, Division of Oral Surgery, Bernhard Gottlieb School of Dentistry, Vienna (Austria); Medical University of Vienna, Department of Diagnostic Radiology, Division of Osteoradiology, General Hospital, Vienna (Austria); Ulm, Christian [Medical University of Vienna, Division of Oral Surgery, Bernhard Gottlieb School of Dentistry, Vienna (Austria); Plenk, Hanns [Medical University of Vienna, Bone and Biomaterials Research, Institute for Histology and Embryology, Vienna (Austria)

    2015-04-01

    CT assessment of the entire course of the inferior alveolar artery (IAA) within the mandibular canal. After contrast medium injection (180 or 400 mg/ml iodine concentration) into the external carotid arteries of 15 fresh human cadaver heads, the main IAA's position in the canal (cranial, buccal, lingual or caudal) was assessed in dental CT images of partially edentulous mandibles. The course of the main IAA could be followed at both iodine concentrations. The higher concentration gave the expected better contrast, without creating artefacts, and improved visibility of smaller arteries, such as anastomotic sections, dental branches and the incisive branch. The main IAA changed its position in the canal more often than so far known (mean 4.3 times, SD 1.24, range 2-7), but with a similar bilateral course. A cranial position was most often detected (42 %), followed by lingual (36 %), caudal (16 %) and buccal (6 %). With this non-invasive radiologic method, the entire course of the main IAA in the mandibular canal could be followed simultaneously with other bone structures on both sides of human cadaver mandibles. This methodology allows one to amend existing anatomical and histological data, which are important for surgical interventions near the mandibular canal. (orig.)

  12. Development of the human fetal testis.

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    O'Shaughnessy, Peter J; Fowler, Paul A

    2014-05-01

    Masculinisation and adult fertility in the male are dependent on appropriate fetal endocrine programming. There is also now increasing evidence to indicate that the same mechanisms which regulate masculinisation also affect the general wellbeing of males throughout their life and, particularly, during ageing. Testosterone, secreted by the fetal testes, is the main factor regulating these processes and an understanding of fetal testis development in the human male is essential if we are to prevent adult reproductive disorders. This review focuses on what is known about human testis development and describes the effects of maternal smoking, a surrogate of possible xenotoxicant exposure on fetal testis and fetal liver function. Copyright © 2014. Published by Elsevier Masson SAS.

  13. Tool use for corpse cleaning in chimpanzees

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    van Leeuwen, Edwin J. C.; Cronin, Katherine A.; Haun, Daniel B. M.

    2017-03-01

    For the first time, chimpanzees have been observed using tools to clean the corpse of a deceased group member. A female chimpanzee sat down at the dead body of a young male, selected a firm stem of grass, and started to intently remove debris from his teeth. This report contributes novel behaviour to the chimpanzee’s ethogram, and highlights how crucial information for reconstructing the evolutionary origins of human mortuary practices may be missed by refraining from developing adequate observation techniques to capture non-human animals’ death responses.

  14. [Difficulties in identification of human corpses and skeletal remains on the basis of dental records and examinations].

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    Lorkiewicz-Muszyńska, Dorota; Łabecka, Marzena; Zaba, Czesław; Kis-Wojciechowska, Margit; Kołowski, Janusz; Sobol, Julia

    2009-01-01

    The entire skull-based complex comparative identification procedure consists of several detailed studies from different disciplines of science. The range of the performed studies predominantly depends on the available and collected comparative material pertaining to the examined individual and the final outcome of the complex identification procedure represents the results of individual stages of the studies. Odontological tests involving the comparison of dentition in the examined human skull with the dentition of the typed person, established by the available comparative material, represent a significant element of the identification procedure. The aim of the investigations was the examination of availability and usefulness of dental records during the identification process. The research was based on expert opinions issued in human-skull based identification processes and performed at Department of Forensic Medicine, University of Medical Sciences in Poznan, in the period between 1996 and 2005. A total of 398 identification procedures carried out in 348 sculls was analyzed. The research was mainly identification of an individual through face reconstruction and a skull/photo comparison. An overall number of 206 computer (digital) face-reconstructions and 263 comparison analyses was done in the above-mentioned period. Statistically, in only 22 cases out of 263 comparison analyses some dental records were available. Even then, dental records were not always relevant. In 4 cases, dental records were either incomplete, inaccurate or unreadable.

  15. ccz-1 mediates the digestion of apoptotic corpses in C. elegans.

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    Nieto, Cristina; Almendinger, Johann; Gysi, Stephan; Gómez-Orte, Eva; Kaech, Andres; Hengartner, Michael O; Schnabel, Ralf; Moreno, Sergio; Cabello, Juan

    2010-06-15

    During development, the processes of cell division, differentiation and apoptosis must be precisely coordinated in order to maintain tissue homeostasis. The nematode C. elegans is a powerful model system in which to study cell death and its control. C. elegans apoptotic cells condense and form refractile corpses under differential interference contrast (DIC) microscopy. Activation of the GTPase CED-10 (Rac) in a neighbouring cell mediates the recognition and engulfment of the cell corpse. After inclusion of the engulfed corpse in a phagosome, different proteins are sequentially recruited onto this organelle to promote its acidification and fusion with lysosomes, leading to the enzymatic degradation of the cell corpse. We show that CCZ-1, a protein conserved from yeasts to humans, mediates the digestion of these apoptotic corpses. CCZ-1 seems to act in lysosome biogenesis and phagosome maturation by recruiting the GTPase RAB-7 over the phagosome.

  16. [Decomposition of corpses--a microbial degradation process with special reference to mummification, formation of adipocere and incomplete putrified corpes].

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    Schoenen, Dirk

    2013-01-01

    Decomposition of the human body is a microbial process. It is influenced by the environmental situation and it depends to a high degree on the exchange of substances between the corpse and the environment. Mummification occurs at low humidity or frost. Adipocere arises from lack of oxygen, incomplete putrified corpses develop when there is no exchange of air or water between the corpse and the environment.

  17. Report on Liver Cell Transplantation Using Human Fetal Liver Cells.

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    Pietrosi, Giada; Chinnici, Cinzia

    2017-01-01

    In an era of organ shortage, human fetuses donated after medically indicated abortion could be considered a potential liver donor for hepatic cell isolation. We investigated transplantation of fetal liver cells as a strategy to support liver functionality in end-stage liver disease. Here, we report our protocol of human fetal liver cells (hFLC) isolation in fetuses from 17 to 22 gestational weeks, and our clinical procedure of hFLC transplantation through the splenic artery.

  18. Human Fetal Brain Connectome: Structural Network Development from Middle Fetal Stage to Birth.

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    Song, Limei; Mishra, Virendra; Ouyang, Minhui; Peng, Qinmu; Slinger, Michelle; Liu, Shuwei; Huang, Hao

    2017-01-01

    Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20-40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20-35 PMW than during 35-40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural

  19. Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain.

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    Luo, Chongyuan; Lancaster, Madeline A; Castanon, Rosa; Nery, Joseph R; Knoblich, Juergen A; Ecker, Joseph R

    2016-12-20

    Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of the human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. Demethylated regions (74% of 35,627) identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain

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    Chongyuan Luo

    2016-12-01

    Full Text Available Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of the human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. Demethylated regions (74% of 35,627 identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development.

  1. 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.

  2. Fetal microchimerism in human brain tumors.

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    Broestl, Lauren; Rubin, Joshua B; Dahiya, Sonika

    2017-09-18

    Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal-in-maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively. © 2017 International Society of Neuropathology.

  3. Microbial community assembly and metabolic function during mammalian corpse decomposition

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    Metcalf, J. L.; Xu, Z. Z.; Weiss, S.; Lax, S.; Van Treuren, W.; Hyde, E. R.; Song, S. J.; Amir, A.; Larsen, P.; Sangwan, N.; Haarmann, D.; Humphrey, G. C.; Ackermann, G.; Thompson, L. R.; Lauber, C.; Bibat, A.; Nicholas, C.; Gebert, M. J.; Petrosino, J. F.; Reed, S. C.; Gilbert, J. A.; Lynne, A. M.; Bucheli, S. R.; Carter, D. O.; Knight, R.

    2015-12-10

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  4. Microbial community assembly and metabolic function during mammalian corpse decomposition

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    Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R.; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C.; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

    2016-01-01

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  5. Natural Disasters, Corpses and the Risk of Infectious Diseases

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    JM Conly

    2005-01-01

    Full Text Available The recent occurrence of the category 4 Hurricane Katrina devastated the United States? Gulf Coast. The hurricane caused widespread destruction and flooding, and left hundreds of thousands of people homeless. The mounting death toll was reported at almost 300 deaths as of September 8, 2005 (1,2. The unfolding events and high death toll have left an unusual situation in which there are many decomposing corpses either lying on the streets or floating in the flood waters. The presence of these corpses in open settings, such as in public places and in the water that has inundated much of the city of New Orleans, naturally raises concerns about the occurrence of infectious disease epidemics (3. In the aftermath of large natural disasters, instinctive uncertainties arise among workers and the general population with respect to the appropriate handling and disposal of dead bodies and human remains. Given the recent occurrence of Hurricane Katrina as a large natural disaster and the unprecedented setting of the numerous corpses requiring disposal, it was considered timely to review the infectious disease risks associated with the handling of dead bodies.

  6. APOPTOSIS DURING HUMAN FETAL KIDNEY DEVELOPMENT

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    Rade Čukuranović

    2005-01-01

    Full Text Available Kidney morphogenesis is a complex and stepwise process. The formation of mature kidney in mammals is preceded by two primitive embryonic kidneys known as pronephros and mesonephros. Metanephros develops as a result of reciprocal inductive interactions between two primordial mesodermal derivates: ureteric bud, an epithelial outgrowth of the Wolffian duct, and metanephric blastema, a group of mesenchymal cells. The ureteric bud induces the metanephric mesenchyme to differentiate and form nephrons, whilst the metanephric mesenchyme induces the ureteric bud to grow and branch to form collecting ducts. The nephron goes through four developmental stages, which are described as: 1 vesicle, 2 comma-shaped and S-shaped stages, 3 developing capillary loop, and finally 4 maturing glomerulus. Apoptosis (programmed cell death is a predominant form of physiological cell death, by which organism eliminate unwanted or damaged cells. It is the major component of normal development and disease. Apoptosis is the result of series of biochemical processes happening in certain order in a dying cell, among which the most important is activation of enzyme families called caspases which influence different cell components. Apoptosis is characterized by membrane blebbing, shrinkage of the cell, nuclear fragmentation and chromatin condensation. Organelles are preserved almost intact. Cell surface molecules change. A variety of physiological and pathological stimuli can initiate apoptosis. They act via receptor mechanisms, through biochemical agents, or cause DNA and cell membrane damage. Apoptosis is an important component of fetal development. It is thought that apoptosis is the one of the main regulatory events involved in kidney morphogenesis, considering that among great number of developed cells, only a few of them are involved in the developing program by escaping apoptosis. In any period during kidney development about 3 to 5%of cells are apoptotic. Thorough

  7. DNA Methylation Landscapes of Human Fetal Development

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    Slieker, Roderick C; Roost, Matthias S; van Iperen, Liesbeth; Suchiman, H Eka D; Tobi, Elmar W; Carlotti, Françoise; de Koning, Eelco J P; Slagboom, P Eline; Heijmans, Bastiaan T; Chuva de Sousa Lopes, Susana M

    2015-01-01

    Remodelling the methylome is a hallmark of mammalian development and cell differentiation. However, current knowledge of DNA methylation dynamics in human tissue specification and organ development largely stems from the extrapolation of studies in vitro and animal models. Here, we report on the DNA

  8. Reprogramming of embryonic human fibroblasts into fetal hematopoietic progenitors by fusion with human fetal liver CD34+ cells.

    Directory of Open Access Journals (Sweden)

    Vladislav M Sandler

    Full Text Available Experiments with somatic cell nuclear transfer, inter-cellular hybrid formation_ENREF_3, and ectopic expression of transcription factors have clearly demonstrated that cell fate can be dramatically altered by changing the epigenetic state of cell nuclei. Here we demonstrate, using chemical fusion, direct reprogramming of the genome of human embryonic fibroblasts (HEF into the state of human fetal liver hFL CD34+ (hFL hematopoietic progenitors capable of proliferating and differentiating into multiple hematopoietic lineages. We show that hybrid cells retain their ploidy and can differentiate into several hematopoietic lineages. Hybrid cells follow transcription program of differentiating hFL cells as shown by genome-wide transcription profiling. Using whole-genome single nucleotide polymorphism (SNP profiling of both donor genomes we demonstrate reprogramming of HEF genome into the state of hFL hematopoietic progenitors. Our results prove that it is possible to convert the fetal somatic cell genome into the state of fetal hematopoietic progenitors by fusion. This suggests a possibility of direct reprogramming of human somatic cells into tissue specific progenitors/stem cells without going all the way back to the embryonic state. Direct reprogramming of terminally differentiated cells into the tissue specific progenitors will likely prove useful for the development of novel cell therapies.

  9. Effects of endocrine disruptors on the human fetal testis.

    Science.gov (United States)

    Rouiller-Fabre, Virginie; Habert, René; Livera, Gabriel

    2014-05-01

    The modern societies are exposing us to a huge variety of potentially harmful pollutants. Among these endocrine disruptors (EDs) have been especially scrutinized as several were proven to display reprotoxic effects in rodent models. In the context of high and growing concerns about the reprotoxicity of EDs, it is crucial to carry out studies in order to assess their impact on the human reproductive function. However, such evidence remains scarce. The fetal period is critical for the proper development of the testis and is known as a period of high sensitivity to many EDs. Our team has shown in 2009 that a phthalate, mono-(2-ethylhexyl) phthalate (MEHP), has a potential deleterious effect on the development of human male germ cells. This result was the first direct experimental proof of the toxic effect of an ED in human testis. More recently, we also reported that bisphenol A (BPA) impaired testosterone production in the human fetal testis. Here, we will summarize the known effects of EDs on the various cell types composing the human developing testis and discuss their relevancy to propose future directions. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. In utero transplantation of fetal liver stem cells in humans.

    Science.gov (United States)

    Touraine, J L

    1991-01-01

    Following 15 years experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutical method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The three fetuses that we treated were 28, 26, and 12 weeks of age (weeks after fecundation). The first two patients had immunodeficiencies, the third one had thalassemia major. Donor cells were obtained from 7- to 10-week-old fetuses, with conditions approved by the National Committee for Bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of the first two patients and injected intraperitoneally into the third one, under ultrasonic visualization. The first patient, born in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% than 26% of lymphocytes of donor origin (with distinct phenotype), T cell responses to tetanus toxoid and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989 and it is too early for a thorough evaluation of the immunological effects of the transplant, although donor cell engraftment has been proven (Y chromosome in this female patient). The third patient has also evidence of donor cell take (Y chromosome in a female patient) but the effect on thalassemia has not yet been fully analyzed (donor hemoglobin present in small quantity). In all three cases, no side effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Maintenance of fetal human pancreatic beta cells in tissue culture.

    Science.gov (United States)

    McEvoy, R C; Thomas, N M; Bowers, C; Ginsberg-Fellner, F

    1986-01-01

    Large quantities of viable human islet tissue (beta cells) are required for transplant and for investigations of the autoimmune basis of Type I diabetes. Fetal pancreas offers a potential advantage over other possible sources of beta cells in that it retains some capacity for growth in vitro. We have cultured a total of 45 human pancreata from fetuses of gestational ages from 18 to 23 weeks. Each pancreas was obtained within minutes after delivery and usually cultured within 30 minutes. Pancreata were dispersed and cultured for up to 32 days. Maintenance and growth of the beta cells was assessed by the content of insulin in extracts of cultured tissue. As has been reported by others, fetal human beta cells survived in vitro for over 4 weeks. In three experiments in which a direct comparison was made, collagenase digestion of the fetal pancreas resulted in a significantly greater loss of insulin content compared to minced tissue cultured without digestion. Storage of three pancreata in medium overnight at 4 degrees C significantly reduced the insulin content of the pancreas compared to pancreata cultured immediately. During culture, the majority of the beta cells (based on insulin content) were found in small, macroscopic clumps attached to the surface of the culture dish, and surrounded by a nearly confluent monolayer of fibroblastoid cells. There was a marked decrease in the insulin content of the tissue during culture, most of it (to less than 25% of the original) occurring over the first 4-6 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation.

    Science.gov (United States)

    Lum, Fok-Moon; Low, Donovan K S; Fan, Yiping; Tan, Jeslin J L; Lee, Bernett; Chan, Jerry K Y; Rénia, Laurent; Ginhoux, Florent; Ng, Lisa F P

    2017-04-01

    The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive. Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays. We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1). Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis.

  13. Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth

    DEFF Research Database (Denmark)

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Brix, Nis

    2015-01-01

    BACKGROUND: Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated with redu......BACKGROUND: Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated...... with reduced fetal growth. However, the results of human studies are inconsistent. OBJECTIVES: To summarize the evidence of an association between exposure to PFASs, particularly PFOS and PFOA, and human fetal growth. METHODS: Systematic literature searches were performed in MEDLINE and EMBASE. We included...... original studies on pregnant women with measurements of PFOA or PFOS in maternal blood during pregnancy or the umbilical cord and associations with birth weight or related outcomes according to the PFAS level. Citations and references from the included articles were investigated to locate more relevant...

  14. Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth

    DEFF Research Database (Denmark)

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Brix Lauridsen, Nis

    Background: Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated with redu......Background: Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated...... with reduced fetal growth. However, the results of human studies are inconsistent. Objectives: To summarize the evidence of an association between exposure to PFASs, particularly PFOS and PFOA, and human fetal growth. Methods: Systematic literature searches were performed in MEDLINE and EMBASE. We included...... original studies on pregnant women with measurements of PFOA or PFOS in maternal blood during pregnancy or the umbilical cord and associations with birth weight or related outcomes according to the PFAS level. Citations and references from the included articles were investigated to locate more relevant...

  15. Immunolocalization of lymphatic vessels in human fetal knee joint tissues.

    Science.gov (United States)

    Melrose, James; Little, Christopher B

    2010-08-01

    We immunolocalized lymphatic and vascular blood vessels in 12- and 14-week-old human fetal knee joint tissues using a polyclonal antibody to a lymphatic vascular endothelium specific hyaluronan receptor (LYVE-1) and a monoclonal antibody to podoplanin (mAb D2-40). A number of lymphatic vessels were identified in the stratified connective tissues surrounding the cartilaginous knee joint femoral and tibial rudiments. These tissues also contained small vascular vessels with entrapped red blood cells which were imaged using Nomarsky DIC microscopy. Neither vascular nor lymphatic vessels were present in the knee joint cartilaginous rudiments. The menisci in 12-week-old fetal knees were incompletely demarcated from the adjacent tibial and femoral cartilaginous rudiments which was consistent with the ongoing joint cavitation process at the femoral-tibial junction. At 14 weeks of age the menisci were independent structural entities; they contained a major central blood vessel containing red blood cells and numerous communicating vessels at the base of the menisci but no lymphatic vessels. In contrast to the 12-week-old menisci, the 14-week meniscal rudiments contained abundant CD-31 and CD-34 positive but no lymphatic vessels. Isolated 14-week-old meniscal cells also were stained with the CD-31 and CD 34 antibodies; CD-68 +ve cells, also abundant in the 14-week-old menisci, were detectable to a far lesser degree in the 12-week menisci and were totally absent from the femoral and tibial rudiments. The distribution of lymphatic vessels and tissue macrophages in the fetal joint tissues was consistent with their roles in the clearance of metabolic waste and extracellular matrix breakdown products arising from the rapidly remodelling knee joint tissues.

  16. Human fetal eye movements: detection in utero by ultrasonography.

    Science.gov (United States)

    Bots, R S; Nijhuis, J G; Martin, C B; Prechtl, H F

    1981-02-01

    Eye movements of the human fetus were detected in utero by means of real-time B-scan and M-mode ultrasonography. In 14 low-risk fetuses studied between 32 weeks menstrual age and term either rapid or slow eye movements or a mixture of both types were detected in 60 +/- 10% (mean +/- SD) of 558 2 min scoring epochs. A comparison of direct echoscopic detection of eye movements in a 3-day-old neonate confirmed that the movements observed in the orbital region with the real-time scanner corresponded well with eye movements seen directly. Thus eye movements can be added to the list of phenomena which can be observed noninvasively for the study of human fetal behaviour.

  17. L-carnitine is synthesized in the human fetal-placental unit: potential roles in placental and fetal metabolism

    NARCIS (Netherlands)

    Oey, N. A.; van Vlies, N.; Wijburg, F. A.; Wanders, R. J. A.; Attie-Bitach, T.; Vaz, F. M.

    2006-01-01

    Carnitine plays an indispensable role in fatty acid oxidation. Previous studies revealed that fetal carnitine is derived from the mother via transplacental transfer. Recent studies demonstrated the presence and importance of an active fatty acid oxidation system in the human placenta and in the

  18. Ex vivo culture of human fetal gonads

    DEFF Research Database (Denmark)

    Jørgensen, A; Nielsen, J.E.; Perlman, S

    2015-01-01

    phenotype in fetal testis cultures. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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...... fetal testis development after treatment with RA indicates that abnormal meiosis regulation can potentially cause gonadal dysgenesis. Further studies will elucidate the exact mechanisms and timing of observed effects. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by an ESPE Research...

  19. [Stimulation of cholinogenesis in the human fetal nerve cells culture].

    Science.gov (United States)

    Tsymbaliuk, V I; Vasyl'ieva, I H; Oleksenko, N P; Chopyk, N H; Tsiubko, O I; Halanta, O S

    2013-01-01

    The aim of the research was to establish cultured population of nerve cells reached by cholinergic neurons and their determinative precursors. The most effective combination of neuroinductors which stimulated cholinergic cells differentiation from the nerve stem cells was retinoic acid and acetylcholine. During the period of culturing the amount of ChAT+ cells reliably increased from 5.3 +/- 2.9% to 21.1 +/- 6.2%. At the same time in the control samples their concentration was 9.1 +/- 4.8% of total cell count. Enrichment of cell population by cholinergic neurons and their determinative precursors correlated with increasing of AChE-activity level. So, addition of retinoic acid and acetylcholine stimulate both neurogenesis and cholinogenesis in the culture of human fetal nerve cells.

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

    DEFF Research Database (Denmark)

    Mamsen, Linn; Petersen, TS; Jeppesen, JV

    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...

  1. 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

  2. Porcine fetal ventral mesencephalic cells are targets for primed xenoreactive human T cells

    NARCIS (Netherlands)

    Koopmans, Jan; de Haan, Aalzen; Bruin -van Dijk, Elinda; van der Gun, Ieneke; Van Dijk, Henk; Rozing, Jan; de Leij, Lou; Staal, Michiel

    2006-01-01

    Xenotransplantation of porcine fetal ventral mesencephalic (pfVM) cells to overcome the dopamine shortage in the striatum of patients with Parkinson's disease seems a viable alternative to allotransplantion of human fetal donor tissue, especially because the latter is complicated by both practical

  3. Evidence of cue synergism in termite corpse response behavior

    Science.gov (United States)

    Ulyshen, Michael D.; Shelton, Thomas G.

    2012-02-01

    Subterranean termites of the genus Reticulitermes are known to build walls and tubes and move considerable amounts of soil into wood but the causes of this behavior remain largely unexplored. In laboratory assays, we tested the hypothesis that Reticulitermes virginicus (Banks) would carry more sand into wooden blocks containing corpses compared to corpse-free controls. We further predicted that the corpses of predatory ants would elicit a stronger response than those of a benign beetle species or nestmates. As hypothesized, significantly more sand was carried into blocks containing corpses and this material was typically used to build partitions separating the dead from the rest of the colony. Contrary to expectations, however, this behavior did not vary among corpse types. We then tested the hypothesis that oleic acid, an unsaturated fatty acid released during arthropod decay and used by ants and other arthropod taxa in corpse recognition, would induce a similar building response in R. virginicus. To additionally determine the role of foreign objects in giving rise to this behavior, the experiment was carried out with and without imitation corpses (i.e., small glass beads). As predicted, oleic acid induced building (a tenfold increase) but only when applied to beads, suggesting strong synergism between tactile and chemical cues. Oleic acid also significantly reduced the amount of wood consumed by R. virginicus and may possess useful repellent properties.

  4. From Anticipatory Corpse to Posthuman God.

    Science.gov (United States)

    Bishop, Jeffrey P

    2016-12-01

    The essays in this issue of JMP are devoted to critical engagement of my book, The Anticipatory Corpse The essays, for the most part, accept the main thrust of my critique of medicine. The main thrust of the criticism is whether the scope of the critique is too totalizing, and whether the proposed remedy is sufficient. I greatly appreciate these interventions because they allow me this occasion to respond and clarify, and to even further extend the argument of my book. In this response essay, I maintain that the regnant social imaginary of medicine is the regnant social imaginary of our time. It is grounded in a specific ontotheology: where ontology is a power ontology; where material is malleable to the open-ended organization of power and dependent only on working out the efficient mechanisms of its enactment; where ethically it is oriented only to the immanent telos of utility maximization in the short run, and ultimately to some posthuman future in the long run. This ontotheology originates in the anticipatory corpse and is ordered toward some god-like posthuman being. The entire ontotheology finds enactment through the political economy of neoliberalism. This social imaginary constantly works to insulate itself from other social imaginaries through the use of its institutional power, through marginalization, circumscription, or absorption. The modern social imaginary of neoliberal societies marginalizes and politically isolates other social imaginaries, or transforms them into something acceptable to the neoliberal imaginary. Yet, these other social imaginaries could influence the larger social imaginary in novel ways, sometimes through withdrawal and sometimes through challenges. These other practices-again, usually practices ordered according to different ontological and teleological purposes-might serve as a source of renewal and transformation, but only if the practitioners of these other social imaginaries understand the ontotheological powers that they

  5. Cryopreservation, Culture, and Transplantation of Human Fetal Mesencephalic Tissue into Monkeys

    Science.gov (United States)

    Redmond, D. E.; Naftolin, F.; Collier, T. J.; Leranth, C.; Robbins, R. J.; Sladek, C. D.; Roth, R. H.; Sladek, J. R.

    1988-11-01

    Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

  6. Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner

    NARCIS (Netherlands)

    Barjaktarovic, M. (Mirjana); T.I.M. Korevaar (Tim); V.W.V. Jaddoe (Vincent); Y.B. de Rijke (Yolanda); T.J. Visser (Theo); R.P. Peeters (Robin); E.A.P. Steegers (Eric)

    2017-01-01

    textabstractHuman chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth

  7. Structural and functional maturation of the fetal human choriocapillaris

    Science.gov (United States)

    Baba, Takayuki; Grebe, Rhonda; Hasegawa, Takuya; Bhutto, Imran; Merges, Carol; McLeod, D. Scott; Lutty, Gerard A.

    2016-01-01

    Purpose The purpose of this study was to examine the structural and functional maturation of the choriocapillaris (CC). We sought to determine when fenestrations formed, pericytes invest the capillaries and endothelial cells became functional. Methods Immunohistochemistry was performed on cryopreserved sections of embryonic/fetal human eyes from 7 to 22 weeks gestation (WG) using antibodies against PAL-E, PV-1 (fenestrations), carbonic anhydrase IV (CA IV), eNOS, and alpha smooth muscle actin (αSMA) and NG2 (two pericyte markers) and endothelial cell (EC) markers (CD34, CD31). Alkaline phosphatase (APase) enzymatic activity was demonstrated by enzyme histochemistry. Transmission electron microscopy (TEM) was performed on 11, 14, 16 and 22 WG eyes. Adult human eyes were used as positive controls. Results All EC markers were present in CC by 7 WG. PAL-E, CA IV and eNOS immunoreactivities and APase activity were present in CC by 7–9 WG. TEM analysis demonstrated how structurally immature this vasculature was even at 11 WG: no basement membrane, absence of pericytes, and poorly formed lumens that were filled with filopodia. The few fenestrations that were observed were often present within the luminal space in the filopodia. Contiguous fenestrations and significant PV-1 were not observed until 21–22 WG. αSMA was prominent at 22 WG and the maturation of pericytes was confirmed by TEM. Conclusions It appears that EC and their precursors have several mature functional characteristics well before they are structurally mature. Although EC make tight junctions early in development, contiguous fenestrations and mature pericytes occur much later in development. PMID:19264887

  8. 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.

  9. [Human lung topography in the early fetal period of ontogenesis].

    Science.gov (United States)

    Zheleznov, L M; Shcherbakov, S M

    2012-01-01

    Lung holotopy, skeletotopy and syntopy were studied in 70 human fetuses at developmental weeks 16-24 with N. I. Pirogov method, macro-microscopical preparation and using histotopographical sections in three imutually perpendicular planes. It was found that during weeks 16-18, the apex of the left lung was located posteriorly at the level of I intercostal space, at weeks 22-24--at the level of lower surface of I rib. At the right side, the apex was located at the level of upper surface of I rib during the whole period. The lower margin of the right lung was located at the level of IV rib during the whole period, while that of the left lung was detected at the level of III rib only during the beginning of the period. In the early fetal period, the projection of the root of the right lung extended from the lower margin of T(III) vertebral body toT(VI), while that one of the left lung was located at the level of the upper margins of T(IV)-T(VII) vertebral bodies. In the late period, these projections were found at the level of T(IV) (upper vertebral margin)--T(VII) (lower vertebral margin), and T(IV) (lower vertebral margin)--T(VIII) (upper vertebral margin) respectively. Intraorgan bronchi and pulmonary vessels were most clearly visualized in horizontal sections at T(III) -T(IX) levels. The results obtained should be taken into account when carrying out of diagnostic ultrasound and magnetic resonance studies of the fetus and surgical interventions on fetuses.

  10. 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......, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45...... the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1...

  11. Expression of stem cell markers in the human fetal kidney.

    Directory of Open Access Journals (Sweden)

    Sally Metsuyanim

    Full Text Available In the human fetal kidney (HFK self-renewing stem cells residing in the metanephric mesenchyme (MM/blastema are induced to form all cell types of the nephron till 34(th week of gestation. Definition of useful markers is crucial for the identification of HFK stem cells. Because wilms' tumor, a pediatric renal cancer, initiates from retention of renal stem cells, we hypothesized that surface antigens previously up-regulated in microarrays of both HFK and blastema-enriched stem-like wilms' tumor xenografts (NCAM, ACVRIIB, DLK1/PREF, GPR39, FZD7, FZD2, NTRK2 are likely to be relevant markers. Comprehensive profiling of these putative and of additional stem cell markers (CD34, CD133, c-Kit, CD90, CD105, CD24 in mid-gestation HFK was performed using immunostaining and FACS in conjunction with EpCAM, an epithelial surface marker that is absent from the MM and increases along nephron differentiation and hence can be separated into negative, dim or bright fractions. No marker was specifically localized to the MM. Nevertheless, FZD7 and NTRK2 were preferentially localized to the MM and emerging tubules (50% of HFK cells and predominantly co-express EpCAM(bright, indicating they are mostly markers of differentiation. Furthermore, localization of NCAM exclusively in the MM and in its nephron progenitor derivatives but also in stroma and the expression pattern of significantly elevated renal stem/progenitor genes Six2, Wt1, Cited1, and Sall1 in NCAM(+EpCAM(- and to a lesser extent in NCAM(+EpCAM(+ fractions confirmed regional identity of cells and assisted us in pinpointing the presence of subpopulations that are putative MM-derived progenitor cells (NCAM(+EpCAM(+FZD7(+, MM stem cells (NCAM(+EpCAM(-FZD7(+ or both (NCAM(+FZD7(+. These results and concepts provide a framework for developing cell selection strategies for human renal cell-based therapies.

  12. 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.

  13. Fetal behavior: Clinical and experimental research in the human

    NARCIS (Netherlands)

    Mulder, EJH; Visser, GHA

    2016-01-01

    The intrauterine environment in which we develop has an enormous impact on our physiology and behavior, displayed not only before but also after birth. Proper knowledge of normal fetal behavior, reflecting central nervous system functioning, is essential to detect and characterize the effect on

  14. Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

    Science.gov (United States)

    Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

    2017-02-01

    Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

  15. Effect of Human Amnion Epithelial Cells on the Acute Inflammatory Response in Fetal Sheep

    Directory of Open Access Journals (Sweden)

    Alana Westover

    2017-11-01

    Full Text Available Intra-amniotic (IA lipopolysaccharide (LPS injection in sheep induces inflammation in the fetus. Human amnion epithelial cells (hAECs moderate the effect of IA LPS on fetal development, but their influence on the acute inflammatory response to IA LPS is unknown. We aimed to determine the effects of hAECs on the acute fetal inflammatory response to IA LPS. After surgical instrumentation at 116 days' gestation (d ewes were randomized to 1 of 4 groups at 123 d: IA LPS (10 mg and intravenous (IV saline (n = 8, IA LPS and IV hAECs (n = 6, IA saline and IV saline (n = 5 or IA saline and IV hAECs (n = 5. IV injections were administered immediately after IA injections. Serial fetal blood samples were collected. At 125 d, placental, fetal lung and liver samples were collected. IA LPS increased inflammatory cell recruitment in the placenta and lungs, increased IL-1β and IL-8 mRNA levels in the lungs and increased serum amyloid A3 (SAA3 and C-reactive protein (CRP mRNA levels in the liver. IV hAECs reduced fetal lung inflammatory cell recruitment but did not otherwise alter indices of placental, fetal lung or liver inflammation. The acute fetal inflammatory response to IA LPS is not substantially altered by IV hAEC treatment.

  16. An Iconography of the Flesh: How Corpses Mean As Matter

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    Margaret Shwartz

    2013-09-01

    Full Text Available The structuring relationship between the material world and the world of culture is variously embodied in the figure of the corpse. To ask how corpses mean as matter is to attend to them as “things themselves”—by bracketing the freighted assumptions and naturally mixed feelings we have when we encounter something that cannot but remind us of our own mortality. Corpses force us to think of putrefaction—and allow us, via a complex system of cultural and representational practices, to just as quickly disavow this unpleasantness. Wherever the corpse appears, then, it brings with it ideas about the relationship between representation and the real, or, more precisely, about the matter of subjectivity. This materiality also crucially constitutes the corpse’s difference from the identity of the deceased, and it is here where the corpse may thus do more than simply reference the past. The end point of the argument, then, is to work towards a vocabulary that allows this difference—this material remainder—to figure meaningfully in practices of grief and mourning that may not point exclusively back towards the deceased (and inevitably a particular version of that person’s legacy but towards the future and towards polysemic, even conflicting ideas of the responsibility placed upon us by this death. This paper opens a discussion of corpses as “vibrant matter” (to borrow Jane Bennett’s provocative term whose materiality is an equal partner to their cultural significance. My reading opens a conversation about the very real work of corpses as things capable of organizing diverse affect that in turn may become considered action. Following Bennett’s reading of Deleuze and Latour, I account for the corpse as both deceased subject and material object by framing it as a kind of assemblage. As remains, the corpse is essentially referential, the remains of someone. But remains are also material, matter that functions as an actant in concert with

  17. In vitro functionality of human fetal liver cells and clonal derivatives under proliferative conditions

    NARCIS (Netherlands)

    Deurholt, Tanja; ten Bloemendaal, Lysbeth; Chhatta, Aniska A.; van Wijk, Albert C. W. A.; Weijer, Kees; Seppen, Jurgen; Elferink, Ronald P. J. Oude; Chamuleau, Robert A. F. M.; Hoekstra, Ruurdtje

    2006-01-01

    Mature human hepatocytes are not suitable for large-scale in vitro applications that rely on hepatocyte function, due to their limited availability and insufficient proliferation capacity in vitro. In contrast, human fetal liver cells (HFLC) can be easily expanded in vitro. In this study we

  18. Uptake and release of amino acids in the fetal-placental unit in human pregnancies.

    Directory of Open Access Journals (Sweden)

    Maia Blomhoff Holm

    Full Text Available The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample.This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein and fetal (umbilical vein and artery sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations.In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake for 14 amino acids and a negative venoarterial difference (fetal release for glutamic acid (p<0.001. In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake for leucine (p = 0.005, isoleucine (p = 0.01, glutamic acid (p<0.001 and arginine (p = 0.04 and a negative arteriovenous difference (uteroplacental release for tyrosine (p = 0.002, glycine (p = 0.01 and glutamine (p = 0.02. The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake.Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is

  19. Human fetal liver cells for regulated ex vivo erythropoietin gene therapy

    Directory of Open Access Journals (Sweden)

    Ebtisam El Filali

    2014-01-01

    Full Text Available Possible risks and lack of donor livers limit application of liver transplantation. Liver cell transplantation is, at this moment, not a feasible alternative because engraftment in the liver is poor. Furthermore, there is also shortage of cells suitable for transplantation. Fetal liver cells are able to proliferate in cell culture and could therefore present an alternative source of cells for transplantation. In this study, we investigated the utility of human fetal liver cells for therapeutic protein delivery. We transplanted human fetal liver cells in immunodeficient mice but were not able to detect engraftment of human hepatocytes. In contrast, transplantation of human adult hepatocytes led to detectable engraftment of hepatocytes in murine liver. Transplantation of fetal liver cells did lead to abundant reconstitution of murine liver with human endothelium, indicating that endothelial cells are the most promising cell type for ex vivo liver cell gene therapy. Human liver endothelial cells were subsequently transduced with a lentiviral autoregulatory erythropoietin expression vector. After transplantation in immunodeficient mice, these cells mediated long-term regulation of murine hematocrits. Our study shows the potential of human liver endothelial cells for long-term regulated gene therapy.

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

    Science.gov (United States)

    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.

  1. Covalent cell surface functionalization of human fetal osteoblasts for tissue engineering.

    Science.gov (United States)

    Borcard, Françoise; Godinat, Aurélien; Staedler, Davide; Blanco, Horacio Comas; Dumont, Anne-Laure; Chapuis-Bernasconi, Catherine; Scaletta, Corinne; Applegate, Lee Ann; Juillerat, Franziska Krauss; Gonzenbach, Urs T; Gerber-Lemaire, Sandrine; Juillerat-Jeanneret, Lucienne

    2011-07-20

    The chemical functionalization of cell-surface proteins of human primary fetal bone cells with hydrophilic bioorthogonal intermediates was investigated. Toward this goal, chemical pathways were developed for click reaction-mediated coupling of alkyne derivatives with cellular azido-expressing proteins. The incorporation via a tetraethylene glycol linker of a dipeptide and a reporter biotin allowed the proof of concept for the introduction of cell-specific peptide ligands and allowed us to follow the reaction in living cells. Tuning the conditions of the click reaction resulted in chemical functionalization of living human fetal osteoblasts with excellent cell survival.

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

    Science.gov (United States)

    Crickard, K; Fujii, D K; Jaffe, R B

    1982-12-01

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

  3. Characterization of Liver-Specific Functions of Human Fetal Hepatocytes in Culture.

    Science.gov (United States)

    Chinnici, Cinzia Maria; Timoneri, Francesca; Amico, Giandomenico; Pietrosi, Giada; Vizzini, Giovanni; Spada, Marco; Pagano, Duilio; Gridelli, Bruno; Conaldi, Pier Giulio

    2015-01-01

    This study was designed to assess liver-specific functions of human fetal liver cells proposed as a potential source for hepatocyte transplantation. Fetal liver cells were isolated from livers of different gestational ages (16-22 weeks), and the functions of cell preparations were evaluated by establishing primary cultures. We observed that 20- to 22-week-gestation fetal liver cell cultures contained a predominance of cells with hepatocytic traits that did not divide in vitro but were functionally competent. Fetal hepatocytes performed liver-specific functions at levels comparable to those of their adult counterpart. Moreover, exposure to dexamethasone in combination with oncostatin M promptly induced further maturation of the cells through the acquisition of additional functions (i.e., ability to store glycogen and uptake of indocyanine green). In some cases, particularly in cultures obtained from fetuses of earlier gestational ages (16-18 weeks gestation), cells with mature hepatocytic traits proved to be sporadic, and the primary cultures were mainly populated by clusters of proliferating cells. Consequently, the values of liver-specific functions detected in these cultures were low. We observed that a low cell density culture system rapidly prompted loss of the mature hepatocytic phenotype with downregulations of all the liver-specific functions. We found that human fetal liver cells can be cryopreserved without significant loss of viability and function and evaluated up to 1 year in storage in liquid nitrogen. They might, therefore, be suitable for cell banking and allow for the transplantation of large numbers of cells, thus improving clinical outcomes. Overall, our results indicate that fetal hepatocytes could be used as a cell source for hepatocyte transplantation. Fetal liver cells have been used so far to treat end-stage liver disease. Additional studies are needed to include these cells in cell-based therapies aimed to treat liver failure and inborn

  4. 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

  5. Uterine Vasculature Remodeling in Human Pregnancy Involves Functional Macrochimerism by Endothelial Colony Forming Cells of Fetal Origin

    Science.gov (United States)

    Sipos, Peter I; Rens, Willem; Schlecht, HÉlène; Fan, Xiaohu; Wareing, Mark; Hayward, Christina; Hubel, Carl A; Bourque, Stephane; Baker, Philip N; Davidge, Sandra T; Sibley, Colin P; Crocker, Ian P

    2013-01-01

    The potency of adult-derived circulating progenitor endothelial colony forming cells (ECFCs) is drastically surpassed by their fetal counterparts. Human pregnancy is associated with robust intensification of blood flow and vascular expansion in the uterus, crucial for placental perfusion and fetal supply. Here, we investigate whether fetal ECFCs transmigrate to maternal bloodstream and home to locations of maternal vasculogenesis, primarily the pregnant uterus. In the first instance, endothelial-like cells, originating from mouse fetuses expressing paternal eGFP, were identified within uterine endothelia. Subsequently, LacZ or enhanced green fluorescent protein (eGFP)-labeled human fetal ECFCs, transplanted into immunodeficient (NOD/SCID) fetuses on D15.5 pregnancy, showed similar integration into the mouse uterus by term. Mature endothelial controls (human umbilical vein endothelial cells), similarly introduced, were unequivocally absent. In humans, SRY was detected in 6 of 12 myometrial microvessels obtained from women delivering male babies. The copy number was calculated at 175 [IQR 149–471] fetal cells per millimeter square endothelium, constituting 12.5% of maternal vessel lumina. Cross-sections of similar human vessels, hybridized for Y-chromosome, positively identified endothelial-associated fetal cells. It appears that through ECFC donation, fetuses assist maternal uterine vascular expansion in pregnancy, potentiating placental perfusion and consequently their own fetal supply. In addition to fetal growth, this cellular mechanism holds implications for materno-fetal immune interactions and long-term maternal vascular health. PMID:23554274

  6. Evaluation of islets derived from human fetal pancreatic progenitor cells in diabetes treatment.

    Science.gov (United States)

    Zhang, Wen-Jian; Xu, Shi-Qing; Cai, Han-Qing; Men, Xiu-Li; Wang, Zai; Lin, Hua; Chen, Li; Jiang, Yong-Wei; Liu, Hong-Lin; Li, Cheng-Hui; Sui, Wei-Guo; Deng, Hong-Kui; Lou, Jin-Ning

    2013-01-01

    With the shortage of donor organs for islet transplantation, insulin-producing cells have been generated from different types of stem cell. Human fetal pancreatic stem cells have a better self-renewal capacity than adult stem cells and can readily differentiate into pancreatic endocrine cells, making them a potential source for islets in diabetes treatment. In the present study, the functions of pancreatic islets derived from human fetal pancreatic progenitor cells were evaluated in vitro and in vivo. Human pancreatic progenitor cells isolated from the fetal pancreas were expanded and differentiated into islet endocrine cells in culture. Markers for endocrine and exocrine functions as well as those for alpha and beta cells were analyzed by immunofluorescent staining and enzyme-linked immunosorbent assay (ELISA). To evaluate the functions of these islets in vivo, the islet-like structures were transplanted into renal capsules of diabetic nude mice. Immunohistochemical staining for human C-peptide and human mitochondrion antigen was applied to confirm the human origin and the survival of grafted islets. Human fetal pancreatic progenitor cells were able to expand in medium containing basic fibroblast growth factor (bFGF) and leukemia inhibitor factor (LIF), and to differentiate into pancreatic endocrine cells with high efficiency upon the actions of glucagon-like peptide-1 and activin-A. The differentiated cells expressed insulin, glucagon, glucose transporter-1 (GLUT1), GLUT2 and voltage-dependent calcium channel (VDCC), and were able to aggregate into islet-like structures containing alpha and beta cells upon suspension. These structures expressed and released a higher level of insulin than adhesion cultured cells, and helped to maintain normoglycemia in diabetic nude mice after transplantation. Human fetal pancreatic progenitor cells have good capacity for generating insulin producing cells and provide a promising potential source for diabetes treatment.

  7. Involvement of the angiotensin II type 2 receptor in apoptosis during human fetal adrenal gland development.

    Science.gov (United States)

    Chamoux, E; Breault, L; Lehoux, J G; Gallo-Payet, N

    1999-12-01

    The aim of this study was to establish a link between the highly expressed angiotensin II (Ang II) type 2 receptor (AT2) in human fetal adrenal cells and the proposed apoptotic activity in the center of the gland. There was an important increase in apoptotic DNA fragmentation with age in adrenal glands of fetuses from 15-20 weeks gestation. Adrenal cells showing the characteristic apoptotic internucleosomal DNA fragmentation were localized in the central portion of the fetal zone. In cells cultured for 24 h, Ang II, via the AT2 receptor, induced DNA fragmentation and cleavage of the DNA repair enzyme, poly-(ADP-ribose) polymerase. Furthermore, characteristic membrane blebbing was observed specifically on cells of the fetal zone. Immunofluorescence studies demonstrated that stimulation with Ang II or CGP 42112 (an agonist of the AT2 receptor) strongly modified the actin network, now localized exclusively along the plasma membrane, with a predominance of labeling at the base of the bleb formation. This rearrangement of actin distribution was different in cells from the definitive zone, corroborating the observation that these cells express many more Ang II type 1 receptors (AT1) than AT2 receptors. Taken together, our data indicate that the AT2 receptor is involved in the apoptotic process observed in the human fetal adrenal gland and could participate in the morphological changes occurring after birth, leading to involution of the fetal zone.

  8. The Dynami(n)cs of cell corpse engulfment.

    Science.gov (United States)

    Shaham, Shai

    2006-06-01

    Engulfment of dying cells plays an important role during animal development and homeostasis, and several proteins involved in this process are known. However, the cell biology underlying phagocyte arm extension and cell corpse degradation is not well understood. A study published in this issue of Developmental Cell (Yu et al., 2006) now demonstrates an important role for the GTPase dynamin in these events.

  9. Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

    Science.gov (United States)

    Shen, Joel; Overland, Maya; Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence

    We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. Copyright © 2016 International Society

  10. Peroxisome Proliferator-Activated Receptors Alpha, Beta, and Gamma mRNA and Protein Expression in Human Fetal Tissues

    Directory of Open Access Journals (Sweden)

    Barbara D. Abbott

    2010-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs regulate lipid and glucose homeostasis, are targets of pharmaceuticals, and are also activated by environmental contaminants. Almost nothing is known about expression of PPARs during human fetal development. This study examines expression of PPAR, , and mRNA and protein in human fetal tissues. With increasing fetal age, mRNA expression of PPAR and increased in liver, but PPAR decreased in heart and intestine, and PPAR decreased in adrenal. Adult and fetal mean expression of PPAR, , and mRNA did not differ in intestine, but expression was lower in fetal stomach and heart. PPAR and mRNA in kidney and spleen, and PPAR mRNA in lung and adrenal were lower in fetal versus adult. PPAR in liver and PPAR mRNA in thymus were higher in fetal versus adult. PPAR protein increased with fetal age in intestine and decreased in lung, kidney, and adrenal. PPAR protein in adrenal and PPAR in kidney decreased with fetal age. This study provides new information on expression of PPAR subtypes during human development and will be important in evaluating the potential for the developing human to respond to PPAR environmental or pharmaceutical agonists.

  11. A comparative biomechanical analysis of term fetal membranes in human and domestic species

    Science.gov (United States)

    The purpose of this study was to biomechanically characterize and compare human, porcine, equine, and ovine fetal membranes. Noncontact metrology was used for topographic analyses. Uniaxial tensile testing was performed to resolve specific biomechanical values. Puncture force and radial stresses we...

  12. Dissecting human cerebral organoids and fetal neocortex using single-cell RNAseq

    Science.gov (United States)

    Treutlein, Barbara

    Cerebral organoids - three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells - have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.

  13. 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,

  14. 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...

  15. Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.

    Directory of Open Access Journals (Sweden)

    Thierry N'Tumba-Byn

    Full Text Available Endocrine disruptors (ED have been incriminated in the current increase of male reproductive alterations. Bisphenol A (BPA is a widely used weak estrogenic environmental ED and it is debated whether BPA concentrations within the average internal exposure are toxic. In the present study we investigated the effects of 10(-12 to 10(-5 M BPA concentrations on fetal Leydig cell function, as fetal life is a critical period of sensitivity to ED effects on male reproductive function. To this aim, fetal testes from human at 6.5-10.5 gestational weeks (GW or from rat and mouse at a comparable critical period of development (14.5 days post-coitum (dpc for rat and 12.5 dpc for mouse were explanted and cultured using our validated organotypic culture system in the presence or absence of BPA for 1-3 days. BPA concentrations as low as 10(-8 M reduced testosterone secretion by human testes from day 1 of culture onwards, but not by mouse and rat testes where concentrations equal to 10(-5 M BPA were required. Similarly, 10(-8 M BPA reduced INSL3 mRNA levels only in human cultured testes. On the contrary, 10(-5 and 10(-6 M diethylstilbestrol (DES, a classical estrogenic compound, affected testosterone secretion only in rat and mouse testis cultures, but not in human testis cultures. Lastly, contrarily to the DES effect, the negative effect of BPA on testosterone produced by the mouse fetal testis was maintained after invalidation of estrogen receptor α (ERα. In conclusion, these results evidenced i a deleterious effect of BPA on fetal Leydig cells function in human for concentrations from 10(-8 M upwards, ii species-specific differences raising concerns about extrapolation of data from rodent studies to human risk assessment, iii a specific signaling pathway for BPA which differs from the DES one and which does not involve ERα.

  16. A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland

    OpenAIRE

    Chamoux E.

    2005-01-01

    The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative...

  17. GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation.

    Science.gov (United States)

    Larijani, Bagher; Aghayan, Hamid-Reza; Goodarzi, Parisa; Arjmand, Babak

    2015-01-01

    Stem cell therapy seems a promising avenue in regenerative medicine. Within various stem cells, mesenchymal stem cells have progressively used for cellular therapy. Because of the age-related decreasing in the frequency and differentiating capacity of adult MSCs, fetal tissues such as fetal liver, lung, pancreas, spleen, etc. have been introduced as an alternative source of MSCs for cellular therapy. On the other hand, using stem cells as advanced therapy medicinal products, must be performed in compliance with cGMP as a quality assurance system to ensure the safety, quality, and identity of cell products during translation from the basic stem cell sciences into clinical cell transplantation. In this chapter the authors have demonstrated the manufacturing of GMP-grade human fetal liver-derived mesenchymal stem cells.

  18. Impact of chorioamnionitis on the development of human fetal lung: an immunohistochemical study.

    Science.gov (United States)

    Boglou, P; Deftereou, T H E; Lambropoulou, M; Katotomichelakis, M; Lambropoulou, V; Pagonopoulou, O; Gkantsinikoudis, N; Papadopoulos, N; Dimitriou, T H

    2015-01-01

    Current studies suggest that changes of chorioamnionitis are associated with the appearance of bronchial-associated lymphoid tissue (BALT), during fetal development. The aim of this study was to examine and analyse apart from the appearance of BALT, the expression of structural proteins in the lung parenchyma during gestation. A series of 149 paraffin-embedded human fetal lung specimens at the second trimester of development were examined by immuunohistochemistry using the monoclonal antibodies CD20, CD3, Tenascin-C, Vimentin, and Fibronectin. The results of this study showed that (1) BALT does not develop in fetal period and (2) BALT which develops during fetal period is probably in response to antigenic stimulation where in the present cases occurs to be changes of chorioamnionitis which decreased the expression of filaments proteins in the intermediate cells of lung parenchyma in comparison with the normal ones. The expressions' pattern of intermediate filaments proteins in the lung parenchyma can be modified by the presence of chorioamnionitis in the fetal membranes.

  19. 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.

  20. Insights in spatio-temporal characterization of human fetal neural stem cells.

    Science.gov (United States)

    Martín-Ibáñez, Raquel; Guardia, Inés; Pardo, Mónica; Herranz, Cristina; Zietlow, Rike; Vinh, Ngoc-Nga; Rosser, Anne; Canals, Josep M

    2017-05-01

    Primary human fetal cells have been used in clinical trials of cell replacement therapy for the treatment of neurodegenerative disorders such as Huntington's disease (HD). However, human fetal primary cells are scarce and difficult to work with and so a renewable source of cells is sought. Human fetal neural stem cells (hfNSCs) can be generated from human fetal tissue, but little is known about the differences between hfNSCs obtained from different developmental stages and brain areas. In the present work we characterized hfNSCs, grown as neurospheres, obtained from three developmental stages: 4-5, 6-7 and 8-9weeks post conception (wpc) and four brain areas: forebrain, cortex, whole ganglionic eminence (WGE) and cerebellum. We observed that, as fetal brain development proceeds, the number of neural precursors is diminished and post-mitotic cells are increased. In turn, primary cells obtained from older embryos are more sensitive to the dissociation process, their viability is diminished and they present lower proliferation ratios compared to younger embryos. However, independently of the developmental stage of derivation proliferation ratios were very low in all cases. Improvements in the expansion rates were achieved by mechanical, instead of enzymatic, dissociation of neurospheres but not by changes in the seeding densities. Regardless of the developmental stage, neurosphere cultures presented large variability in the viability and proliferation rates during the initial 3-4 passages, but stabilized achieving significant expansion rates at passage 5 to 6. This was true also for all brain regions except cerebellar derived cultures that did not expand. Interestingly, the brain region of hfNSC derivation influences the expansion potential, being forebrain, cortex and WGE derived cells the most expandable compared to cerebellar. Short term expansion partially compromised the regional identity of cortical but not WGE cultures. Nevertheless, both expanded cultures were

  1. Fetal hyperglycemia changes human preadipocyte function in adult life

    DEFF Research Database (Denmark)

    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...... hyperglycemic groups, O-GDM and O-T1DM, and, as a control group, offspring from the background population (O-BP). Subcutaneous fat biopsies were obtained and preadipocyte cell cultures were established from adult male O-GDM (n = 18, age 30.1 ± 2.5 years), O-T1DM (n = 18, age 31.6 ± 2.2 years), and O-BP (n = 16......; age, 31.5 ± 2.7 years) and cultured in vitro. Main Outcome Measures: First, we studied in vivo adipocyte histology. Second, we studied in vitro preadipocyte leptin secretion, gene expression, and LEP DNA methylation. This was studied in combination with in vitro preadipocyte lipogenesis, lipolysis...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. Localization of G protein alpha-subunits in the human fetal adrenal gland.

    Science.gov (United States)

    Breault, L; Chamoux, E; Lehoux, J G; Gallo-Payet, N

    2000-12-01

    The aim of the present study was to investigate the presence and localization of the main G protein alpha-subunits in the human fetal adrenal gland during the second trimester of gestation. Immunofluorescence studies conducted on sections from frozen glands obtained immediately after therapeutic abortion indicated that the alpha s subunit of the heterotrimeric Gs protein was detected in all adrenal cell types, except for endothelial cells. The other alpha-subunits had a more specific pattern of distribution. Indeed, the alpha il-2 protein was restricted to the definitive zone, whereas alpha i3 labeling was mainly expressed in the fetal zone. The alpha q protein subunit was localized in vascular endothelial cells at the periphery of the adrenal gland and in fetal cells at the center. Finally, chromaffin cells expressed alpha s, alpha q, and alpha o1, but not alpha o2 nor alpha i. Altogether, these results indicate that the human fetal adrenal gland is not only unique in its particular morphology and expression of steroidogenic enzymes, but also by the differential expression of G protein alpha-subunits. Such cell specific distribution in glands from midgestational fetuses may account for the absence or the different responses to stimuli, when compared with the adult adrenal gland.

  5. Bronchus-associated lymphoid tissue (BALT) in human fetal and infant lung.

    Science.gov (United States)

    Gould, S J; Isaacson, P G

    1993-02-01

    Bronchus-associated lymphoid tissue (BALT) has been defined as the organized lymphoid tissue of the lung. Although well described in a variety of animal species, documentation of its presence and development in human lung is limited. Because the tissue to volume ratio in adult lungs is so low, a systematic search for BALT would involve so many sections as to be impractical. In this study, therefore, we have studied post-mortem specimens of fetal (n = 102) and infant (n = 17) lungs, which have a much higher tissue to volume ratio. Fetal death was due to various causes but all but two infants died from sudden infant death syndrome. In the fetal lungs, the presence of BALT was almost invariably associated with chorioamnionitis or intrauterine pneumonia, being present in 24 of 51 of these cases (47 per cent). The earliest ill-defined lymphoid aggregate was seen at 16 weeks' gestation, while lymphoepithelium, a hallmark of mucosa-associated lymphoid tissue, could be identified at 20 weeks. In 51 fetuses without infection, BALT was found in only five cases (10 per cent). BALT was identified in 13/17 (77 per cent) of infant lungs and well-developed lymphoepithelium was evident in four cases. This study shows that BALT may be present in the human fetal and infant lung, but that its appearance is probably dependent on antigenic stimulation.

  6. Comparison between right and left ventricular myocardia during the human fetal period. Stereological evaluation

    Directory of Open Access Journals (Sweden)

    Ricardo Xavier-Vidal

    1999-05-01

    Full Text Available PURPOSE: To develop a stereological comparison between right (RV and left ventricle (LV myocardium during the third human gestational trimester. METHODS: Five human fetal hearts of the third trimester provided representative samples of 5 RV myocardium and 4 LV myocardium. The material was fixed in 10% buffered formaldehyde, and processed through routine methods. Fifteen microscopic fields were randomly chosen and counted in each ventricular myocardium using an "M-42" test system. The following stereological parameters were assessed: Vv (%, Lv (µm², Sv (µm²/µm³, Vp (µm³, Nv (1/mm³ and total N. RESULTS: No significant difference between the stereological parameters of the myocardial structures assessed was evidenced, when comparing RV and LV. CONCLUSION: Right and left human ventricular myocardium are very similar during the fetal period at least in regard to their structural aspects.

  7. 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-stimulating factor

  8. [Euripides and Heraclitus on the attitude towards the corpse--an unrecognized fragment of Heraclitus in Electra, v. 289].

    Science.gov (United States)

    Moog, Ferdinand Peter

    2007-01-01

    Among the fragments of Heraclitus preserved to our times there is one saying that corpses ought to be disposed of more urgently than excrements Diels/Kranz 22 B 96. This sentence of an aphoristic nature, as frequently in the case of Heraclitus' scripts, allows many different interpretations. Even in antiquity these words led to vitriolic reactions and perplexed other writers. It is why they have been frequently quoted. Nevertheless, it has been overlooked until now that Euripides, the youngest of the three great Attic tragedians, had inserted them into one of his dramas. In his Electra it is the title figure who uses them while reporting the slaughter of Agamemnon. The quotation bears witness to Euripides' erudition as of one of the earliest men known to have possessed a private library. He must, therefore, have had access to many treatises on various subjects, among them to the work by Heraclitus. The Electra is a kind of homage to the obscure thinker from Ephesus. From this fact, and from the plot of this particular play, we may gain some insight into an ambivalent attitude of the ancient Greeks towards the corpse that certainly influenced ideas about human anatomy in particular and medical knowledge in general. A characteristic feature of the malefactors, namely Aigisthos and Clytaimestra, is the deliberate dishonouring of their victims corpse. By contrast, the noble characters Orestes and Electra never violate the corpse of their arch-enemy Aigisthos, but see to it that he is properly buried. Burial was, particularly in Athens, so essential that in the well-known Arginusai trial the failure to bury the fallen soldiers resulted in capital punishment for the accused. Nevertheless, it is likely that Euripides, following Heraclitus, did not reject the anatomical examination of corpses for scientific purposes, as he was not only in this regard a supporter of science and progress. Perhaps Plato's notion of the human body as the tomb of the soul is foreshadowed here

  9. Psychische Belastungen durch die Dissektion am Leichnam im anatomischen Präparierkurs bei Erstsemestern des Studienfachs Medizin [Psychological Stress In First Year Medical Students In Response To The Dissection Of A Human Corpse

    Directory of Open Access Journals (Sweden)

    Bernhardt, Veronika

    2012-02-01

    were very worried about the confrontation with corpses. Furthermore, personality tests were shown to be only partly reliable for selecting affected people in advance. With regard to these results capabilities to provide support to the first year medical students should be discussed.[german] Ziel der Studie: Das Fachgebiet der Anatomie ist eines der wichtigsten und lernintensivsten Fächer im vorklinischen Studienabschnitt eines Medizinstudierenden. An der Otto-von-Guericke-Universität in Magdeburg stellten sich im Oktober 2007 186 Studierende, davon 126 weiblich und 60 männlich, der Begegnung mit der anatomischen Dissektion von Verstorbenen. Das Ziel dieser Studie ist es, herauszufinden welche Rolle der emotionale Aspekt im Bezug auf diesen Kurs spielt. Es wurde untersucht, wie die Studierenden die erste Konfrontation und den weiteren Umgang mit den Präparaten von Verstorbenen subjektiv wahrnehmen und verarbeiten und inwieweit diesbezügliche Unterschiede zwischen verschiedenen Gruppen (Alter, Geschlecht, Vorerfahrung aufzufinden sind.Methoden: Die Studie wurde an 155 Erstsemestern durchgeführt (112 w, 43 m; 21,4±2,9 J.. Es wurden selbstkonstruierte Fragebögen benutzt, die schwerpunktmäßig Befürchtungen hinsichtlich des anatomischen Präparierkurses erfragen und mit Erfahrungen hinsichtlich des Sterbens und eigenen Ängsten vor dem Tod verglichen. Es wurde je ein Fragebogen zu Beginn des ersten Semesters und nach dem ersten Semester ausgehändigt (n=94, 66 w, 28 m, um Entwicklungen und Veränderungen erkennen zu können. Zur Erfassung der Persönlichkeitseigenschaften wurde außerdem zwei Skalen aus dem Freiburger Persönlichkeitsinventar (FPI-R vorgelegt. Ergebnisse: Der selbstentwickelte Fragebogen zeigte hohe Reliabilität. Der Präparierkurs stellte für einige Studierende eine subjektive psychische Belastung dar; rund 50% hatten sich Sorgen gemacht, wie sie die erste Begegnung vertragen, allerdings nur 12% in einem wirklich schweren Ausmaß. Die

  10. Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.

    Science.gov (United States)

    Ardehali, Reza; Ali, Shah R; Inlay, Matthew A; Abilez, Oscar J; Chen, Michael Q; Blauwkamp, Timothy A; Yazawa, Masayuki; Gong, Yongquan; Nusse, Roeland; Drukker, Micha; Weissman, Irving L

    2013-02-26

    A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown. Here, we have prospectively identified a population of hESC-derived ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. We observed rare clusters of ROR2(+) cells and diffuse expression of KDR and PDGFRα in first-trimester human fetal hearts. We then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, we show structural and functional integration of hESC-derived cardiovascular progenitors into human heart.

  11. Phases I-II Matched Case-Control Study of Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Disease

    National Research Council Canada - National Science Library

    Pietrosi, Giada; Vizzini, Giovanni; Gerlach, Jorg; Chinnici, Cinzia; Luca, Angelo; Amico, Giandomenico; D'amato, Monica; Conaldi, Pier Giulio; Petri, Sergio Li; Spada, Marco; Tuzzolino, Fabio; Alio, Luigi; Schmelzer, Eva; Gridelli, Bruno

    2015-01-01

    Fetal hepatocytes have a high regenerative capacity. The aim of the study was to assess treatment safety and clinical efficacy of human fetal liver cell transplantation through splenic artery infusion...

  12. Identification of extracellular matrix components and their integrin receptors in the human fetal adrenal gland.

    Science.gov (United States)

    Chamoux, E; Bolduc, L; Lehoux, J G; Gallo-Payet, N

    2001-05-01

    The development of the human fetal adrenal gland is characterized by a gradient of mitotic activity, cell migration, and cell apoptosis, all of which dictate its particular function. Such plasticity may possibly be under the control of the extracellular environment. The goal of this study was to identify components of the extracellular matrix in second-trimester fetal adrenal glands. Whereas collagen IV was expressed evenly throughout the gland, both fibronectin and laminin demonstrated a mirror-imaged distribution, with higher expression of fibronectin in the central portion and laminin at the periphery of the gland. The integrin subunit alpha1 was found mainly in the definitive zone and the alpha2-subunit mainly in the transitional zone, whereas integrin alpha3 (which binds both fibronectin and laminin) was detected only in the fetal zone. The beta2-subunit was observed solely in chromaffin cells. Such specific gradients of integrin and MEC component expression suggest that the extracellular environment does play a definite role during adrenal gland development. Indeed, compared with that in untreated plastic dishes, ACTH stimulation of dehydroepiandrosterone sulfate and cortisol was enhanced by collagen IV. In addition, fibronectin enhanced dehydroepiandrosterone sulfate but decreased cortisol secretion, compared with collagen IV substrates. These results provide fundamental insight into the contribution of the microenvironment in cellular processes leading to fetal adrenal gland development.

  13. 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...

  14. Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice.

    Science.gov (United States)

    Sapparapu, Gopal; Fernandez, Estefania; Kose, Nurgun; Bin Cao; Fox, Julie M; Bombardi, Robin G; Zhao, Haiyan; Nelson, Christopher A; Bryan, Aubrey L; Barnes, Trevor; Davidson, Edgar; Mysorekar, Indira U; Fremont, Daved H; Doranz, Benjamin J; Diamond, Michael S; Crowe, James E

    2016-12-15

    Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, we isolated a panel of human monoclonal antibodies from subjects that were previously infected with ZIKV. We show that a subset of antibodies recognize diverse epitopes on the envelope (E) protein and exhibit potent neutralizing activity. One of the most inhibitory antibodies, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African and Asian-American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer-dimer interface. We evaluated the therapeutic efficacy of ZIKV-117 in pregnant and non-pregnant mice. Monoclonal antibody treatment markedly reduced tissue pathology, placental and fetal infection, and mortality in mice. Thus, neutralizing human antibodies can protect against maternal-fetal transmission, infection and disease, and reveal important determinants for structure-based rational vaccine design efforts.

  15. Neuropeptide Y in the adult and fetal human pineal gland

    DEFF Research Database (Denmark)

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma...... inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland....... In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally....

  16. In vivo transplantation of fetal human gut-derived enteric neural crest cells.

    Science.gov (United States)

    Cooper, J E; Natarajan, D; McCann, C J; Choudhury, S; Godwin, H; Burns, A J; Thapar, N

    2017-01-01

    The prospect of using neural cell replacement for the treatment of severe enteric neuropathies has seen significant progress in the last decade. The ability to harvest and transplant enteric neural crest cells (ENCCs) that functionally integrate within recipient intestine has recently been confirmed by in vivo murine studies. Although similar cells can be harvested from human fetal and postnatal gut, no studies have as yet verified their functional viability upon in vivo transplantation. We sought to determine whether ENCCs harvested from human fetal bowel are capable of engraftment and functional integration within recipient intestine following in vivo transplantation into postnatal murine colon. Enteric neural crest cells selected and harvested from fetal human gut using the neurotrophin receptor p75(NTR) were lentivirally labeled with either GFP or calcium-sensitive GCaMP and transplanted into the hindgut of Rag2(-) /γc(-) /C5(-) -immunodeficient mice at postnatal day 21. Transplanted intestines were assessed immunohistochemically for engraftment and differentiation of donor cells. Functional viability and integration with host neuromusculature was assessed using calcium imaging. Transplanted human fetal gut-derived ENCC showed engraftment within the recipient postnatal colon in 8/15 mice (53.3%). At 4 weeks posttransplantation, donor cells had spread from the site of transplantation and extended projections over distances of 1.2 ± 0.6 mm (n = 5), and differentiated into enteric nervous system (ENS) appropriate neurons and glia. These cells formed branching networks located with the myenteric plexus. Calcium transients (change in intensity F/F0 = 1.25 ± 0.03; 15 cells) were recorded in transplanted cells upon stimulation of the recipient endogenous ENS demonstrating their viability and establishment of functional connections. © 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

  17. Qualitative changes in fetal trabecular meshwork fibers at the human iridocorneal angle

    OpenAIRE

    Hosaka, Fumio; Rodr?guez-V?zquez, Jose Francisco; Abe, Hiroshi; Murakami, Gen; Fujimiya, Mineko; Ohguro, Hiroshi

    2013-01-01

    We examined a series of changes that occur in the trabecular meshwork fibers of human eyes during fetal development at 12-30 weeks of gestation. At 12 and 15 weeks, the uveal meshwork was stained black with silver impregnation (indicating the predominance of collagen types III and IV) in the endomysium of the ciliary muscle. At 20 weeks, in combination with Schlemm's canal, a dense fibrous tissue mass corresponding to the trabecular meshwork anlage appeared and was colored black. The anlage w...

  18. Anatomical Characterization of Human Fetal Brain Development with Diffusion Tensor Magnetic Resonance Imaging

    Science.gov (United States)

    Huang, Hao; Xue, Rong; Zhang, Jiangyang; Ren, Tianbo; Richards, Linda J.; Yarowsky, Paul; Miller, Michael I.; Mori, Susumu

    2009-01-01

    The human brain is extraordinarily complex, and yet its origin is a simple tubular structure. Characterizing its anatomy at different stages of human fetal brain development not only aids in understanding this highly ordered process but also provides clues to detecting abnormalities caused by genetic or environmental factors. During the second trimester of human fetal development, neural structures in the brain undergo significant morphological changes. Diffusion tensor imaging (DTI), a novel method of magnetic resonance imaging, is capable of delineating anatomical components with high contrast and revealing structures at the microscopic level. In this study, high-resolution and high-signal-to-noise-ratio DTI data of fixed tissues of second-trimester human fetal brains were acquired and analyzed. DTI color maps and tractography revealed that important white matter tracts, such as the corpus callosum and uncinate and inferior longitudinal fasciculi, become apparent during this period. Three-dimensional reconstruction shows that major brain fissures appear while most of the cerebral surface remains smooth until the end of the second trimester. A dominant radial organization was identified at 15 gestational weeks, followed by both laminar and radial architectures in the cerebral wall throughout the remainder of the second trimester. Volumetric measurements of different structures indicate that the volumes of basal ganglia and ganglionic eminence increase along with that of the whole brain, while the ventricle size decreases in the later second trimester. The developing fetal brain DTI database presented can be used for education, as an anatomical research reference, and for data registration. PMID:19339620

  19. Covalent Cell Surface Functionalization of Human Fetal Osteoblasts for Tissue Engineering

    OpenAIRE

    Borcard, Françoise; Godinat, Aurélien; Städler, Davide; Comas Blanco, Horacio; Dumont, Anne-Laure; Chapuis-Bernasconi,Catherine; Scaletta, Corinne; Applegate, Lee Ann; Krauss Juillerat, Franziska; Gonzenbach, Urs T.; Gerber-Lemaire, Sandrine; Juillerat-Jeanneret, Lucienne

    2011-01-01

    The chemical functionalization of cell-surface proteins of human primary fetal bone cells with hydrophilic bioorthogonal intermediates was investigated. Toward this goal, chemical pathways were developed for click reaction-mediated coupling of alkyne derivatives with cellular azido-expressing proteins. The incorporation via a tetraethylene glycol linker of a dipeptide and a reporter biotin allowed the proof of concept for the introduction of cell-specific peptide ligands and to follow the rea...

  20. Development of the hyaloid, choroidal and retinal vasculatures in the fetal human eye.

    Science.gov (United States)

    Lutty, Gerard A; McLeod, D Scott

    2017-11-01

    The development of the ocular vasculatures is perfectly synchronized to provide the nutritional and oxygen requirements of the forming human eye. The fetal vasculature of vitreous, which includes the hyaloid vasculature, vasa hyaloidea propria, and tunica vasculosa lentis, initially develops around 4-6 weeks gestation (WG) by hemo-vasculogenesis (development of blood and blood vessels from a common progenitor, the hemangioblast). This transient fetal vasculature expands around 12 WG by angiogenesis (budding from primordial vessels) and remains until a retinal vasculature begins to form. The fetal vasculature then regresses by apoptosis with the assistance of macrophages/hyalocytes. The human choroidal vasculature also forms by a similar process and will supply nutrients and oxygen to outer retina. This lobular vasculature develops in a dense collagenous tissue juxtaposed with a cell constitutively producing vascular endothelial growth factor (VEGF), the retinal pigment epithelium. This epithelial/endothelial relationship is critical in maintaining the function of this vasculature throughout life and maintaining it's fenestrated state. The lobular capillary system (choriocapillaris) develops first by hemo-vasculogenesis and then the intermediate choroidal blood vessels form by angiogenesis, budding from the choriocapillaris. The human retinal vasculature is the last to develop. It develops by vasculogenesis, assembly of CXCR4(+)/CD39(+) angioblasts or vascular progenitors perhaps using Muller cell Notch1 or axonal neuropilinin-1 for guidance of semaphorin 3A-expressing angioblasts. The fovea never develops a retinal vasculature, which is probably due to the foveal avascular zone area of retina expressing high levels of antiangiogenic factors. From these studies, it is apparent that development of the mouse ocular vasculatures is not representative of the development of the human fetal, choroidal and retinal vasculatures. Copyright © 2017 Elsevier Ltd. All rights

  1. Cytokeratin expression in human fetal tongue and buccal mucosa

    Indian Academy of Sciences (India)

    Our earlier studies on CK expression in human oral tumours and pre-cancerous lesions have shown specific changes in CK expression. ... Cancer Research Institute, Parel, Mumbai 400 012, India; Tata Memorial Hospital, Tata Memorial Centre, Parel, Mumbai 400 012, India; Nowrosjee Wadia Maternity Hospital, Parel, ...

  2. Partial isolation and identification of hepatic stimulator substance mRNA extracted from human fetal liver

    Science.gov (United States)

    Yang, Xiao-Ming; Xie, Ling; Xing, Gui-Chun; Wu, Zu-Ze; He, Fu-Chu

    1998-01-01

    AIM: To partially isolate and identify hepatic stimulator substance mRNA from human fetal liver tissues. METHODS: The poly (A) mRNA was extracted from human fetal liver tissues of 4-5 month gestation, fractionated by size on sucrose gradient centrifugation, translated into protein from each fraction in vitro and then its products were tested for HSS activity. RESULTS: Twenty-two 500 μg total RNA was obtained from human fetal liver tissues and pooled. mRNA of 420 μg was yielded, processed by oligo (dT)-cellulose column chromatography, then was size-fractionated by ultracentrifution on a continuous sucrose density gradient (5%-25%), and separated into 18 fractions. Translated products of mRNA in fraction 8 and 9 could produce a two-fold increase in the incorporation of 3H-TdR into DNA of SMMC-7721 hepatoma cells and in a heat resistant and organ-specific way. CONCLUSION: The partially purified HSS mRNA was obtained and this would facilitate the cloning of HSS using expression vectors. PMID:11819247

  3. Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2.

    Science.gov (United States)

    Hiby, Susan E; Apps, Richard; Sharkey, Andrew M; Farrell, Lydia E; Gardner, Lucy; Mulder, Arend; Claas, Frans H; Walker, James J; Redman, Christopher W; Redman, Christopher C; Morgan, Linda; Tower, Clare; Regan, Lesley; Moore, Gudrun E; Carrington, Mary; Moffett, Ashley

    2010-11-01

    Many common disorders of pregnancy are attributed to insufficient invasion of the uterine lining by trophoblast, fetal cells that are the major cell type of the placenta. Interactions between fetal trophoblast and maternal uterine NK (uNK) cells--specifically interactions between HLA-C molecules expressed by the fetal trophoblast cells and killer Ig-like receptors (KIRs) on the maternal uNK cells--influence placentation in human pregnancy. Consistent with this, pregnancies are at increased risk of preeclampsia in mothers homozygous for KIR haplotype A (KIR AA). In this study, we have demonstrated that trophoblast expresses both paternally and maternally inherited HLA-C surface proteins and that maternal KIR AA frequencies are increased in affected pregnancies only when the fetus has more group 2 HLA-C genes (C2) than the mother. These data raise the possibility that there is a deleterious allogeneic effect stemming from paternal C2. We found that this effect also occurred in other pregnancy disorders (fetal growth restriction and recurrent miscarriage), indicating a role early in gestation for these receptor/ligand pairs in the pathogenesis of reproductive failure. Notably, pregnancy disorders were less frequent in mothers that possessed the telomeric end of the KIR B haplotype, which contains activating KIR2DS1. In addition, uNK cells expressed KIR2DS1, which bound specifically to C2+ trophoblast cells. These findings highlight the complexity and central importance of specific combinations of activating KIR and HLA-C in maternal-fetal immune interactions that determine reproductive success.

  4. Neuropeptide Y in the Adult and Fetal Human Pineal Gland

    OpenAIRE

    Morten Møller; Pansiri Phansuwan-Pujito; Corin Badiu

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passag...

  5. Neuropeptide Y in the adult and fetal human pineal gland.

    Science.gov (United States)

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  6. Neuropeptide Y in the Adult and Fetal Human Pineal Gland

    Directory of Open Access Journals (Sweden)

    Morten Møller

    2014-01-01

    Full Text Available Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  7. Differential undertaking response of a lower termite to congeneric and conspecific corpses.

    Science.gov (United States)

    Sun, Qian; Haynes, Kenneth F; Zhou, Xuguo

    2013-01-01

    Undertaking behaviour is an essential activity in social insects. Corpses are often recognized by a postmortem change in a chemical signature. Reticulitermes flavipes responded to corpses within minutes of death. This undertaking behaviour did not change with longer postmortem time (24 h); however, R. flavipes exhibited distinctively different behaviours toward dead termites from various origins. Corpses of the congeneric species, Reticulitermes virginicus, were buried onsite by workers with a large group of soldiers guarding the burial site due to the risk of interspecific competition; while dead conspecifics, regardless of colony origin, were pulled back into the holding chamber for nutrient recycling and hygienic purposes. The burial task associated with congeneric corpses was coupled with colony defence and involved ten times more termites than retrieval of conspecific corpses. Our findings suggest elicitation of undertaking behaviour depends on the origin of corpses which is associated with different types of risk.

  8. Human autologous serum as a substitute for fetal bovine serum in human Schwann cell culture.

    Directory of Open Access Journals (Sweden)

    Parisa Goodarzi

    2014-04-01

    Full Text Available Nowadays, cell -based and tissue engineered products have opened new horizons in treatment of incurable nervous system disorders. The number of studies on the role of Schwann cells (SC in treating nervous disorders is higher than other cell types. Different protocols have been suggested for isolation and expansion of SC which most of them have used multiple growth factors, mitogens and fetal bovine sera (FBS in culture medium. Because of potential hazards of animal-derived reagents, this study was designed to evaluate the effect of replacing FBS with human autologous serum (HAS on SC's yield and culture parameters. Samples from 10 peripheral nerve biopsies were retrieved and processed under aseptic condition. The isolated cells cultured in FBS (1st group or autologous serum (2nd group. After primary culture the cells were seeded at 10000 cell/cm2 in a 12 wells cell culture plate for each group. At 100% confluency, the cell culture parameters (count, viability, purity and culture duration of 2 groups were compared using paired t-test. The average donors' age was 35.80 (SD=13.35 and except for 1 sample the others cultured successfully. In first group, the averages of cell purity, viability and culture duration were 97% (SD=1.32, 97/33% (SD=1.22 and 11.77 (SD=2.58 days respectively. This parameters were 97.33% (SD=1.00, 97.55% (SD=1.33 and 10.33 days (SD=1.65 in second group. The difference of cell count, purity and viability were not significant between 2 groups (P>0.05. The cells of second group reached to 100% confluency in shorter period of time (P=0.03. The results of this study showed that autologous serum can be a good substitute for FBS in human SC culture. This can reduce the costs and improve the safety of cell product for clinical application.

  9. Differential undertaking response of a lower termite to congeneric and conspecific corpses

    OpenAIRE

    Qian Sun; Haynes, Kenneth F.; Xuguo Zhou

    2013-01-01

    Undertaking behaviour is an essential activity in social insects. Corpses are often recognized by a postmortem change in a chemical signature. Reticulitermes flavipes responded to corpses within minutes of death. This undertaking behaviour did not change with longer postmortem time (24?h); however, R. flavipes exhibited distinctively different behaviours toward dead termites from various origins. Corpses of the congeneric species, Reticulitermes virginicus, were buried onsite by workers with ...

  10. Potential of human fetal chorionic stem cells for the treatment of osteogenesis imperfecta.

    Science.gov (United States)

    Jones, Gemma N; Moschidou, Dafni; Abdulrazzak, Hassan; Kalirai, Bhalraj Singh; Vanleene, Maximilien; Osatis, Suchaya; Shefelbine, Sandra J; Horwood, Nicole J; Marenzana, Massimo; De Coppi, Paolo; Bassett, J H Duncan; Williams, Graham R; Fisk, Nicholas M; Guillot, Pascale V

    2014-02-01

    Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oim mice) improved the phenotype. However, the clinical use of fetal MSC is constrained by their limited number and low availability. In contrast, human fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions and isolated in high numbers from the placenta during ongoing pregnancy. Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. Exogenous cells preferentially homed to long bone epiphyses, expressed osteoblast genes, and produced collagen COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. In conclusion, the placenta is a practical source of stem cells for the treatment of OI.

  11. Production of embryonic and fetal-like red blood cells from human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Chan-Jung Chang

    Full Text Available We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications.

  12. Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans

    Science.gov (United States)

    Mold, Jeff E.; Venkatasubrahmanyam, Shivkumar; Burt, Trevor D.; Michaëlsson, Jakob; Rivera, Jose M.; Galkina, Sofiya A.; Weinberg, Kenneth; Stoddart, Cheryl A.; McCune, Joseph M.

    2012-01-01

    Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or “layering”) of unique hematopoietic stem cells (HSC) that give rise to distinct lymphocyte lineages at different stages of development. Here, we provide evidence of an analogous “layered” immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSC present at different stages of development. We also provide evidence that the fetal T cell lineage is biased towards immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth. PMID:21164017

  13. The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5-CED-12 in C. elegans.

    Science.gov (United States)

    Neukomm, Lukas Jakob; Nicot, Anne-Sophie; Kinchen, Jason Michael; Almendinger, Johann; Pinto, Sérgio Morgado; Zeng, Sheng; Doukoumetzidis, Kimon; Tronchère, Hélène; Payrastre, Bernard; Laporte, Jocelyn Franck; Hengartner, Michael Otmar

    2011-05-01

    Multicellular organisms use programmed cell death to eliminate unwanted or potentially harmful cells. Improper cell corpse removal can lead to autoimmune diseases. The development of interventional therapies that increase engulfment activity could represent an attractive approach to treat such diseases. Here, we describe mtm-1, the Caenorhabditis elegans homolog of human myotubularin 1, as a potential negative regulator of apoptotic cell corpse clearance. Loss of mtm-1 function leads to substantially reduced numbers of persistent cell corpses in engulfment mutants, which is a result of a restoration of engulfment function rather than of impaired or delayed programmed cell death. Epistatic analyses place mtm-1 upstream of the ternary GEF complex, which consists of ced-2, ced-5 and ced-12, and parallel to mig-2. Over-activation of engulfment results in the removal of viable cells that have been brought to the verge of death under limiting caspase activity. In addition, mtm-1 also promotes phagosome maturation in the hermaphrodite gonad, potentially through CED-1 receptor recycling. Finally, we show that the CED-12 PH domain can bind to PtdIns(3,5)P(2) (one target of MTM-1 phosphatase activity), suggesting that MTM-1 might regulate CED-12 recruitment to the plasma membrane.

  14. Maternal-fetal transport kinetics of manganese in perfused human placental lobule in vitro.

    Science.gov (United States)

    Nandakumaran, Moorkath; Al-Sannan, Baydaa; Al-Sarraf, Hameed; Al-Shammari, Majed

    2016-01-01

    There have been no detailed reports relating to maternal-fetal transport kinetics of manganese, an essential trace element in the human pregnancies, and hence we have attempted to study the transport kinetics of this trace element in the human placenta in vitro. Human placentae from normal uncomplicated pregnancies were collected postpartum. Manganese chloride solution (GFS Chem Inc., Columbus, OH), 10 times the physiological concentrations, along with antipyrine (Sigma Chem Co., St. Louis, MO) as reference marker were then injected as a single bolus (100 µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples collected from maternal and fetal circulations over a period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate and serial perfusate samples from fetal venous perfusate collected for a period of 30 min. Concentration of manganese in perfusate samples was assessed by atomic absorption spectrophotometry, while that of antipyrine was assessed by spectrophotometry. Transport kinetics of substances studied were computed using established permeation parameters. Differential transport rates of manganese and antipyrine in 12 perfusions differed significantly for 25.75, 90% efflux fractions (ANOVA test, p manganese averaged 54.9% of bolus dose in 12 perfusions, whereas that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of manganese and antipyrine was statistically significant (Student's t-test, p manganese compared to reference marker were significantly different (ANOVA test, p manganese in human placenta in vitro. Considering the restricted transfer of this essential trace element despite its small molecular weight, we hypothesize possibility of active transport of manganese across the human placental membrane. Further studies relating to manganese placental

  15. Cytokeratin (CK5, CK8, CK14) expression and presence of progenitor stem cells in human fetal thymuses.

    Science.gov (United States)

    Gupta, Richa; Gupta, Tulika; Kaur, Harjeet; Sehgal, Shobha; Aggarwal, Anjali; Kapoor, Kanchan; Sharma, Anshu; Sahni, Daisy; Singla, Suhalika

    2016-09-01

    The aim of the current study was to observe the expression of cytokeratins in human fetal thymuses. Specific cytokeratin markers in adult humans and mice have been well described but there has been little similar work on human fetuses. We also aimed to see whether progenitor stem cells that could be harvested to treat various immunodeficiency disorders are present in fetal thymic tissue. Thymuses obtained from 30 aborted human fetuses (12 to 31 weeks) were examined immunohistochemically to investigate changes in cytokeratin expression in the epithelial cells (TEC) at various gestational ages. Before 16 weeks of gestation, cortical (cTEC) and medullary (mTEC) TEC exhibited homogenous staining for cytokeratins CK8 and CK5. After 16 weeks there was differential staining, with cTEC positive for CK8 and mTEC for CK5 and CK14. Interestingly, both CK5 + CK8+ progenitor stem cells were present in the fetal thymic cortex at all gestational ages, with a relatively high number from 12 to 16 weeks. Cytokeratin expression in fetal thymuses was quite different from that in the adult thymus owing to the presence of undifferentiated progenitor stem cells in fetal thymic stroma along with differentiated TEC. The best time to harvest these progenitor stem cells from fetal thymic stroma in order to treat various immune deficiency disorders appears to be 12-16 weeks. Clin. Anat. 29:711-717, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Transplantation of human fetal tissue for neurodegenerative diseases: validation of a new protocol for microbiological analysis and bacterial decontamination.

    Science.gov (United States)

    Piroth, Tobias; Pauly, Marie-Christin; Schneider, Christian; Wittmer, Annette; Möllers, Sven; Döbrössy, Máté; Winkler, Christian; Nikkhah, Guido

    2014-01-01

    Restorative cell therapy concepts in neurodegenerative diseases are aimed at replacing lost neurons. Despite advances in research on pluripotent stem cells, fetal tissue from routine elective abortions is still regarded as the only safe cell source. Progenitor cells isolated from distinct first-trimester fetal CNS regions have already been used in clinical trials and will be used again in a new multicenter trial funded by the European Union (TRANSEURO). Bacterial contamination of human fetal tissue poses a potential risk of causing infections in the brain of the recipient. Thus, effective methods of microbial decontamination and validation of these methods are required prior to approval of a neurorestorative cell therapy trial. We have developed a protocol consisting of subsequent washing steps at different stages of tissue processing. Efficacy of microbial decontamination was assessed on rat embryonic tissue incubated with high concentrations of defined microbe solutions including representative bacterial and fungal species. Experimental microbial contamination was reduced by several log ranks. Subsequently, we have analyzed the spectrum of microbial contamination and the effect of subsequent washing steps on aborted human fetal tissue; 47.7% of the samples taken during human fetal tissue processing were positive for a microbial contamination, but after washing, no sample exhibited bacterial growth. Our data suggest that human fetal tissue for neural repair can carry microbes of various species, highlighting the need for decontamination procedures. The decontamination protocol described in this report has been shown to be effective as no microbes could be detected at the end of the procedure.

  17. Systemic human T cell developmental processes in humanized mice cotransplanted with human fetal thymus/liver tissue and hematopoietic stem cells.

    Science.gov (United States)

    Joo, Sung-Yeon; Chung, Yun Shin; Choi, Bongkum; Kim, Miyoung; Kim, Jong-Hwa; Jun, Tae-Gook; Chang, Jun; Sprent, Jonathan; Surh, Charles D; Joh, Jae-won; Kim, Sung Joo

    2012-12-15

    In many humanized mouse models, there are few T cells in the engrafted human cell, whereas the number of B cells is high. We attempted to overcome this limitation and investigate whether the entire process of human T cell development arose similarly to the process in humans, as previously reported. To produce an advanced humanized mice model, we transplanted human fetal liver/thymus tissue subrenally and injected human CD34(+) stem cells intravenously into NOD/SCID/IL2Rgamma null (NSG) mice. Humanized mice transplanted with fetal thymus/liver tissues and fetal liver-derived CD34(+) stem cells (FLT+FLCD34) showed higher levels of human cells and T cells than mice transplanted with fetal liver-derived CD34(+) stem cells only (FLCD34). In the transplanted thymus tissue of FLT+FLCD34 mice, thymus seeding progenitors (TSPs), early thymic progenitors (ETPs), pre-T cells, and all the other human T cell populations were identified. In the periphery, FLT+FLCD34 mice have high levels of CD45RA(+) T cells; conversely, FLCD34 mice have higher levels of CD45RO(+) T cells. The CD45RO(+) T cells of FLCD34 mice proliferated rapidly after stimulation and exhibited innate T cells properties, expressing PLZF (promyelocytic leukemia zinc finger protein). Human T cells educated by mouse MHC II in mice without a human thymus differ from normal human T cells. On the basis of these findings, numerous T cell-tropic human diseases could be explored in our humanized mice and molecular aspects of human T cell development could be also studied extensively.

  18. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

    2009-09-15

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  19. Factors influencing the flow rate through a surgical defect in human fetal membranes.

    Science.gov (United States)

    Devlieger, R; Gratacos, E; Ardon, H; Vanstraelen, S; Deprest, J

    2002-03-01

    In order to determine factors influencing the flow rate trough a created defect in human fetal membranes, an ex vivo set-up was used with fetal membranes collected from patients undergoing Caesarean section at term. The membranes were secured at the bottom of a plastic tube and traumatised with needles ranging from 14-26 Gauges (Ga), under a hydrostatic pressure of 10 to 20 cm H(2)O and an angle of 45 degrees or 90 degrees. The column was filled with amniotic fluid or Hartmann's solution. The duration of the puncture was 1 s or the time it takes to aspirate 10 ml through the needle. The flow rate through the defect in the fetal membranes and size of the defect were measured. The flow rate and defect size increased with increasing diameter of the needle. Increasing the pressure in the column resulted in a significant linear increase in the flow rate. Replacing the saline solution with amniotic fluid did not result in significant changes in the measured flow rates, except for the small needle size (24 Ga). Increasing the duration of the puncture did not result in increased flow rates, except for small needle size (24 Ga). These experiments suggest that needle diameter, angle of needle insertion, duration of the procedure, amniotic fluid pressure and composition could influence the incidence of amniotic fluid leakage following amniocentesis. Copyright 2002 John Wiley & Sons, Ltd.

  20. Effect of Thrombin on Human Amnion Mesenchymal Cells, Mouse Fetal Membranes, and Preterm Birth*

    Science.gov (United States)

    Mogami, Haruta; Keller, Patrick W.; Shi, Haolin; Word, R. Ann

    2014-01-01

    Here, we investigated the effects of thrombin on matrix metalloproteinases (MMPs) and prostaglandin (PG) synthesis in fetal membranes. Thrombin activity was increased in human amnion from preterm deliveries. Treatment of mesenchymal, but not epithelial, cells with thrombin resulted in increased MMP-1 and MMP-9 mRNA and enzymatic activity. Thrombin also increased COX2 mRNA and PGE2 in these cells. Protease-activated receptor-1 (PAR-1) was localized to amnion mesenchymal and decidual cells. PAR-1-specific inhibitors and activating peptides indicated that thrombin-induced up-regulation of MMP-9 was mediated via PAR-1. In contrast, thrombin-induced up-regulation of MMP-1 and COX-2 was mediated through Toll-like receptor-4, possibly through thrombin-induced release of soluble fetal fibronectin. In vivo, thrombin-injected pregnant mice delivered preterm. Mmp8, Mmp9, and Mmp13, and PGE2 content was increased significantly in fetal membranes from thrombin-injected animals. These results indicate that thrombin acts through multiple mechanisms to activate MMPs and PGE2 synthesis in amnion. PMID:24652285

  1. Transplantation Tolerance Induced in Humans at the Fetal or the Neonatal Stage

    Directory of Open Access Journals (Sweden)

    Jean-Louis Touraine

    2011-01-01

    Full Text Available Patients transplanted with HLA-mismatched stem cells from fetal livers develop transplantation tolerance to donor antigens. Engraftment needs no conditioning regimen prior to transplantation in neonates with severe combined immunodeficiency disease or in human fetal patients having not yet developed any immune maturity, especially T-cell differentiation. The chimeric patients have donor-derived T lymphocytes which progressively demonstrate positive interactions with other host cells. They also can be shown to be tolerant toward both host and donor antigens. The latter tolerance relies upon clonal deletion from the T-cell repertoire, and it results from the contact between thymocytes of donor origin and dendritic cells or macrophages also deriving from donor stem cells. The former tolerance does not imply clonal deletion of T-cells with host reactivity. Numerous T-cells recognizing the allogeneic, host-type antigens are identified in these patients, but these cells are anergized, following interaction with epithelial cells of the host thymus. Induction of transplantation tolerance at the fetal stage requires minimal engraftment only; in the future it will be possible to further amplify the clinical benefit, using additional cell transplants after birth.

  2. Transplantation tolerance induced in humans at the fetal or the neonatal stage.

    Science.gov (United States)

    Touraine, Jean-Louis; Sanhadji, Kamel

    2011-01-01

    Patients transplanted with HLA-mismatched stem cells from fetal livers develop transplantation tolerance to donor antigens. Engraftment needs no conditioning regimen prior to transplantation in neonates with severe combined immunodeficiency disease or in human fetal patients having not yet developed any immune maturity, especially T-cell differentiation. The chimeric patients have donor-derived T lymphocytes which progressively demonstrate positive interactions with other host cells. They also can be shown to be tolerant toward both host and donor antigens. The latter tolerance relies upon clonal deletion from the T-cell repertoire, and it results from the contact between thymocytes of donor origin and dendritic cells or macrophages also deriving from donor stem cells. The former tolerance does not imply clonal deletion of T-cells with host reactivity. Numerous T-cells recognizing the allogeneic, host-type antigens are identified in these patients, but these cells are anergized, following interaction with epithelial cells of the host thymus. Induction of transplantation tolerance at the fetal stage requires minimal engraftment only; in the future it will be possible to further amplify the clinical benefit, using additional cell transplants after birth.

  3. LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

    Science.gov (United States)

    Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

    2015-02-15

    Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development. Copyright © 2015 the American Physiological

  4. Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI.

    Science.gov (United States)

    Scott, Julia A; Habas, Piotr A; Kim, Kio; Rajagopalan, Vidya; Hamzelou, Kia S; Corbett-Detig, James M; Barkovich, A James; Glenn, Orit A; Studholme, Colin

    2011-08-01

    In the latter half of gestation (20-40 gestational weeks), human brain growth accelerates in conjunction with cortical folding and the deceleration of ventricular zone progenitor cell proliferation. These processes are reflected in changes in the volume of respective fetal tissue zones. Thus far, growth trajectories of the fetal tissue zones have been extracted primarily from 2D measurements on histological sections and magnetic resonance imaging (MRI). In this study, the volumes of major fetal zones-cortical plate (CP), subplate and intermediate zone (SP+IZ), germinal matrix (GMAT), deep gray nuclei (DG), and ventricles (VENT)--are calculated from automatic segmentation of motion-corrected, 3D reconstructed MRI. We analyzed 48 T2-weighted MRI scans from 39 normally developing fetuses in utero between 20.57 and 31.14 gestational weeks (GW). The supratentorial volume (STV) increased linearly at a rate of 15.22% per week. The SP+IZ (14.75% per week) and DG (15.56% per week) volumes increased at similar rates. The CP increased at a greater relative rate (18.00% per week), while the VENT (9.18% per week) changed more slowly. Therefore, CP increased as a fraction of STV and the VENT fraction declined. The total GMAT volume slightly increased then decreased after 25 GW. We did not detect volumetric sexual dimorphisms or total hemispheric volume asymmetries, which may emerge later in gestation. Further application of the automated fetal brain segmentation to later gestational ages will bridge the gap between volumetric studies of premature brain development and normal brain development in utero. Published by Elsevier Ltd.

  5. In utero fetal liver cell transplantation in the treatment of immunodeficient or thalassemic human fetuses.

    Science.gov (United States)

    Touraine, J L

    1993-07-01

    Following 18 years' experience in postnatal fetal liver transplantation (FLT), we have developed a new therapeutic method, namely the in utero transplantation of stem cells from the human fetal liver. This early transplant takes advantage of the immunological tolerance that exists in young fetal recipients. The four fetuses that we treated were 28, 26, 17 and 12 weeks of gestation. The first two patients had immunodeficiencies, the two others had thalassemia major. Donor cells were obtained from 7- to 12-week-old fetuses, with conditions approved by the National Committee for Bioethics. Donors and recipients were not matched. The fetal cells were infused through the umbilical vein of three patients and injected intraperitoneally into the other one, under ultrasonic visualization. The first patient, born in 1988, has evidence of engraftment and reconstitution of cell-mediated immunity: initially 10% then 26% of lymphocytes of donor origin (with distinct phenotype), T-cell responses to tetanus toxoid, CMV and candida antigens. This child, who had bare lymphocyte syndrome, has no clinical manifestation of the disease and lives normally at home. The second child was born in 1989; donor cell engraftment has been proven (Y-chromosome in this female patient) and immunological reconstitution is in progress, allowing a normal life at home. The third patient also has evidence of donor cell take (Y-chromosome in a female patient) and a partial effect on thalassemia has been documented (donor hemoglobin present in peripheral blood). In all three cases, no side-effect of any kind developed in the mother nor in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. 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 C; 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

    2015-04-01

    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. Tumor necrosis factor (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 (IECs) 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. 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. 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 IECs and directly modulates IEC innate immune gene expression.

  7. Developmental exposure to estrogen alters differentiation and epigenetic programming in a human fetal prostate xenograft model.

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    Camelia M Saffarini

    Full Text Available Prostate cancer is the most frequent non-cutaneous malignancy in men. There is strong evidence in rodents that neonatal estrogen exposure plays a role in the development of this disease. However, there is little information regarding the effects of estrogen in human fetal prostate tissue. This study explored early life estrogen exposure, with and without a secondary estrogen and testosterone treatment in a human fetal prostate xenograft model. Histopathological lesions, proliferation, and serum hormone levels were evaluated at 7, 30, 90, and 200-day time-points after xenografting. The expression of 40 key genes involved in prostatic glandular and stromal growth, cell-cycle progression, apoptosis, hormone receptors and tumor suppressors was evaluated using a custom PCR array. Epigenome-wide analysis of DNA methylation was performed on whole tissue, and laser capture-microdissection (LCM isolated epithelial and stromal compartments of 200-day prostate xenografts. Combined initial plus secondary estrogenic exposures had the most severe tissue changes as revealed by the presence of hyperplastic glands at day 200. Gene expression changes corresponded with the cellular events in the KEGG prostate cancer pathway, indicating that initial plus secondary exposure to estrogen altered the PI3K-Akt signaling pathway, ultimately resulting in apoptosis inhibition and an increase in cell cycle progression. DNA methylation revealed that differentially methylated CpG sites significantly predominate in the stromal compartment as a result of estrogen-treatment, thereby providing new targets for future investigation. By using human fetal prostate tissue and eliminating the need for species extrapolation, this study provides novel insights into the gene expression and epigenetic effects related to prostate carcinogenesis following early life estrogen exposure.

  8. Apoptosis of human fetal pancreatic islets during short-term culture

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    Đorđević P.B.

    2009-01-01

    Full Text Available We investigated the influence of short-term culture in vitro on the appearance of apoptosis of human fetal pancreatic islets (HFIs and its effect on the mass and insulin-secretory capacity (ISC of β-cells. It was found that apoptosis was present from the end of the culture period, increasing as a function of time and leading to decrease of β-cell mass. At the same time, ISC decreased. The decrease of β-cell mass and ISC may influence significantly the clinical outcome of HFIs transplantation in type 1 diabetic patients.

  9. Hepatocytic Differentiation Potential of Human Fetal Liver Mesenchymal Stem Cells: In Vitro and In Vivo Evaluation

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    Hoda El-Kehdy

    2016-01-01

    Full Text Available In line with the search of effective stem cell population that would progress liver cell therapy and because the rate and differentiation potential of mesenchymal stem cells (MSC decreases with age, the current study investigates the hepatogenic differentiation potential of human fetal liver MSCs (FL-MSCs. After isolation from 11-12 gestational weeks’ human fetal livers, FL-MSCs were shown to express characteristic markers such as CD73, CD90, and CD146 and to display adipocytic and osteoblastic differentiation potential. Thereafter, we explored their hepatocytic differentiation potential using the hepatogenic protocol applied for adult human liver mesenchymal cells. FL-MSCs differentiated in this way displayed significant features of hepatocyte-like cells as demonstrated in vitro by the upregulated expression of specific hepatocytic markers and the induction of metabolic functions including CYP3A4 activity, indocyanine green uptake/release, and glucose 6-phosphatase activity. Following transplantation, naive and differentiated FL-MSC were engrafted into the hepatic parenchyma of newborn immunodeficient mice and differentiated in situ. Hence, FL-MSCs appeared to be interesting candidates to investigate the liver development at the mesenchymal compartment level. Standardization of their isolation, expansion, and differentiation may also support their use for liver cell-based therapy development.

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

    Science.gov (United States)

    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.

  11. Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans.

    Science.gov (United States)

    Lombardo, Michael V; Ashwin, Emma; Auyeung, Bonnie; Chakrabarti, Bhismadev; Lai, Meng-Chuan; Taylor, Kevin; Hackett, Gerald; Bullmore, Edward T; Baron-Cohen, Simon

    2012-11-15

    Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fetal development influences later neural sensitivity to valenced facial cues and approach-avoidance behavioral tendencies. With functional magnetic resonance imaging we scanned 25 8-11-year-old children while viewing happy, fear, neutral, or scrambled faces. Fetal testosterone (FT) was measured via amniotic fluid sampled between 13 and 20 weeks gestation. Behavioral approach-avoidance tendencies were measured via parental report on the Sensitivity to Punishment and Sensitivity to Rewards questionnaire. Increasing FT predicted enhanced selectivity for positive compared with negatively valenced facial cues in reward-related regions such as caudate, putamen, and nucleus accumbens but not the amygdala. Statistical mediation analyses showed that increasing FT predicts increased behavioral approach tendencies by biasing caudate, putamen, and nucleus accumbens but not amygdala to be more responsive to positive compared with negatively valenced cues. In contrast, FT was not predictive of behavioral avoidance tendencies, either through direct or neurally mediated paths. This work suggests that testosterone in humans acts as a fetal programming mechanism on the reward system and influences behavioral approach tendencies later in life. As a mechanism influencing atypical development, FT might be important across a range of neuropsychiatric conditions that asymmetrically affect the sexes, the reward system, emotion processing, and approach behavior. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Co-transplantation of fetal bone tissue facilitates the development and reconstitution in human B cells in humanized NOD/SCID/IL-2Rγnull (NSG) mice.

    Science.gov (United States)

    Kim, Miyoung; Choi, Bongkum; Kim, So Yong; Yang, Ji-Hyuk; Roh, Cheong Rae; Lee, Ki-Young; Kim, Sung Joo

    2011-08-01

    In terms of the function and reconstitution efficacy of human immune cells, co-transplantation of human fetal tissues, such as thymus and liver, with CD34(+) hematopoietic stem cells (HSCs) has potential advantages in the generation of humanized mice. To examine the effects of bone tissues in the reconstitution of human immune cells, particularly in B cells, we generated a new humanized mice co-transplanted with human fetal thymus (hFT)/fetal bone (hFB) tissues and human fetal liver-derived CD34(+) cells. Humanized mice exhibited effective reconstitution of human immune cells earlier compared to control humanized mice. In terms of quantity, the number of immune cells, such as human T, B, and monocyte/macrophages was significantly increased. Furthermore, significant increase of B cell progenitors and immature/naïve B cells could be detected in the bone marrow and spleen of humanized mice. Our results demonstrate that co-transplantation of hFB tissue may facilitate the reconstitution of human B and T cells, and therefore the humanized model may be used to develop therapeutic human antibodies for clinical use.

  13. Radial and tangential neuronal migration pathways in the human fetal brain: anatomically distinct patterns of diffusion MRI coherence

    Science.gov (United States)

    Kolasinski, James; Takahashi, Emi; Stevens, Allison A.; Benner, Thomas; Fischl, Bruce; Zöllei, Lilla; Grant, P. Ellen

    2014-01-01

    Corticogenesis is underpinned by a complex process of subcortical neuroproliferation, followed by highly orchestrated cellular migration. A greater appreciation of the processes involved in human fetal corticogenesis is vital to gaining an understanding of how developmental disturbances originating in gestation could establish a variety of complex neuropathology manifesting in childhood, or even in adult life. Magnetic resonance imaging modalities offer a unique insight into anatomical structure, and increasingly infer information regarding underlying microstructure in the human brain. In this study we applied a combination of high-resolution structural and diffusion-weighted magnetic resonance imaging to a unique cohort of three post-mortem fetal brain specimens, aged between 19 and 22 post-conceptual weeks. Specifically, we sought to assess patterns of diffusion coherence associated with subcortical neuroproliferative structures: the pallial ventricular/subventricular zone and subpallial ganglionic eminence. Two distinct three-dimensional patterns of diffusion coherence were evident: a clear radial pattern originating in ventricular/subventricular zone, and a tangentio-radial patterns originating in ganglionic eminence. These patterns appeared to regress in a caudo-rostral and lateral-ventral to medial-dorsal direction across the short period of fetal development under study. Our findings demonstrate for the first time distinct patterns of diffusion coherence associated with known anatomical proliferative structures. The radial pattern associated with dorsopallial ventricular/subventricular zone and the tangentio-radial pattern associated with subpallial ganglionic eminence are consistent with reports of radial-glial mediated neuronal migration pathways identified during human corticogenesis, supported by our prior studies of comparative fetal diffusion MRI and histology. The ability to assess such pathways in the fetal brain using MR imaging offers a unique

  14. Transplantation of human fetal pancreatic progenitor cells ameliorates renal injury in streptozotocin-induced diabetic nephropathy.

    Science.gov (United States)

    Jiang, Yongwei; Zhang, Wenjian; Xu, Shiqing; Lin, Hua; Sui, Weiguo; Liu, Honglin; Peng, Liang; Fang, Qing; Chen, Li; Lou, Jinning

    2017-06-27

    Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Pancreas or islet transplantation has been reported to prevent the development of DN lesions and ameliorate or reverse existing glomerular lesions in animal models. Shortage of pancreas donor is a severe problem. Islets derived from stem cells may offer a potential solution to this problem. To evaluate the effect of stem cell-derived islet transplantation on DN in a rat model of streptozotocin-induced DM. Pancreatic progenitor cells were isolated from aborted fetuses of 8 weeks of gestation. And islets were prepared by suspension culture after a differentiation of progenitor cells in medium containing glucagon-like peptide-1 (Glp-1) and nicotinamide. Then islets were transplanted into the liver of diabetic rats via portal vein. Blood glucose, urinary volume, 24 h urinary protein and urinary albumin were measured once biweekly for 16 weeks. Graft survival was evaluated by monitoring human C-peptide level in rat sera and by immunohistochemical staining for human mitochondrial antigen and human C-peptide in liver tissue. The effect of progenitor-derived islets on filtration membrane was examined by electron microscopy and real-time polymerase chain reaction (PCR). Immunohistochemical staining, real-time PCR and western blot were employed for detecting fibronectin, protein kinase C beta (PKCβ), protein kinase A (PKA), inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD). Islet-like clusters derived from 8th gestational-week human fetal pancreatic progenitors survived in rat liver. And elevated serum level of human C-peptide was detected. Blood glucose, 24 h urinary protein and urinary albumin were lower in progenitor cell group than those in DN or insulin treatment group. Glomerular basement membrane thickness and fibronectin accumulation decreased significantly while podocytes improved morphologically in progenitor cell group. Furthermore, receptor of advanced glycation

  15. Human fetal adrenal transplant: a possible role in relieving intractable pain in advanced rheumatoid arthritis.

    Science.gov (United States)

    Bhattacharya, N; Chhetri, M K; Mukherjee, K L; Das, S Prasad; Mukherjee, A; Bhattacharya, M; Bhattacharya, S

    2002-01-01

    The art of transplant surgery has gone a long way in establishing itself as an important discipline in medicine with the support of molecular biology, immunology, biochemistry, etc., as the ultimate treatment for the restoration of function of a failing organ. With the progressive increase in the life expectancy of human beings, there is an increasing discrepancy in the demand and supply of organ grafts. A less efficient alternative could be synthetic or mechanical grafts. Nucleated cell therapy, that is, cellular transplant, is a promising new area of study with its proven efficacy in neuro-degenerative disorders, hematopoietic disorders, diabetes and trauma-induced tissue loss, to name a few. Human fetal cell/tissue with its intrinsic hypo-antigenic advantage (up to 20 weeks of study), could be an interesting area of cellular/tissue transplant. Our research group has earlier reported on the safe use of umbilical cord whole blood and the successful transplant of a human fetal lung, heart, pancreas, liver, thymus, in an artificially prepared vascular subcutaneous axillary fold in which there was no feature of hyper-acute, acute or chronic rejection of the graft in HLA- and sex-randomized adult recipients, without concomitant immunosuppressives or radiation of the host to potentiate the survival of the fetal graft (within 20 weeks of gestation) within the lowest observation period of one month. The present study was aimed at examining the role of developing fetal adrenal transplants for patients with rheumatoid arthritis and severe pain due to involvement of inflammatory and neuropathic components. Ten cases were enrolled in the present study after thorough informed consent and approval by the ethical committee of the institute. The age of the patients varied from 50 to 76 years and the group was comprised of three males and seven females. The age of the adrenal grafts varied from 16 to 20 weeks and these were collected from mothers admitted for hysterotomy and

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

    Science.gov (United States)

    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.

  17. Microarray Analysis of Differential Gene Expression Profile Between Human Fetal and Adult Heart.

    Science.gov (United States)

    Geng, Zhimin; Wang, Jue; Pan, Lulu; Li, Ming; Zhang, Jitai; Cai, Xueli; Chu, Maoping

    2017-04-01

    Although many changes have been discovered during heart maturation, the genetic mechanisms involved in the changes between immature and mature myocardium have only been partially elucidated. Here, gene expression profile changed between the human fetal and adult heart was characterized. A human microarray was applied to define the gene expression signatures of the fetal (13-17 weeks of gestation, n = 4) and adult hearts (30-40 years old, n = 4). Gene ontology analyses, pathway analyses, gene set enrichment analyses, and signal transduction network were performed to predict the function of the differentially expressed genes. Ten mRNAs were confirmed by quantificational real-time polymerase chain reaction. 5547 mRNAs were found to be significantly differentially expressed. "Cell cycle" was the most enriched pathway in the down-regulated genes. EFGR, IGF1R, and ITGB1 play a central role in the regulation of heart development. EGFR, IGF1R, and FGFR2 were the core genes regulating cardiac cell proliferation. The quantificational real-time polymerase chain reaction results were concordant with the microarray data. Our data identified the transcriptional regulation of heart development in the second trimester and the potential regulators that play a prominent role in the regulation of heart development and cardiac cells proliferation.

  18. Taurine enhances the growth of neural precursors derived from fetal human brain and promotes neuronal specification.

    Science.gov (United States)

    Hernández-Benítez, Reyna; Vangipuram, Sharada D; Ramos-Mandujano, Gerardo; Lyman, William D; Pasantes-Morales, Herminia

    2013-01-01

    Taurine is present at high concentrations in the fetal brain and is required for optimal brain development. Recent studies have reported that taurine causes increased proliferation of neural stem/progenitor neural cells (neural precursor cells, NPCs) obtained from embryonic and adult rodent brain. The present study is the first to show that taurine markedly increases cell numbers in cultures and neuronal generation from human NPCs (hNPCs). hNPCs obtained from 3 fetal brains (14-15 weeks of gestation) were cultured and expanded as neurospheres, which contained 76.3% nestin-positive cells. Taurine (5-20 mM) increased the number of hNPCs in culture, with maximal effect found at 10 mM and 4 days of culture. The taurine-induced increase ranged from 57 to 188% in the 3 brains examined. Taurine significantly enhanced the percentage of neurons formed from hNPCs under differentiating conditions, with increases ranging from 172 to 480% over controls without taurine. Taurine also increased the cell number and neuronal generation in cultures of the immortalized human cell line ReNcell VM. These results suggest that taurine has a positive influence on hNPC growth and neuronal formation. Copyright © 2013 S. Karger AG, Basel.

  19. Curious afterlives: the enduring appeal of the criminal corpse

    Science.gov (United States)

    Tarlow, Sarah

    2016-01-01

    Abstract Not only did the criminal corpse have actual medicinal and magical power for Europeans, it also had social and cultural meaning as an object, a curio or secular relic. This paper considers the appeal of notorious bodies. From books bound in the skin of a criminal, to preserved and exhibited heads, from fragments of the hangman’s rope to the exhibition of the skeleton, the story of the afterlife of criminal bodies and the material culture most immediately associated with them begins with the collection and exchange of bodies and moves into contemporary preoccupations with authenticity. This paper considers the bodies of three notorious criminals of the eighteenth century: Eugene Aram, William Burke and William Corder. It ends with some reflections on the glamour of the authentic body of a notorious or celebrated individual – using the response to the discovery of the body of Richard III as an example. PMID:27366110

  20. Curious afterlives: the enduring appeal of the criminal corpse.

    Science.gov (United States)

    Tarlow, Sarah

    2016-07-02

    Not only did the criminal corpse have actual medicinal and magical power for Europeans, it also had social and cultural meaning as an object, a curio or secular relic. This paper considers the appeal of notorious bodies. From books bound in the skin of a criminal, to preserved and exhibited heads, from fragments of the hangman's rope to the exhibition of the skeleton, the story of the afterlife of criminal bodies and the material culture most immediately associated with them begins with the collection and exchange of bodies and moves into contemporary preoccupations with authenticity. This paper considers the bodies of three notorious criminals of the eighteenth century: Eugene Aram, William Burke and William Corder. It ends with some reflections on the glamour of the authentic body of a notorious or celebrated individual - using the response to the discovery of the body of Richard III as an example.

  1. Ethanol alters cell fate of fetal human brain-derived stem and progenitor cells.

    Science.gov (United States)

    Vangipuram, Sharada D; Lyman, William D

    2010-09-01

    Prenatal ethanol (ETOH) exposure can lead to fetal alcohol spectrum disorder (FASD). We previously showed that ETOH alters cell adhesion molecule gene expression and increases neurosphere size in fetal brain-derived neural stem cells (NSC). Here, our aim was to determine the effect of ETOH on the cell fate of NSC, premature glial-committed precursor cells (GCP), and premature neuron-committed progenitor cells (NCP). NSC, GCP, and NCP were isolated from normal second-trimester fetal human brains (n = 3) by positive selection using magnetic microbeads labeled with antibodies to CD133 (NSC), A2B5 (GCP), or PSA-NCAM (NCP). As a result of the small percentage in each brain, NSC were cultured in mitogenic media for 72 hours to produce neurospheres. The neurospheres from NSC and primary isolates of GCP and NCP were used for all experiments. Equal numbers of the 3 cell types were treated either with mitogenic media or with differentiating media, each containing 0 or 100 mM ETOH, for 120 hours. Expression of Map2a, GFAP, and O4 was determined by immunoflourescence microscopy and western blot analysis. Fluorescence intensities were quantified using Metamorph software by Molecular Devices, and the bands of western blots were quantified using densitometry. ETOH in mitogenic media promoted formation of neurospheres by NSC, GCP, and NCP. Under control conditions, GCP attached and differentiated, NSC and NCP formed neurospheres that were significantly smaller in size than those in ETOH. Under differentiating conditions, Map2a expression increased significantly in NSC and GCP and reduced significantly in NCP, and GFAP expression reduced significantly in GCP and NCP, and Gal-C expression reduced significantly in all 3 cell types in the presence of ETOH compared to controls. This study shows that ETOH alters the cell fate of neuronal stem and progenitor cells. These alterations could contribute to the mechanism for the abnormal brain development in FASD.

  2. Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.

    Science.gov (United States)

    Blodgett, David M; Nowosielska, Anetta; Afik, Shaked; Pechhold, Susanne; Cura, Anthony J; Kennedy, Norman J; Kim, Soyoung; Kucukural, Alper; Davis, Roger J; Kent, Sally C; Greiner, Dale L; Garber, Manuel G; Harlan, David M; diIorio, Philip

    2015-09-01

    Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic α- and β-cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase β-cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify α-, β-, and δ-cells from human fetal and adult pancreata by intracellular staining for the cell-specific hormone content, sorting the subpopulations by flow cytometry, and, using next-generation RNA sequencing, we report the detailed transcriptomes of fetal and adult α- and β-cells. We observed that human islet composition was not influenced by age, sex, or BMI, and transcripts for inflammatory gene products were noted in fetal β-cells. In addition, within highly purified adult glucagon-expressing α-cells, we observed surprisingly high insulin mRNA expression, but not insulin protein expression. This transcriptome analysis from highly purified islet α- and β-cell subsets from fetal and adult pancreata offers clear implications for strategies that seek to increase insulin expression in type 1 and type 2 diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  3. Expression pattern of RAGE and IGF-1 in the human fetal ovary and ovarian serous carcinoma.

    Science.gov (United States)

    Poljicanin, Ana; Filipovic, Natalija; Vukusic Pusic, Tanja; Soljic, Violeta; Caric, Ana; Saraga-Babic, Mirna; Vukojevic, Katarina

    2015-01-01

    The expression pattern of RAGE and IGF-1 proteins in different ovarian cell lineages was histologically analyzed in six fetal, nine adult human ovaries, and nine serous ovarian carcinomas (OSC) using immunohistochemical methods. Mild expression of IGF-1 in ovarian surface epithelium (Ose) and oocytes in the 15-week human ovaries increased to moderate or strong in the stromal cells, oocytes and follicular cells in week 22. Occasional mild RAGE expression was observed in Ose during week 15, while strong expression characterized primordial follicles in week 22. In the reproductive human ovary, IGF-1 was mildly to moderately expressed in all ovarian cell lineages except in theca cells of the tertiary follicle where IGF-1 was negative. RAGE was strongly positive in the granulosa cells and some theca cells of the tertiary follicle, while negative to mildly positive in all cells of the secondary follicle. In the postmenopausal human ovary IGF-1 and RAGE were mildly expressed in Ose and stroma. In OSC, cells were strongly positive to IGF-1 and RAGE, except for some negative stromal cells. Different levels of IGF-1 and RAGE co-expression characterized fetal ovarian cells during development. In reproductive ovaries, IGF-1 and RAGE were co-localized in the granulosa and theca interna cells of tertiary follicles, while in postmenopausal ovaries and OSC, IGF-1 and RAGE were co-localized in Ose and OSC cells respectively. Our results indicate that intracellular levels of IGF-1 and RAGE protein might regulate the final destiny of the ovarian cell populations prior and during folliculogenesis, possibly controlling the metastatic potential of OSC as well. Copyright © 2015. Published by Elsevier GmbH.

  4. Comparative Proteomic Profile of the Human Placenta in Normal and Fetal Growth Restriction Subjects

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    Zhijing Miao

    2014-11-01

    Full Text Available Background: Fetal growth restriction (FGR is the main cause of intrauterine fetal death and the second leading cause of death in the neonatal period. A large body of evidence suggests that FGR may be associated with the placenta, although its etiology and pathogenesis remain to be fully elucidated. Methods and Results: To better understand the molecular mechanisms underlying the pathological development of the placenta in FGR, we used tandem mass tags (TMTs to construct a large-scale comparative proteomic profile of human placentas from normal and FGR pregnancies. A total of 1,198 kinds of proteins were identified in the control and FGR placentas, of which 95 were differentially expressed between two groups. Ingenuity Pathway Analysis (IPA was used to organize these differentially expressed proteins into networks of interacting proteins and to identify the modules of functionally related proteins. Western blotting was used to verify the expression patterns of several randomly selected proteins. Conclusion: The placentas of women with FGR displayed significant proteome differences compared with normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of FGR. Further studies and validations are required to elucidate the exact roles of these proteins in FGR pathogenesis.

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

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    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.)

  6. 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.

  7. Endothelial progenitor cells from human fetal aorta cure diabetic foot in a rat model.

    Science.gov (United States)

    Zhao, Wan-Ni; Xu, Shi-Qing; Liang, Jian-Feng; Peng, Liang; Liu, Hong-Lin; Wang, Zai; Fang, Qing; Wang, Meng; Yin, Wei-Qin; Zhang, Wen-Jian; Lou, Jin-Ning

    2016-12-01

    Recent evidence has suggested that circulating endothelial progenitor cells (EPCs) can repair the arterial endothelium during vascular injury. However, a reliable source of human EPCs is needed for therapeutic applications. In this study, we isolated human fetal aorta (HFA)-derived EPCs and analyzed the capacity of EPCs to differentiate into endothelial cells. In addition, because microvascular dysfunction is considered to be the major cause of diabetic foot (DF), we investigated whether transplantation of HFA-derived EPCs could treat DF in a rat model. EPCs were isolated from clinically aborted fetal aorta. RT-PCR, fluorescence-activated cell sorting, immunofluorescence, and an enzyme-linked immunosorbent assay were used to examine the expressions of CD133, CD34, CD31, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), von Willebrand Factor (vWF), and Endothelial Leukocyte Adhesion Molecule-1 (ELAM-1). Morphology and Dil-uptake were used to assess function of the EPCs. We then established a DF model by injecting microcarriers into the hind-limb arteries of Goto-Kakizaki rats and then transplanting the cultured EPCs into the ischemic hind limbs. Thermal infrared imaging, oxygen saturation apparatus, and laser Doppler perfusion imaging were used to monitor the progression of the disease. Immunohistochemistry was performed to examine the microvascular tissue formed by HFA-derived EPCs. We found that CD133, CD34, and VEGFR2 were expressed by HFA-derived EPCs. After VEGF induction, CD133 expression was significantly decreased, but expression levels of vWF and ELAM-1 were markedly increased. Furthermore, tube formation and Dil-uptake were improved after VEGF induction. These observations suggest that EPCs could differentiate into endothelial cells. In the DF model, temperature, blood flow, and oxygen saturation were reduced but recovered to a nearly normal level following injection of the EPCs in the hind limb. Ischemic symptoms also improved. Injected EPCs were

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

    Science.gov (United States)

    Zamudio, Stacy; Torricos, Tatiana; Fik, Ewa; Oyala, Maria; Echalar, Lourdes; Pullockaran, Janet; Tutino, Emily; Martin, Brittney; Belliappa, Sonia; Balanza, Elfride; Illsley, Nicholas P

    2010-01-01

    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 placentally

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Maternal and fetal stress are associated with impaired lactogenesis in humans.

    Science.gov (United States)

    Dewey, K G

    2001-11-01

    Studies in animals indicate that various types of stressful stimuli can depress lactation, but there is much less information in humans. Experimental studies in breastfeeding women have shown that acute physical and mental stress can impair the milk ejection reflex by reducing the release of oxytocin during a feed. If this occurs repeatedly, it could reduce milk production by preventing full emptying of the breast at each feed. Prospective observational studies indicate that both maternal and fetal stress during labor and delivery (e.g., urgent Cesarean sections or long duration of labor in vaginal deliveries) are associated with delayed onset of lactation. The effects of chronic emotional stress on lactation are not known. Mothers who experience high levels of stress during and after childbirth should receive additional lactation guidance during the first week or two postpartum.

  11. Radiolabeling and in vivo imaging of transplanted renal lineages differentiated from human embryonic stem cells in fetal rhesus monkeys.

    Science.gov (United States)

    Tarantal, Alice F; Lee, C Chang I; Batchelder, Cynthia A; Christensen, Jared E; Prater, Daniel; Cherry, Simon R

    2012-04-01

    The goals of this study were to optimize radiolabeling of renal lineages differentiated from human embryonic stem (hES) cells and use noninvasive imaging (positron emission tomography (PET) and bioluminescence imaging (BLI)) to detect the cells in fetal monkeys post-transplant. hES cells expressing firefly luciferase (5 × 10(6)) were radiolabeled with the optimized concentration of 10 μCi/ml (64)Cu-PTSM then transplanted under ultrasound guidance into early second trimester fetal monkey kidneys. Fetuses were imaged in utero with PET and tissues collected for analysis 3 days post-transplant. Fetal kidneys were imaged ex vivo (PET and BLI) post-tissue harvest, and serial kidney sections were assessed by PCR for human-specific DNA sequences, fluorescent in situ hybridization (FISH) for human-specific centromere probes, and immunohistochemistry (IHC) to assess engrafted cells. Transplanted cells were readily imaged in vivo and identified at the site of injection; tissue analyses confirmed the imaging findings. Using a semi-quantitative method, one in approximately 650 cells in the kidney was shown to be of human origin by PCR and FISH. These studies suggest that hES cells differentiated toward renal lineages can be effectively radiolabeled, transplanted into fetal monkey kidneys under ultrasound guidance, monitored with PET post-transplant, and identified by PET, BLI, PCR, FISH, and IHC post-tissue harvest.

  12. 1ST-TRIMESTER MATERNAL SERUM HUMAN CHORIONIC-GONADOTROPIN AS A MARKER FOR FETAL CHROMOSOMAL DISORDERS

    NARCIS (Netherlands)

    VANLITH, JMM

    The Dutch Working Party on Prenatal Diagnosis has initiated a study on the possibilities of first-trimester screening for fetal chromosomal disorders. We report on maternal serum human chorionic gonadotrophin (MS-hCG) measurements in 1348 pregnancies with a chromosomally normal fetus and 53

  13. Bleomycin induces upregulation of lysyl oxidase in cultured human fetal lung fibroblasts

    Science.gov (United States)

    Chen, Li-jun; Li, Wan-de; Li, Shi-feng; Su, Xing-wen; Lin, Guang-yun; Huang, Yi-jun; Yan, Guang-mei

    2010-01-01

    Aim: To investigate the mechanism of bleomycin (BLM)-induced pulmonary fibrosis. Methods: Cultured human fetal lung fibroblast (HLF) cells were exposed to bleomycin (BLM) at 0–30 μg/mL for 24 h. Western blot analysis was used to detect lysyl oxidase (LO) protein expression. Real-time RT-PCR was used to detect LO mRNA level. LO catalytic activity was measured using diaminopentane as a substrate and Amplex red as a hydrogen peroxide probe. Copper (Cu) concentration was detected by flame atomic absorption spectrophotometry. Results: Exposure of HLF cells to BLM at 10 μg/mL and 30 μg/mL increased LO catalytic activity to 130% and 158% of the control in the conditioned media. The expression of LO mRNA was increased to 5.5-fold of the control in HLF cells exposure to BLM at 3 μg/mL. BLM at 3 μg/mL also increased the expression of 46 kDa preproLO, 50 kDa proLO and 32 kDa mature LO to 219%, 130%, and 135% of the control, respectively. The Cu concentrations in conditioned media of cultured HLF cells exposed to BLM (10 and 30 μg/mL) were increased significantly to 1.48 and 2.46-fold of the control, respectively. Conclusion: Bleomycin induces upregulation of LO in cultured human fetal lung fibroblasts, which may be the mechanism of bleomycin-induced pulmonary fibrosis. PMID:20418892

  14. Transplantation of human fetal-derived neural stem cells improves cognitive function following cranial irradiation.

    Science.gov (United States)

    Acharya, Munjal M; Christie, Lori-Ann; Hazel, Thomas G; Johe, Karl K; Limoli, Charles L

    2014-01-01

    Treatment of central nervous system (CNS) malignancies typically involves radiotherapy to forestall tumor growth and recurrence following surgical resection. Despite the many benefits of cranial radiotherapy, survivors often suffer from a wide range of debilitating and progressive cognitive deficits. Thus, while patients afflicted with primary and secondary malignancies of the CNS now experience longer local regional control and progression-free survival, there remains no clinical recourse for the unintended neurocognitive sequelae associated with their cancer treatments. Multiple mechanisms contribute to disrupted cognition following irradiation, including the depletion of radiosensitive populations of stem and progenitor cells in the hippocampus. We have explored the potential of using intrahippocampal transplantation of human stem cells to ameliorate radiation-induced cognitive dysfunction. Past studies demonstrated the capability of cranially transplanted human embryonic (hESCs) and neural (hNSCs) stem cells to functionally restore cognition in rats 1 and 4 months after cranial irradiation. The present study employed an FDA-approved fetal-derived hNSC line capable of large scale-up under good manufacturing practice (GMP). Animals receiving cranial transplantation of these cells 1 month following irradiation showed improved hippocampal spatial memory and contextual fear conditioning performance compared to irradiated, sham surgery controls. Significant newly born (doublecortin positive) neurons and a smaller fraction of glial subtypes were observed within and nearby the transplantation core. Engrafted cells migrated and differentiated into neuronal and glial subtypes throughout the CA1 and CA3 subfields of the host hippocampus. These studies expand our prior findings to demonstrate that transplantation of fetal-derived hNSCs improves cognitive deficits in irradiated animals, as assessed by two separate cognitive tasks.

  15. Human fetal osteoblast behavior on zirconia dental implants and zirconia disks with microstructured surfaces. An experimental in vitro study.

    Science.gov (United States)

    Delgado-Ruíz, Rafael Arcesio; Gomez Moreno, Gerardo; Aguilar-Salvatierra, Antonio; Markovic, Aleksa; Mate-Sánchez, Jose Eduardo; Calvo-Guirado, José Luis

    2016-11-01

    To measure the lateral surface area of microgrooved zirconia implants, to evaluate the cell geometry and cell density of human fetal osteoblasts seeded on zirconia microgrooved implants, to describe the surface roughness and chemistry, and to evaluate the activity of human fetal osteoblasts seeded on zirconia microgrooved disks. This experimental in vitro study used 62 zirconia implants and 130 zirconia disks. Two experimental groups were created for the implants: 31 non-microgrooved implants (Control) and 31 microgrooved implants (Test); two experimental groups were created for the disks: 65 non-microgrooved disks (Control) and 65 microgrooved disks (Test). The following evaluations of the implants were made: lateral surface area (LSA), cell morphology, and density of human fetal osteoblasts seeded on implant surfaces. On the disks, surface parameters (roughness and chemistry) and cell activity (alkaline phosphatase - ALP and alizarin red - ALZ) were evaluated at 7 and 15 days. LSA was lower for control implants (62.8 mm) compared with test implants (128.74 mm) (P implants presented cells rich in lamellipodia prolongations, attached to the inner walls or to the borders of the microgrooves and in the flat areas between the microgrooves. Cell density was higher in the test group compared with controls (P implants with microgrooves. (ii) The LSA of microgrooved zirconia implants is greater and provides more available surface compared with implants of the same dimensions without microgrooves. (iii) Microgrooves on zirconia implants modify the morphology and guide the size and alignment of human fetal osteoblasts. (iv) Zirconia surfaces with microgrooves of 30 μm width and 70 μm separation between grooves enhance ALP and ALZ expression by human fetal osteoblasts. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. An Investigation of the Endocrine-Disruptive Effects of Bisphenol A in Human and Rat Fetal Testes

    Science.gov (United States)

    Maamar, Millissia Ben; Lesné, Laurianne; Desdoits-Lethimonier, Christèle; Coiffec, Isabelle; Lassurguère, Julie; Lavoué, Vincent; Deceuninck, Yoann; Antignac, Jean-Philippe; Le Bizec, Bruno; Perdu, Elisabeth; Zalko, Daniel; Pineau, Charles; Chevrier, Cécile; Dejucq-Rainsford, Nathalie; Mazaud-Guittot, Séverine; Jégou, Bernard

    2015-01-01

    Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5–17.5 days post-coitum) and humans (8–12 gestational weeks) and under different culture conditions. BPA concentrations of 10-8M and 10-5M for 72h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48h in both strains. BPA at 10-7-10-5M for 72h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10-8M, 10-7M, and 10-5M for 72h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA. PMID:25706302

  17. 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.

  18. /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.

  19. Human fetal striatum-derived neural stem (NS) cells differentiate to mature neurons in vitro and in vivo.

    Science.gov (United States)

    Monni, Emanuela; Cusulin, Carlo; Cavallaro, Maurizio; Lindvall, Olle; Kokaia, Zaal

    2014-01-01

    Clonogenic neural stem (NS) cell lines grown in adherent cultures have previously been established from embryonic stem cells and fetal and adult CNS in rodents and from human fetal brain and spinal cord. Here we describe the isolation of a new cell line from human fetal striatum (hNS cells). These cells showed properties of NS cells in vitro such as monolayer growth, high proliferation rate and expression of radial glia markers. The hNS cells expressed an early neuronal marker while being in the proliferative state. Under appropriate conditions, the hNS cells were efficiently differentiated to neurons, and after 4 weeks about 50% of the cells were βIII tubulin positive. They also expressed the mature neuronal marker NeuN and markers of neuronal subtypes, GABA, calbindin, and DARPP32. After intrastriatal implantation into newborn rats, the hNS cells survived and many of them migrated outside the transplant core into the surrounding tissue. A high percentage of cells in the grafts expressed the neuroblast marker DCX, indicating their neurogenic potential, and some of the cells differentiated to NeuN+ mature neurons. The human fetal striatum-derived NS cell line described here should be a useful tool for studies on cell replacement strategies in models of the striatal neuronal loss occurring in Huntington's disease and stroke.

  20. Human Fetal Membranes at Term: Dead Tissue or Signalers of Parturition?

    OpenAIRE

    Menon, Ramkumar

    2016-01-01

    Various endocrine, immune, and mechanical factors produced by feto-maternal compartments at term increase intrauterine inflammatory loads to induce labor. The role of fetal (placental) membranes (amniochorion) as providers of parturition signals has not been well investigated. Fetal membranes line the intrauterine cavity and grow with and protect the fetus. Fetal membranes exist as an entity between the mother and fetus and perform unique functions during pregnancy. Membranes undergo a telome...

  1. Anatomical model for dissection in corpses of the palate vascularization

    Directory of Open Access Journals (Sweden)

    Pinheiro Neto, Carlos Diógenes

    2010-03-01

    Full Text Available Introduction: The main artery that supplies the mucoperiosteum of the hard palate is the greater palatine artery. The knowledge detailed of the vascular anatomy of the palate and, in special, of the region of the greater palatine foramen is important for prevention of lesions vascular during procedures in this region. Among these procedures, it included the making of shreds for correction of failures in the hard palate, soft palate and cranial base. Objective: To develop an anatomical model that can illustrate the endoscopic anatomy of the greater palatine foramen and analyze the technical of injection intra vascular of colored silicone is sufficient for fill the lower arterial branches than irrigate the hard palate. Method: The form of study was experimental through the endoscopic dissection of 10 greater palatine arteries in five heads of corpses prepared with injection intra vascular of colored silicone. Results: Of the total of 10 arteries dissected, 8 properly were colored by the technique of injection employed. What corresponds to an efficacy of 80%. Conclusion: The anatomical model showed to be a feasible approach for the endoscopic study of the greater palatine foramen, being the injection of efficient silicone in the terminals vessels coloring in 80% of the cases.

  2. Neuronal Migration and Axonal Pathways Linked to Human Fetal Insular Development Revealed by Diffusion MR Tractography.

    Science.gov (United States)

    Das, Avilash; Takahashi, Emi

    2017-08-31

    The insula is a multimodal sensory integration structure that, in addition to serving as a gateway between somatosensory areas and limbic structures, plays a crucial role in autonomic nervous system function. While anatomical studies following the development of the insula have been conducted, currently, no studies have been published in human fetuses tracking the development of neuronal migration or of white matter tracts in the cortex. In this study, we aimed to follow the neuronal migration and subsequent maturation of axons in and around the insula in human fetal ages. Using high-angular resolution diffusion magnetic resonance imaging tractography, major white matter pathways to/from the insula and its surrounding operculum were identified at a number of time points during human gestation. Pathways likely linked to neuronal migration from the ventricular zone to the inferior frontal gyrus, superior temporal region, and the insular cortex were detected in the earliest gestational age studied (15 GW). Tractography reveals neuronal migration to areas surrounding the insula occurred at different time points. These results, in addition to demonstrating key time points for neuronal migration, suggest that neurons and axonal fiber pathways underlying the insula and its surrounding gyri mature differentially despite their relationship during cortical folding. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Pancreatic β-Cells Express the Fetal Islet Hormone Gastrin in Rodent and Human Diabetes.

    Science.gov (United States)

    Dahan, Tehila; Ziv, Oren; Horwitz, Elad; Zemmour, Hai; Lavi, Judith; Swisa, Avital; Leibowitz, Gil; Ashcroft, Frances M; In't Veld, Peter; Glaser, Benjamin; Dor, Yuval

    2017-02-01

    β-Cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of β-cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. Although gastrin in mice is expressed in insulin+ cells, gastrin expression in humans with T2D occurs in both insulin+ and somatostatin+ cells. Genetic lineage tracing in mice indicates that gastrin expression is turned on in a subset of differentiated β-cells after exposure to severe hyperglycemia. Gastrin expression in adult β-cells does not involve the endocrine progenitor cell regulator neurogenin3 but requires membrane depolarization, calcium influx, and calcineurin signaling. In vivo and in vitro experiments show that gastrin expression is rapidly eliminated upon exposure of β-cells to normal glucose levels. These results reveal the fetal hormone gastrin as a novel marker for reversible human β-cell reprogramming in diabetes. © 2017 by the American Diabetes Association.

  4. Fetal Testosterone Influences Sexually Dimorphic Gray Matter in the Human Brain

    Science.gov (United States)

    Lombardo, Michael V.; Ashwin, Emma; Auyeung, Bonnie; Chakrabarti, Bhismadev; Taylor, Kevin; Hackett, Gerald; Bullmore, Edward T.; Baron-Cohen, Simon

    2012-01-01

    In non-human species, testosterone is known to have permanent ‘organizing’ effects early in life that predict later expression of sex differences in brain and behavior. However, in humans it is still unknown if such mechanisms have organizing effects on neural sexual dimorphism. In human males, we show that variation in fetal testosterone (FT) predicts later local gray matter volume of specific brain regions in a direction that is congruent with sexual dimorphism observed in a large independent sample of age-matched males and females from the NIH Pediatric MRI Data Repository. Right temporo-parietal junction/posterior superior temporal sulcus (RTPJ/pSTS), planum temporale/parietal operculum (PT/PO), and posterior lateral orbitofrontal cortex (plOFC) had local gray matter volume that was both sexually dimorphic and predicted in a congruent direction by FT. That is, gray matter volume in RTPJ/pSTS was greater for males compared to females and was positively predicted by FT. Conversely, gray matter volume in PT/PO and plOFC was greater in females compared to males and was negatively predicted by FT. Subregions of both amygdala and hypothalamus were also sexually dimorphic in the direction of Male>Female, but were not predicted by FT. However, FT positively predicted gray matter volume of a non-sexually dimorphic subregion of the amygdala. These results bridge a longstanding gap between human and non-human species in showing that FT acts as an organizing mechanism for the development of regional sexual dimorphism in the human brain. PMID:22238103

  5. Multilineage potential of stable human mesenchymal stem cell line derived from fetal marrow.

    Directory of Open Access Journals (Sweden)

    Atsushi Nagai

    Full Text Available Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs and mesenchymal stem cells (MSCs. MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following transplantation into the brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10, was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1, neurons (neurofilament protein, synapsin and MAP2, astrocytes (glial fibrillary acidic protein, GFAP and oligodendrocytes (myelin basic protein, MBP as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells, neurofilament protein and beta-tubulin III (neurons GFAP (astrocytes, and galactocerebroside (oligodendrocytes. Following brain transplantation in mouse ICH stroke model, B10 human MSCs integrate into host brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cell therapy studies in animal models of stroke and other neurological disorders.

  6. Fetal topographical anatomy of the female urethra and descending vagina: a histological study of the early human fetal urethra.

    Science.gov (United States)

    Masumoto, Hiroshi; Rodríguez-Vázquez, Jose Francisco; Verdugo-López, Samuel; Murakami, Gen; Matsubara, Akio

    2011-12-20

    Which parts of the male urethra correspond to the female urethra? To resolve this question, we need to understand fetal topographical changes in the urethra, its external sphincter and vagina. The vagina joins the mid-course of the primitive urethra and, later "descends" to the vaginal vestibulum. We examined histological sections of 14 female and 4 male mid-term fetuses. The inferior end of the vagina was consistently embedded in the posterior wall of the urethra at 9-12 weeks. The supero-inferior level of the vaginal merging was lower in larger fetuses. Thus, the sequential variation in levels appeared to reflect the process of vaginal descent. However, in spite of penetration of the vaginal end into the posterior urethral wall, we found no sign of destruction of the urethral wall after vaginal descent in the low-merging types. Before vaginal descent, the female external sphincter extended posterolaterally around the urethra. The vaginal descent is classically regarded as a relative topographical change, but it is likely to be a result of elongation of the proximal urethra in the superior side of the vaginal merging. Conversely, the distal urethra is likely to be incorporated into the vaginal vestibulum by 15 weeks. During these processes, most of the female external sphincter seems to be expelled from the original anterior position into the vestibular wall as the urethrovaginal sphincter. The adult female urethra seems to correspond to the male prostatic urethra superior to the prostatic colliculus. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. Fibrin supports human fetal islet-epithelial cell differentiation via p70(s6k) and promotes vascular formation during transplantation.

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    Riopel, Matthew; Li, Jinming; Trinder, Mark; Fellows, George F; Wang, Rennian

    2015-08-01

    The human fetal pancreas expresses a variety of extracellular matrix (ECM) binding receptors known as integrins. A provisional ECM protein found in blood clots that can bind to integrin receptors and promote β cell function and survival is fibrin. However, its role in support of human fetal pancreatic cells is unknown. We investigated how fibrin promotes human fetal pancreatic cell differentiation in vitro and in vivo. Human fetal pancreata were collected from 15 to 21 weeks of gestation and collagenase digested. Cells were then plated on tissue-culture polystyrene, or with 2D or 3D fibrin gels up to 2 weeks, or subcutaneously transplanted in 3D fibrin gels. The human fetal pancreas contained rich ECM proteins and expressed integrin αVβ3. Fibrin-cultured human fetal pancreatic cells had significantly increased expression of PDX-1, glucagon, insulin, and VEGF-A, along with increased integrin αVβ3 and phosphorylated FAK and p70(s6k). Fibrin-cultured cells treated with rapamycin, the mTOR pathway inhibitor, had significantly decreased phospho-p70(s6k) and PDX-1 expression. Transplanting fibrin-mixed cells into nude mice improved vascularization compared with collagen controls. These results suggest that fibrin supports islet cell differentiation via p70(s6k) and promotes vascularization in human fetal islet-epithelial clusters in vivo.

  8. Fetal Cardiac Interventions

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    Shi-Min Yuan

    2015-04-01

    Full Text Available The present article aims to highlight fetal cardiac interventions (FCIs in terms of indications, strategies, and fetal prognoses. FCIs of the early years were predominantly pharmacological therapies for fetal arrhythmia or heart block. A transplacental transmission of therapeutic agents has now become the main route of pharmacological FCIs. There have been various FCI strategies, which can be categorized into three types: pharmacological, open FCIs, and closed FCIs. Rather than as a routine management for materno-fetal cardiac disorders, however, FCIs are only applied in those fetal cardiac disorders that are at an increased risk of mortality and morbidity and warrant an interventional therapy. Pharmacological FCIs have been well applied in fetal arrhythmias but require further investigations for novel therapeutic agents. The development of open FCI in humans is an issue for the long run. Closed FCIs may largely rely on advanced imaging techniques. Hybrid FCIs might be the future goal in the treatment of fetal heart diseases.

  9. 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.

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

    Science.gov (United States)

    He, Jing; Stewart, Kayleigh; Kinnell, Hazel L; Anderson, Richard A; Childs, Andrew J

    2013-01-01

    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.

  11. Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.

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    Nelle Lambert

    2011-03-01

    Full Text Available The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits.

  12. A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland

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    E. Chamoux

    2005-10-01

    Full Text Available The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative zone at the periphery, a concentric migration accompanied by cell differentiation (cortisol secretion and apoptosis in the central androgen-secreting fetal zone. After birth, a strong reorganization occurs in the adrenal gland so that it better fulfills the newborn's needs, with aldosterone production in the external zona glomerulosa, cortisol secretion in the zona fasciculata and androgens in the central zona reticularis. In addition to the major hormonal stimuli provided by angiotensin II and adrenocorticotropin, we have tested for some years the hypotheses that such plasticity may be under the control of the extracellular matrix. A growing number of data have been harvested during the last years, in particular about extracellular matrix expression and its putative role in the development of the human adrenal cortex. Laminin, collagen and fibronectin have been shown to play important roles not only in the plasticity of the adrenal cortex, but also in cell responsiveness to hormones, thus clarifying some of the unexplained observations that used to feed controversies.

  13. A connection between extracellular matrix and hormonal signals during the development of the human fetal adrenal gland.

    Science.gov (United States)

    Chamoux, E; Otis, M; Gallo-Payet, N

    2005-10-01

    The human adrenal cortex, involved in adaptive responses to stress, body homeostasis and secondary sexual characters, emerges from a tightly regulated development of a zone-specific secretion pattern during fetal life. Its development during fetal life is critical for the well being of pregnancy, the initiation of delivery, and even for an adequate adaptation to extra-uterine life. As early as from the sixth week of pregnancy, the fetal adrenal gland is characterized by a highly proliferative zone at the periphery, a concentric migration accompanied by cell differentiation (cortisol secretion) and apoptosis in the central androgen-secreting fetal zone. After birth, a strong reorganization occurs in the adrenal gland so that it better fulfills the newborn's needs, with aldosterone production in the external zona glomerulosa, cortisol secretion in the zona fasciculata and androgens in the central zona reticularis. In addition to the major hormonal stimuli provided by angiotensin II and adrenocorticotropin, we have tested for some years the hypotheses that such plasticity may be under the control of the extracellular matrix. A growing number of data have been harvested during the last years, in particular about extracellular matrix expression and its putative role in the development of the human adrenal cortex. Laminin, collagen and fibronectin have been shown to play important roles not only in the plasticity of the adrenal cortex, but also in cell responsiveness to hormones, thus clarifying some of the unexplained observations that used to feed controversies.

  14. Comparative effects of ACTH, PACAP, and VIP on fetal human adrenal cells.

    Science.gov (United States)

    Chamoux, E; Breault, L; LeHoux, J G; Gallo-Payet, N

    1998-01-01

    ACTH is a well-known stimulus of human adrenal cells, both in the adult and in the fetus. Two other stimuli, acting via the cAMP pathway, are also involved in the regulation of steroidogenesis and growth of the adult gland, the Pituitary Adenylate Cyclase Activating Peptide (PACAP) and the Vasoactive Intestinal Polypeptide (VIP). The aim of this study was to compare the effects of the three peptides on cAMP production and to investigate their possible effect on cytoskeletal organization in the different cell types present in the human fetal adrenal gland, i.e steroidogenic cells and chromaffin cells. Using phalloidin-rhodamine labeling of actin microfilaments, we observed that VIP and ACTH strongly affect cytoskeletal organization. Application of ACTH rapidly induces steroidogenic cells to elaborate fillopodia and junctions with neighboring cells. Application of VIP strongly stimulates the chromaffin cells to elaborate neurite-like extensions, suggesting that the effects of VIP could be, as in adult glands, mediated by the adrenal medulla.

  15. Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research.

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    Tania Ramos-Moreno

    Full Text Available A major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural stem cell (NSC line derived from the human fetal ventral mesencephalon (hVM1. This line has been biochemically, genetically, immunocytochemically and electrophysiologically characterized to document its usefulness as a model system for the generation of A9 dopaminergic neurons (DAn. Long-term in vivo transplantation studies in parkinsonian rats showed that the grafts do not mature evenly. We reasoned that diverse clones in the hVM1 line might have different abilities to differentiate. In the present study, we have analyzed 9 hVM1 clones selected on the basis of their TH generation potential and, based on the number of v-myc copies, v-myc down-regulation after in vitro differentiation, in vivo cell cycle exit, TH⁺ neuron generation and expression of a neuronal mature marker (hNSE, we selected two clones for further in vivo PD cell replacement studies. The conclusion is that homogeneity and clonality of characterized NSCs allow transplantation of cells with controlled properties, which should help in the design of long-term in vivo experiments.

  16. 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.

  17. 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.

  18. Formation of the periotic space during the early fetal period in humans.

    Science.gov (United States)

    Ishikawa, Aoi; Ohtsuki, Sae; Yamada, Shigehito; Uwabe, Chigako; Imai, Hirohiko; Matsuda, Tetsuya; Takakuwa, Tetsuya

    2018-01-02

    The inner ear is a very complicated structure, composed of a bony labyrinth (otic capsule; OC), membranous labyrinth, with a space between them, named the periotic labyrinth or periotic space. We investigated how periotic tissue fluid spaces covered the membranous labyrinth 3-dimensionally, leading to formation of the periotic labyrinth encapsulated in the OC during human fetal development. Digital data sets from magnetic resonance images and phase-contrast X-ray tomography images of 24 inner ear organs from 24 human fetuses from the Kyoto Collection (fetuses in trimesters 1 and 2; crown-rump length: 14.4-197 mm) were analyzed. The membranous labyrinth was morphologically differentiated in samples at the end of the embryonic period (Carnegie stage 23), and had grown linearly to more than 8 times in size during the observation period. The periotic space was first detected at the 35-mm samples, around the vestibule and basal turn of the cochlea, which elongated rapidly to the tip of the cochlea and semicircular ducts, successively, and almost covered the membranous labyrinth at the 115-mm CRL stage or later. In those samples, several ossification centers were detected around the space. This paper thus demonstrated that formation of the membranous labyrinth, periotic space (labyrinth), and ossification of the OC occurs successively, according to an intricate timetable. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  19. War and Violence in Sinan Antoon’s The Corpse Washer

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    Radwa Ramadan Mahmoud

    2016-03-01

    Full Text Available War is the greatest source of violence in the world. It is the most disastrous expression of tendencies to violence innate to human nature. Iraq has suffered for a long time from the repercussions of war and violence and in this country ravaged by war trauma; the only space left for memory has been literature. Personal and political traumas have characterized the works of Iraqi writers who have been either victims of traumatic experience themselves or have been firsthand witnesses to trauma in Iraq. Literature provides them with an avenue to reclaim the humanity of all those who have been traumatized by the violence represented by war. Drawing on the theory of trauma, the paper seeks to explore the notions of war trauma and violence in Sinan Antoon's novel The Corpse Washer (2014 that reveals Iraq’s traumatic and violent history. The paper examines the ways in which the novel bears witness to, protests against and exposes the devastating effects of war and violence.

  20. 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

  1. [Comparison of human cord blood mesenchymal stem cell culture between using human umbilical cord plasma and using fetal bovine serum].

    Science.gov (United States)

    Ding, Yan; Lu, Zhiyong; Yuan, Yahong; Wang, Xiaoli; Li, Dongsheng; Zeng, Yi

    2013-12-01

    To investigate whether human umbilical cord plasma (HUP) can be used to culture human cord blood mesenchymal stem cells (HUCMSCs), we collected 20 surplus HUP. After being treated with salting out and diasysis, the HUP were used to culture HUCMSCs as 10% volume, and compared with fetal bovine serum (FBS). Morphological characteristics, growth curve and reproductive activity of HUCMSCs cells were observed. The concentration of bFGF and noggin secreted by HUCMSCs cultured with HUP and FBS medium were detected by ELISA. It was found that compared to FBS, the morphology, reproductive activity and characteristic of HUCMSCs cell cultured with HUP were not distinctively different from FBS. The concentration of bFGF in HUP group was significantly higher than that of FBS group, and the concentration of noggin was also different in the two groups. So we concluded that HUP could be used to culture HUCMSCs for a long-time, and the HUP mediumcoild could be more suitable for the culture of human embryonic stem cell (hESC).

  2. Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse.

    Science.gov (United States)

    Chan, Jerry; Waddington, Simon N; O'Donoghue, Keelin; Kurata, Hitoshi; Guillot, Pascale V; Gotherstrom, Cecilia; Themis, Michael; Morgan, Jennifer E; Fisk, Nicholas M

    2007-04-01

    Duchenne muscular dystrophy (DMD) is a common X-linked disease resulting from the absence of dystrophin in muscle. Affected boys suffer from incurable progressive muscle weakness, leading to premature death. Stem cell transplantation may be curative, but is hampered by the need for systemic delivery and immune rejection. To address these barriers to stem cell therapy in DMD, we investigated a fetal-to-fetal transplantation strategy. We investigated intramuscular, intravascular, and intraperitoneal delivery of human fetal mesenchymal stem cells (hfMSCs) into embryonic day (E) 14-16 MF1 mice to determine the most appropriate route for systemic delivery. Intramuscular injections resulted in local engraftment, whereas both intraperitoneal and intravascular delivery led to systemic spread. However, intravascular delivery led to unexpected demise of transplanted mice. Transplantation of hfMSCs into E14-16 mdx mice resulted in widespread long-term engraftment (19 weeks) in multiple organs, with a predilection for muscle compared with nonmuscle tissues (0.71% vs. 0.15%, p transplantation of ontologically relevant hfMSCs into fully immunocompetent dystrophic fetal mice, with systemic spread across endothelial barriers leading to widespread long-term engraftment in multiple organ compartments. Although the low-level of chimerism achieved is not curative for DMD, this approach may be useful in other severe mesenchymal or enzyme deficiency syndromes, where low-level protein expression may ameliorate disease pathology.

  3. Biocompatibility and osteogenic potential of human fetal femur-derived cells on surface selective laser sintered scaffolds.

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    Kanczler, Janos M; Mirmalek-Sani, Sayed-Hadi; Hanley, Neil A; Ivanov, Alexander L; Barry, John J A; Upton, Clare; Shakesheff, Kevin M; Howdle, Steven M; Antonov, Eugeuni N; Bagratashvili, Victor N; Popov, Vladimir K; Oreffo, Richard O C

    2009-07-01

    For optimal bone regeneration, scaffolds need to fit anatomically into the requisite bone defects and, ideally, augment cell growth and differentiation. In this study we evaluated novel computationally designed surface selective laser sintering (SSLS) scaffolds for their biocompatibility as templates, in vitro and in vivo, for human fetal femur-derived cell viability, growth and osteogenesis. Fetal femur-derived cells were successfully cultured on SSLS-poly(d,l)-lactic acid (SSLS-PLA) scaffolds expressing alkaline phosphatase activity after 7days. Cell proliferation, ingrowth, Alcian blue/Sirius red and type I collagen positive staining of matrix deposition were observed for fetal femur-derived cells cultured on SSLS-PLA scaffolds in vitro and in vivo. SSLS-PLA scaffolds and SSLS-PLA scaffolds seeded with fetal femur-derived cells implanted into a murine critical-sized femur segmental defect model aided the regeneration of the bone defect. SSLS techniques allow fabrication of biocompatible/biodegradable scaffolds, computationally designed to fit any defect, providing a template for cell osteogenesis in vitro and in vivo.

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

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    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.

  5. Human Platelet Lysate as a Replacement for Fetal Bovine Serum in Limbal Stem Cell Therapy.

    Science.gov (United States)

    Suri, Kunal; Gong, Hwee K; Yuan, Ching; Kaufman, Stephen C

    2016-10-01

    To evaluate the use of human platelet lysate (HPL) as an alternative supplement for limbal explant culture. Culture media were prepared using either 10% pooled HPL (PHPL), single donor HPL, or fetal bovine serum (FBS). Limbal tissues, obtained from the Minnesota Lions Eye Bank, were cultured in each medium on plastic plates or on denuded amniotic membrane (AM). Immunofluorescence staining was performed for ABCG2, tumor protein p63α, and cytokeratin 3 (K3). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of ABCG2 and p63. Limbal explants grown in each medium were labeled with bromodeoxyuridine (BrdU) to assess the proliferative capacity in each medium. Concentration of growth factors including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and platelet derived growth factor (PDGF) in HPL and PHPL was compared to that in human serum (HS). Immunofluorescence staining on AM showed prominent expression of ABCG2, p63α but sparse expression of K3 in HPL and PHPL supplemented medium. Real time-PCR showed 1.7 fold higher expression of ABCG2 in PHPL supplemented medium (p = 0.03), and similar expression of p63 in HPL and PHPL supplemented medium compared to FBS medium. The proliferation assay showed that LSCs retained their proliferative potential in HPL supplemented medium. Higher concentration of growth factors were found in HPL, compared to HS. Human platelet lysate has higher concentration of grown factors and is effective in maintaining growth and stem cell phenotype of corneal limbal explant cultures.

  6. Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases

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    Carmen F Bjurström

    2016-01-01

    Full Text Available We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs, transcriptional activator-like effector nucleases (TALENs, and clustered regularly interspaced short palindromic repeat (CRISPR/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA (pU6.g1 or in vitro transcribed gRNA (gR.1. Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34+ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34+ cells had the capacity to engraft in NOD-PrkdcSCID-IL2Rγnull mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34+ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs, highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs.

  7. Development and morphogenesis of human wrist joint during embryonic and early fetal period.

    Science.gov (United States)

    Hita-Contreras, Fidel; Martínez-Amat, Antonio; Ortiz, Raúl; Caba, Octavio; Alvarez, Pablo; Prados, José C; Lomas-Vega, Rafael; Aránega, Antonia; Sánchez-Montesinos, Indalecio; Mérida-Velasco, Juan A

    2012-06-01

    The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O'Rahilly stages 17-23 and 9-14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

  8. THE EFFECT OF FETAL CALF SERUM ON HUMAN DENTAL PULP STEM CELLS

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    Jakub Suchánek

    2013-01-01

    Full Text Available Aims: Authors studied potential side effects of fetal calf serum (FCS in cultivation media on human dental pulp stem cells (DPSC during long term cultivation. Methods: Two lines of DPSC obtained healthy donors (male 22 years, female 23 years were used. Both lines were cultivated under standard cultivation conditions in four different media containing 10% or 2% FCS and substituted with growth factors. During long term cultivation proliferation ability, karyotype and phenotype of DPSC were measured. Results: Both lines of DPSC cultivated in a media containing 2% FCS and ITS supplement showed the highest number of population doublings. On the other hand the proliferation rate of DPSC cultivated in a media with 2% FCS without ITS supplement was slowest. Proliferation rate of DPSC cultivated in 10% FCS media with or without FGF-2 was comparable. DPSC cultivated in a media with 10% FCS showed a significantly higher amount of chromosomal aberrations. These chromosomal aberrations do not seem to be clonal but surprisingly we found large amounts of tetraploid cells in the 9th passage in both media containing 10% FCS. Conclusions: Our study proved that cultivation of DPSC in media containing higher concentration of FCS has critical side effects on cell chromosomal stability.

  9. Qualitative changes in fetal trabecular meshwork fibers at the human iridocorneal angle.

    Science.gov (United States)

    Hosaka, Fumio; Rodríguez-Vázquez, Jose Francisco; Abe, Hiroshi; Murakami, Gen; Fujimiya, Mineko; Ohguro, Hiroshi

    2013-03-01

    We examined a series of changes that occur in the trabecular meshwork fibers of human eyes during fetal development at 12-30 weeks of gestation. At 12 and 15 weeks, the uveal meshwork was stained black with silver impregnation (indicating the predominance of collagen types III and IV) in the endomysium of the ciliary muscle. At 20 weeks, in combination with Schlemm's canal, a dense fibrous tissue mass corresponding to the trabecular meshwork anlage appeared and was colored black. The anlage was continuous with the corneal endothelium rather than with the ciliary muscle. Until 25 weeks, the trabecular meshwork was identifiable as fragmented fiber bundles that stained red-black, suggesting a mixture of collagen types I, III, and IV. At 30 weeks, half of the ciliary muscle fibers were inserted into the scleral spur and not into the meshwork. Therefore, any contribution of ciliary muscle contraction to the differentiation of the trabecular meshwork would appear to be limited. We hypothesize that an uneven distribution of mechanical stresses in the area of the cornea-sclera junction causes a tear thereby creating Schlemm's canal and is accompanied by a change in the collagen fiber types comprising the meshwork.

  10. BD PuraMatrix peptide hydrogel as a culture system for human fetal Schwann cells in spinal cord regeneration.

    Science.gov (United States)

    Moradi, Fateme; Bahktiari, Mehrdad; Joghataei, Mohammad Taghi; Nobakht, Maliheh; Soleimani, Masoud; Hasanzadeh, Gholamreza; Fallah, Ali; Zarbakhsh, Sam; Hejazian, Leila Beigom; Shirmohammadi, Maryam; Maleki, Fatemeh

    2012-12-01

    BD PuraMatrix peptide hydrogel, a three-dimensional cell culture model of nanofiber scaffold derived from the self-assembling peptide RADA16, has been applied to regenerative tissue repair in order to develop novel nanomedicine systems. In this study with PuraMatrix, self-assembling nanofiber scaffold (SAPNS) and Schwann cells (SCs) were isolated from human fetal sciatic nerves, cultured within SAPNS, and then transplanted into the spinal cord after injury (SCI) in rats. First, the peptide nanofiber scaffold was evaluated via scanning electron microscopy and atomic force microscopy. With phase-contrast microscopy, the appearance of representative human fetal SCs encapsulated in PuraMatrix on days 3, 5, and 7 in 12-well plates was revealed. The Schwann cells in PuraMatrix were cultured for 2 days, and the SCs had active proliferative potential. Spinal cord injury was induced by placing a 35-g weight on the dura of T9-T10 segments for 15 min, followed by in vivo treatment with SAPNS and human fetal SCs (100,000 cells/10 μl/injection) grafted into spinal cord 7 days after SCI. After treatment, the recovery of motor function was assessed periodically using the Basso, Beattie, and Bresnahan scoring system. Eight weeks after grafting, animals were perfusion fixed, and the survival of implanted cells was analyzed with antibody recognizing SCs. Immunohistochemical analysis of grafted lumber segments at 8 weeks after grafting revealed reduced asterogliosis and considerably increased infiltration of endogenous S100(+) cells into the injury site, suggesting that PuraMatrix may play an important role in the repair observed after SAPNS and human fetal SC transplantation. Copyright © 2012 Wiley Periodicals, Inc.

  11. 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....

  12. Transplantation of human fetal biliary tree stem/progenitor cells into two patients with advanced liver cirrhosis.

    Science.gov (United States)

    Cardinale, Vincenzo; Carpino, Guido; Gentile, Raffaele; Napoletano, Chiara; Rahimi, Hassan; Franchitto, Antonio; Semeraro, Rossella; Nuti, Marianna; Onori, Paolo; Berloco, Pasquale Bartolomeo; Rossi, Massimo; Bosco, Daniela; Brunelli, Roberto; Fraveto, Alice; Napoli, Cristina; Torrice, Alessia; Gatto, Manuela; Venere, Rosanna; Bastianelli, Carlo; Aliberti, Camilla; Salvatori, Filippo Maria; Bresadola, Luciano; Bezzi, Mario; Attili, Adolfo Francesco; Reid, Lola; Gaudio, Eugenio; Alvaro, Domenico

    2014-12-04

    Efforts to identify cell sources and approaches for cell therapy of liver diseases are ongoing, taking into consideration the limits recognized for adult liver tissue and for other forms of stem cells. In the present study, we described the first procedure of via hepatic artery transplantation of human fetal biliary tree stem cells in patients with advanced cirrhosis. The cells were immune-sorted from human fetal biliary tree by protocols in accordance with current good manufacturing practice (cGMP) and extensively characterized. Two patients with advanced liver cirrhosis (Child-Pugh C) have been submitted to the procedure and observed through a 12 months follow-up. The resulting procedure was found absolutely safe. Immuno-suppressants were not required, and the patients did not display any adverse effects correlated with cell transplantation or suggestive of immunological complications. From a clinical point of view, both patients showed biochemical and clinical improvement during the 6 month follow-up and the second patient maintained a stable improvement for 12 months. This report represents proof of the concept that the human fetal biliary tree stem cells are a suitable and large source for cell therapy of liver cirrhosis. The isolation procedure can be carried out under cGMP conditions and, finally, the infusion procedure is easy and safe for the patients. This represents the basis for forthcoming controlled clinical trials.

  13. Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks.

    Science.gov (United States)

    Matz, Peggy; Wruck, Wasco; Fauler, Beatrix; Herebian, Diran; Mielke, Thorsten; Adjaye, James

    2017-07-24

    Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells and can be generated from somatic cells. We have generated episomal plasmid-based and integration-free iPSCs (E-iPSCs) from human fetal foreskin fibroblast cells (HFF1). We used an E-iPSC-line to model hepatogenesis in vitro. The HLCs were characterized biochemically, i.e. glycogen storage, ICG uptake and release, UREA and bile acid production, as well as CYP3A4 activity. Ultra-structure analysis by electron microscopy revealed the presence of lipid and glycogen storage, tight junctions and bile canaliculi- all typical features of hepatocytes. Furthermore, the transcriptome of undifferentiated E-iPSC, DE, HE and HLCs were compared to that of fetal liver and primary human hepatocytes (PHH). K-means clustering identified 100 clusters which include developmental stage-specific groups of genes, e.g. OCT4 expression at the undifferentiated stage, SOX17 marking the DE stage, DLK and HNF6 the HE stage, HNF4α and Albumin is specific to HLCs, fetal liver and adult liver (PHH) stage. We use E-iPSCs for modeling gene regulatory networks associated with human hepatogenesis and gastrulation in general.

  14. 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.

  15. Asymmetry of Radial and Symmetry of Tangential Neuronal Migration Pathways in Developing Human Fetal Brains.

    Science.gov (United States)

    Miyazaki, Yuta; Song, Jae W; Takahashi, Emi

    2016-01-01

    The radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest (ROIs). Thus, little evidence is available about their three-dimensional (3-D) fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI) tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW), 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW) and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW) brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional differences in

  16. Fetal exposure to maternal human platelet antigen-1a does not induce tolerance. An analytical observational study.

    Directory of Open Access Journals (Sweden)

    Mette Kjær

    Full Text Available Fetal and neonatal alloimmune thrombocytopenia (FNAIT is a disease that may cause severe bleeding complications with risk of perinatal death or lifelong disability. The main cause of FNAIT is maternal antibodies against human platelet antigen (HPA-1a. Both fetomaternal bleeding and transplacental trafficking of fetal cells during pregnancy could be the cause of alloimmunization. Persistence of fetal cells in the mother (fetal microchimerism and maternal cells in the child (maternal microchimerism are well-recognized phenomena. Thus, it could be envisaged that fetal exposure to the HPA-1a antigen could tolerize an HPA-1a negative female fetus and prevent production of anti-HPA-1a antibodies later in life if she becomes pregnant with an HPA-1a positive fetus. The objective of the current study was to assess if the risk of producing anti-HPA-1a antibodies and the severity of neonatal thrombocytopenia in HPA-1a negative women with HPA-1a positive mothers (i.e. the mother is HPA-1a/b, was lower than in HPA-1a negative women with HPA-1a negative mothers. HPA-1a negative women with HPA-1a antibodies, identified from a Norwegian screening study (1996-2004, where HPA-1 genotype of their mothers was available, were included in the study. The frequency of HPA-1a positive mothers to HPA-1a immunized daughters were compared to the calculated frequency in the general population. We did not find any difference in the frequency of HPA-1ab among mothers to daughters with HPA-1a antibodies as compared with the general population. Furthermore, acknowledging sample-size limitations, we neither found an association between the mothers' HPA type and their daughters' anti-HPA-1a antibody levels or any difference between the two groups of mothers (HPA-1ab vs HPA-1bb, with respect to frequency of thrombocytopenia in the children of their daughters with HPA-1a antibodies. Hence, there was no indication of tolerance against fetal HPA-1a antigen in HPA-1bb women who had

  17. Fetal Bone Marrow-Derived Mesenchymal Stem/Stromal Cells Enhance Humanization and Bone Formation of BMP7 Loaded Scaffolds.

    Science.gov (United States)

    Shafiee, Abbas; Baldwin, Jeremy G; Patel, Jatin; Holzapfel, Boris M; Fisk, Nicholas M; Khosrotehrani, Kiarash; Hutmacher, Dietmar W

    2017-09-01

    Tissue engineered constructs built with human cells capable of generating a bone-like organ within the mouse have attracted considerable interest over the past decade. Here, we aimed to compare the utility of human mesenchymal stem/stromal cells (MSC) isolated from fetal term placenta (fPL-MSC) and fetal first trimester bone marrow (fBM-MSC) in a polycaprolactone scaffold/BMP7-based model in nude mice. Furthermore, fPL-MSC were co-seeded with fetal placenta-derived endothelial colony forming cells (ECFC) to assess the impact of ECFC on fPL-MSC osteogenesis. X-ray radiography and micro computed tomography analyses showed enhanced bone formation in all BMP7 groups; however there was no difference after 2 months in bone formation between scaffolds seeded with fPL-MSC alone or combination of ECFC and fPL-MSC. Of interest, fBM-MSC showed the highest level of bone formation. Additionally, endochondral ossification contributed in generation of bone in fBM-MSC. Histological analysis showed the primary role of BMP in generation of cortical and trabecular bone, and the recruitment of hematopoietic cells to the scaffolds. Current in vivo engineered bone organs can potentially be used for drug screening or as models to study bone tissue development in combination with haematopoiesis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Fetal antigen 2: an amniotic protein identified as the aminopropeptide of the alpha 1 chain of human procollagen type I

    DEFF Research Database (Denmark)

    Teisner, B; Rasmussen, H B; Højrup, P

    1992-01-01

    with the aminopropeptide of the alpha 1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio-iodination (iodogen and chloramine-T), FA2 lost its immunoreactivity. An antigen which cross-reacted with polyclonal rabbit anti-human FA2 was demonstrated...... in fetal calf serum. Gel filtration with analysis of fractions by inhibition ELISA showed that the bovine homologue was present in the same molecular forms as those in human amniotic fluid, and immunohistochemical analysis with anti-human FA2 showed that its distribution in bovine skin was identical...... to that of FA2 in human skin. FA2 is a circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I, and this is the first description of its isolation and structural characterization in humans. Udgivelsesdato: 1992-Dec...

  19. Differential behavioral outcomes following neonatal versus fetal human retinal pigment epithelial cell striatal implants in parkinsonian rats

    DEFF Research Database (Denmark)

    Russ, Kaspar; Flores, Joseph; Brudek, Tomasz

    2017-01-01

    Following the failure of a Phase II clinical study evaluating human retinal pigment epithelial (hRPE) cell implants as a potential treatment option for Parkinson's disease, speculation has centered on implant function and survival as possible contributors to the therapeutic outcomes. We recently...... reported that neonatal hRPE cells, similar to hRPE cells used in the Phase II clinical study, produced short-lived in vitro and limited in vivo trophic factors, which supports that assumption. We hypothesize that the switch from fetal to neonatal hRPE cells, between the Phase I and the Phase II clinical...... trial may be partly responsible for the later negative outcomes. To investigate this hypothesis, we used two neonatal hRPE cell lots, prepared in a similar manner to neonatal hRPE cells used in the Phase II clinical study, and compared them to previously evaluated fetal hRPE cells for behavioral changes...

  20. Fetal Research

    Science.gov (United States)

    Hansen, John T.; Sladek, John R.

    1989-11-01

    This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

  1. Androgenic potential of human fetal adrenals at the end of the first trimester

    Directory of Open Access Journals (Sweden)

    I Savchuk

    2017-07-01

    Full Text Available The onset of steroidogenesis in human fetal adrenal glands (HFA during the first trimester is poorly investigated. An unresolved question is the capacity of the HFA to produce potent androgen DHT via conventional and/or the backdoor pathway(s at the end of first trimester, when androgen-responsive organs are developed. Our aim was to explore steroidogenesis and the expression of steroidogenic enzymes and transcription factors in HFA at gestational weeks (GW 9–12 with focus on their androgenic potential. Steroids in the HFA were analyzed by gas chromatography/mass spectrometry. The expression of steroidogenic enzymes and transcription factors in the HFA at GW9–12 was investigated by qPCR, automated Western blotting and immunohistochemistry. We demonstrated that during GW9–12 HFA produced steroids of the Δ5, Δ4 and the backdoor pathways of the biosynthesis of DHT, though the latter was limited to production of 17α-OH-dihydroprogesterone, androsterone and androstanedione without further conversion to DHT. The only androgens identified in the HFA were testosterone and androsterone, a precursor in the biosynthesis of DHT. We also observed higher levels of CYP17A1 but low expression of 3βHSD2 at GW11–12 in the HFA. Elevated levels of CYP17A1 were associated with an increased expression of SF-1 and GATA-6. Altogether, our data demonstrate that of those steroids analyzed, the only potent androgen directly produced by the HFA at GW9–12 was testosterone. The onset of steroidogenesis in the HFA is a complex process that is regulated by the coordinated action of related transcription factors.

  2. Fetal development of the elastic-fiber-mediated enthesis in the human middle ear.

    Science.gov (United States)

    Takanashi, Yoshitaka; Shibata, Shunichi; Katori, Yukio; Murakami, Gen; Abe, Shinichi; Rodríguez-Vázquez, Jose Francisco; Kawase, Tetsuaki

    2013-10-01

    In the human middle ear, the annular ligament of the incudostapedial joint and the insertions of the tensor tympani and stapedius muscles contain abundant elastic fibers; i.e., the elastic-fiber-mediated entheses. Hyaluronan also coexists with the elastic fibers. In the present study using immunohistochemistry, we demonstrated the distribution of elastin not only in the incudostapedial joint but also in the other two joints of the middle ear in adults and fetuses. In adults, the expression of elastin did not extend out of the annular ligament composed of mature elastic fibers but clearly overlapped with it. Electron microscopic observations of the annular ligament demonstrated a few microfibrils along the elastic fibers. Thus, in contrast to the vocal cord, the middle ear entheses seemed not to contain elaunin and oxytalan fibers. In mid-term fetuses (at approximately 15-16 weeks of gestation) before opening of the external acoustic meatus, the incudostapedial joint showed abundant elastic fibers, but the incudomalleolar and stapediovestibular joints did not. At this stage, hyaluronan was not colocalized, but distributed diffusely in loose mesenchymal tissues surrounding the ear ossicles. Therefore, fetal development of elastin and elastic fibers in the middle ear entheses is unlikely to require acoustic oscillation. In late-stage fetuses (25-30 weeks), whose ear ossicles were almost the same size as those in adults, we observed bundling and branching of elastic fibers. However, hyaluronan expression was not as strong as in adults. Colocalization between elastic fibers and hyaluronan appeared to be a result of postnatal maturation of the entheses. Copyright © 2013 Elsevier GmbH. All rights reserved.

  3. Determination of selected endocrine disrupting compounds in human fetal and newborn tissues by GC-MS.

    Science.gov (United States)

    Cappiello, Achille; Famiglini, Giorgio; Palma, Pierangela; Termopoli, Veronica; Lavezzi, Anna Maria; Matturri, Luigi

    2014-05-01

    Endocrine disrupting compounds (EDCs) include organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), carbamate pesticides, and plasticizers, such as bisphenol A (BPA). They persist in the environment because of their degradation resistance and bioaccumulate in the body tissues of humans and other mammals. Many studies are focused on the possible correlation between in utero exposure to EDCs and adverse health hazards in fetuses and newborns. In the last decade, environmental pollution has been considered a possible trigger for Sudden Infant Death Syndrome (SIDS) and Sudden Intrauterine Unexplained Death Syndrome (SIUDS), the most important death-causing syndromes in fetuses and newborns in developed countries. In this work, a rapid and sensitive analytical method was developed to determine the level of OCPs and OPPs, carbamates, and phenols in human fetal and newborn tissues (liver and brain) and to unveil the possible presence of non-targeted compounds. The target analytes where selected on the basis of their documented presence in the Trentino-Alto Adige region, an intensive agricultural area in northern Italy. A liquid-solid extraction procedure was applied on human and animal tissues and the extracts, after a solid phase extraction (SPE) clean-up procedure, were analyzed by gas chromatography coupled to a quadrupole mass spectrometric detector (GC-qMS). A GC-TOFMS (time-of-flight) instrument, because of its higher full-scan sensitivity, was used for a parallel detection of non-targeted compounds. Method validation included accuracy, precision, detection, and quantification limits (LODs; LOQs), and linearity response using swine liver and lamb brain spiked at different concentrations in the range of 0.4-8000.0 ng/g. The method gave good repeatability and extraction efficiency. Method LOQs ranged from 0.4-4.0 ng/g in the selected matrices. Good linearity was obtained over four orders of magnitude starting from LOQs. Isotopically labeled internal

  4. 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...... of formalin-fixed paraffin-imbedded tissue using monoclonal antibodies with defined specificity. In fetal thymus the epithelial cells of the medulla and the Hassal's bodies strongly expressed elongated carbohydrate structures (Le-y, Le-x and sialyl-Le-x). In a few cases the cortical epithelial cells weakly...... expressed Le-x and sialyl-Le-x. Compared with fetal thymus 16 of the thymomas showed a total loss, or a very much reduced expression of elongated carbohydrate structures. Three thymomas, which histologically had been reclassified according to Kirchner & Müller-Hermelink (14) as high grade thymic carcinomas...

  5. Effect of human autologous serum and fetal bovine serum on human corneal epithelial cell viability, migration and proliferation in vitro

    Directory of Open Access Journals (Sweden)

    Ming-Feng Wu

    2017-06-01

    Full Text Available AIM: To analyze the concentration-dependent effects of autologous serum (AS and fetal bovine serum (FBS on human corneal epithelial cell (HCEC viability, migration and proliferation. METHODS: AS was prepared from 13 patients with non-healing epithelial defects Dulbecco's modified eagle medium/Ham’s F12 (DMEM/F12 with 5% FBS, 0.5% dimethyl sulphoxide (DMSO, 10 ng/mL human epidermal growth factor, 1% insulin-transferrin-selenium, then were incubated in serum media: DMEM/F12 supplemented by 5%, 10%, 15% or 30% AS or FBS. HCEC viability was analyzed using cell proliferation kit XTT, migration using a wound healing assay, proliferation by the cell proliferation enzyme-linked immunosorbent assay (ELISA BrdU kit. Statistical analysis was performed using the generalized linear model, the values at 30% AS or 30% FBS were used as the baselines. RESULTS: HCEC viability was the highest at 30% AS or 15% FBS and the lowest at 10% AS or 30% FBS application. HCEC migration was the quickest through 30% AS or 30% FBS and the slowest through 5% AS or 5% FBS concentrations. Proliferation was the most increased through 15% AS or 5% FBS and the least increased through 30% AS or 30% FBS concentrations. HCEC viability at 10% and 15% AS was significantly worse (P=0.001, P=0.023 compared to baseline and significantly better at 15% FBS (P=0.003 concentrations. HCEC migration was significantly worse (P≤0.007 and HCEC proliferation significantly better (P<0.001 in all concentration groups compared to baseline. CONCLUSION: For the best viability of HCEC 30% AS or 15% FBS, for HCEC migration 30% AS or 30% FBS, for proliferation 15% AS or 5% FBS should be used. Therefore, we suggest the use of 30% AS in clinical practice.

  6. Effect of human autologous serum and fetal bovine serum on human corneal epithelial cell viability, migration and proliferation in vitro.

    Science.gov (United States)

    Wu, Ming-Feng; Stachon, Tanja; Seitz, Berthold; Langenbucher, Achim; Szentmáry, Nóra

    2017-01-01

    To analyze the concentration-dependent effects of autologous serum (AS) and fetal bovine serum (FBS) on human corneal epithelial cell (HCEC) viability, migration and proliferation. AS was prepared from 13 patients with non-healing epithelial defects Dulbecco's modified eagle medium/Ham's F12 (DMEM/F12) with 5% FBS, 0.5% dimethyl sulphoxide (DMSO), 10 ng/mL human epidermal growth factor, 1% insulin-transferrin-selenium, then were incubated in serum media: DMEM/F12 supplemented by 5%, 10%, 15% or 30% AS or FBS. HCEC viability was analyzed using cell proliferation kit XTT, migration using a wound healing assay, proliferation by the cell proliferation enzyme-linked immunosorbent assay (ELISA) BrdU kit. Statistical analysis was performed using the generalized linear model, the values at 30% AS or 30% FBS were used as the baselines. HCEC viability was the highest at 30% AS or 15% FBS and the lowest at 10% AS or 30% FBS application. HCEC migration was the quickest through 30% AS or 30% FBS and the slowest through 5% AS or 5% FBS concentrations. Proliferation was the most increased through 15% AS or 5% FBS and the least increased through 30% AS or 30% FBS concentrations. HCEC viability at 10% and 15% AS was significantly worse (P=0.001, P=0.023) compared to baseline and significantly better at 15% FBS (P=0.003) concentrations. HCEC migration was significantly worse (P≤0.007) and HCEC proliferation significantly better (Pmigration 30% AS or 30% FBS, for proliferation 15% AS or 5% FBS should be used. Therefore, we suggest the use of 30% AS in clinical practice.

  7. Human Fetal Exposure to Triclosan and Triclocarban in an Urban Population from Brooklyn, New York

    Science.gov (United States)

    2015-01-01

    Triclosan (TCS) and triclocarban (TCC) are antimicrobial agents formulated in a wide variety of consumer products (including soaps, toothpaste, medical devices, plastics, and fabrics) that are regulated by the U.S. Food and Drug Administration (FDA) and U.S. Environmental Protection Agency. In late 2014, the FDA will consider regulating the use of both chemicals, which are under scrutiny regarding lack of effectiveness, potential for endocrine disruption, and potential contribution to bacterial resistance to antibiotics. Here, we report on body burdens of TCS and TCC resulting from real-world exposures during pregnancy. Using liquid chromatography tandem mass spectrometry, we determined the concentrations of TCS, TCC, and its human metabolites (2′-hydroxy-TCC and 3′-hydroxy-TCC) as well as the manufacturing byproduct (3′-chloro-TCC) as total concentrations (Σ−) after conjugate hydrolysis in maternal urine and cord blood plasma from a cohort of 181 expecting mother/infant pairs in an urban multiethnic population from Brooklyn, NY recruited in 2007–09. TCS was detected in 100% of urine and 51% of cord blood samples after conjugate hydrolysis. The interquartile range (IQR) of detected TCS concentrations in urine was highly similar to the IQR reported previously for the age-matched population of the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004, but typically higher than the IQR reported previously for the general population (detection frequency = 74.6%). Urinary levels of TCC are reported here for the first time from real-world exposures during pregnancy, showing a median concentration of 0.21 μg/L. Urinary concentrations of TCC correlated well with its phase-I metabolite ∑-2′-hydroxy-TCC (r = 0.49) and the manufacturing byproduct ∑-3′-chloro-TCC C (r = 0.79), and ∑-2′-hydroxy-TCC correlated strongly with ∑-3′-hydroxy-TCC (r = 0.99). This human biomonitoring study presents the first body burden data for TCC

  8. CRISPLD2 (LGL1) inhibits proinflammatory mediators in human fetal, adult, and COPD lung fibroblasts and epithelial cells.

    Science.gov (United States)

    Zhang, Hui; Kho, Alvin T; Wu, Qing; Halayko, Andrew J; Limbert Rempel, Karen; Chase, Robert P; Sweezey, Neil B; Weiss, Scott T; Kaplan, Feige

    2016-09-01

    Chronic lung disease of prematurity/bronchopulmonary dysplasia (BPD) is the leading cause of perinatal morbidity in developed countries. Inflammation is a prominent finding. Currently available interventions have associated toxicities and limited efficacy. While BPD often resolves in childhood, survivors of preterm birth are at risk for acquired respiratory disease in early life and are more likely to develop chronic obstructive pulmonary disease (COPD) in adulthood. We previously cloned Crispld2 (Lgl1), a glucocorticoid-regulated mesenchymal secretory protein that modulates lung branching and alveogenesis through mesenchymal-epithelial interactions. Absence of Crispld2 is embryonic lethal. Heterozygous Crispld2+/- mice display features of BPD, including distal airspace enlargement, disruption of elastin, and neonatal lung inflammation. CRISPLD2 also plays a role in human fetal lung fibroblast cell expansion, migration, and mesenchymal-epithelial signaling. This study assessed the effects of endogenous and exogenous CRISPLD2 on expression of proinflammatory mediators in human fetal and adult (normal and COPD) lung fibroblasts and epithelial cells. CRISPLD2 expression was upregulated in a lipopolysaccharide (LPS)-induced human fetal lung fibroblast line (MRC5). LPS-induced upregulation of the proinflammatory cytokines IL-8 and CCL2 was exacerbated in MRC5-CRISPLD2(knockdown) cells. siRNA suppression of endogenous CRISPLD2 in adult lung fibroblasts (HLFs) led to augmented expression of IL-8, IL-6, CCL2. LPS-stimulated expression of proinflammatory mediators by human lung epithelial HAEo- cells was attenuated by purified secretory CRISPLD2. RNA sequencing results from HLF-CRISPLD2(knockdown) suggest roles for CRISPLD2 in extracellular matrix and in inflammation. Our data suggest that suppression of CRISPLD2 increases the risk of lung inflammation in early life and adulthood. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of

  9. 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.

  10. Fetal calcium regulates branching morphogenesis in the developing human and mouse lung: involvement of voltage-gated calcium channels.

    Directory of Open Access Journals (Sweden)

    Sarah C Brennan

    Full Text Available Airway branching morphogenesis in utero is essential for optimal postnatal lung function. In the fetus, branching morphogenesis occurs during the pseudoglandular stage (weeks 9-17 of human gestation, embryonic days (E11.5-16.5 in mouse in a hypercalcaemic environment (~1.7 in the fetus vs. ~1.1-1.3 mM for an adult. Previously we have shown that fetal hypercalcemia exerts an inhibitory brake on branching morphogenesis via the calcium-sensing receptor. In addition, earlier studies have shown that nifedipine, a selective blocker of L-type voltage-gated Ca(2+ channels (VGCC, inhibits fetal lung growth, suggesting a role for VGCC in lung development. The aim of this work was to investigate the expression of VGCC in the pseudoglandular human and mouse lung, and their role in branching morphogenesis. Expression of L-type (CaV1.2 and CaV1.3, P/Q type (CaV2.1, N-type (CaV2.2, R-type (CaV2.3, and T-type (CaV3.2 and CaV3.3 VGCC was investigated in paraffin sections from week 9 human fetal lungs and E12.5 mouse embryos. Here we show, for the first time, that Cav1.2 and Cav1.3 are expressed in both the smooth muscle and epithelium of the developing human and mouse lung. Additionally, Cav2.3 was expressed in the lung epithelium of both species. Incubating E12.5 mouse lung rudiments in the presence of nifedipine doubled the amount of branching, an effect which was partly mimicked by the Cav2.3 inhibitor, SNX-482. Direct measurements of changes in epithelial cell membrane potential, using the voltage-sensitive fluorescent dye DiSBAC2(3, demonstrated that cyclic depolarisations occur within the developing epithelium and coincide with rhythmic occlusions of the lumen, driven by the naturally occurring airway peristalsis. We conclude that VGCC are expressed and functional in the fetal human and mouse lung, where they play a role in branching morphogenesis. Furthermore, rhythmic epithelial depolarisations evoked by airway peristalsis would allow for branching to

  11. Comparative Analysis of KnockOut™ Serum with Fetal Bovine Serum for the In Vitro Long-Term Culture of Human Limbal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Shaokun Zhang

    2016-01-01

    Full Text Available The limbal epithelial cells can be maintained on 3T3 feeder layer with fetal bovine serum supplemented culture medium, and these cells have been used to successfully treat limbal stem cell deficiency. However, fetal bovine serum contains unknown components and displays quantitative and qualitative lot-to-lot variations. To improve the culture condition, the defined KnockOut serum replacement was investigated to replace fetal bovine serum for culturing human limbal epithelial cell. Human primary limbal epithelial cells were cultured in KnockOut serum and fetal bovine serum supplemented medium, respectively. The cell growth rate, gene expression, and maintenance of limbal epithelial stem cells were studied and compared between these two groups. Human primary limbal epithelial cells were isolated and successfully serially cultivated in this novel KnockOut serum supplemented medium; the cell proliferation and stem cell maintenance were similar to those of cells grown in fetal bovine serum supplemented medium. These data suggests that this KnockOut serum supplemented medium is an efficient replacement to traditional fetal bovine serum supplemented medium for limbal epithelial cell culture, and this medium has great potential for long term maintenance of limbal epithelial cells, limbal epithelial stem cells transplantation, and tissue regeneration.

  12. Doppler echocardiography in the human fetus : normal flow velocities and the effect of fetal variables

    NARCIS (Netherlands)

    K. van der Mooren (Karin)

    1992-01-01

    textabstractThe objectives of this thesis were as follows. 1. To establish the intra-observer variability in the assessment of fetal atrioventricular flow velocity parameters in the second half of pregnancy. The results are discussed in chapter 3 .2. 2. To assess the distribution of flow velocity

  13. Human umbilical cord blood plasma can replace fetal bovine serum for in vitro expansion of functional human endothelial colony-forming cells.

    Science.gov (United States)

    Huang, Lan; Critser, Paul J; Grimes, Brenda R; Yoder, Mervin C

    2011-07-01

    A hierarchy of endothelial colony-forming cells (ECFC) with different levels of proliferative potential has been identified in human circulating blood and blood vessels. ECFC has recently become an attractive target for new vascular regenerative therapies; however, in vitro expansion of ECFC typically depends on the presence of fetal bovine serum (FBS) or fetal calf serum (FCS) in the culture medium, which is not appropriate for its therapeutic application. To identify optimal conditions for in vitro expansion of ECFC, the effects of human endothelial serum-free medium (SFM) supplemented with six pro-angiogenic cytokines and human umbilical cord blood plasma (HCP) were investigated. The in vitro morphology, proliferation, surface antigen expression and in vivo vessel-forming ability were utilized for examining the effects of medium on ECFC. This novel formulation of endothelial cell culture medium allows us, for the first time, to isolate and expand human ECFC efficiently in vitro with a low concentration of HCP (1.5%) and without bovine serum additives. In this serum-reduced medium (SRM), human ECFC colony yields remained quantitatively similar to those cultured in a high concentration (10%) of bovine serum-supplemented medium. SRM-cultured ECFC displayed a robust clonal proliferative ability in vitro and human vessel-forming capacity in vivo. The present study provides a novel method for the expansion of human ECFC in vitro and will help to advance approaches for using the cells in human therapeutic trials.

  14. Mice engrafted with human fetal thymic tissue and hematopoietic stem cells develop pathology resembling chronic graft-versus-host disease.

    Science.gov (United States)

    Lockridge, Jennifer L; Zhou, Ying; Becker, Yusof A; Ma, Shidong; Kenney, Shannon C; Hematti, Peiman; Capitini, Christian M; Burlingham, William J; Gendron-Fitzpatrick, Annette; Gumperz, Jenny E

    2013-09-01

    Chronic graft-versus-host disease (cGVHD) is a significant roadblock to long-term hematopoietic stem cell (HSC) transplantation success. Effective treatments for cGVHD have been difficult to develop, in part because of a paucity of animal models that recapitulate the multiorgan pathologies observed in clinical cGVHD. Here we present an analysis of the pathology that occurs in immunodeficient mice engrafted with human fetal HSCs and implanted with fragments of human fetal thymus and liver. Starting at time points generally later than 100 days post-transplantation, the mice developed signs of illness, including multiorgan cellular infiltrates containing human T cells, B cells, and macrophages; fibrosis in sites such as lungs and liver; and thickened skin with alopecia. Experimental manipulations that delayed or reduced the efficiency of the HSC engraftment did not affect the timing or progression of disease manifestations, suggesting that pathology in this model is driven more by factors associated with the engrafted human thymic organoid. Disease progression was typically accompanied by extensive fibrosis and degradation of the thymic organoid, and there was an inverse correlation of disease severity with the frequency of FoxP3(+) thymocytes. Hence, the human thymic tissue may contribute T cells with pathogenic potential, but the generation of regulatory T cells in the thymic organoid may help to control these cells before pathology resembling cGVHD eventually develops. This model thus provides a new system to investigate disease pathophysiology relating to human thymic events and to evaluate treatment strategies to combat multiorgan fibrotic pathology produced by human immune cells. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Human Brain Abnormalities Associated With Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder.

    Science.gov (United States)

    Jarmasz, Jessica S; Basalah, Duaa A; Chudley, Albert E; Del Bigio, Marc R

    2017-09-01

    Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental problem, but neuropathologic descriptions are rare and focused on the extreme abnormalities. We conducted a retrospective survey (1980-2016) of autopsies on 174 individuals with prenatal alcohol exposure or an FASD diagnosis. Epidemiologic details and neuropathologic findings were categorized into 5 age groups. Alcohol exposure was difficult to quantify. When documented, almost all mothers smoked tobacco, many abused other substances, and prenatal care was poor or nonexistent. Placental abnormalities were common (68%) in fetal cases. We identified micrencephaly (brain weight brain abnormalities associated with prenatal alcohol exposure are varied; cause-effect relationships cannot be determined. FASD is likely not a monotoxic disorder. The animal experimental literature, which emphasizes controlled exposure to ethanol alone, is therefore inadequate. Prevention must be the main societal goal, however, a clear understanding of the neuropathology is necessary for provision of care to individuals already affected. © 2017 American Association of Neuropathologists, Inc.

  16. Baby on board: olfactory cues indicate pregnancy and fetal sex in a non-human primate

    Science.gov (United States)

    Crawford, Jeremy Chase; Drea, Christine M.

    2015-01-01

    Olfactory cues play an integral, albeit underappreciated, role in mediating vertebrate social and reproductive behaviour. These cues fluctuate with the signaller's hormonal condition, coincident with and informative about relevant aspects of its reproductive state, such as pubertal onset, change in season and, in females, timing of ovulation. Although pregnancy dramatically alters a female's endocrine profiles, which can be further influenced by fetal sex, the relationship between gestation and olfactory cues is poorly understood. We therefore examined the effects of pregnancy and fetal sex on volatile genital secretions in the ring-tailed lemur (Lemur catta), a strepsirrhine primate possessing complex olfactory mechanisms of reproductive signalling. While pregnant, dams altered and dampened their expression of volatile chemicals, with compound richness being particularly reduced in dams bearing sons. These changes were comparable in magnitude with other, published chemical differences among lemurs that are salient to conspecifics. Such olfactory ‘signatures’ of pregnancy may help guide social interactions, potentially promoting mother–infant recognition, reducing intragroup conflict or counteracting behavioural mechanisms of paternity confusion; cues that also advertise fetal sex may additionally facilitate differential sex allocation. PMID:25716086

  17. Western Zika Virus in Human Fetal Neural Progenitors Persists Long Term with Partial Cytopathic and Limited Immunogenic Effects.

    Science.gov (United States)

    Hanners, Natasha W; Eitson, Jennifer L; Usui, Noriyoshi; Richardson, R Blake; Wexler, Eric M; Konopka, Genevieve; Schoggins, John W

    2016-06-14

    The recent Zika virus (ZIKV) outbreak in the Western hemisphere is associated with severe pathology in newborns, including microcephaly and brain damage. The mechanisms underlying these outcomes are under intense investigation. Here, we show that a 2015 ZIKV isolate replicates in multiple cell types, including primary human fetal neural progenitors (hNPs). In immortalized cells, ZIKV is cytopathic and grossly rearranges endoplasmic reticulum membranes similar to other flaviviruses. In hNPs, ZIKV infection has a partial cytopathic phase characterized by cell rounding, pyknosis, and activation of caspase 3. Despite notable cell death, ZIKV did not activate a cytokine response in hNPs. This lack of cell intrinsic immunity to ZIKV is consistent with our observation that virus replication persists in hNPs for at least 28 days. These findings, supported by published fetal neuropathology, establish a proof-of-concept that neural progenitors in the developing human fetus can be direct targets of detrimental ZIKV-induced pathology. Copyright © 2016. Published by Elsevier Inc.

  18. Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 genea from human fetal brain.

    Science.gov (United States)

    Wu, Q; Xu, M; Cheng, C; Zhou, Z; Huang, Y; Zhao, W; Zeng, L; Xu, J; Fu, X; Ying, K; Xie, Y; Mao, Y

    2001-01-01

    Short-chain dehydrogenases/reductases (SDR) constitute a large protein family of NAD(P)(H)-dependent oxidoreductase. They are defined by distinct, common sequence motifs and show a wide range of substrate specialisms. By large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a novel human SDR-type dehydrogenase/reductase gene named Dehydrogenase/reductase (SDR family) member 1 (DHRS1). The DHRS1 cDNA is 1411 base pair in length, encoding a 314-amino-acid polypeptide which has a SDR motif. Northern blot reveals two bands, of about 0.9 and 1.4 kb in size. These two forms are expressed in many tissues. The DHRS1 gene is localized on chromosome 14q21.3. It has 9 exons and spans 9.2 kb of the genomic DNA.

  19. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    Science.gov (United States)

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary

  20. 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

    Directory of Open Access Journals (Sweden)

    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.

  1. Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves.

    Science.gov (United States)

    van Geemen, Daphne; Soares, Ana L F; Oomen, Pim J A; Driessen-Mol, Anita; Janssen-van den Broek, Marloes W J T; van den Bogaerdt, Antoon J; Bogers, Ad J J C; Goumans, Marie-José T H; Baaijens, Frank P T; Bouten, Carlijn V C

    2016-01-01

    There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation-but more pronounced in aortic valves-the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age.

  2. Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves.

    Directory of Open Access Journals (Sweden)

    Daphne van Geemen

    Full Text Available There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation-but more pronounced in aortic valves-the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age.

  3. Human fetal malformations associated with the use of an angiotensin II receptor antagonist: Case Report

    Directory of Open Access Journals (Sweden)

    Henri Augusto Korkes

    2014-09-01

    Full Text Available Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs and angiotensin receptor antagonists (ARAs are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant.

  4. Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells

    DEFF Research Database (Denmark)

    Jørgensen, N; Rajpert-De Meyts, E; Graem, N

    1995-01-01

    -like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first......-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out of the ten first-trimester gonads. The relative number of germ cells positive for all the markers studied declined rapidly during the first part of the second trimester...

  5. Comprehensive Characterization of Mesenchymal Stem Cells from Human Placenta and Fetal Membrane and Their Response to Osteoactivin Stimulation

    Directory of Open Access Journals (Sweden)

    C. M. Raynaud

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs are the most promising seed cells for cell therapy and can be isolated from various sources of human adult tissues such as bone marrow (BM-MSC and adipose tissue. However, cells from these tissues must be obtained through invasive procedures. We, therefore, characterized MSCs isolated from fresh placenta (Pl-MSC and fetal membrane (Mb-MSC through morphological and fluorescent-activated cell sorting (FACS. MSC frequency is higher in membrane than placenta (2.14%  ± 0.65 versus 15.67%  ± 0.29%. Pl/Mb-MSCs in vitro expansion potential was significantly higher than BM-MSCs. We demonstrated that one of the MSC-specific marker is sufficient for MSC isolation and that culture in specific media is the optimal way for selecting very homogenous MSC population. These MSCs could be differentiated into mesodermal cells expressing cell markers and cytologic staining consistent with mature osteoblasts and adipocytes. Transcriptomic analysis and cytokine arrays demonstrated broad similarity between placenta- and membrane-derived MSCs and only discrete differences with BM-MSCs with enrichment of networks involved in bone differentiation. Pl/Mb-MSCs displayed higher osteogenic differentiation potential than BM-MSC when their response to osteoactivin was evaluated. Fetal-tissue-derived mesenchymal cells may, therefore, be considered as a major source of MSCs to reach clinical scale banking in particular for bone regeneration.

  6. Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells

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    Dehai Yu

    2017-01-01

    Full Text Available Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal. By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.

  7. Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.

    Science.gov (United States)

    Vanleene, Maximilien; Saldanha, Zahraa; Cloyd, Kristy L; Jell, Gavin; Bou-Gharios, George; Bassett, J H Duncan; Williams, Graham R; Fisk, Nicholas M; Oyen, Michelle L; Stevens, Molly M; Guillot, Pascale V; Shefelbine, Sandra J

    2011-01-20

    Osteogenesis imperfecta (OI or brittle bone disease) is a disorder of connective tissues caused by mutations in the collagen genes. We previously showed that intrauterine transplantation of human blood fetal stem/stromal cells in OI mice (oim) resulted in a significant reduction of bone fracture. This work examines the cellular mechanisms and mechanical bone modifications underlying these therapeutic effects, particularly examining the direct effects of donor collagen expression on bone material properties. In this study, we found an 84% reduction in femoral fractures in transplanted oim mice. Fetal blood stem/stromal cells engrafted in bones, differentiated into mature osteoblasts, expressed osteocalcin, and produced COL1a2 protein, which is absent in oim mice. The presence of normal collagen decreased hydroxyproline content in bones, altered the apatite crystal structure, increased the bone matrix stiffness, and reduced bone brittleness. In conclusion, expression of normal collagen from mature osteoblast of donor origin significantly decreased bone brittleness by improving the mechanical integrity of the bone at the molecular, tissue, and whole bone levels.

  8. c-Kit⁺ cells isolated from human fetal retinas represent a new population of retinal progenitor cells.

    Science.gov (United States)

    Zhou, Peng-Yi; Peng, Guang-Hua; Xu, Haiwei; Yin, Zheng Qin

    2015-06-01

    Definitive surface markers for retinal progenitor cells (RPCs) are still lacking. Therefore, we sorted c-Kit(+) and stage-specific embryonic antigen-4(-) (SSEA4(-)) retinal cells for further biological characterization. RPCs were isolated from human fetal retinas (gestational age of 12-14 weeks). c-Kit(+)/SSEA4(-) RPCs were sorted by fluorescence-activated cell sorting, and their proliferation and differentiation capabilities were evaluated by using immunocytochemistry and flow cytometry. The effectiveness and safety were assessed following injection of c-Kit(+)/SSEA4(-) cells into the subretina of Royal College of Surgeons (RCS) rats. c-Kit(+) cells were found in the inner part of the fetal retina. Sorted c-Kit(+)/SSEA4(-) cells expressed retinal stem cell markers. Our results clearly demonstrate the proliferative potential of these cells. Moreover, c-Kit(+)/SSEA4(-) cells differentiated into retinal cells that expressed markers of photoreceptor cells, ganglion cells and glial cells. These cells survived for at least 3 months after transplantation into the host subretinal space. Teratomas were not observed in the c-Kit(+)/SSEA4(-)-cell group. Thus, c-Kit can be used as a surface marker for RPCs, and c-Kit(+)/SSEA4(-) RPCs exhibit the ability to self-renew and differentiate into retinal cells. © 2015. Published by The Company of Biologists Ltd.

  9. Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

    Science.gov (United States)

    Vadasz, Brian; Chen, Pingguo; Yougbaré, Issaka; Zdravic, Darko; Li, June; Li, Conglei; Carrim, Naadiya; Ni, Heyu

    2017-01-01

    Platelets play critical roles in hemostasis and thrombosis. Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states. Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy. Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus, and ultimately lead to maternal alloimmunization. FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage. Proper diagnosis, prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies. Given the ethical difficulties in performing basic research on human fetuses and neonates, animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT. The aim of this review is to provide an overview on platelets, hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models. PMID:28345015

  10. Early fetal development of hard tissue pulleys for the human superior oblique and tensor veli palatini muscles.

    Science.gov (United States)

    Katori, Yukio; Rodríguez-Vázquez, Jose Francisco; Kawase, Tetsuaki; Murakami, Gen; Cho, Baik Hwan; Abe, Shin-ichi

    2011-03-01

    The trochlea for the superior oblique muscle as well as the hamulus for the tensor veli palatini muscle is well known as a fibrocartilage-associated, hard tissue pulley that changes the direction of the tendon. However, details of the fetal development of these structures remain obscure. We carried out a histological study of hematoxylin-eosin-stained preparations from 20 human fetuses (7-15 weeks of gestation) and clarified a common rule for the formation of these pulleys: changing in the location of a structure for the muscle insertion. At the early stage, the muscle and insertion exhibit an almost straight course alongside the primitive pulley, but because the structure for insertion later moves away from a straight line along which the muscle acts, the tendon begins to turn around the cartilage by 12 weeks. The posterior shift of the soft palate is clearly evident, but rotation of the sclera or eyeball is difficult to identify in sections. To some degree, the trochlea may originate from a common anlage with the sclera. We hypothesize that, from the evolutionary point of view, the hamulus or trochlea do not form for the pulley itself but as a structure independent of the related muscle function. The fetal topographical anatomy around the tensor veli palatini, as well as its relationship to the tensor tympani, is also described. Copyright © 2011 Elsevier GmbH. All rights reserved.

  11. Zika virus damages the human placental barrier and presents marked fetal neurotropism

    Directory of Open Access Journals (Sweden)

    Lucia de Noronha

    2016-01-01

    Full Text Available An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

  12. Human fetal skin fibroblasts: Extremely potent and allogenic candidates for treatment of diabetic wounds.

    Science.gov (United States)

    Larijani, Bagher; Ghahari, Aziz; Warnock, Garth L; Aghayan, Hamid Reza; Goodarzi, Parisa; Falahzadeh, Khadijeh; Arjmand, Babak

    2015-06-01

    The number of patients with diabetes has been expected around 300 million by 2025 and 366 million by 2030 by WHO. On the other hand, diabetic wounds as one of the common complications of diabetes represent major health challenges. Recently, wound care biological products have been proposed for treatment of chronic wounds such as the diabetic wound. Accordingly, tissue-engineered skin substitutes have demonstrated promising effects. Some of these products have used adult skin and neonatal foreskin fibroblasts to produce a tissue-engineered skin substitute. Although adult skin and neonatal foreskin fibroblasts have demonstrated promising effects, but fetal skin fibroblasts and keratinocytes have depicted some unique and considerable properties over adult and neonatal skin cells for instance, skin regeneration with no inflammation and scar formation, low immunogenicity, more VEGF-A secretion than their adult counterparts, immunomodulatory effect by the expression of Indoleamine 2,3 dioxygenase, more resistance to oxidative and physical stresses, etc. On the other hand fetal dermal cells with intrinsic IDO-dependent immunosuppressive activity have introduced them as an allogeneic alternative for treatment of chronic wounds. Therefore, based on the mentioned advantages they are ideal skin substitutes. Accordingly, we suggest that using these cells alone or in combination with biocompatible scaffolds for treatment of different types of ulcers such as diabetic wounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Fetal Polydactyly

    National Research Council Canada - National Science Library

    Filges, Isabel; Kang, Anjeung; Hench, Jürgen; Wenzel, Friedel; Bruder, Elisabeth; Miny, Peter; Tercanli, Sevgi

    2011-01-01

    Records of 24 pregnancies with fetal polydactyly were reviewed for the type of polydactyly, family history, associated sonographic findings, genetic testing, and postnatal/postmortem examination findings...

  14. Clinical grade cultivation of human Schwann cell, by the using of human autologous serum instead of fetal bovine serum and without growth factors.

    Science.gov (United States)

    Aghayan, Hamid-Reza; Arjmand, Babak; Norouzi-Javidan, Abbas; Saberi, Hooshang; Soleimani, Masoud; Tavakoli, Seyed Amir-Hossein; Khodadadi, Abbas; Tirgar, Niloufar; Mohammadi-Jahani, Fereshteh

    2012-06-01

    Clinical grade cultivation of human schwann cell by the utilization of human autologous serum instead of fetal bovine serum, and also avoiding any growth factors, can increase safety level of this procedure in cases of clinical cell transplantation. The aim of this study was demonstration of the feasibility of clinical grade schwann cell cultivation. In this experimental study after obtaining consent from close relatives we harvested 10 sural nerves from brain death donors and then cultured in 10 seperated culture media plus autologous serum. We also prepared autologous serum from donor's whole blood. Then cultured cells were evaluated by S100 antibody staining for both morphology and purity. Cell purity range was from 97% to 99% (mean=98.11 ± 0.782%). Mean of the cell count was 14,055.56 ± 2,480.479 per micro liter. There was not significant correlation between cell purity and either the culture period or the age of donors (P>0.05). The spearman correlation coefficient for the cell purity with the period or the age of donors was 0.21 and 0.09, respectively. We demonstrated the feasibility of clinical grade schwann cell cultivation by the using of human autologous serum instead of fetal bovine serum and also without the using of growth factors. We also recommended all cell preparation facilities to adhere to the GMP and other similar quality disciplines especially in the preparation of clinically-used cell products.

  15. 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,...

  16. Absence of oncogenic transformation despite acquisition of cytogenetic aberrations in long-term cultured telomerase-immortalized human fetal hepatocytes.

    Science.gov (United States)

    Haker, Björn; Fuchs, Sigrid; Dierlamm, Judith; Brümmendorf, Tim H; Wege, Henning

    2007-10-18

    As a culture model to study hepatocarcinogenesis, telomerase-immortalized human fetal hepatocytes were monitored for karyotype changes evolving in long-term culture and development of functional defects in DNA damage response. G-banding revealed acquisition of characteristic karyotype abnormalities, e.g., trisomy 7 and monosomy X, in two independently immortalized and cultured populations after 80-100 population doublings. Interestingly, the detected aneuploidies resemble some of the genetic events observed in hepatocellular cancer. However, these genetic changes were not sufficient to induce oncogenic transformation reflected by absence of anchorage-independent growth. Furthermore, long-term cultured telomerase-immortalized cells preserved p53 expression levels and effective p53-mediated damage response.

  17. Cultured primary human fetal retinal pigment epithelium (hfRPE) as a model for evaluating RPE metabolism.

    Science.gov (United States)

    Adijanto, Jeffrey; Philp, Nancy J

    2014-09-01

    Mitochondrial dysfunction has been shown to contribute to age-related and proliferative retinal diseases. Over the past decade, the primary human fetal RPE (hfRPE) culture model has emerged as an effective tool for studying RPE function and mechanisms of retinal diseases. This model system has been rigorously characterized and shown to closely resemble native RPE cells at the genomic and protein level, and that they are capable of accomplishing the characteristic functions of a healthy native RPE (e.g., rod phagocytosis, ion and fluid transport, and retinoid cycle). In this review, we demonstrated that the metabolic activity of the RPE is an indicator of its health and state of differentiation, and present the hfRPE culture model as a valuable in vitro system for evaluating RPE metabolism in the context of RPE differentiation and retinal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Linn S Strandberg

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  19. Germ cell numbers in human embryonic and fetal gonads during the first two trimesters of pregnancy: analysis of six published studies

    DEFF Research Database (Denmark)

    Mamsen, LS; Lutterodt, Melissa Catherine R; Andersen, Elisabeth Anne Wreford

    2011-01-01

    The number of germ cells in human embryonic and fetal ovaries in relation to age is currently based on volumetric estimations from one study including a total of 12 ovaries. Six recent publications present stereological estimations of the number of germ cells in ovaries and testes for the first t...

  20. 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

  1. Where the O2 goes to: preservation of human fetal oxygen delivery and consumption at high altitude.

    Science.gov (United States)

    Postigo, Lucrecia; Heredia, Gladys; Illsley, Nicholas P; Torricos, Tatiana; Dolan, Caitlin; Echalar, Lourdes; Tellez, Wilma; Maldonado, Ivan; Brimacombe, Michael; Balanza, Elfride; Vargas, Enrique; Zamudio, Stacy

    2009-02-01

    Fetal growth is decreased at high altitude (> 2700 m). We hypothesized that variation in fetal O(2) delivery might account for both the altitude effect and the relative preservation of fetal growth in multigenerational natives to high altitude. Participants were 168 women of European or Andean ancestry living at 3600 m or 400 m. Ancestry was genetically confirmed. Umbilical vein blood flow was measured using ultrasound and Doppler. Cord blood samples permitted calculation of fetal O(2) delivery and consumption. Andean fetuses had greater blood flow and oxygen delivery than Europeans and weighed more at birth, regardless of altitude (+208 g, P 200 g lower for Europeans at any given level of blood flow or O(2) delivery. Fetal haemoglobin concentration was increased, decreased, and the fetal / curve was left-shifted at 3600 m. Fetuses receiving less O(2) extracted more (r(2) = 0.35, P < 0.0001). These adaptations resulted in similar fetal O(2) delivery and consumption across all four groups. Increased umbilical venous O(2) delivery correlated with increased fetal O(2) consumption per kg weight (r(2) = 0.50, P < 0.0001). Blood flow (r(2) = 0.16, P < 0.001) and O(2) delivery (r(2) = 0.17, P < 0.001) correlated with birth weight at 3600 m, but not at 400 m (r(2) = 0.04, and 0.03, respectively). We concluded that the most pronounced difference at high altitude is reduced fetal blood flow, but fetal haematological adaptation and fetal capacity to increase O(2) extraction indicates that deficit in fetal oxygen delivery is unlikely to be causally associated with the altitude- and ancestry-related differences in fetal growth.

  2. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells

    Science.gov (United States)

    Zalzman, Michal; Gupta, Sanjeev; Giri, Ranjit K.; Berkovich, Irina; Sappal, Baljit S.; Karnieli, Ohad; Zern, Mark A.; Fleischer, Norman; Efrat, Shimon

    2003-06-01

    Beta-cell replacement is considered to be the most promising approach for treatment of type 1 diabetes. Its application on a large scale is hindered by a shortage of cells for transplantation. Activation of insulin expression, storage, and regulated secretion in stem/progenitor cells offers novel ways to overcome this shortage. We explored whether fetal human progenitor liver cells (FH) could be induced to differentiate into insulin-producing cells after expression of the pancreatic duodenal homeobox 1 (Pdx1) gene, which is a key regulator of pancreatic development and insulin expression in beta cells. FH cells possess a considerable replication capacity, and this was further extended by introduction of the gene for the catalytic subunit of human telomerase. Immortalized FH cells expressing Pdx1 activated multiple beta-cell genes, produced and stored considerable amounts of insulin, and released insulin in a regulated manner in response to glucose. When transplanted into hyperglycemic immunodeficient mice, the cells restored and maintained euglycemia for prolonged periods. Quantitation of human C-peptide in the mouse serum confirmed that the glycemia was normalized by the transplanted human cells. This approach offers the potential of a novel source of cells for transplantation into patients with type 1 diabetes.

  3. Quantitative structure-activity relationship model for the fetal-maternal blood concentration ratio of chemicals in humans.

    Science.gov (United States)

    Takaku, Tomoyuki; Nagahori, Hirohisa; Sogame, Yoshihisa; Takagi, Tatsuya

    2015-01-01

    A quantitative structure-activity relationship (QSAR) model of the fetal-maternal blood concentration ratio (F/M ratio) of chemicals was developed to predict the placental transfer in humans. Data on F/M ratio of 55 compounds found in the literature were separated into training (75%, 41 compounds) and testing sets (25%, 14 compounds). The training sets were then subjected to multiple linear regression analysis using the descriptors of molecular weight (MW), topological polar surface area (TopoPSA), and maximum E-state of hydrogen atom (Hmax). Multiple linear regression analysis and a cross-validation showed a relatively high adjusted coefficient of determination (Ra(2)) (0.73) and cross-validated coefficient of determination (Q(2)) (0.71), after removing three outliers. In the external validation, R(2) for external validation (R(2)pred) was calculated to be 0.51. These results suggested that the QSAR model developed in this study can be considered reliable in terms of its robustness and predictive performance. Since it is difficult to examine the F/M ratio in humans experimentally, this QSAR model for prediction of the placental transfer of chemicals in humans could be useful in risk assessment of chemicals in humans.

  4. Multiparametric Phenotypic Screening System for Profiling Bioactive Compounds Using Human Fetal Hippocampal Neural Stem/Progenitor Cells.

    Science.gov (United States)

    Tabata, Yoshikuni; Murai, Norio; Sasaki, Takeo; Taniguchi, Sachie; Suzuki, Shuichi; Yamazaki, Kazuto; Ito, Masashi

    2015-10-01

    Stem cell research has been progressing rapidly, contributing to regenerative biology and regenerative medicine. In this field, small-molecule compounds affecting stem cell proliferation/differentiation have been explored to understand stem cell biology and support regenerative medicine. In this study, we established a multiparametric screening system to detect bioactive compounds affecting the cell fate of human neural stem/progenitor cells (NSCs/NPCs), using human fetal hippocampal NSCs/NPCs, HIP-009 cells. We examined effects of 410 compounds, which were collected based on mechanisms of action (MOAs) and chemotypes, on HIP-009's cell fate (self-renewal, neuronal and astrocytic differentiation) and morphology by automated multiparametric assays and profiled induced cellular phenotypes. We found that this screening classified compounds with the same MOAs into subgroups according to additional pharmacological effects (e.g., mammalian target of rapamycin complex 1 [mTORC1] inhibitors and mTORC1/mTORC2 dual inhibitors among mTOR inhibitors). Moreover, it identified compounds that have off-target effects under matrix analyses of MOAs and structure similarities (e.g., neurotropic effects of amitriptyline among tri- and tetracyclic compounds). Therefore, this automated, medium-throughput and multiparametric screening system is useful for finding compounds that affect the cell fate of human NSCs/NPCs for supporting regenerative medicine and to fingerprint compounds based on human stem cells' multipotency, leading to understanding of stem cell biology. © 2015 Society for Laboratory Automation and Screening.

  5. Beyond The Anticipatory Corpse-Future Perspectives for Bioethics.

    Science.gov (United States)

    Haker, Hille

    2016-12-01

    This essay explores the two main objectives of Bishop's book, which he analyzes in the context of the care for the dying: (1) the medical metaphysics underlying medical science and (2) biopolitics as governance of the human body. This essay discusses Bishop's claims in view of newer developments in medicine, especially the turn to the construction of life, and confronts the concept of the patient's sovereignty with an alternative model of vulnerable agency. In order to overcome the impasses of contemporary bioethics, the essay argues that practical reason requires a two-fold ethics: first, it must develop a new hermeneutics of illness and disease, and second, in order to protect the individuals in the process of dying, moral claims concerning death must be based on the concept of human rights. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Fetal Abuse.

    Science.gov (United States)

    Kent, Lindsey; And Others

    1997-01-01

    Five cases of fetal abuse by mothers suffering from depression are discussed. Four of the women had unplanned pregnancies and had considered termination of the pregnancy. Other factors associated with fetal abuse include pregnancy denial, pregnancy ambivalence, previous postpartum depression, and difficulties in relationships. Vigilance for…

  7. An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.

    Directory of Open Access Journals (Sweden)

    Martha J Harding

    2010-04-01

    Full Text Available Widely accessible small animal models suitable for the study of hepatitis C virus (HCV in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice.We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH within a vascularized rat collagen type I/human fibronectin (rCI/hFN gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC in severe combined immunodeficient X beige (SCID/bg mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7 mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM components and/or hepatocyte growth factor (HGF-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM analyses of gel tissue.The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo.

  8. An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.

    Science.gov (United States)

    Harding, Martha J; Lepus, Christin M; Gibson, Thomas F; Shepherd, Benjamin R; Gerber, Scott A; Graham, Morven; Paturzo, Frank X; Rahner, Christoph; Madri, Joseph A; Bothwell, Alfred L M; Lindenbach, Brett D; Pober, Jordan S

    2010-04-01

    Widely accessible small animal models suitable for the study of hepatitis C virus (HCV) in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice. We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH) within a vascularized rat collagen type I/human fibronectin (rCI/hFN) gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC) in severe combined immunodeficient X beige (SCID/bg) mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7) mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM) components and/or hepatocyte growth factor (HGF)-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM) analyses of gel tissue. The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo.

  9. Engraftment potential of adipose tissue-derived human mesenchymal stem cells after transplantation in the fetal rabbit.

    Science.gov (United States)

    Martínez-González, Itziar; Moreno, Rafael; Petriz, Jordi; Gratacós, Eduard; Aran, Josep M

    2012-12-10

    Due to their favorable intrinsic features, including engraftment, differentiation, and immunomodulatory potential, adult mesenchymal stem cells (MSCs) have been proposed for therapeutic in utero intervention. Further improvement of such attributes for particular diseases might merely be achieved by ex vivo MSC genetic engineering previous to transplantation. Here, we evaluated for the first time the feasibility, biodistribution, long-term engraftment, and transgenic enhanced green fluorescent protein (EGFP) expression of genetically engineered human adipose tissue-derived MSCs (EGFP(+)-ASCs) after intra-amniotic xenotransplantation at E17 of gestation into our validated pregnant rabbit model. Overall, the procedure was safe (86.4% survival rate; absence of anatomical defects). Stable, low-level engraftment of EGFP(+)-ASCs was confirmed by assessing the presence of the pWT-EGFP lentiviral provirus in the young transplanted rabbit tissues. Accordingly, similar frequencies of provirus-positive animals were found at both 8 weeks (60%) and 16 weeks (66.7%) after in utero intervention. The presence of EGFP(+)-ASCs was more frequent in respiratory epithelia (lung and trachea), according to the route of administration. However, we were unable to detect EGFP expression, neither by real-time polymerase chain reaction nor by immunohistochemistry, in the provirus-positive tissues, suggesting EGFP transgene silencing mediated by epigenetic events. Moreover, we noticed lack of both host cellular immune responses against xenogeneic ASCs and humoral immune responses against transgenic EGFP. Therefore, the fetal microchimerism achieved by the EGFP(+)-ASCs in the young rabbit hosts indicates induction of donor-specific tolerance after fetal rabbit xenotransplantation, which should boost postnatal transplantation for the early treatment/prevention of many devastating congenital disorders.

  10. Human fetal anatomy of the posterior semimembranosus complex at the knee with special reference to the gastrocnemio-semimembranosus bursa.

    Science.gov (United States)

    Nakamura, Takuo; Suzuki, Daisuke; Murakami, Gen; Cho, Baik Hwan; Fujimiya, Mineko; Kozuka, Naoki

    2011-08-01

    There is little information on the fetal anatomy of the posterior semimembranosus tendinous complex and its associated bursa. We examined histological sections (transverse or sagittal) of the right or left knee in 13 mid-term human fetuses (12-25 weeks of gestation). The medial head of the gastrocnemius provided an aponeurosis facing or attached to the muscles of the pes anserinus by 12 weeks of gestation. The peritendinous tissue of the semimembranosus provided a bursa continuous with a laterally extending plate-like tissue by 15 weeks, but sometimes the typical bursa was absent. The aponeurosis of the medial head consistently accompanied a bursa-like space (false bursa) surrounded by heterogenous structures including the popliteus and a wall of the semimembranosus bursa. Sagittal sections displayed notches on the medial head surface that received the semimembranosus and semitendinosus overriding the medial head of the gastrocnemius. In contrast to a real bursa originating from the peritendinous tissue of the semimembranosus, a false bursa without a homogeneous wall consistently develops at the origin of the medial head of the gastrocnemius. Due to mechanical stress from the tendons, the false bursa is likely to develop into a structure similar to a real bursa with a synovial lining even if the real bursa is absent in the fetus. We hypothesize that the adult gastrocnemio-semimembranosus bursa, largely or partly, originates from the fetal false bursa. Absolute resection of the false bursa is difficult because it is a mere gap between normal tissues. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Modeling of coarctation of aorta in human fetuses using 3D/4D fetal echocardiography and computational fluid dynamics.

    Science.gov (United States)

    Chen, Zhuo; Zhou, Yue; Wang, Jingying; Liu, Xiaowei; Ge, Shuping; He, Yihua

    2017-12-01

    We sought to develop a hemodynamic model of aortic and ductal arches using computational fluid dynamics (CFD) and 3D/4D spatio-temporal image correlation (STIC) fetal echocardiography and to investigate the hemodynamics of coarctation of aorta (CoA) in human fetuses using this approach. We obtained 3D/4D STIC fetal echocardiographic images of the aortic and ductal arches (DA) in five normal fetuses. Based on these images, we simulated the hemodynamics in the two arches using CFD. Subsequently, we reduced the dimensions of aortic isthmus from 100% to 85%, 70%, 55%, 40%, and 25% of the original dimension digitally. Numerical simulation was repeated in each condition, and flow profile, velocity, pressure, and wall shear stress (WSS) were compared with those of the baseline normal aortic and ductal arches. With the progressive narrowing in the aortic isthmus, there were alterations in the flow profile, velocity, pressure, and WSS. The downstream vortexes disappeared, and the double helix profile became single helix. When the aortic isthmus reduced by 55% in dimension, there was an exponential increase in velocity and WSS and decrease in pressure. The aortic and ductal arch geometry and flow lead to the alterations in flow profile, velocity, pressure, and WSS in the aortic isthmus in normal and CoA models, which are conductive of ductal issue migration into these areas. A 55% reduction in the dimension of aortic isthmus is associated with exponential change in velocity, pressure, and WSS, a probable threshold for hemodynamically significant CoA. © 2017, Wiley Periodicals, Inc.

  12. Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans.

    Science.gov (United States)

    Wiputra, Hadi; Lai, Chang Quan; Lim, Guat Ling; Heng, Joel Jia Wei; Guo, Lan; Soomar, Sanah Merchant; Leo, Hwa Liang; Biwas, Arijit; Mattar, Citra Nurfarah Zaini; Yap, Choon Hwai

    2016-12-01

    There are 0.6-1.9% of US children who were born with congenital heart malformations. Clinical and animal studies suggest that abnormal blood flow forces might play a role in causing these malformation, highlighting the importance of understanding the fetal cardiovascular fluid mechanics. We performed computational fluid dynamics simulations of the right ventricles, based on four-dimensional ultrasound scans of three 20-wk-old normal human fetuses, to characterize their flow and energy dynamics. Peak intraventricular pressure gradients were found to be 0.2-0.9 mmHg during systole, and 0.1-0.2 mmHg during diastole. Diastolic wall shear stresses were found to be around 1 Pa, which could elevate to 2-4 Pa during systole in the outflow tract. Fetal right ventricles have complex flow patterns featuring two interacting diastolic vortex rings, formed during diastolic E wave and A wave. These rings persisted through the end of systole and elevated wall shear stresses in their proximity. They were observed to conserve ∼25.0% of peak diastolic kinetic energy to be carried over into the subsequent systole. However, this carried-over kinetic energy did not significantly alter the work done by the heart for ejection. Thus, while diastolic vortexes played a significant role in determining spatial patterns and magnitudes of diastolic wall shear stresses, they did not have significant influence on systolic ejection. Our results can serve as a baseline for future comparison with diseased hearts. Copyright © 2016 the American Physiological Society.

  13. Human Serum is as Efficient as Fetal Bovine Serum in Supporting Proliferation and Differentiation of Human Multipotent Stromal (Mesenchymal) Stem Cells In Vitro and In Vivo

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Haack-Sørensen, Mandana; Al-Nbaheen, May

    2011-01-01

    BACKGROUND: Human multipotent stromal (skeletal, mesenchymal) stem cells (hMSC) are employed in an increasing number of clinical trials for tissue regeneration of age-related degenerative diseases. However, routine use of fetal bovine sera (FBS) for their in vitro expansion is not optimal and may...... pose a health risk for patients. METHODS: We carried out a side-by-side comparison of the effects of allogenic pooled human serum (HuS) versus FBS on hMSC proliferation and differentiation in vitro and in vivo. As a model for hMSC, we employed telomerase-immortalized hMSC; hMSC-TERT cell line. RESULTS....... FBS. hMSC-TERT or primary bone marrow derived hMSC induced to osteoblastic or adipocytic differentiation in the presence of HuS or FBS showed comparable levels of gene expression and protein production of osteoblastic markers (CBFA1/Runx2, alkaline phosphastase, collagen type I and osteocalcin...

  14. Increased fetal hemoglobin levels in patients infected with human immunodeficiency virus (HIV1/2

    Directory of Open Access Journals (Sweden)

    A. Poli-Neto

    2000-11-01

    Full Text Available Fetal hemoglobin was measured in HIV1/2 patients under treatment with combined therapy (zidovudine and a protease inhibitor. A total of 143 patients and 103 normal individuals were investigated by the quantitative method of Betke and the semi-quantitative acid elution method of Kleihauer. In the normal person, hemoglobin F makes up less than 1% and an increase higher than 1.5% was observed in 21.4% of HIV patients by the method of Betke and in 24.8% of HIV-infected patients by the method of Kleihauer. The quantitative biochemical method of Betke showed that the populations were significantly different (two-tailed Mann-Whitney test. The reason for this hemoglobin F increase might be ascribed to the effect of zidovudine or to direct viral action on gamma chain expression. The finding of a higher F cell frequency indicated by the method of Kleihauer rather suggests that there is an increased F cell clone proliferation rather than an increase in hemoglobin F level in every cell.

  15. Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders: From Animal Models to Human Studies.

    Science.gov (United States)

    Murawski, Nathen J; Moore, Eileen M; Thomas, Jennifer D; Riley, Edward P

    2015-01-01

    Prenatal alcohol exposure can cause a number of physical, behavioral, cognitive, and neural impairments, collectively known as fetal alcohol spectrum disorders (FASD). This article examines basic research that has been or could be translated into practical applications for the diagnosis or treatment of FASD. Diagnosing FASD continues to be a challenge, but advances are being made at both basic science and clinical levels. These include identification of biomarkers, recognition of subtle facial characteristics of exposure, and examination of the relation between face, brain, and behavior. Basic research also is pointing toward potential new interventions for FASD involving pharmacotherapies, nutritional therapies, and exercise interventions. Although researchers have assessed the majority of these treatments in animal models of FASD, a limited number of recent clinical studies exist. An assessment of this literature suggests that targeted interventions can improve some impairments resulting from developmental alcohol exposure. However, combining interventions may prove more efficacious. Ultimately, advances in basic and clinical sciences may translate to clinical care, improving both diagnosis and treatment.

  16. 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...

  17. Human CD34(lo)CD133(lo) fetal liver cells support the expansion of human CD34(hi)CD133(hi) hematopoietic stem cells.

    Science.gov (United States)

    Yong, Kylie Su Mei; Keng, Choong Tat; Tan, Shu Qi; Loh, Eva; Chang, Kenneth Te; Tan, Thiam Chye; Hong, Wanjin; Chen, Qingfeng

    2016-09-01

    We have recently discovered a unique CD34(lo)CD133(lo) cell population in the human fetal liver (FL) that gives rise to cells in the hepatic lineage. In this study, we further characterized the biological functions of FL CD34(lo)CD133(lo) cells. Our findings show that these CD34(lo)CD133(lo) cells express markers of both endodermal and mesodermal lineages and have the capability to differentiate into hepatocyte and mesenchymal lineage cells by ex vivo differentiation assays. Furthermore, we show that CD34(lo)CD133(lo) cells express growth factors that are important for human hematopoietic stem cell (HSC) expansion: stem cell factor (SCF), insulin-like growth factor 2 (IGF2), C-X-C motif chemokine 12 (CXCL12), and factors in the angiopoietin-like protein family. Co-culture of autologous FL HSCs and allogenic HSCs derived from cord blood with CD34(lo)CD133(lo) cells supports and expands both types of HSCs.These findings are not only essential for extending our understanding of the HSC niche during the development of embryonic and fetal hematopoiesis but will also potentially benefit adult stem cell transplantations in clinics because expanded HSCs demonstrate the same capacity as primary cells to reconstitute the human immune system and mediate long-term hematopoiesis in vivo. Together, CD34(lo)CD133(lo) cells not only serve as stem/progenitor cells for liver development but are also an essential component of the HSC niche in the human FL.

  18. Human rights begin at birth: international law and the claim of fetal rights.

    Science.gov (United States)

    Copelon, Rhonda; Zampas, Christina; Brusie, Elizabeth; Devore, Jacqueline

    2005-11-01

    In the Universal Declaration of Human Rights, the foundation of human rights, the text and negotiating history of the "right to life" explicitly premises human rights on birth. Likewise, other international and regional human rights treaties, as drafted and/or subsequently interpreted, clearly reject claims that human rights should attach from conception or any time before birth. They also recognise that women's right to life and other human rights are at stake where restrictive abortion laws are in place. This paper reviews the International Covenant on Civil and Political Rights, the Convention on the Rights of the Child, and the Convention on the Elimination of All Forms of Discrimination Against Women, the European Convention for the Protection of Human Rights and Fundamental Freedoms, the Inter-American Human Rights Agreements and African Charter on Human and People's Rights in this regard. No one has the right to subordinate another in the way that unwanted pregnancy subordinates a woman by requiring her to risk her own health and life to save her own child. Thus, the long-standing insistence of women upon voluntary motherhood is a demand for minimal control over one's destiny as a human being. From a human rights perspective, to depart from voluntary motherhood would impose upon women an extreme form of discrimination and forced labour.

  19. Pseudotyped AAV vector-mediated gene transfer in a human fetal trachea xenograft model: implications for in utero gene therapy for cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Sundeep G Keswani

    Full Text Available Lung disease including airway infection and inflammation currently causes the majority of morbidities and mortalities associated with cystic fibrosis (CF, making the airway epithelium and the submucosal glands (SMG novel target cells for gene therapy in CF. These target cells are relatively inaccessible to postnatal gene transfer limiting the success of gene therapy. Our previous work in a human-fetal trachea xenograft model suggests the potential benefit for treating CF in utero. In this study, we aim to validate adeno-associated virus serotype 2 (AAV2 gene transfer in a human fetal trachea xenograft model and to compare transduction efficiencies of pseudotyping AAV2 vectors in fetal xenografts and postnatal xenograft controls.Human fetal trachea or postnatal bronchus controls were xenografted onto immunocompromised SCID mice for a four-week engraftment period. After injection of AAV2/2, 2/1, 2/5, 2/7 or 2/8 with a LacZ reporter into both types of xenografts, we analyzed for transgene expression in the respiratory epithelium and SMGs. At 1 month, transduction by AAV2/2 and AAV2/8 in respiratory epithelium and SMG cells was significantly greater than that of AAV2/1, 2/5, and 2/7 in xenograft tracheas. Efficiency in SMG transduction was significantly greater in AAV2/8 than AAV2/2. At 3 months, AAV2/2 and AAV2/8 transgene expression was >99% of respiratory epithelium and SMG. At 1 month, transduction efficiency of AAV2/2 and AAV2/8 was significantly less in adult postnatal bronchial xenografts than in fetal tracheal xenografts.Based on the effectiveness of AAV vectors in SMG transduction, our findings suggest the potential utility of pseudotyped AAV vectors for treatment of cystic fibrosis. The human fetal trachea xenograft model may serve as an effective tool for further development of fetal gene therapy strategies for the in utero treatment of cystic fibrosis.

  20. First-trimester screening biochemical markers (free beta-subunit human chorionic gonadotropin, pregnancy-associated plasma protein-A) and risk of early fetal loss.

    Science.gov (United States)

    Valbuena, Henar; Ramis, Jordi; Sagalá, Juan; Sánchez, M Ángeles; Aulesa, Carlos

    2015-01-01

    The aim of this work was to assess the risk of early fetal loss (first trimester of pregnancy, 8-13 weeks of gestation) using the results of first-trimester screening (FTS) biochemical markers independently and combined. FTS results of 152 women who suffered early fetal loss were compared to a control group of 150 women with normal pregnancy outcomes. FTS biochemical markers were measured with a Delfia Xpress 6000 analyzer and biochemical risks for Down's and Edward's syndromes were calculated using Prenatal-Lifecycle version 3.0 software. Marker levels were standardized by calculating the gestational-specific multiple of the medians (MoM), further adjusted by maternal age, maternal weight, cigarette consumption and pre-existing type 1 diabetes mellitus. Receiver-operator curves were built to evaluate each marker and its combination. Our results show that values of biochemical risk of t21 of more than 1 in 310 have a poor sensitivity to predict early fetal loss (31.4%) with a positive predictive value (PPV) for fetal loss of 67.7%. Values of pregnancy-associated plasma protein A (PAPP-A) MoM of less than 0.48 show a sensitivity of 62.1% and a PPV of 84.5% for early fetal loss; whereas for free β-human chorionic gonadotropin, values of MoM of less than 0.44 have a sensitivity of 66.4% with a PPV of 85.3%. A novel algorithm, consisting in the multiplication of both markers, shows for values of less than 0.48 a sensitivity of 83.1%, a specificity of 78.7% and a PPV of 77.1%. Combined analysis of PAPP-A and free β-hCG appears to be a potential candidate to predict early fetal loss. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  1. MicroRNA expression profiles of human iPS cells, retinal pigment epithelium derived from iPS, and fetal retinal pigment epithelium.

    Science.gov (United States)

    Greene, Whitney A; Muñiz, Alberto; Plamper, Mark L; Kaini, Ramesh R; Wang, Heuy-Ching

    2014-06-24

    The objective of this report is to describe the protocols for comparing the microRNA (miRNA) profiles of human induced-pluripotent stem (iPS) cells, retinal pigment epithelium (RPE) derived from human iPS cells (iPS-RPE), and fetal RPE. The protocols include collection of RNA for analysis by microarray, and the analysis of microarray data to identify miRNAs that are differentially expressed among three cell types. The methods for culture of iPS cells and fetal RPE are explained. The protocol used for differentiation of RPE from human iPS is also described. The RNA extraction technique we describe was selected to allow maximal recovery of very small RNA for use in a miRNA microarray. Finally, cellular pathway and network analysis of microarray data is explained. These techniques will facilitate the comparison of the miRNA profiles of three different cell types.

  2. MRI of human brain in the fetal period; Especially during the second trimester

    Energy Technology Data Exchange (ETDEWEB)

    Watabe, Yasuharu (Nara Medical Univ., Kashihara (Japan))

    1990-10-01

    Magnetic resonance (MR) images were compared with histological and anatomical observations in 31 fetuses ranging from 10 to 25 weeks of gestation to study the relationship between MR images and the development of the neopallium during the second trimester. T1 weighted MR images and T2 weighted MR images taken within 8 hours after delivery were compared with H.E. stained histological slices. On T1-weighted MR images after 18 weeks of gestation, the neopallium consisted of four layers which appeared as areas of high, relatively high, low and high signal intensity, respectively, from the ventricular side to the brain surface. These layers corresponded to the ventricular zone, the subventricular zone, the intermediate zone and the cortical plate respectively. On T2 weighted images, these areas appeared only as three layers of low, relatively low and high signal intensity, respectively, from the ventricular side, and the most lateral layer was not distinct from the adjacent layer. Beyond 14 weeks of gestation, the ganglionic eminence showed almost the same signal intensity as the ventricular zone. The visualization of the primary fissures by MR images was compared with reported anatomical studies in all fetuses, and with anatomical sections from 18 fetuses. These studies revealed little variation in the time of the first appearance of primary fissures, except that there was a few weeks delay on MR imaging (MRI) of mesially located fissures. Thus MRI was confirmed to be useful in estimating the development of the fetal brain on the basis of imaging of the laminal structures of the neopallium and the appearance of primary fissures. (author).

  3. [Expression of aquaporin 8 in human fetal membrane and placenta of idiopathic polyhydramnios].

    Science.gov (United States)

    Huang, Jin; Qi, Hong-bo

    2009-01-01

    To determine the expression of Aquaporin 8(AQP8) in the fetal membrane and placenta of idiopathic polyhydramnios. The amnion, chorion and placenta were collected from 12 term pregnancies with idiopathic polyhydramnios( polyhydramnios group) and 12 term pregnancies who were normal (control group). The expression of AQP8 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of AQP8 protein was detected by immunohistochemistry. The expression of AQP8 mRNA in amnion, chorion and placenta of polyhydramnios group was (0.78 +/- 0.13), (0.58 +/- 0.10), and (0.86 +/- 0.15) respectively, and that of control group was (0. 39 0.07), (0.45 +/- 0.09), and (0.34 +/- 0.09) respectively. The expression of AQP8 protein in amnion, chorion and placenta of polyhydramnios group was (0.195 +/- 0.024), (0.170 +/- 0.028), and (0.193 +/- 0.024) respectively, and that of control group was (0.151 +/- 0.018), (0.156 +/- 0.024), and (0.152 +/- 0.023) respectively. In all 3 types of tissues the expression of AQP8 mRNA of polyhydramnios group was higher than that of control group (P polyhydramnios group was also increased compared to that of control group (P 0.05). The expression of AQP8 mRNA and protein is significantly increased in the amnion and placenta of polyhydramnios, suggesting that AQP8 may play an important role in the regulation of amniotic fluid volume.

  4. The phenotype of the human materno-fetal endothelial barrier: molecular occupancy of paracellular junctions dictate permeability and angiogenic plasticity.

    Science.gov (United States)

    Leach, Lopa

    2002-06-01

    In vitro models predict that molecular occupancy of endothelial junctions may regulate both barrier function and angiogenesis. Whether this is true in human vascular beds undergoing physiological angiogenesis has not been shown. This review presents data which demonstrate there are two distinct junctional phenotypes, 'activated' and 'stable', present in the vascular tree of the human placenta taken from two distinct highly angiogenic gestational periods (first and last trimester). Stability is conferred by the presence of occludin in tight junctions and plakoglobin in adherens junctions. Their localization may be influenced by vascular endothelial growth factor and angiopoietins 1 and 2 that have a similar temporal and site-specific differential expression. The junctional phenotypes are reversible, as shown in studies with endothelial cells isolated from placental microvessels and grown in the presence/absence of cAMP-enhancing agents. Reductions in protein levels and loss of junctional localization of adhesion molecules result in increased permeability to macromolecules, whilst up-regulation and re-targeting of these molecules inhibit cell proliferation and increase transendothelial resistance. These studies suggest junctional adhesion molecules can regulate physiological angiogenesis and vascular re-modelling. Moreover, the activated junctional phenotype of placental microvessels allows them to participate in increased growth and proliferation. This junctional immaturity appears to be at the expense of barrier function resulting in sites of maximal materno-fetal solute exchange.

  5. Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.

    Directory of Open Access Journals (Sweden)

    Sandy A van Gool

    Full Text Available 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 chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFβ3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.

  6. Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.

    Science.gov (United States)

    van Gool, Sandy A; Emons, Joyce A M; Leijten, Jeroen C H; Decker, Eva; Sticht, Carsten; van Houwelingen, Johannes C; Goeman, Jelle J; Kleijburg, Carin; Scherjon, Sicco A; Gretz, Norbert; Wit, Jan Maarten; Rappold, Gudrun; Post, Janine N; Karperien, Marcel

    2012-01-01

    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 chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFβ3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.

  7. Fetal behavior and the cardiovascular-system

    NARCIS (Netherlands)

    Visser, G. H. A.

    With increasing gestation both in the human and in animals clear fetal behavioural state cycles develop. Fetal heart rate patterns are closely related to the phenomenon of behavioural state. In this review article fetal heart rate patterns will be analysed in relation to particular behavioural

  8. Fetal Macrosomia

    Science.gov (United States)

    ... identification of fetal macrosomia useful? European Journal of Obstetrics & Gynecology and Reproductive Biology. 2012;161:170. Negrato CA, et al. Adverse pregnancy outcomes in women with diabetes. 2012;4:41. Frequently ...

  9. Fetal Macrosomia

    Science.gov (United States)

    ... lifestyle counts Fetal macrosomia Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  10. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Ying-Jan Weng

    Full Text Available Fetal and neonatal alloimmune thrombocytopenia (FNAIT is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig G (IgG from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D, purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80% and purity (>99.5%, and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality

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

    Science.gov (United States)

    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

    2011-01-25

    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 top candidates for the elevated HbF levels. Indeed, increased expression of these microRNAs in primary human erythroid progenitor cells results in elevated fetal and embryonic hemoglobin gene expression. Moreover, we show that a direct target of these microRNAs, MYB, plays an important role in silencing the fetal and embryonic hemoglobin genes. Thus we demonstrate how the developmental regulation of a clinically important human trait can be better understood through the genetic and functional study of aneuploidy syndromes and suggest that miR-15a, -16-1, and MYB may be important therapeutic targets to increase HbF levels in patients with sickle cell disease and β-thalassemia.

  12. CED-10-WASP-Arp2/3 signaling axis regulates apoptotic cell corpse engulfment in C. elegans.

    Science.gov (United States)

    Wu, Dou; Chai, Yongping; Zhu, Zhiwen; Li, Wenjing; Ou, Guangshuo; Li, Wei

    2017-08-01

    Efficient clearance of apoptotic cells is essential for tissue homeostasis in metazoans. Genetic studies in Caenorhabditis elegans have identified signaling cascades that activate CED-10/Rac1 GTPase and promote actin cytoskeletal rearrangement during apoptotic cell engulfment. However, the molecular connection between CED-10 activation and actin reorganization remains elusive. Here, we provide evidence that CED-10 binds to the Arp2/3 nucleation promoting factor WASP; CED-10 recruits WASP and Arp2/3 to apoptotic cell corpses in the phagocytes. The loss of WASP and Arp2/3 impaired cell corpse engulfment. Furthermore, we uncover that a WASP-activating factor SEM-5/GRB2 functions in the phagocytes to promote cell corpse clearance. Together, our results suggest CED-10 reorganizes the actin cytoskeleton by recruiting the WASP-Arp2/3 actin nucleation factors during apoptotic cell engulfment. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

    Directory of Open Access Journals (Sweden)

    Danica Ryan

    2018-01-01

    Interpretation: These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.

  14. Human Fetal Testis Xenografts Are Resistant to Phthalate-Induced Endocrine Disruption

    National Research Council Canada - National Science Library

    Nicholas E. Heger; Susan J. Hall; Moses A. Sandrof; Elizabeth V. McDonnell; Janan B. Hensley; Erin N. McDowell; Kayla A. Martin; Kevin W. Gaido; Kamin J. Johnson; Kim Boekelheide

    2012-01-01

    .... Impomntly, ex vivo phthalate exposure of the letal testis does not recapitulate the species-specific endocrine disruption, demonstrating me need for a new bioassay to assess the human response to phthalates. Objectives...

  15. Media and Propaganda: The Northcliffe Press and the Corpse Factory Story of World War I

    Directory of Open Access Journals (Sweden)

    Randal Marlin

    2010-01-01

    Full Text Available Demonization of Germans was an early feature of British propaganda in World War I, with numerous atrocities reported in the Bryce Report, 1915. But in April, 1917, a particularly gripping, gruesome, and odium-inducing tale was given credence by the press of Lord Northcliffe, notably The Times and The Daily Mail.These papers seemed to provide convincing proof that the Germans boiled down corpses of their own soldiers for the purpose of producing useful products such as fats, bone meal, pig food and the like. The story is well known, but significant details have been obscured or misrepresented with regard to the way in which it came to be so widely believed. Our purpose here is to straighten out key elements of the record, based on archival findings, and to draw attention to the techniques employed to ensure widespread credence in this false tale. These techniques, and the principles behind their use, have recent and contemporary parallels, some of which are drawn in this paper. The Corpse Factory story succeeded in its goal, but may have made a lasting peace more difficult. Also, official repudiation of the story in 1925 encouraged later disbelief when early reports circulated about the Holocaust under Hitler, thus contributing to the early lack of response by nations asked to accept Jewish refugees.

  16. Serum-converted platelet lysate can substitute for fetal bovine serum in human mesenchymal stromal cell cultures.

    Science.gov (United States)

    Mojica-Henshaw, Mariluz P; Jacobson, Pam; Morris, Julie; Kelley, Linda; Pierce, Jan; Boyer, Michael; Reems, Jo-Anna

    2013-12-01

    Fetal bovine serum (FBS) is commonly used as a serum supplement for culturing human mesenchymal stromal cells (hMSCs). However, human cells grown in FBS, especially for extended periods, risk potential exposure to bovine immunogenic proteins and infectious agents. To address this issue, we investigated the ability of a novel human platelet serum supplement to substitute for FBS in hMSC cultures. Platelet lysate-serum (PL-serum) was converted from platelet lysate-plasma (PL-plasma) that was manufactured from pooled platelet-rich plasma (PRP) apheresis units. Growth factor levels and the number of residual intact platelets in PL-serum and PL-plasma were compared with enzyme-linked immunosorbent assays and flow cytometry, respectively. Proliferation responses of hMSCs cultured in PL-serum, PL-plasma, or FBS were assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the immunophenotype of harvested hMSCs was evaluated by flow cytometry and tri-lineage differentiation potential was evaluated by assessing adipogenic, osteogenic and chondrogenic development. Selected growth factor levels in PL-serum were not significantly different from PL-plasma (P > 0.05). hMSC cultures supplemented with PL-serum had comparable growth kinetics to PL-plasma, and hMSC yields were consistently greater than with FBS. hMSCs harvested from cultures supplemented with PL-serum, PL-plasma or FBS had similar cell surface phenotypes and maintained tri-lineage differentiation potential. PL-serum, similar to PL-plasma, can substitute for FBS in hMSC cultures. Use of PL-serum, in contrast to PL-plasma, has an added advantage of not requiring addition of a xenogeneic source of heparin, providing a completely xeno-free culture medium. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. Innate and adaptive immune interactions at the fetal-maternal interface in healthy human pregnancy and preeclampsia

    Directory of Open Access Journals (Sweden)

    Peter eHsu

    2014-03-01

    Full Text Available Maternal immune tolerance of the fetus is indispensible for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal-maternal interface – the decidua, the site of implantation and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, preeclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3+ regulatory T (Treg cells are crucial for ensuring immune tolerance towards the semi-allogeneic fetus. Additionally, another population of CD4+HLA-G+ suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy.

  18. Diarrheal response of gnotobiotic pigs after fetal infection and neonatal challenge with homologous and heterologous human rotavirus strains.

    Science.gov (United States)

    Torres, A; Ji-Huang, L

    1986-12-01

    Pigs exposed in utero to human rotavirus (HRV) strain Wa serotype 1 from 15 to 36 days prior to birth responded immunologically by modifying their clinical response to neonatal oral challenge with a pathogenic dose of homologous Wa or heterologous M serotype 3 HRV. In these cases, diarrhea was prevented in 12 of 14 pigs and greatly reduced in the other two. However, fecal virus shedding was not significantly modified, since it was detected in 12 of 14 pigs. These results suggest the existence of a closer antigenic relationship between these two different HRV serotypes which may only be expressed in an in vivo test system. Exposure of fetal pigs to HRV DS-1 serotype 2 failed to cause infection or to induce any protection when pigs were challenged at birth with HRV Wa. This model for cross-protection studies in gnotobiotic piglets offers good possibilities for the evaluation of potential HRV vaccine candidates, for the in vivo study of antigenic similarities between rotavirus serotypes, and for the understanding of protective immune responses against diarrhea and virus shedding.

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

    Directory of Open Access Journals (Sweden)

    Hanna M Vesterinen

    Full Text Available 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.

  20. Magnesium and fetal growth

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, K.

    1988-01-01

    Fetal growth retardation and premature labor are major problems in perinatal medicine today and account for a great deal of the observed fetal morbidity. While the neonatal death rate has steadily declined over the past decade, there has been a lack of concommitant decrease in these two leading problems. Magnesium (Mg/sup ++/) plays a major role in both of these areas of concern. The fact that it is used as a treatment for premature labor has led investigators to look at low Mg/sup ++/ as a possible cause of this poorly understood phenomenon. The second major cause of small for gestational age infants is intrauterine growth retardation, a condition which may be of either fetal or maternal origin. In either case, Mg/sup ++/ may be implicated since it exerts a strong influence on the underlying pathophysiology of placental failure and maternal hypertension. Both of these conditions are mediated by vascular and platelet hyperactivity as well as by and increase in the ration of thromboxane to prostacyclin. Studies in both the human and animal species are beginning to show how Mg/sup ++/ interacts in these conditions to produce such a damaging fetal outcome. The recent use of Doppler velocimetry of the developing fetus has shown reduced fetal vascular and maternal uterine vascular compliance as early as 14 weeks of gestation in those who would be so affected.

  1. Early human brain development : the impact of periconceptional maternal and fetal factors

    NARCIS (Netherlands)

    I.V. Koning (Irene)

    2017-01-01

    textabstractEarly human brain development is an extremely complex process which is highly susceptible to genetic and environmental conditions. These factors may cause subtle changes in early brain development and subsequent neurodevelopmental impairment. The main objective of this thesis is to

  2. Histological evidence of oxidative stress and premature senescence in preterm premature rupture of the human fetal membranes recapitulated in vitro

    National Research Council Canada - National Science Library

    Menon, Ramkumar; Boldogh, Istvan; Hawkins, Hal K; Woodson, Michael; Polettini, Jossimara; Syed, Tariq Ali; Fortunato, Stephen J; Saade, George R; Papaconstantinou, John; Taylor, Robert N

    2014-01-01

    Preterm prelabor rupture of the membranes (pPROM) may lead to preterm births (PTBs). We investigated premature senescence of fetal membranes in women with pPROM and spontaneous PTB with intact membranes...

  3. Serial measurements of serum human placental lactogen (hPL) and serial ultrasound examinations in the evaluation of fetal growth

    DEFF Research Database (Denmark)

    Sørensen, Steen; von Tabouillot, D; Schioler, V

    2000-01-01

    was associated with a trend towards low and decreasing hPL and with an increasing intrauterine growth velocity and birth weight deviation. In conclusion the rate of change of serial hPL measurements correlated well to intrauterine fetal growth velocity in the third trimester as estimated by ultrasound......Serial serum hPL measurements and serial ultrasound fetometry were compared in the evaluation of fetal growth by relating these two parameters to size at birth and to clinical factors known to influence size at birth. The data were from a prospective study of 1000 consecutive pregnant women...... considered to be at risk for fetal growth retardation with retrospective analysis. Serum hPL was measured by radioimmunoassay and fetal weight estimated by ultrasound every 3 weeks during the last trimester. hPL values were expressed as multiples of the median (MoM) and linear regression analysis of the h...

  4. High Resolution MRI Reveals Detailed Layer Structures in Early Human Fetal Stages: In Vitro Study with Histologic Correlation.

    Science.gov (United States)

    Wang, Rongpin; Dai, Guangping; Takahashi, Emi

    2015-01-01

    An understanding of normal fetal brain development is essential in detecting the early onset of brain disorders. It is challenging to obtain high-quality images that show detailed local anatomy in the early fetal stages because the fetal brain is very small with rapidly-changing complex structures related to brain development, including neurogenesis, neuronal migration, and axonal elongation. Previous magnetic resonance imaging (MRI) studies detected three layers throughout the fetal cerebral wall that showed differences in MR contrasts at 10 gestational weeks (GW), which is one of the earliest ages studied using MRI. Contrary to the MRI studies, histological studies found more layers at this fetal age. The purpose of this work is to study the development of brain structures from an early fetal period to an early second trimester stage using ex vivo MRI and compare it to histology. Special attention was paid to laminar structures in the cerebral wall. T2-weighted imaging was performed on fetal brain specimens ranging from 10 GW to 18 GW on a 4.7 tesla MR scanner. We obtained standard grayscale as well as color-coded images using weighted red-green-blue scales, and compared them with the histological images. Our study confirmed laminar structure in the cerebral wall in all the fetal specimens studied. We found that MRI detected four layers within the cerebral wall as early as 10 GW during the early fetal period (10-13 GW). Early second trimester (15-18 GW) was characterized by the emergence of subplate structures and five layers within the cerebral wall. The color-coded images were more useful than the standard grayscale images in detecting the laminar structures. Scans with appropriate parameters from a high tesla MR scanner showed detailed laminar structures even through a very small and thin cerebral wall at 10 GW ex vivo. A combination of high-resolution structural imaging and color-coding processing with histological analysis may be a potential tool for

  5. High resolution MRI reveals detailed layer structures in early human fetal stages: In vitro study with histologic correlation

    Directory of Open Access Journals (Sweden)

    Rongpin eWang

    2015-11-01

    Full Text Available An understanding of normal fetal brain development is essential in detecting the early onset of brain disorders. It is challenging to obtain high-quality images that show detailed local anatomy in the early fetal stages because the fetal brain is very small with rapidly-changing complex structures related to brain development, including neurogenesis, neuronal migration, and axonal elongation. Previous magnetic resonance imaging (MRI studies detected three layers throughout the fetal cerebral wall that showed differences in MR contrasts at 10 gestational weeks (GW, which is one of the earliest ages studied using MRI. Contrary to the MRI studies, histological studies found more layers at this fetal age. The purpose of this work is to study the development of brain structures from an early fetal period to an early second trimester stage using ex vivo MRI and compare it to histology. Special attention was paid to laminar structures in the cerebral wall. T2-weighted imaging was performed on fetal brain specimens ranging from 10 GW to 18 GW on a 4.7 tesla MR scanner. We obtained standard grayscale as well as color-coded images using weighted red-green-blue scales, and compared them with the histological images. Our study confirmed laminar structure in the cerebral wall in all the fetal specimens studied. We found that MRI detected four layers within the cerebral wall as early as 10 GW during the early fetal period (10-13 GW. Early second trimester (15-18 GW was characterized by the emergence of subplate structures and five layers within the cerebral wall. The color-coded images were more useful than the standard grayscale images in detecting the laminar structures. Scans with appropriate parameters from a high tesla MR scanner showed detailed laminar structures even through a very small and thin cerebral wall at 10 GW ex vivo. A combination of high-resolution structural imaging and color-coding processing with histological analysis may be a potential

  6. Fetal programming of the human brain: is there a link with insurgence of neurodegenerative disorders in adulthood?

    Science.gov (United States)

    Faa, G; Marcialis, M A; Ravarino, A; Piras, M; Pintus, M C; Fanos, V

    2014-01-01

    In recent years, evidence is growing on the role played by gestational factors in shaping brain development and on the influence of intrauterine experiences on later development of neurodegenerative diseases including Parkinson's (PD) and Alzheimer's disease (AD). The nine months of intrauterine development and the first three years of postnatal life are appearing to be extremely critical for making connections among neurons and among neuronal and glial cells that will shape a lifetime of experience. Here, the multiple epigenetic factors acting during gestation - including maternal diet, malnutrition, stress, hypertension, maternal diabetes, fetal hypoxia, prematurity, low birth weight, prenatal infection, intrauterine growth restriction, drugs administered to the mother or to the baby - are reported, and their ability to modulate brain development, resulting in interindividual variability in the total neuronal and glial burden at birth is discussed. Data from recent literature suggest that prevention of neurodegeneration should be identified as the one method to halt the diffusion of neurodegenerative diseases. The "two hits" hypothesis, first introduced for PD and successfully applied to AD and other neurodegenerative human pathologies, should focus our attention on a peculiar period of our life: the intrauterine and perinatal periods. The first hit to our nervous system occurs early in life, determining a PD or AD imprinting to our brain that will condition our resistance or, alternatively, our susceptibility to develop a neurodegenerative disease later in life. In conclusion, how early life events contribute to late-life development of adult neurodegenerative diseases, including PD and AD, is emerging as a new fascinating research focus. This assumption implies that research on prevention of neurodegenerative diseases should center on events taking place early in life, during gestation and in the perinatal periods, thus presenting a new challenge to

  7. Activating the expression of human K-rasG12D stimulates oncogenic transformation in transgenic goat fetal fibroblast cells.

    Directory of Open Access Journals (Sweden)

    Jianhua Gong

    Full Text Available Humane use of preclinical large animal cancer models plays a critical role in understanding cancer biology and developing therapeutic treatments. Among the large animal candidates, goats have great potentials as sustainable sources for large animal cancer model development. Goats are easier to handle and cheaper to raise. The genome of the goats has been sequenced recently. It has been known that goats develop skin, adrenal cortex, breast and other types of cancers. Technically, goats are subject to somatic cell nuclear transfer more efficiently and exhibit better viability through the cloning process. Towards the development of a goat cancer model, we created a transgenic goat fetal fibroblast (GFF cell as the donor cell for SCNT. Human mutated K-ras (hK-rasG12D was chosen as the transgene, as it is present in 20% of cancers. Both hK-rasG12D and a herpes simplex viral thymidine kinase (HSV1-tk reporter genes, flanked by a pair of LoxP sites, were knocked in the GFF endogenous K-ras locus through homologous recombination. Following Cre-mediated activation (with a 95% activation efficiency, hK-rasG12D and HSV1-tk were expressed in the transgenic GFF cells, evidently through the presence of corresponding mRNAs, and confirmed by HSV1-tk protein function assay. The hK-rasG12D expressing GFF cells exhibited enhanced proliferation rates and an anchorage-independent growth behavior. They were able to initiate tumor growth in athymic nude mice. In conclusion, after activating hK-rasG12D gene expression, hK-rasG12D transgenic GFF cells were transformed into tumorgenesis cells. Transgenic goats via SCNT using the above-motioned cells as the donor cells have been established.

  8. Human Plasma and Human Platelet-rich Plasma as a Substitute for Fetal Calf Serum during Long-term Cultivation of Mesenchymal Dental Pulp Stem Cells

    Directory of Open Access Journals (Sweden)

    Tereza Suchánková Kleplová

    2014-01-01

    Full Text Available Aims: Our aims were to isolate and cultivate mesenchymal dental pulp stem cells (DPSC in various media enriched with human blood components, and subsequently to investigate their basic biological properties. Methods: DPSC were cultivated in five different media based on α MEM containing different concentrations of human plasma (HP, platelet-rich plasma (PRP, or fetal calf serum (FCS. The DPSC biological properties were examined periodically. Results: We cultivated DPSC in the various cultivation media over 15 population doublings except for the medium supplemented with 10% HP. Our results showed that DPSC cultivated in medium supplemented with 10% PRP showed the shortest average population doubling time (DT (28.6 ± 4.6 hours, in contrast to DPSC cultivated in 10% HP which indicated the longest DT (156.2 ± 17.8 hours; hence this part of the experiment had been cancelled in the 6th passage. DPSC cultivated in media with 2% FCS+ITS (DT 47.3 ± 10.4 hours, 2% PRP (DT 40.1 ± 5.7 hours and 2% HP (DT 49.0 ± 15.2 hours showed almost the same proliferative activity. DPSC’s viability in the 9th passage was over 90% except for the DPSC cultivated in the 10% HP media. Conclusions: We proved that human blood components are suitable substitution for FCS in cultivation media for long-term DPSC cultivation.

  9. Human plasma and human platelet-rich plasma as a substitute for fetal calf serum during long-term cultivation of mesenchymal dental pulp stem cells.

    Science.gov (United States)

    Suchánková Kleplová, Tereza; Soukup, Tomáš; Řeháček, Vít; Suchánek, Jakub

    2014-01-01

    Our aims were to isolate and cultivate mesenchymal dental pulp stem cells (DPSC) in various media enriched with human blood components, and subsequently to investigate their basic biological properties. DPSC were cultivated in five different media based on α MEM containing different concentrations of human plasma (HP), platelet-rich plasma (PRP), or fetal calf serum (FCS). The DPSC biological properties were examined periodically. We cultivated DPSC in the various cultivation media over 15 population doublings except for the medium supplemented with 10% HP. Our results showed that DPSC cultivated in medium supplemented with 10% PRP showed the shortest average population doubling time (DT) (28.6 ± 4.6 hours), in contrast to DPSC cultivated in 10% HP which indicated the longest DT (156.2 ± 17.8 hours); hence this part of the experiment had been cancelled in the 6th passage. DPSC cultivated in media with 2% FCS+ITS (DT 47.3 ± 10.4 hours), 2% PRP (DT 40.1 ± 5.7 hours) and 2% HP (DT 49.0 ± 15.2 hours) showed almost the same proliferative activity. DPSC's viability in the 9th passage was over 90% except for the DPSC cultivated in the 10% HP media. We proved that human blood components are suitable substitution for FCS in cultivation media for long-term DPSC cultivation.

  10. 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

  11. Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface.

    Science.gov (United States)

    Weisblum, Yiska; Oiknine-Djian, Esther; Vorontsov, Olesya M; Haimov-Kochman, Ronit; Zakay-Rones, Zichria; Meir, Karen; Shveiky, David; Elgavish, Sharona; Nevo, Yuval; Roseman, Moshe; Bronstein, Michal; Stockheim, David; From, Ido; Eisenberg, Iris; Lewkowicz, Aya A; Yagel, Simcha; Panet, Amos; Wolf, Dana G

    2017-02-15

    Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn

  12. Comparison between fingerprints of the epidermis and dermis: Perspectives in the identifying of corpses.

    Science.gov (United States)

    Mizokami, Leila Lopes; Silva, Lara Rosana Vieira; Kückelhaus, Selma Aparecida Souza

    2015-07-01

    In forensic science, the putrefaction, maceration, mummification or burning make it difficult to collect the fingerprints of the epidermis for identification purposes. In such cases, the comparison between fingerprints collected from the dermal surface and the ante mortem pattern of the epidermal surface archived in databases must be performed. Therefore, considering that the identification of corpses is done by comparison of fingerprints on different surfaces, this study aimed to compare the epidermal and the dermal fingerprints to determine the discrepancies between the minutiae of both surfaces. The study was conducted with excised fingers of 19 fresh adult corpses. Once selected, excised and photographed, the fingers were subjected to maceration with 0.5% acetic acid solution for the removal of the epidermal glove and for registering the dermal fingerprint. Then, an area of 1cm(2) in the epidermal and dermal photographies was selected and the minutiae of each were separately marked by an expert in identification. The comparison between minutiae of the epidermal and dermal surfaces showed that: (1) both surfaces maintained the patterns and characteristics of fingerprints (arch, whorl or loop) and the characteristics related to the systems and the disposal of the lines, meaning the formation or not of deltas; (2) the total number of marked minutiae did not differ between both surfaces for the group of individuals (paired t test, p=0.48); (3) the percentage of coincidences and divergences (minutiae present on only one surface) between minutiae were 63.0±20.0% and 37.0±20.0%, respectively; (4) identification was possible for 16 fingers/individuals, but not for 3 of them; (5) the increase in the number of marked minutiae does not affect the percentage of coincidences. Our results demonstrate the feasibility of the dermal surface for identification purposes due to the high percentage of matching minutiae, but considering the discrepancies and the inconclusive

  13. Dissection of Lower and Upper Jaws Could They Be Efficiently Examined Without Isolation From the Corpse

    Directory of Open Access Journals (Sweden)

    Hüseyin Afşin

    2001-04-01

    Full Text Available In some cases, for detailed intraoral examination it may be necessary that the upper and lower jaws of a corpse should be removed in such a way to cause the least traumatic change. It is difficult but compulsory to identify by dental examination the corpses particularly who/which are found to have foreign bodies such as stones and/or soil in the mouths because of being hurried under the ground and who have completed mortal rigidness or are frozen. At the end of this process, it is important that, the external view of the corpse not be spoiled. In this study a dissection technique which had been developed before was improved, and attempts were made to modifiy it. For this aim the muscular tissues sur-ronding the mouth of one case were dissected and the lower and upper jaws removed from the body by cutting the bone tissues. The most difficult problem faced when examining the structures forming the oral cavity is the elimination of mortal rigidness in cases in which it has reached a maximum level. Applying improper force on the teeth and mucosa may cause demage which makes it difficult to distinguish whether such damage has happened antemortem or postmortem. Even if it is possible for the mouth to be fully opened it is still not easy to obtain sample tissue and furthermore dental modelling or getting an x-ray of the area is impossible. External suturing following the autopsy in the case of an incorrect method applied while dissecting the cheeks may make the kins of dead person irritated. When identification is necessary, findings about the number of teeth, the number of decayed ones, fillings crowns and bridges should be recorded without fail. The modelling of the teeth is important from the view of making easy comparisons in future and obtaining reliable evidence. A good photography in which the teeth are clearly discernible will enable the dead persons relatives to remember his/her features that can not be described when asked to. A dental model

  14. Isolation of Progenitors that Exhibit Myogenic/Osteogenic Bipotency In Vitro by Fluorescence-Activated Cell Sorting from Human Fetal Muscle

    Directory of Open Access Journals (Sweden)

    Alessandra Castiglioni

    2014-01-01

    Full Text Available Fluorescence-activated cell sorting (FACS strategies to purify distinct cell types from the pool of fetal human myofiber-associated (hMFA cells were developed. We demonstrate that cells expressing the satellite cell marker PAX7 are highly enriched within the subset of CD45−CD11b−GlyA−CD31−CD34−CD56intITGA7hi hMFA cells. These CD45−CD11b−GlyA−CD31−CD34−CD56intITGA7hi cells lack adipogenic capacity but exhibit robust, bipotent myogenic and osteogenic activity in vitro and engraft myofibers when transplanted into mouse muscle. In contrast, CD45−CD11b−GlyA−CD31−CD34+ fetal hMFA cells represent stromal constituents of muscle that do not express PAX7, lack myogenic function, and exhibit adipogenic and osteogenic capacity in vitro. Adult muscle likewise contains PAX7+ CD45−CD11b−GlyA−CD31−CD34−CD56intITGA7hi hMFA cells with in vitro myogenic and osteogenic activity, although these cells are present at lower frequency in comparison to their fetal counterparts. The ability to directly isolate functionally distinct progenitor cells from human muscle will enable novel insights into muscle lineage specification and homeostasis.

  15. 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

  16. Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth.

    Science.gov (United States)

    Zamudio, Stacy; Postigo, Lucrecia; Illsley, Nicholas P; Rodriguez, Carmelo; Heredia, Gladys; Brimacombe, Michael; Echalar, Lourdes; Torricos, Tatiana; Tellez, Wilma; Maldonado, Ivan; Balanza, Elfride; Alvarez, Tatiana; Ameller, Julio; Vargas, Enrique

    2007-07-15

    Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O(2) delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O(2) delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n=180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphism. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P<0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O(2) delivery regardless of ancestry. But the hypothesis was rejected as O(2) delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O(2) delivery, regardless of altitude (P<0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P<0.01), but admixture was not related to any of the O(2) transport variables. Genetically mediated differences in maternal O(2) delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O(2) and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O(2) delivery in these pregnancies was 99 +/- 3 ml min(-1), approximately 5-fold greater than near-term fetal O(2) consumption. Deficits in maternal O(2) transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth.

  17. Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans.

    Science.gov (United States)

    Neukomm, L J; Zeng, S; Frei, A P; Huegli, P A; Hengartner, M O

    2014-06-01

    The rapid clearance of dying cells is important for the well-being of multicellular organisms. In C. elegans, cell corpse removal is mainly mediated by three parallel engulfment signaling cascades. These pathways include two small GTPases, MIG-2/RhoG and CED-10/Rac1. Here we present the identification and characterization of CDC-42 as a third GTPase involved in the regulation of cell corpse clearance. Genetic analyses performed by both loss of cdc-42 function and cdc-42 overexpression place cdc-42 in parallel to the ced-2/5/12 signaling module, in parallel to or upstream of the ced-10 module, and downstream of the ced-1/6/7 module. CDC-42 accumulates in engulfing cells at membranes surrounding apoptotic corpses. The formation of such halos depends on the integrins PAT-2/PAT-3, UNC-112 and the GEF protein UIG-1, but not on the canonical ced-1/6/7 or ced-2/5/12 signaling modules. Together, our results suggest that the small GTPase CDC-42 regulates apoptotic cell engulfment possibly upstream of the canonical Rac GTPase CED-10, by polarizing the engulfing cell toward the apoptotic corpse in response to integrin signaling and ced-1/6/7 signaling in C. elegans.

  18. Fetal pain

    NARCIS (Netherlands)

    Adama van Scheltema, Phebe

    2011-01-01

    Recent studies have suggested that the fetus is capable of exhibiting a stress response to intrauterine needling, resulting in alterations in fetal stress hormone levels. Intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI),

  19. The symbiotic bacterial surface factor polysaccharide A on Bacteroides fragilis inhibits IL-1β-induced inflammation in human fetal enterocytes via toll receptors 2 and 4.

    Directory of Open Access Journals (Sweden)

    Fei Jiang

    Full Text Available Colonizing bacteria interacting with the immature, unlike the mature, human intestine favors inflammation over immune homeostasis. As a result, ten percent of premature infants under 1500 grams weight develop an inflammatory necrosis of the intestine after birth, e.g., necrotizing enterocolitis (NEC. NEC is a major health problem in this population causing extensive morbidity and mortality and an enormous expenditure of health care dollars. NEC can be prevented by giving preterm infants their mother's expressed breast milk or ingesting selective probiotic organisms. Vaginally delivered, breast fed newborns develop health promoting bacteria ("pioneer" bacteria which preferentially stimulate intestinal host defense and anti-inflammation. One such "pioneer" organism is Bacteroides fragilis with a polysaccharide (PSA on its capsule. B. fragilis has been shown developmentally in intestinal lymphocytes and dendritic cells to produce a balanced T-helper cell (TH1/TH2 response and to reduce intestinal inflammation by activity through the TLR2 receptor stimulating IL-10 which inhibits IL-17 causing inflammation. No studies have been done on the role of B. fragilis PSA on fetal enterocytes and its increased inflammation. Accordingly, using human and mouse fetal intestinal models, we have shown that B. fragilis with PSA and PSA alone inhibits IL-1β-induced IL-8 inflammation in fetal and NEC intestine. We have also begun to define the mechanism for this unique inflammation noted in fetal intestine. We have shown that B. fragilis PSA anti-inflammation requires both the TLR2 and TLR4 receptor and is in part mediated by the AP1 transcription factor (TLR2 which is developmentally regulated. These observations may help to devise future preventative treatments of premature infants against NEC.

  20. Collection of intraoral findings in corpse with small-scale color dental scanner system.

    Science.gov (United States)

    Yoshida, Masaki; Hanaoka, Yoichi; Tsuzuki, Tamiyuki; Ueno, Asao; Takagi, Tetsuya; Iwahara, Kaori; Yasuda, Mamoru; Sato, Yoshinobu; Minaguchi, Kiyoshi

    2009-03-10

    Together with X-ray radiography and the description in the dental chart (odontogram), the collection of intraoral images is extremely important in dental identification. Recently, thanks to advances in digital devices for taking images in the oral cavity, problems with developing images and images being lost due to scanning errors have been minimized. However, in corpses where postmortem rigidity has firmly set in and burned bodies where the jaw has to be forced open, it is difficult to open the jaw enough to allow images to be taken. In addition, collection of intraoral images requires skill. Our goal was to determine the efficacy of a newly developed, small-scale color dental scanner in collecting intraoral images. The results showed that it was comparatively easy to obtain an entire image of the oral cavity with even a minimum degree of jaw opening. This should enable even a non-expert to perform oral image collection.

  1. Corpse dismemberment in the material collected by the Department of Forensic Medicine, Cracow, Poland.

    Science.gov (United States)

    Konopka, Tomasz; Strona, Marcin; Bolechała, Filip; Kunz, Jerzy

    2007-01-01

    In this study, we present 23 cases of dismembered bodies examined by the Cracow Department of Forensic Medicine in 1968-2005 period. Presented material includes 17 instances of defensive mutilation, three instances of offensive mutilation and two cases when dismemberment (decapitation) was a direct cause of death. One case is hard to classified, the perpetrator dissected free skin from the all torso. Analysis of all presented cases and other publications concentrating on the problem of dismemberment gave us the possibility to perform some conclusions. Apart from rare cases of necrophilia, the victim of dismemberment is always a victim of homicide. Homicides ending with corpse dismemberment are most commonly committed by a person close to, or at least acquainted with the victim and they are performed at the site of homicide, generally in the place inhabited by the victim, the perpetrator or shared by both. Such instances are generally not planned by the perpetrator and rarely serial in character.

  2. Quality improvement of fingerprints of decayed corpses by local thanatopractical processing (Thanatoprint).

    Science.gov (United States)

    Gahr, Britta; Drewitz, M; Vöth, R; Ritz-Timme, S

    2013-01-01

    Thanatopractical processing allows morphological reconstruction of even advanced decayed bodies. By extracting fluids from the body's tissue antemortem tenseness and volume can be restored. If bodies are partly subject to thanatopractical processing in the hand region ("Thanatoprint"), fingerprints of high quality can be gathered even in cases of advanced decay. Without this treatment fingerprinting can be extremely difficult, if not impossible. Thanatopractical processing could be applied successfully in cases of partial to subtotal detachment of the epidermis as well. In an interdisciplinary study 400 fingerprints of bodies in various states of decay were examined after application of Thanatoprint. In 76.75% fingerprints were applicable for data entry into AFIS (Automated Fingerprint Identification System); another 11.00% of the fingerprints could be used for the process of non-elimination. Further advantages of the method are low invasivity while maintaining the integrity of the corpse, less time- and material requirement as well as its long-lasting effect.

  3. May Ingestion of Leachate from Decomposed Corpses Cause Appendicitis? A Case Report

    Directory of Open Access Journals (Sweden)

    Maurício Domingues-Ferreira

    2011-01-01

    Full Text Available The general consensus is that appendicitis is basically provoked by fecaliths or lymphoid hyperplasic obstruction. Several studies based on histological diagnosis have not confirmed this hypothesis. On the contrary, obstruction has been proved in only a minority of cases. Diverse infections by parasites, bacteria, fungus, and noninfective agents have been associated with appendicitis in the medical literature. We describe a firefighter, who ingested a small quantity of leachate from decomposing corpses while working and developed enteritis a few hours later, which lasted several days and evolved to appendicitis. This case raises the possibility that the high quantity of bacteria concentration present in the leachate could have provoked enteritis and the subsequent appendicitis due to a direct effect of the bacteria on the appendix.

  4. Fusion of Human Fetal Mesenchymal Stem Cells with "Degenerating" Cerebellar Neurons in Spinocerebellar Ataxia Type 1 Model Mice.

    Science.gov (United States)

    Huda, Fathul; Fan, Yiping; Suzuki, Mamiko; Konno, Ayumu; Matsuzaki, Yasunori; Takahashi, Nobutaka; Chan, Jerry K Y; Hirai, Hirokazu

    2016-01-01

    Mesenchymal stem cells (MSCs) migrate to damaged tissues, where they participate in tissue repair. Human fetal MSCs (hfMSCs), compared with adult MSCs, have higher proliferation rates, a greater differentiation capacity and longer telomeres with reduced senescence. Therefore, transplantation of quality controlled hfMSCs is a promising therapeutic intervention. Previous studies have shown that intravenous or intracortical injections of MSCs result in the emergence of binucleated cerebellar Purkinje cells (PCs) containing an MSC-derived marker protein in mice, thus suggesting a fusion event. However, transdifferentiation of MSCs into PCs or transfer of a marker protein from an MSC to a PC cannot be ruled out. In this study, we unequivocally demonstrated the fusion of hfMSCs with murine PCs through a tetracycline-regulated (Tet-off) system with or without a Cre-dependent genetic inversion switch (flip-excision; FLEx). In the FLEx-Tet system, we performed intra-cerebellar injection of viral vectors expressing tetracycline transactivator (tTA) and Cre recombinase into either non-symptomatic (4-week-old) or clearly symptomatic (6-8-month-old) spinocerebellar ataxia type 1 (SCA1) mice. Then, the mice received an injection of 50,000 genetically engineered hfMSCs that expressed GFP only in the presence of Cre recombinase and tTA. We observed a significant emergence of GFP-expressing PCs and interneurons in symptomatic, but not non-symptomatic, SCA1 mice 2 weeks after the MSC injection. These results, together with the results obtained using age-matched wild-type mice, led us to conclude that hfMSCs have the potential to preferentially fuse with degenerating PCs and interneurons but not with healthy neurons.

  5. Replication of different clones of human immunodeficiency virus type 1 in primary fetal human astrocytes: enhancement of viral gene expression by Nef.

    Science.gov (United States)

    Bencheikh, M; Bentsman, G; Sarkissian, N; Canki, M; Volsky, D J

    1999-04-01

    Dementia is a common complication of AIDS which is associated with human immunodeficiency virus type 1 (HIV-1) infection of brain macrophages and microglia. Recent studies have shown that astrocytes are also infected in the brain but HIV-1 replication in these cells is restricted. To determine virus specificity of this restriction we tested the expression of 15 HIV-1 molecular clones in primary human fetal astrocytes by infection and DNA transfection. Infection with cell-free viruses was poorly productive and revealed no clone-specific differences. In contrast, transfected cells produced transiently high levels of HIV-1 p24 core antigen, up to 50 nanograms per ml culture supernatant, and nanogram levels of p24 were detected 3-4 weeks after transfection of some viral clones. The average peak expression of HIV-1 in astrocytes varied as a function of viral clone used by a factor of 15 but the differences and the subsequent virus spread did not correlate with the tropism of the viral clones to T cells or macrophages. Functional vif, vpu, and vpr genes were dispensable for virus replication from transfected DNA, but intact nef provided a detectable enhancement of early viral gene expression and promoted maintenance of HIV-1 infection. We conclude that primary astrocytes present no fundamental barriers to moderate expression of different strains of HIV-1 and that the presence of functional Nef is advantageous to virus infection in these cells.

  6. Efficient peripheral construction of functional human regulatory CD4(+)CD25(high)Foxp3(+) T cells in NOD/SCID mice grafted with fetal human thymus/liver tissues and CD34(+) cells.

    Science.gov (United States)

    Duan, Kaizhong; Zhang, Baojun; Zhang, Wenying; Zhao, Yunan; Qu, Yanyan; Sun, Chenming; Zhao, Yong

    2011-12-01

    Regulatory T cells, especially CD4(+)CD25(+) regulatory T cells are critical regulators of immune tolerance in humans and mice. Mice with humanized immunity have been developed by various transplantation strategies of human tissues or cells related to immunity, which are being extensively applied in biomedical research. However, it is unclear whether human CD4(+)CD25(+) regulatory T cells can normally develop in human thymic grafts and efficiently populate in the periphery in NOD/SCID mouse recipients. In human thymic grafts, high percentage of mature human CD4(+)CD25(high) regulatory T cells was detected. Human CD4(+)CD25(+) regulatory T cells maturing in fetal human thymus grafts could subsequently output to the periphery of NOD/SCID mouse recipients. Importantly, these cells exhibited Foxp3(+)CD45RO(+)CTLA4(+)CD127(-) phenotype, similarly to those in healthy individuals. In addition, human CD4(+)CD25(+) regulatory T cells maturing in human thymic grafts suppressed proliferative response of CD4(+)CD25(-) T cells to allogeneic antigens, though the peripheral CD4(+)CD25(+) regulatory T cells in fetal human thymus-grafted NOD/SCID mice showed somewhat decreased immunosuppressive ability compared with normal CD4(+)CD25(+) regulatory T cells. Thus, this humanized animal model is suitable for examining development and function of human CD4(+)CD25(+) regulatory T cells in vivo. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Salivary glands and human congenital cytomegalovirus infection: What happens in early fetal life?

    Science.gov (United States)

    Gabrielli, Liliana; Bonasoni, Maria Paola; Chiereghin, Angela; Piccirilli, Giulia; Santini, Donatella; Pavia, Claudia; Turello, Gabriele; Squarzoni, Diego; Lazzarotto, Tiziana

    2017-02-01

    Salivary glands are a site of human cytomegalovirus (CMV) replication, latency, and persistence. Prolonged secretion of virus in saliva for months following a primary infection contribute to horizontal transmission. In order to better understand the early effects of CMV on salivary glands and the mechanisms of viral persistent replication, submandibular glands of six CMV congenitally infected fetuses at 21 weeks gestation were studied. Three fetuses at the same gestational age from CMV-seronegative women were compared as negative controls. Tissue viral load and the type of inflammatory infiltrate were evaluated. Moreover, development and branching of salivary glands, the number of myoepithelial cells, cellular proliferation, and expression of secretory proteins of the saliva (Gross Cystic Disease Fluid Protein-15 and lysozyme) were studied. A low viral load and rare CMV-positive cells associated with T CD8 cytotoxic lymphocytes were observed. Branching was impaired with a decrease in terminal acinar structures, the number of myoepithelial cells, and cellular proliferation were reduced. In addition, a compromised secretion of defense proteins involved in the oral humoral immunity was observed. These findings suggest that CMV may affect salivary glands, impairing structure development and secretion of defense proteins, probably responsible for the prolonged viral shedding in saliva. J. Med. Virol. 89:318-323, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. [Analysis of growth model in vestibular aqueduct during human fetal development].

    Science.gov (United States)

    Lei, Li; Han, De-min; Yu, Zhen-kun; Zhu, Xiao-nong; Liu, Sha; Chen, Shu-bin; Fan, Er-zhong

    2003-08-01

    To characterize the growth of the developing vestibular aqueduct in order to gain a better understanding of the possible origins of enlarged vestibular aqueduct. Serial sections from 32 temporal bones for every other week from human embryos ranging in age from 6 to 38 weeks were studied with 3DMed medical image analysis software. The internal, external aperture, midpoint diameter and length vestibular aqueduct were analyzed with regression analysis to obtain a growth curve. The internal aperture of vestibular aqueduct was began to form at 6 weeks' gestation. It grew to reach the posterior surface of the petrous bone in the posterior cranial fossa by 10 weeks' gestation. All width parameter mean value in our embryos nerve reached the maximum average width in the adult. Statistical analysis showed that the vestibular aqueduct grew in a nonlinear continuous fashion and instability trend throughout embryonic life, except length parameter. The vestibular aqueduct grows in a nonlinear fashion throughout embryonic life. The widest aqueduct measured in embryonic life does not reach the maximum average width in the adult. These results suggest that it would be possible for vestibular aqueduct to develop postnatally.

  9. Homicides with corpse dismemberment in the material collected by the Department of Forensic Medicine, Krakow, Poland

    Directory of Open Access Journals (Sweden)

    Tomasz Konopka

    2017-06-01

    Full Text Available Aim of the study : To determine the circumstances which can be useful for offenders profiling in homicide cases with victim’s body dismemberment. Material and methods: Study of all homicide cases with victim’s corpse dismemberment examined in Krakow Department of Forensic Medicine over the last 50 years. Results : Within the past 50 years, a total number of 30 cases of homicides with dismembered bodies were examined in Krakow. 22 cases represent defensive mutilations performed by offender, 3 cases can be classified as offensive muti­lations and 3 cases represent aggressive mutilations – decapitation as a method of committing homicide. In this period the only 1 case of necrophilic mutilations was examined, when the body was dismembered without murder. In most cases the background of homicide was the family conflict, 6 was cause of mental illness of perpetrator and in 3 was sexual motive. Only in 3 cases (from 25 when the offender was known perpetrator kill a stranger. In the other the offender belonged to the family or friends of the victim. In all cases where the perpetrator was determined, homicide and dismemberment was performed in his place of residence. The findings of the Police investigations indicate that in most cases homicides were not planned, occurred under the influence of emotion, only two have been previously scheduled. Conclusions : Homicides with corpses dismemberment usually are committed by offenders who is in close relationship with victim (family or friend. Dismemberment is almost always performed in the same place as murder – home of perpetrator. This type of homicide usually is not planned.

  10. Fetal Development of the Human Obturator Internus Muscle With Special Reference to the Tendon and Pulley.

    Science.gov (United States)

    Naito, Michiko; Suzuki, Ryoji; Abe, Hiroshi; Rodriguez-Vazquez, Jose Francisco; Murakami, Gen; Aizawa, Shin

    2015-07-01

    To examine the development of the tendon pulley of the obturator internus muscle (OI), we observed paraffin sections of 26 human embryos and fetuses (∼6-15 weeks of gestation). The OI was characterized by early maturation of the proximal tendon in contrast to the delayed development of the distal tendon. At 6 weeks, the ischium corresponded to a simple round mass similar to the tuberosity in adults. At 8 weeks, before development of the definite lesser notch of the ischium, initial muscle fibers of the OI, running along the antero-posterior axis, converged onto a thick and tight but short tendon running along the left-right axis. Thus, at the beginning of development, the OI muscle belly and tendon met almost at a right angle. At 10 weeks, the OI tendon extended inferiorly along the sciatic nerve, but the distal part remained thin and loose and it was embedded in the gluteus medius tendon. At 15 weeks, in association with the gemellus muscles, the distal OI tendon was established. The mechanically strong sciatic nerve was first likely to catch the OI muscle fibers to provide a temporary insertion. Next, the ischium developing upward seemed to push the tendon to make the turn more acute along the cartilaginous ridge. Finally, the gemellus muscle appeared to provide inferior traction to the OI tendon for separation from the gluteus medius to create the final, independent insertion. Without such guidance, the piriformis tendon first attached to the OI tendon and then merged with the gluteus medius tendon. © 2015 Wiley Periodicals, Inc.

  11. Secretion of bioactive interleukin-6 and tumor necrosis factor-alpha proteins from primary cultured human fetal membrane chorion cells infected with influenza virus.

    Science.gov (United States)

    Uchide, N; Suzuki, A; Ohyama, K; Bessho, T; Toyoda, H

    2006-01-01

    Influenza virus infection during pregnancy is implicated in one of the causes of premature delivery, abortion and stillbirth. Pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha produced by fetal membranes, are postulated to facilitate premature delivery. We investigated the secretion of IL-6 and TNF-alpha from primary cultured human fetal membrane chorion and amnion cells infected with influenza virus at protein and bioactivity levels in order to understand the pathology of premature delivery during influenza virus infection. Concentrations of IL-6 and TNF-alpha proteins were significantly increased in culture supernatants of chorion cells by influenza virus infection. Culture supernatants of the virus-infected chorion cells stimulated the proliferation of IL-6-sensitive 7-TD-1 cells and induced the cytolysis of TNF-alpha-sensitive L929 cells, both activities of which were inhibited by the addition of respective antibody, whereas no such phenomena were observed in amnion cells. The results demonstrated that only chorion cells secreted significant amounts of bioactive IL-6 and TNF-alpha proteins responding to influenza virus infection. The present study suggests a possibility that the secretion of bioactive IL-6 and TNF-alpha proteins from fetal membrane chorion cells is implicated in the pathogenesis of premature delivery during influenza virus infection.

  12. Creatine supplementation during pregnancy: summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy

    Science.gov (United States)

    2014-01-01

    While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid–base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity – actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn. PMID:24766646

  13. Fetal Metabolic Stress Disrupts Immune Homeostasis and Induces Proinflammatory Responses in Human Immunodeficiency Virus Type 1- and Combination Antiretroviral Therapy-Exposed Infants.

    Science.gov (United States)

    Schoeman, Johannes C; Moutloatse, Gontse P; Harms, Amy C; Vreeken, Rob J; Scherpbier, Henriette J; Van Leeuwen, Liesbeth; Kuijpers, Taco W; Reinecke, Carools J; Berger, Ruud; Hankemeier, Thomas; Bunders, Madeleine J

    2017-08-15

    Increased morbidity and fetal growth restriction are reported in uninfected children born to human immunodeficiency virus type 1 (HIV-1)-infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress, skewing the cell's immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART) exposure on the infants' immune metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1-exposed infants, indicating altered mitochondrial functioning. The lipid metabolism was further dysregulated with increased triglyceride species and a subsequent decrease in phospholipids in cART/HIV-1-exposed infants compared to control infants. Proinflammatory immune mediators, lysophospholipids as well as cytokines such as CXCL10 and CCL3, were increased whereas anti-inflammatory metabolites from the cytochrome P450 pathway were reduced in cART/HIV-1-exposed infants. Taken together, these data demonstrate that the fetal metabolism is impacted by maternal factors (cART and HIV-1) and skews physiological immune responses toward inflammation in the newborn infant. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Fetal syringomyelia

    OpenAIRE

    Guo, Anne; Chitayat, David; Blaser, Susan; Keating, Sarah; Shannon, Patrick

    2014-01-01

    We explored the prevalence of syringomyelia in a series of 113 cases of fetal dysraphism and hindbrain crowding, of gestational age ranging from 17.5 to 34 weeks with the vast majority less than 26 weeks gestational age. We found syringomyelia in 13 cases of Chiari II malformations, 5 cases of Omphalocele/Exostrophy/Imperforate anus/Spinal abnormality (OEIS), 2 cases of Meckel Gruber syndrome and in a single pair of pyopagus conjoined twins. Secondary injury was not uncommon, with vernicomyel...

  15. Muerte fetal

    Directory of Open Access Journals (Sweden)

    G. Andrés Pons, DR

    2014-11-01

    Full Text Available La muerte fetal es un evento poco frecuente pero de gran repercusión afectiva para los padres involucrados y su entorno. En el presente artículo revisaremos la epidemiología, las causas, orientaremos a los médicos en los pasos a seguir para realizar adecuadamente el estudio, la resolución del embarazo y el manejo del embarazo siguiente junto con las estrategias para prevenirlo.

  16. Muerte fetal

    OpenAIRE

    Andrés Pons, G.; Eduardo Sepúlveda, S.; Juan Luis Leiva, B.; Gustavo Rencoret, P.; Alfredo Germain, A.

    2014-01-01

    La muerte fetal es un evento poco frecuente pero de gran repercusión afectiva para los padres involucrados y su entorno. En el presente artículo revisaremos la epidemiología, las causas, orientaremos a los médicos en los pasos a seguir para realizar adecuadamente el estudio, la resolución del embarazo y el manejo del embarazo siguiente junto con las estrategias para prevenirlo.

  17. Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications.

    Science.gov (United States)

    Naaijkens, B A; Niessen, H W M; Prins, H-J; Krijnen, P A J; Kokhuis, T J A; de Jong, N; van Hinsbergh, V W M; Kamp, O; Helder, M N; Musters, R J P; van Dijk, A; Juffermans, L J M

    2012-04-01

    Adipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically, transmission of pathogens and antibody development against FBS are possible. In this study, we investigated whether FBS can be substituted by human platelet lysate (PL) in ASC culture, without affecting functional capacities particularly important for cardiac repair application of ASC. We found that PL-cultured ASC had a significant 3-fold increased proliferation rate and a significantly higher attachment to tissue culture plastic as well as to endothelial cells compared with FBS-cultured ASC. PL-cultured ASC remained a significant 25% smaller than FBS-cultured ASC. Both showed a comparable surface marker profile, with the exception of significantly higher levels of CD73, CD90, and CD166 on PL-cultured ASC. PL-cultured ASC showed a significantly higher migration rate compared with FBS-cultured ASC in a transwell assay. Finally, FBS- and PL-cultured ASC had a similar high capacity to differentiate towards cardiomyocytes. In conclusion, this study showed that culturing ASC is more favorable in PL-supplemented medium compared with FBS-supplemented medium.

  18. Effects of Macromolecular Crowding on Human Adipose Stem Cell Culture in Fetal Bovine Serum, Human Serum, and Defined Xeno-Free/Serum-Free Conditions

    Science.gov (United States)

    Lee, Michelle Hui Ching; Mäkinen, Laura; Ang, Xiu Min; Mannerström, Bettina; Raghunath, Michael; Miettinen, Susanna

    2017-01-01

    Microenvironment plays an important role for stem cell proliferation and differentiation. Macromolecular crowding (MMC) was recently shown to assist stem cells in forming their own matrix microenvironment in vitro. The ability of MMC to support adipose stem cell (ASC) proliferation, metabolism, and multilineage differentiation was studied under different conditions: fetal bovine serum- (FBS-) and human serum- (HS-) based media and xeno- and serum-free (XF/SF) media. Furthermore, the immunophenotype of ASCs under MMC was evaluated. The proliferative capacity of ASCs under MMC was attenuated in each condition. However, osteogenic differentiation was enhanced under MMC, shown by increased deposition of mineralized matrix in FBS and HS cultures. Likewise, significantly greater lipid droplet accumulation and increased collagen IV deposition indicated enhanced adipogenesis under MMC in FBS and HS cultures. In contrast, chondrogenic differentiation was attenuated in ASCs expanded under MMC. The ASC immunophenotype was maintained under MMC with significantly higher expression of CD54. However, MMC impaired metabolic activity and differentiation capacity of ASCs in XF/SF conditions. Both the supportive and inhibitory effects of MMC on ASC are culture condition dependent. In the presence of serum, MMC maintains ASC immunophenotype and enhances adipogenic and osteogenic differentiation at the cost of reduced proliferation. PMID:28465691

  19. Effects of Macromolecular Crowding on Human Adipose Stem Cell Culture in Fetal Bovine Serum, Human Serum, and Defined Xeno-Free/Serum-Free Conditions

    Directory of Open Access Journals (Sweden)

    Mimmi Patrikoski

    2017-01-01

    Full Text Available Microenvironment plays an important role for stem cell proliferation and differentiation. Macromolecular crowding (MMC was recently shown to assist stem cells in forming their own matrix microenvironment in vitro. The ability of MMC to support adipose stem cell (ASC proliferation, metabolism, and multilineage differentiation was studied under different conditions: fetal bovine serum- (FBS- and human serum- (HS- based media and xeno- and serum-free (XF/SF media. Furthermore, the immunophenotype of ASCs under MMC was evaluated. The proliferative capacity of ASCs under MMC was attenuated in each condition. However, osteogenic differentiation was enhanced under MMC, shown by increased deposition of mineralized matrix in FBS and HS cultures. Likewise, significantly greater lipid droplet accumulation and increased collagen IV deposition indicated enhanced adipogenesis under MMC in FBS and HS cultures. In contrast, chondrogenic differentiation was attenuated in ASCs expanded under MMC. The ASC immunophenotype was maintained under MMC with significantly higher expression of CD54. However, MMC impaired metabolic activity and differentiation capacity of ASCs in XF/SF conditions. Both the supportive and inhibitory effects of MMC on ASC are culture condition dependent. In the presence of serum, MMC maintains ASC immunophenotype and enhances adipogenic and osteogenic differentiation at the cost of reduced proliferation.

  20. BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands.

    Science.gov (United States)

    Alves, Daniel Berretta Moreira; Bingle, Lynne; Bingle, Colin David; Lourenço, Silvia Vanessa; Silva, Andréia Aparecida; Pereira, Débora Lima; Vargas, Pablo Agustin

    2017-01-16

    The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

  1. Intersection-based registration of slice stacks to form 3D images of the human fetal brain

    DEFF Research Database (Denmark)

    Kim, Kio; Hansen, Mads Fogtmann; Habas, Piotr

    2008-01-01

    Clinical fetal MR imaging of the brain commonly makes use of fast 2D acquisitions of multiple sets of approximately orthogonal 2D slices. We and others have previously proposed an iterative slice-to-volume registration process to recover a geometrically consistent 3D image. However, these approac...

  2. Fetus specific immune recognition and regulation by T cells at the fetal-maternal inferface in human pregnancy

    NARCIS (Netherlands)

    Tilburgs, Tamara

    2008-01-01

    During pregnancy the maternal immune system tolerates the persistence of fetal cells in maternal tissue. The fetus expresses maternal as well as paternal encoded molecules but is not rejected by the maternal immune system. The aim of this thesis was to determine whether maternal T cells contribute

  3. Fluid mechanics of blood flow in human fetal left ventricles based on patient-specific 4D ultrasound scans.

    Science.gov (United States)

    Lai, Chang Quan; Lim, Guat Ling; Jamil, Muhammad; Mattar, Citra Nurfarah Zaini; Biswas, Arijit; Yap, Choon Hwai

    2016-10-01

    The mechanics of intracardiac blood flow and the epigenetic influence it exerts over the heart function have been the subjects of intense research lately. Fetal intracardiac flows are especially useful for gaining insights into the development of congenital heart diseases, but have not received due attention thus far, most likely because of technical difficulties in collecting sufficient intracardiac flow data in a safe manner. Here, we circumvent such obstacles by employing 4D STIC ultrasound scans to quantify the fetal heart motion in three normal 20-week fetuses, subsequently performing 3D computational fluid dynamics simulations on the left ventricles based on these patient-specific heart movements. Analysis of the simulation results shows that there are significant differences between fetal and adult ventricular blood flows which arise because of dissimilar heart morphology, E/A ratio, diastolic-systolic duration ratio, and heart rate. The formations of ventricular vortex rings were observed for both E- and A-wave in the flow simulations. These vortices had sufficient momentum to last until the end of diastole and were responsible for generating significant wall shear stresses on the myocardial endothelium, as well as helicity in systolic outflow. Based on findings from previous studies, we hypothesized that these vortex-induced flow properties play an important role in sustaining the efficiency of diastolic filling, systolic pumping, and cardiovascular flow in normal fetal hearts.

  4. [Prognosis of basic somatic characteristics of humans in expert examination of fragments of human body].

    Science.gov (United States)

    Zviagin, V N; Grigor'eva, M A

    2006-01-01

    To develop a method of assessing human body somatometric parameters by its fragmentation, we used individual data on the series G. van Vark (1975) from corpses of 62 males and 39 females aged from 23 to 95 years. Statistical processing with SPSS package calculated regression equations allowing prediction of head size, length of the upper and lower limbs and their segments. The data can be used in forensic medicine in expert examination of dismembered corpses and in emergency situations with mass human victims.

  5. 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.

  6. Differential proteomic expression of human placenta and fetal development following e-waste lead and cadmium exposure in utero

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    Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Lau, Andy T.Y. [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China); Xu, Xijin, E-mail: xuxj@stu.edu.cn [Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041 (China)

    2016-04-15

    ABSTRACT: Prenatal exposure to lead (Pb) and cadmium (Cd) has been associated with a series of physiological problems resulting in fetal growth restriction. We aimed to investigate the effects of Pb and Cd exposure on placental function and the potential mechanisms involved in fetal development. Placental specimens and questionnaires were collected from an e-waste area and a reference area in China. Two-dimensional electrophoresis combined with MALDI-TOF-MS/MS and molecular network relationship were performed to analyze differentially expressed proteins using a compositing sample pool. Compared with the reference group, the exposed group exhibited significantly higher levels of placental Pb and Cd (p < 0.01), shorter body length and higher gestational age (p < 0.01). After bivariate adjustment in a linear regression model, decreases of 205.05 g in weight and 0.44 cm in body length were associated with a 10 ng/g wt increase in placental Cd. Pb showed a negative trend but lacked statistical significance. Proteomic analysis showed 32 differentially-expressed proteins and were predominantly involved in protein translocation, cytoskeletal structure, and energy metabolism. Fumarate hydratase was down-regulated in the exposed placenta tissues and validated by ELISA. Alterations in placental proteome suggest that imbalances in placental mitochondria respiration might be a vital pathway targeting fetal growth restriction induced by exposure to Cd. - Highlights: • The placental Pb and Cd levels were higher in the e-waste polluted area. • Proteome in placenta tissues was performed by two-dimensional gel electrophoresis. • Cd exposure in the placenta was associated with the reduced fetal development. • 32 proteins covered in translocation, energy metabolism and cytoskeletal structure. • Dysregulated mitochondrial respiration may act in the Cd-reduced fetal development.

  7. Influence of oxygen tension on dopaminergic differentiation of human fetal stem cells of midbrain and forebrain origin.

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    Christina Krabbe

    Full Text Available Neural stem cells (NSCs constitute a promising source of cells for transplantation in Parkinson's disease (PD, but protocols for controlled dopaminergic differentiation are not yet available. Here we investigated the influence of oxygen on dopaminergic differentiation of human fetal NSCs derived from the midbrain and forebrain. Cells were differentiated for 10 days in vitro at low, physiological (3% versus high, atmospheric (20% oxygen tension. Low oxygen resulted in upregulation of vascular endothelial growth factor and increased the proportion of tyrosine hydroxylase-immunoreactive (TH-ir cells in both types of cultures (midbrain: 9.1 ± 0.5 and 17.1 ± 0.4 (P<0.001; forebrain: 1.9 ± 0.4 and 3.9 ± 0.6 (P<0.01 percent of total cells. Regardless of oxygen levels, the content of TH-ir cells with mature neuronal morphologies was higher for midbrain as compared to forebrain cultures. Proliferative Ki67-ir cells were found in both types of cultures, but the relative proportion of these cells was significantly higher for forebrain NSCs cultured at low, as compared to high, oxygen tension. No such difference was detected for midbrain-derived cells. Western blot analysis revealed that low oxygen enhanced β-tubulin III and GFAP expression in both cultures. Up-regulation of β-tubulin III was most pronounced for midbrain cells, whereas GFAP expression was higher in forebrain as compared to midbrain cells. NSCs from both brain regions displayed less cell death when cultured at low oxygen tension. Following mictrotransplantation into mouse striatal slice cultures predifferentiated midbrain NSCs were found to proliferate and differentiate into substantial numbers of TH-ir neurons with mature neuronal morphologies, particularly at low oxygen. In contrast, predifferentiated forebrain NSCs microtransplanted using identical conditions displayed little proliferation and contained few TH-ir cells, all of which had an immature appearance. Our data may reflect

  8. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Almstrup, K; Nielsen, J E

    2005-01-01

    AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG...... earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG......; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down-regulation occurring...

  9. 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))....

  10. A scream from the past: a multidisciplinary approach in a concealment of a corpse found mummified.

    Science.gov (United States)

    Gitto, Lorenzo; Bonaccorso, Luigi; Maiese, Aniello; dell'Aquila, Massimiliano; Arena, Vincenzo; Bolino, Giorgio

    2015-05-01

    When a mummified body is found, it requires the forensic pathologist to determine the manner and cause of death. The mummified body of an older man was found walled in an alcove in a silicon-sealed bedroom, in a semi-supine position with the back on the floor and the legs on the wall. Two plastic bags covered the body. Having removed the plastic bags, the body was fully wrapped in a brown adhesive tape. At the scene, there was no evidence of microfauna. The subject's son stated that after his father's death, he concealed the corpse in order to obtain his annual pension. A postmortem CT scan was performed before the autopsy, which excluded traumatic injuries. The autopsy together with the toxicological and microscopic findings helped us to understand the manner of death. In this case, the mummification process developed under specific environmental conditions and a multidisciplinary approach was required in order to solve it. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  11. Corpses of Metaphor. Images of Death in David Leavitt and Jamaica Kincaid

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    Fiorenzo Iuliano

    2010-10-01

    Full Text Available This essay analyzes two works, My Brother by Jamaica Kincaid, and "Saturn Street" by David Leavitt, investigating the construction of homosexuality as a process accomplished by resorting to illness (AIDS and death. In both works, indeed, the slow and dramatic course of AIDS amounts to the progressive unveiling of homosexuality as a social threat or a cause of anxiety and repulsion. The two works are set in different contexts: whereas Jamaica Kincaid refers to the problematic situation of homosexuality in the Caribbean, David Leavitt explores the social and cultural scenario of the 1990s Los Angeles, in the wake of a by now ended utopian confidence in science and technology.  This comparative approach helps us understand the political dynamics through which, in different and, to some extents, opposite realities, the social stigma of AIDS worked as a means to construct homosexual identity and set it apart from the sanitized spectrum of normal and sanctioned sexual behaviors. The point I want to make in this essay is that the corpse is used as an effective metaphor for a dehumanized depiction of male homosexual and ill subjects.

  12. Quality improvement of fingerprints of decayed corpses by local thanatopractical processing (Thanatoprint

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    Gahr, Britta

    2013-11-01

    Full Text Available Thanatopractical processing allows morphological reconstruction of even advanced decayed bodies. By extracting fluids from the body’s tissue antemortem tenseness and volume can be restored. If bodies are partly subject to thanatopractical processing in the hand region (“Thanatoprint”, fingerprints of high quality can be gathered even in cases of advanced decay. Without this treatment fingerprinting can be extremely difficult, if not impossible. Thanatopractical processing could be applied successfully in cases of partial to subtotal detachment of the epidermis as well. In an interdisciplinary study 400 fingerprints of bodies in various states of decay were examined after application of Thanatoprint. In 76.75% fingerprints were applicable for data entry into AFIS (Automated Fingerprint Identification System; another 11.00% of the fingerprints could be used for the process of non-elimination. Further advantages of the method are low invasivity while maintaining the integrity of the corpse, less time- and material requirement as well as its long-lasting effect.

  13. Cultures of death and politics of corpse supply: anatomy in Vienna, 1848-1914.

    Science.gov (United States)

    Buklijas, Tatjana

    2008-01-01

    Nineteenth-century Vienna is well known to medical historians as a leading center of medical research and education, offering easy access to patients and corpses to students from all over the world. The author seeks to explain how this enviable supply of cadavers was achieved, why it provoked so little opposition at a time when Britain and the United States saw widespread protests against dissection, and how it was threatened from mid-century onward. To understand permissive Viennese attitudes, we need to place them in a longue durée history of death and dissection and to pay close attention to the city's political geography as it was transformed into a major imperial capital. The tolerant stance of the Roman Catholic Church, strong links to Southern Europe, and the weak position of individuals in the absolutist state all contributed to an idiosyncratic anatomical culture. But as the fame of the Vienna medical school peaked in the later 1800s, the increased demand created by rising numbers of students combined with intensified interdisciplinary competition to produce a shortfall that professors found increasingly difficult to meet. Around 1900, new religious groups and mass political parties challenged long-standing anatomical practice by refusing to supply cadavers and making dissection into an instrument of political struggle. This study of the material preconditions for anatomy at one of Europe's most influential medical schools provides a contrast to the dominant Anglo-American histories of death and dissection.

  14. Distinction among the puparia of three blowfly species (Diptera: Calliphoridae) frequently found on unburied corpses.

    Science.gov (United States)

    Amorim, J A; Ribeiro, O B

    2001-08-01

    Calliphorid larvae are important in the decomposition of carrion. Since these larvae are present in the primary stages of succession on carcasses, they may be important indicators of death time and the movement of corpses in homicide investigations. In this study we examined the morphological differences among puparia of Chrysomya megacephala, C. putoria and Cochliomyia macellaria. Puparia of the three species (N=30, each) were obtained from the F2 generation bred in culture medium at 25 degrees C, and 60% relative humidity on a 12 h photoperiod. The interspecific differences found were related to the conspicuousness of six tubercles located in the region near the posterior spiracles and to the distance between the two peritrema involving the spiracles. The latter were (mean +/- SD) 15.2 +/- 3.1 microm for C. megacephala, 18.8 +/- 2.8 microm for C. putoria and 16.5 +/- 3.5 microm for C. macellaria. The results of the present study may be useful in forensic entomology.

  15. Distinction among the puparia of three blowfly species (Diptera: Calliphoridae frequently found on unburied corpses

    Directory of Open Access Journals (Sweden)

    Amorim JA

    2001-01-01

    Full Text Available Calliphorid larvae are important in the decomposition of carrion. Since these larvae are present in the primary stages of succession on carcasses, they may be important indicators of death time and the movement of corpses in homicide investigations. In this study we examined the morphological differences among puparia of Chrysomya megacephala, C. putoria and Cochliomyia macellaria. Puparia of the three species (N=30, each were obtained from the F2 generation bred in culture medium at 25° C, and 60% relative humidity on a 12 h photoperiod. The interspecific differences found were related to the conspicuousness of six tubercles located in the region near the posterior spiracles and to the distance between the two peritrema involving the spiracles. The latter were (mean ± SD 15.2 ± 3.1 mum for C. megacephala, 18.8 ± 2.8 mum for C. putoria and 16.5 ± 3.5 mum for C. macellaria. The results of the present study may be useful in forensic entomology.

  16. Anatomical departments in Bavaria and the corpses of executed victims of National Socialism.

    Science.gov (United States)

    Noack, Thorsten

    2012-06-01

    While it is known that the bodies of executed victims of National Socialism (NS) were used for anatomical research and teaching, detailed studies are still missing for many anatomical departments. This analysis focuses on the institutes in Bavaria. From 1933 on the institutes of Munich, Würzburg and Erlangen were actively involved in and competed over the procurement of bodies of NS victims, particularly between 1937 and 1941. While the body supply was sufficient thereafter it became again critical in the first years after the war. During that period, anatomists complained about a lack of bodies for dissection courses and tended to use the corpses remaining from the NS-period for teaching purposes. Their position was supported by the popular view that resistance fighters were seen as traitors to the Fatherland and not as honorable political victims. At the same time, relatives and aid organizations were in search of the dead victims of German terror. These conflicting interests created a situation full of tension, in which Philipp Auerbach, state commissioner for religious, political and racial victims of the Nazis in Bavaria, played a crucial role. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. Fibronectin, laminin, and collagen IV interact with ACTH and angiotensin II to dictate specific cell behavior and secretion in human fetal adrenal cells in culture.

    Science.gov (United States)

    Chamoux, E; Narcy, A; Lehoux, J G; Gallo-Payet, N

    2002-11-01

    Whereas collagen IV is expressed throughout the fetal adrenal gland during the second trimester of human development, fibronectin, and laminin demonstrate a rather mirror-image distribution, with higher expression of fibronectin in the central portion and laminin at the periphery of the gland. In the present study, extracellular matrices were able to modulate the profile of steroid secretion in primary cultures: collagen IV favored cortisol secretion following adrenocorticotropin (ACTH) or angiotensin II (Ang II) stimulation while specific stimulation of the AT2 receptor of Ang II elicited dehydroepiandrostenedione (DHEA) production. These effects were correlated by changes in mRNA levels of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and cytochrome P450C17. In contrast, fibronectin and laminin decreased cell responsiveness to ACTH in terms of cortisol secretion, but enhanced ACTH-stimulated androgen secretion. Finally, extracellular matrices were able to orchestrate cell behavior: collagen IV and laminin enhanced cell proliferation whereas fibronectin incited cell death. These results indicate that the nature of extracellular matrix coordinates specific steroidogenic pathways and cell turnover in the developing human fetal adrenal gland.

  18. Antiproliferative effect of synthetic lignin against human breast cancer and normal fetal lung cell lines. Potency of low molecular weight fractions.

    Science.gov (United States)

    Andrijevic, Lj; Radotic, K; Bogdanovic, J; Mutavdzic, D; Bogdanovic, G

    2008-01-01

    Due to a lack of chemotherapeutics to efficiently control neoplastic processes, there is a need for discovering new, more efficient anticancer drugs that would distinguish malignant from normal cells. We studied the effect of short (4 h) and long (72 h) treatment with different concentrations of the enzymatically synthesized lignin model compound (DHP) on the proliferation of two human cell lines grown in tissue culture: breast adenocarcinoma (MCF7) and normal fetal lung fibroblast (MRC5) cell lines. The growth of both MRC5 and MCF7 cell lines was inhibited by DHP after 4 h-treatment, while the carcinoma cell line was also sensitive to the long-term treatment with lower dose of DHP in comparison with the fetal cells. The low molecular weight DHP fractions inhibited growth of the MRC5 cells at lower concentrations compared to the treatment with all DHP fractions. The higher sensitivity to DHP of the human malignant cells compared to the normal transformed ones gives the possibility to further study DHP as a therapeutic agent.

  19. 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].

  20. Erythropoietin elevation in the chronically hyperglycemic fetal lamb

    Energy Technology Data Exchange (ETDEWEB)

    Philipps, A.F. (Univ. of Connecticut Health Center, Farmington) Widness, J.A.; Garcia, J.F.; Raye, J.R.; Swartz, R.

    1982-05-01

    The effects of chronic fetal glucose infusion upon fetal oxygenation and endogenous erythropoietin (Ep) production were studied using the chronically catheterized fetal lamb. Fetal glucose infusion at rates between 5 and 20 mg/kg/min resulted in sustained fetal hyperglycemia. During glucose infusion (maximal glucose concentration achieved = 55.4 +/- 3.7 mg/dl) fetal arterial oxygen contents fell from 5.8 +/- 0.9 to 4.2 +/- 1.0 ml/dl while no changes were observed in simultaneously sampled, noninfused twins. Although plasma insulin concentration rose in the infused fetuses, the elevations were inconstant and no relationship between fetal plasma insulin concentration and decrement in fetal oxygen content was evident. The changes in plasma Ep concentration were noted prior to any significant fetal metabolic acidosis (as evidence of tissue hypoxia) and no changes in plasma Ep concentration were observed in simultaneously sampled noninfused twins. No relationship was apparent between fetal arterial plasma insulin and Ep concentrations. Since neither fetal anemia nor hemodilution occurred in these preparations, glucose-induced fetal hyposemia is the likely mechanism behind elevated fetal Ep concentrations in these experiments. Similarities between this animal model and human fetuses and infants of diabetic mothers suggest that chronic in utero hypoxemia may be a common feature responsible for such diverse abnomalities as polycythemia, hyperbilirubinemia, and late fetal demise. The mechanism behind the glucose-induced fetal hypoxemia is not known.

  1. Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labour

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    Hana A Alzamil

    2014-07-01

    Full Text Available Background: Human labour is a complex series of cellular and molecular events that occur at the materno-fetal and uterine levels. Many hypotheses have been proposed for the initiation of human labour, one hypothesis suggests that maturation of the fetus releases a signal in the amniotic fluid that will be transmitted to myometrium via the fetal membranes and initiate uterine contractions. There is strong evidence that prostaglandins (PGs play a central role in initiation and progression of human labour. Objectives: In this study we intended to investigate the expression of prostaglandin F synthase and the prostaglandin transporter in the human fetal membranes and to explore the relationship between cytokines and PGs in the mechanism of human labour. Methods: We used fetal membranes obtained before labour at term and after spontaneous labour at term or preterm to identify the changes in prostaglandin F synthase (AKR1B1 and human prostaglandin transporter (SLCO2A1 proteins in relation to parturition. Using fetal membranes explants we tested the effect of cytokines (interleukin-1 and tumour necrosis factor alpha on PG production and the concomitant changes in cyclooxygenase-2 (PTGS2, AKR1B1 and SLCO2A1 expression. Results: Expression of PTGS2 and AKR1B1 was upregulated in the fetal membranes in association with term labour while SLCO2A1 was downregulated with advancing gestation and during term labour. Before labour, IL-1 increased the expression of PTGS2, however during labour TNF upregulated PTGS2 and AKR1B1 proteins. Conclusions: The prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labour. The amnion is more responsive than choriodecidua to stimulation with pro-inflammatory cytokines. The mechanisms of term and preterm labour are different.

  2. 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.

  3. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

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    Maximilian Y Emmert

    Full Text Available Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI, key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days were included. Ten animals either received an intra-uterine induction of MI only (n = 4 or MI+intra-myocardial injection (IMI;n = 6 using micron-sized, iron-oxide (MPIO labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3 or the bone-marrow (BMMSCs;n = 3. Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1. All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5-5×10(5 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow

  4. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

    Science.gov (United States)

    Emmert, Maximilian Y; Weber, Benedikt; Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P

    2013-01-01

    Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5)-5×10(5) human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow

  5. Medio ambiente fetal Fetal environment

    Directory of Open Access Journals (Sweden)

    César Bernardo Ospina Arcila

    1996-04-01

    Full Text Available Con base en el artículo clásico "Monte Everest in utero" se hace un análisis de la situación que afronta el feto con respecto a la disponibilidad de oxígeno; para una mejor comprensión del sufrimiento fetal se revisan los siguientes conceptos: presión barométrica, presión parcial del oxígeno atmosférico, presión parcial del oxígeno inspirado, presión barométrica intranasal, ecuación del gas alveolar y difusión de gases a través de la membrana alvéolo capilar. Based on the classical paper by Eastman "Mount Everest in utero" an analysis is made of the situation faced by the fetus with respect to the availability of oxygen; for a better under. standing of fetal distress the following concepts are reviewed: barometric pressure, partial pressure of atmosferic oxygen, partial pressure of inspired oxygen, barometric intranasal pressure, alveolar gas equation and gas diffusion through alveolo-capilar membrane.

  6. Monomethylfumarate induces γ-globin expression and fetal hemoglobin production in cultured human retinal pigment epithelial (RPE) and erythroid cells, and in intact retina.

    Science.gov (United States)

    Promsote, Wanwisa; Makala, Levi; Li, Biaoru; Smith, Sylvia B; Singh, Nagendra; Ganapathy, Vadivel; Pace, Betty S; Martin, Pamela M

    2014-05-13

    Sickle retinopathy (SR) is a major cause of vision loss in sickle cell disease (SCD). There are no strategies to prevent SR and treatments are extremely limited. The present study evaluated (1) the retinal pigment epithelial (RPE) cell as a hemoglobin producer and novel cellular target for fetal hemoglobin (HbF) induction, and (2) monomethylfumarate (MMF) as an HbF-inducing therapy and abrogator of oxidative stress and inflammation in SCD retina. Human globin gene expression was evaluated by RT-quantitative (q)PCR in the human RPE cell line ARPE-19 and in primary RPE cells isolated from Townes humanized SCD mice. γ-Globin promoter activity was monitored in KU812 stable dual luciferase reporter expressing cells treated with 0 to 1000 μM dimethylfumarate, MMF, or hydroxyurea (HU; positive control) by dual luciferase assay. Reverse transcriptase-qPCR, fluorescence-activated cell sorting (FACS), immunofluorescence, and Western blot techniques were used to evaluate γ-globin expression and HbF production in primary human erythroid progenitors, ARPE-19, and normal hemoglobin producing (HbAA) and homozygous β(s) mutation (HbSS) RPE that were treated similarly, and in MMF-injected (1000 μM) HbAA and HbSS retinas. Dihydroethidium labeling and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), IL-1β, and VEGF expression were also analyzed. Retinal pigment epithelial cells express globin genes and synthesize adult and fetal hemoglobin MMF stimulated γ-globin expression and HbF production in cultured RPE and erythroid cells, and in HbSS mouse retina where it also reduced oxidative stress and inflammation. The production of hemoglobin by RPE suggests the potential involvement of this cell type in the etiology of SR. Monomethylfumarate influences multiple parameters consistent with improved retinal health in SCD and may therefore be of therapeutic potential in SR treatment. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  7. Can Fetal Macrosomia be Prevented? | Inegbenebor | International ...

    African Journals Online (AJOL)

    Fetal macrosomia is an obstetric complication that makes child birth hazardous to women in labor, and sometimes an enigma to medical practitioners. It tasks the skills of obstetricians and places a burden on human and material medical resources. There is therefore a need for the prevention of fetal macrosomia in order to ...

  8. On the fetal magnetocardiogram

    NARCIS (Netherlands)

    Peters, M.J.; Stinstra, J.G.; van den Broek, S.P.; van den Broek, S.P.; Huirne, J.A.F.; ter Brake, Hermanus J.M.; Rogalla, Horst

    1998-01-01

    Fetal magnetocardiography is a non-invasive technique for studying the electrical activity of the fetal heart. Fetal magnetocardiograms (fMCG) can be used to diagnose and classify fetal cardiac arrhythmias reliably. An averaged fMCG shows a QRS-complex, a P-wave, and a T-wave. However, it is still

  9. Serial measurements of serum human placental lactogen (hPL) and serial ultrasound examinations in the evaluation of fetal growth

    DEFF Research Database (Denmark)

    Sørensen, Steen; von Tabouillot, D; Schioler, V

    2000-01-01

    Serial serum hPL measurements and serial ultrasound fetometry were compared in the evaluation of fetal growth by relating these two parameters to size at birth and to clinical factors known to influence size at birth. The data were from a prospective study of 1000 consecutive pregnant women...... weakly to intrauterine growth velocity (r=0.08). hPL-slope and intrauterine growth velocity independently predicted birth weight deviation. Heavy smoking which was stopped before the third trimester was not associated with low intrauterine growth velocity, but with a low hPL-slope. Preeclampsia...

  10. The effect of intraumbilical fetal nutrition via a subcutaneously implanted port system on amino acid concentration by severe IUGR human fetuses.

    Science.gov (United States)

    Tchirikov, Michael; Zhumadilov, Zhaxybay Sh; Bapayeva, Gauri; Bergner, Michael; Entezami, Michael

    2017-02-01

    To determine if intrauterine intraumbilical supplementation with amino acids (AA) and glucose can improve neonatal outcome of severe growth restricted human fetuses (IUGR). Prospective pilot study of intrauterine treatment of severe IUGR fetuses [n=14, 27 weeks of gestation (range 23-31)] with cerebroplacental ratio IUGR fetuses in both groups. Long-term supplementation with a commercial AA formula led to a slight, but not significant, reduction of histidine, threonine, lysine, arginine, asparagine and glutamine. However, the concentration of tryptophan and glutamic acid slightly increased. HBO can be combined with AA supplementation via a port system. In one case, the port system was also successfully used for fetal blood transfusion. Intravascular treatment of IUGR with fetal nutrition can prolong pregnancy with severe placental insufficiency and brain sparing for many weeks. However, rather than normalizing AA concentrations, an enhanced AA imbalance was observed in IUGR fetuses following supplementation. These deviations in AA concentrations prevent the recommendation for use of commercial AA solutions for prenatal treatment of extreme preterm IUGR fetuses.

  11. Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications

    NARCIS (Netherlands)

    B. Naaijkens (Benno); H.W.M. Niessen (Hans ); H.-J. Prins (H.); P.A.J. Krijnen (Paul); T.J.A. Kokhuis (Tom); N. de Jong (Nico); V.W.M. van Hinsbergh (Victor); O. Kamp (Otto); K. Helder MScN (Onno); R.J.P. Musters (René); A. van Dijk (Annemieke); L.J.M. Juffermans (Lynda)

    2012-01-01

    textabstractAdipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically,

  12. Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications

    NARCIS (Netherlands)

    Naaijkens, B.A.; Niessen, H.W.M.; Prins, H.J.; Krijnen, P.A.J.; Kokhuis, T.J.A.; de Jong, N.; van Hinsbergh, V.W.M.; Kamp, O.; Helder, M.N.; Musters, R.J.P.; van Dijk, A.; Juffermans, L.J.M.

    2012-01-01

    Adipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically,

  13. Release of LHRH-activity from human fetal membranes upon exposure to PGE/sub 2/, oxytocin and isoproterenol

    Energy Technology Data Exchange (ETDEWEB)

    Poisner, A.M.; Poisner, R.; Becca, C.R.; Conn, P.M.

    1986-03-01

    The authors have previously reported that superfused chorion laeve (fetal membranes) release LHRH-like immunoreactivity upon exposure to angiotensin II. They have now studied the effects of other agonists on the release of LHRH-activity and something of its chemical nature. Fetal membranes were obtained from placentas delivered by cesarean section, the amnion stripped from the chorion, and the chorion superfused in an Amicon thin-channel device with the maternal surface facing up. The whole device was submerged in a 37 C water bath and perfused with a modified Locke's solution at 0.4 - 1.0 ml/min. LHRH-activity was measured by radioimmunoassay using three different antisera against LHRH. The release of LHRH-activity was stimulated by 6-10 min exposure to PGE/sub 2/, oxytocin, and isoproterenol. Extracts of chorion were studied using gel filtration on Sephacryl S-200 and ultrafiltration with Amicon PM-10 filters. The bulk of the LHRH-activity appeared as a higher molecular weight form (about 70,000 daltons). Since oxytocin has been reported to release PGE/sub 2/ from chorion, it may release LHRH-activity by virtue of liberating endogenous PGE/sub 2/. The chemical nature of the LHRH-activity is presently under investigation.

  14. Histological evidence of oxidative stress and premature senescence in preterm premature rupture of the human fetal membranes recapitulated in vitro.

    Science.gov (United States)

    Menon, Ramkumar; Boldogh, Istvan; Hawkins, Hal K; Woodson, Michael; Polettini, Jossimara; Syed, Tariq Ali; Fortunato, Stephen J; Saade, George R; Papaconstantinou, John; Taylor, Robert N

    2014-06-01

    Preterm prelabor rupture of the membranes (pPROM) may lead to preterm births (PTBs). We investigated premature senescence of fetal membranes in women with pPROM and spontaneous PTB with intact membranes (membrane senescence phenotype by oxidative stress in vitro. IHC was performed for p53, p21, and phospho (p)-p38 mitogen-activated protein kinase (MAPK) as markers of senescence phenotype in pPROM, PTBs, and term births. Term fetal membranes were exposed to cigarette smoke extract to induce oxidative stress. Western blots documented p-p53 and p-p38 MAPK. Transmission electron microscopy assessed cellular morphologic features in clinical and cigarette smoke extract-treated membranes. A total of 80% of pPROM cells and >60% of term cells were positive for all three senescence phenotype markers, and concentrations were higher than in PTBs (P membranes from PTB and term birth pregnancies, whereas only membranes in vivo and after cigarette smoke extract treatment in vitro but was less apparent in PTBs. Histologic and biochemical resemblance of pPROM and term membranes suggests premature senescence of the membranes is a mechanistic feature in pPROM, and this can be phenocopied in an in vitro model. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. 21 CFR 884.2600 - Fetal cardiac monitor.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal cardiac monitor. 884.2600 Section 884.2600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 884.2600 Fetal cardiac monitor. (a) Identification. A fetal cardiac monitor is a device used to...

  16. Fetal gender specific expression of tandem-repeat galectins in placental tissue from normally progressed human pregnancies and intrauterine growth restriction (IUGR).

    Science.gov (United States)

    Hutter, Stefan; Knabl, Julia; Andergassen, Ulrich; Mayr, Doris; Hofmann, Simone; Kuhn, Christina; Mahner, Sven; Arck, Petra; Jeschke, Udo

    2015-12-01

    The tandem-repeat type galectins, which comprise of gal-4, -6, -8, -9, and -12, form a sub-family of galectins. Gal-6 is expressed only in rodents, whereas the other four galectins, tandem-repeat galectins, are also detectable in human tissue. The placental expression of individual members of the tandem-repeat gal family is increasingly known, however, systematic, comparative analysis especially in the human placenta from normal or pathological pregnancies is still lacking. Within this study, third trimester placentas obtained at delivery (n = 14 IUGR, n = 15 controls, equally divided in placentas from male and female fetuses) were analyzed for the expression of gal-4, -8, -9 and -12 by immunohistology and immunofluorescence, data were obtained by using a semiquantitative scoring system. Double immune-fluorescence with trophoblast specific markers was used to identify co-expression in the decidua. We identified dysregulation of tandem repeat galectins in IUGR placentas with a strong connection to the fetal gender. We identified a significantly lower expression of gal-4 and gal-9 in villous trophoblast tissue of IUGR placentas with male fetuses and a downregulation of gal-4 and gal-8 in extravillous trophoblast (EVT) from IUGR and male fetuses. Conversely, expression of gal-9 and gal-12 was higher in EVT of IUGR cases in placentas with female fetuses. Double immunofluorescence using cytokeratin-7 confirmed the expression of tandem-repeat galectins in EVT. The human placenta expresses tandem-repeat type galectins in villous trophoblasts, EVT, endothelial cells and decidual stromal cells. Summarizing all effects, there is significant down-regulation of gal-4, -8 and gal-9 in the IUGR trophoblast of male fetuses. In contrast, in IUGR pregnancies with female fetus gal-9 and gal-12 are upregulated in the EVT and in endothelial cells in the cases of gal-12. Therefore we propose a fetal-gender specific action of tandem repeat galectins in IUGR placentas. Copyright © 2015

  17. Aryl hydrocarbon receptor is necessary to protect fetal human pulmonary microvascular endothelial cells against hyperoxic injury: Mechanistic roles of antioxidant enzymes and RelB

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shaojie; Patel, Ananddeep; Chu, Chun; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2015-07-15

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Activation of the aryl hydrocarbon receptor (AhR) protects adult and newborn mice against hyperoxic lung injury by mediating increases in the expression of phase I (cytochrome P450 (CYP) 1A) and phase II (NADP(H) quinone oxidoreductase (NQO1)) antioxidant enzymes (AOE). AhR positively regulates the expression of RelB, a component of the nuclear factor-kappaB (NF-κB) protein that contributes to anti-inflammatory processes in adult animals. Whether AhR regulates the expression of AOE and RelB, and protects fetal primary human lung cells against hyperoxic injury is unknown. Therefore, we tested the hypothesis that AhR-deficient fetal human pulmonary microvascular endothelial cells (HPMEC) will have decreased RelB activation and AOE, which will in turn predispose them to increased oxidative stress, inflammation, and cell death compared to AhR-sufficient HPMEC upon exposure to hyperoxia. AhR-deficient HPMEC showed increased hyperoxia-induced reactive oxygen species (ROS) generation, cleavage of poly(ADP-ribose) polymerase (PARP), and cell death compared to AhR-sufficient HPMEC. Additionally, AhR-deficient cell culture supernatants displayed increased macrophage inflammatory protein 1α and 1β, indicating a heightened inflammatory state. Interestingly, loss of AhR was associated with a significantly attenuated CYP1A1, NQO1, superoxide dismutase 1(SOD1), and nuclear RelB protein expression. These findings support the hypothesis that decreased RelB activation and AOE in AhR-deficient cells is associated with increased hyperoxic injury compared to AhR-sufficient cells. - Highlights: • AhR deficiency potentiates oxygen toxicity in human fetal lung cells. • Deficient AhR signaling increases hyperoxia-induced cell death. • AhR deficiency increases hyperoxia-induced ROS generation and inflammation. • Anti-oxidant enzyme levels are attenuated in AhR-deficient lung cells

  18. Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

    Directory of Open Access Journals (Sweden)

    Radek Bukowski

    2017-09-01

    Full Text Available Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183 were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL and without labor (PNL, term with (TL and without labor (TNL. Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8, PNL (n = 10, TL (n = 7 and TNL (n = 10. Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed

  19. Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

    Science.gov (United States)

    Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R.; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M.; Andrews, William; Saade, George R.; Ilekis, John V.; Reddy, Uma M.; Baldwin, Donald A.

    2017-01-01

    Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of

  20. Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

    Science.gov (United States)

    Bukowski, Radek; Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M; Andrews, William; Saade, George R; Ilekis, John V; Reddy, Uma M; Baldwin, Donald A

    2017-01-01

    Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL

  1. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, Thomas N; Højrup, Peter

    1994-01-01

    The present paper describes the primary structure, glycosylation and tissue localization of fetal antigen 1 (FA1) isolated from second-trimester human amniotic fluid. FA1 is a single-chained, heterogeneous glycoprotein of 225-262 amino acid residues. FA1 has six well conserved epidermal...

  2. 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

    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...... development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus......, there was a negative correlation between FA1 and glucagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet cell differentiation. Udgivelsesdato: 1996-Dec...

  3. Co-transplantation of human fetal thymus, bone and CD34(+) cells into young adult immunodeficient NOD/SCID IL2Rγ(null) mice optimizes humanized mice that mount adaptive antibody responses.

    Science.gov (United States)

    Chung, Yun Shin; Son, Jin Kyung; Choi, Bongkum; Joo, Sung-Yeon; Lee, Yong-Soo; Park, Jae Berm; Moon, Hana; Kim, Tae Jin; Kim, Se Ho; Hong, Seokmann; Chang, Jun; Kang, Myung-Soo; Kim, Sung Joo

    2015-04-01

    Both the thymus (T) and bone (B) are necessary hematopoietic niches in adult humans. We previously showed that co-transplantation of human fetal T and B tissues into neonatal immunodeficient NOD/SCID IL2Rγ(null) (NSG, N) mice facilitated hematopoiesis. However, transplantation into neonatal mice resulted in high frequency of early death, making it unrealistic for repetitive experiments. In this study, young adult N mice were pre-engrafted with T and B, T alone, B alone or no tissues. The animals were irradiated and injected with autologous fetal liver (FL)-derived CD34(+) cells (34). The resultant mice were TB34N, T34N, B34N and 34N, respectively, and challenged with T cell dependent antigens (Ags). The humanized TB34N mice showed best performance of these mouse models in many aspects resembling the adult human Ag-experienced spleen. The TB34N mice exhibited better hematopoietic reconstitution; balanced development of T- and B-cell, and common progenitor cells; follicular lymphoid structures with a functional germinal center (GC) enriched with follicular dendritic cells (FDCs) and plasma cells (PCs); secretion of hIgG in the sera in response to Ags at comparable levels to those of human; derivations of hIgG mAb-secreting hybridoma clones. Collectively, the humanized TB34N mice could develop an adaptive immunity that was capable of producing Ag-specific hIgG at a significant level via class switching. This unprecedented TB34N platform in humanized mice would be useful in dissecting human immunity, for generating human Abs and clinical applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

    Science.gov (United States)

    Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

    2016-01-01

    Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms

  5. Restricted spontaneous in vitro differentiation and region-specific migration of long-term expanded fetal human neural precursor cells after transplantation into the adult rat brain.

    Science.gov (United States)

    Maciaczyk, Jaroslaw; Singec, Ilyas; Maciaczyk, Donata; Klein, Alexander; Nikkhah, Guido

    2009-09-01

    Human fetal neural stem/progenitor cells (hNSCs) are investigated for their potential as a cell source for cell-based therapies in neurodegenerative diseases. However, the limited availability of fetal tissue and insufficient understanding of the lineage-dependent pattern of survival, migration, and differentiation following engraftment are still unresolved issues. In the current study hNSCs derived from different brain regions were long-term expanded in vitro to yield proliferating neurospheres giving rise to neurons, astro-, and oligodendroglial cells and assessed for their potential for migration, differentiation, and anatomical integration following intracerebral grafting into rats. hNSCs isolated from neocortex, striatum, midbrain, and spinal cord (SC) proliferated following in vitro differentiation, and showed a significant decrease of newly formed neurons along the rostrocaudal axis of the developing central nervous system (CNS). Most of the mature neurons were positive for the neurotransmitter GABA. In vivo all cell types survived up to 9 weeks posttransplantation. Intrastriatally grafted hNSCs migrated extensively along white matter tracts reaching both rostral (forceps minor) and caudal (midbrain, cerebral peduncle) brain regions. The majority of migratory cells expressed the stem cell marker, nestin. A fraction of grafted cells acquired a neuronal phenotype expressing doublecortin, beta-III-tubulin, or GABA. These data demonstrate efficient in vitro propagation, region-specific long-term survival, long-distance migration, and neuronal differentiation of hNSCs after transplantation into the adult rat brain. The availability of a large pool of in vitro expanded nestin-positive cells offers the possibility for further ex vivo manipulations and the recruitment of different neuronal phenotypes for cell replacement strategies for CNS disorders.

  6. European Council of Legal Medicine (ECLM) principles for on-site forensic and medico-legal scene and corpse investigation.

    Science.gov (United States)

    Cusack, D; Ferrara, S D; Keller, E; Ludes, B; Mangin, P; Väli, M; Vieira, N

    2017-07-01

    Forensic medical practitioners need to define the general principles governing procedures to be used for the on-site examination of a body where the death has occurred in unnatural, violent or suspicious circumstances. These principles should be followed whenever a medical expert is required to perform an on-site corpse inspection and should be utilised as a set of general guidelines to be adapted to the specific situation in hand and interpreted using common sense and scientific knowledge of the relevant procedures and facts of the case. The aim of these principles is to ensure that forensic evidence at the scene of a death is properly observed and assessed and all necessary relevant evidence gathered in order to ensure that a comprehensive report is available to the judicial authority (investigating judge or coroner) in the justice system. The on-site corpse inspection by a forensic practitioner is a mandatory and essential stage of the forensic and medico-legal autopsy, as it may provide important information for subsequent investigation stages.

  7. Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ cells of the human fetal ovary and testis

    Directory of Open Access Journals (Sweden)

    Coutts Shona

    2007-12-01

    Full Text Available Abstract Background Germ cells arise from a small group of cells that express markers of pluripotency including OCT4. In humans formation of gonadal compartments (cords in testis, nests in ovary takes place during the 1st trimester (6–8 weeks gestation. In the 2nd trimester germ cells can enter meiotic prophase in females whereas in males this does not occur until puberty. We have used qRTPCR, Westerns and immunohistochemical profiling to determine which of the germ cell subtypes in the human fetal gonads express OCT4, DAZL and VASA, as these have been shown to play an essential role in germ cell maturation in mice. Results OCT4 mRNA and protein were detected in extracts from both 1st and 2nd trimester ovaries and testes. In ovarian extracts a marked increase in expression of VASA and DAZL mRNA and protein occurred in the 2nd trimester. In testicular extracts VASA mRNA and protein were low/undetectable in 1st trimester and increased in the 2nd trimester whereas the total amount of DAZL did not seem to change. During the 1st trimester, germ cells were OCT4 positive but did not express VASA. These results are in contrast to the situation in mice where expression of Vasa is initiated in Oct4 positive primordial germ cells as they enter the gonadal ridge. In the 2nd trimester germ cells with intense cytoplasmic staining for VASA were present in both sexes; these cells were OCT4 negative. DAZL expression overlapped with both OCT4 and VASA and changed from the nuclear to the cytoplasmic compartment as cells became OCT4-negative. In males, OCT4-positive and VASA-positive subpopulations of germ cells coexisted within the same seminiferous cords but in the ovary there was a distinct spatial distribution of cells with OCT4 expressed by smaller, peripherally located, germ cells whereas DAZL and VASA were immunolocalised to larger (more mature centrally located cells. Conclusion OCT4, DAZL and VASA are expressed by human fetal germ cells but their

  8. [Biometric ranging of the corpses destroyed at the site of a catastrophe in terms of gender, longitudinal and circumferencial dimensions, and the degree of subcutaneous fat distribution].

    Science.gov (United States)

    Zviagin, V N; Galitskaia, O I; Negasheva, M A

    2012-01-01

    The quantitative criteria for biometric ranging of destroyed corpses in terms of anatomical localization, gender, longitudinal length, trunk circumference, and the folds of subcutaneous fat are proposed. The wealth of anthropometric materials obtained in the studies of various Caucasoid populations was used to calculate the normative tables for biometric ranging of the decomposed corpses. The proposed technology excludes the subjective assessments for the purpose of such classification at the sites of catastrophes. Moreover, it promotes the accumulation of the variety of valuable information, such as the size of the collar, headwear, and footwear, clothing size and height, and portrait features, that can be used for victim identification.

  9. Human platelet lysate is an alternative to fetal bovine serum for large-scale expansion of bone marrow-derived mesenchymal stromal cells.

    Science.gov (United States)

    Gottipamula, Sanjay; Sharma, Archana; Krishnamurthy, Sagar; Majumdar, Anish Sen; Seetharam, Raviraja N

    2012-07-01

    Human platelet lysate (HPL) was evaluated as an alternative to fetal bovine serum (FBS) in large-scale culturing of bone marrow-derived mesenchymal stromal cells (BM-MSCs) for therapeutic applications. Dulbecco's modified Eagle medium (DMEM)of low glucose (LG) and Knock Out (KO) were used with human platelet lysate (HPL) as LG-HPL and KO-HPL, and with FBS as LG-FBS and KO-FBS to culture the BM-MSCs. HPL at 10 % (v/v) supported BM-MSCs growth and subsequent isolation efficiency generated >90 × 10(6) MSCs in LG-HPL. Population doublings (PDs) and population doubling times of LG-HPL and KO-HPL (PDT) were not significantly different but LG-HPL showed a significant clonogenic potential and HPL cultures had an average PDT of 36.5 ± 6.5 h and an average PDs of 5 ± 0.7/passage. BM-MSCs cultured with LG-HPL had significantly higher immunosuppression compared to LG-FBS, but KO-HPL and KO-FBS-grown cultures were not significantly different. HPL is therefore alternative to FBS for large-scale production of BM-MSCs for therapeutic applications.

  10. Phenotypical and functional characteristics of mesenchymal stem cells from bone marrow: comparison of culture using different media supplemented with human platelet lysate or fetal bovine serum.

    Science.gov (United States)

    Ben Azouna, Nesrine; Jenhani, Faouzi; Regaya, Zohra; Berraeis, Lamia; Ben Othman, Tarek; Ducrocq, Elfi; Domenech, Jorge

    2012-02-14

    Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into several mesenchymal lineages, classically derived from bone marrow (BM) but potentially from umbilical cord blood (UCB). Although they are becoming a good tool for regenerative medicine, they usually need to be expanded in fetal bovine serum (FBS)-supplemented media. Human platelet lysate (HPL) has recently been proposed as substitute for safety reasons, but it is not yet clear how this supplement influences the properties of expanded MSCs. In the present study, we compared the effect of various media combining autologous HPL with or without FBS on phenotypic, proliferative and functional (differentiation, cytokine secretion profile) characteristics of human BM-derived MSCs. Despite less expression of adipogenic and osteogenic markers, MSCs cultured in HPL-supplemented media fully differentiated along osteoblastic, adipogenic, chondrogenic and vascular smooth muscle lineages. The analyses of particular specific proteins expressed during osteogenic differentiation (calcium-sensing receptor (CaSR) and parathormone receptor (PTHR)) showed their decrease at D0 before any induction for MSC cultured with HPL mostly at high percentage (10%HPL). The cytokine dosage showed a clear increase of proliferation capacity and interleukin (IL)-6 and IL-8 secretion. This study shows that MSCs can be expanded in media supplemented with HPL that can totally replace FBS. HPL-supplemented media not only preserves their phenotype as well as their differentiation capacity, but also shortens culture time by increasing their growth rate.

  11. Signal management in pharmacovigilance and human risk assessment of CpG 7909, integrating embryo-fetal and post-natal developmental toxicity studies in rats and rabbits.

    Science.gov (United States)

    Delannois, Frédérique; Planty, Camille; Giordano, Giulia; Destexhe, Eric; Stanislaus, Dinesh; Da Silva, Fernanda Tavares; Stegmann, Jens-Ulrich; Thacker, Karen; Reynaud, Lucie; Garçon, Nathalie; Segal, Lawrence

    2018-01-01

    The potential reproductive and developmental toxicity of the synthetic oligodeoxynucleotide (ODN) CpG 7909, a component of GSK's AS15 immunostimulant, was examined in rat and rabbit studies following intermittent intramuscular injections. Previous studies using subcutaneous and intraperitoneal injections in mice, rats and rabbits revealed that CpG ODNs induced developmental effects. To analyze the safety signal, GSK conducted additional animal studies using the intended clinical route of administration. CpG 7909 injections were administered intramuscularly to rats or rabbits 28 and 14days before pairing, on 4 or 5 occasions during gestation, and on lactation day 7. The No Observed Adverse Effect Level for female fertility, embryo-fetal and pre- and post-natal development was 4.2mg/kg in both species, approximately 500-fold higher than the anticipated human dose. In conclusion, the anticipated risk to humans is considered low for sporadic intramuscular exposure to CpG 7909. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Analysis of the symmetric configuration of the circle of Willis in a series of autopsied corpses.

    Science.gov (United States)

    Stojanović, Nebojga; Stefanović, Ivica; Kostić, Aleksandar; Radisavejević, Misa; Stojanov, Dragan; Petrović, Sladjana

    2015-04-01

    The forming of the blood vessels network configuration at the base of the brain and interconnecting of blood vessels during the embryogenesis is directly related to the phylogenetic development of the brain and brain structures. A blood vessel configuration at the brain base, in the form of a ring or a hexagon, stands in direct relation to the perfusion needs of certain parts of the brain during its primary differentiation. The aim of this paper was to determine the incidence of certain blood vessel configurations at the base of the brain and understanding their symmetry or asymmetry. Analysis of the blood vessels at the base of the brain was performed on the autopsied subjects. The object of observation was the anterior segment of the circle of Willis consisting of C1- a. carotis interna (ICA), above a. communicaus posterior (PcoA), the segment A1 a. cerebri anterior (ACA) from a. carotis interna bifurcation to the a. communicans anterior (AcoA) and a communicans anterior itself, as well as the posterior segment consisting of PcoA and the segment P1--a. cerebri posterior (PCA) from the a. basilaris bifurcation to the PcoA. For the purpose of grouping the findings, the four basic configuration types of the circle of Willis were identified based on its symmetry or asymmetry. Type-A (symmetric circle of Willis), type-B (asymmetric circle of Willis' due to the unilateral hypoplastic A1-ACA); type-C (symmetric circle of Willis with bilateral symmetric changes on PcoA) and type-D (asymmetric circle of Willis due to the asymmetric changes on PcoA). Autosy was performed on 56 corpses. A total of 41 (73.2%) subjects were recorded with a symmetric configuration of the circle of Willis', of which 27 (48.2%) subjects had type A and 14 (25%) type C. The asymmetric configuration was present in 15 (26.8%) subjects, of whom 9 (16%) had type B and 6 (10.8%) subjects, of whom 9 (16%) had type B and 6 (10.8%) type D. The symmetric Willis group (73.2%) did not have a homogeneous

  13. Are 1st-trimester β-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels predictive of intrapartum fetal compromise in a selected normal population?

    Science.gov (United States)

    Prior, Tomas; Mullins, Edward; Bennett, Phillip; Kumar, Sailesh

    2014-10-01

    The incidence of cerebral palsy in term infants has not changed over the last 30 years. Current intrapartum monitoring techniques are limited by their inherent poor specificity. Changes in fetal haemodynamics in the term fetus, similar to those seen in fetal growth restriction, have been associated with an increased risk of subsequent intrapartum fetal compromise. Alterations in first-trimester β-hCG and PAPP-A levels are predictive of fetal growth restriction. In this study, we aimed to establish whether first-trimester β-hCG and PAPP-A levels were predictive of fetal compromise in labour and whether these first-trimester markers could be correlated with fetal haemodynamics at term in a low-risk population. Over a two-year period, 427 women with low risk, uncomplicated pregnancies were recruited to this study. All participants underwent a prelabour ultrasound examination during which fetal biometry and haemodynamics were assessed. First-trimester β-hCG and PAPP-A levels were recorded from the case notes. All cases were followed up within 48 hours of delivery, and first-trimester β-hCG and PAPP-A levels correlated with intrapartum outcomes and fetal haemodynamics. No significant relationship between first-trimester β-hCG and PAPP-A levels and subsequent intrapartum fetal compromise was observed. Weak but significant correlations were observed between β-hCG levels and umbilical venous flow rate, as well as PAPP-A levels and uterine artery pulsatility index. β-hCG and PAPP-A levels measured during the first trimester are not predictive of subsequent intrapartum fetal compromise within a low-risk population. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  14. Maternal plasma fetal DNA fractions in pregnancies with low and high risks for fetal chromosomal aneuploidies.

    Directory of Open Access Journals (Sweden)

    Irena Hudecova

    Full Text Available Recently published international guidelines recommend the clinical use of noninvasive prenatal test (NIPT for aneuploidy screening only among pregnant women whose fetuses are deemed at high risk. The applicability of NIPT to aneuploidy screening among average risk pregnancies requires additional supportive evidence. A key determinant of the reliability of aneuploidy NIPT is the fetal DNA fraction in maternal plasma. In this report, we investigated if differences in fetal DNA fractions existed between different pregnancy risk groups. One hundred and ninety-five singleton pregnancies with male fetuses divided into 3 groups according to first trimester screening parameters were examined for fetal DNA percentage by counting Y chromosome DNA sequences using massively parallel sequencing. Fetal DNA fractions were compared between risk groups and assessed for correlations with first trimester screening parameters. There was no statistically significant difference in fetal DNA fractions across the high, intermediate and low risk groups. Fetal DNA fraction showed a strong negative correlation with maternal weight. Fetal DNA fraction also showed weak but significant correlations with gestational age, crown-rump length, multiple of medians of free β-subunit of human chorionic gonadotropin and pregnancy-associated plasma protein A. Similar fetal DNA fractions in maternal plasma between high, intermediate and low risk pregnant women is a precondition for uniform performance of the aneuploidy NIPTs for the general population. This study thus shows that the aneuploidy screening by NIPT is likely to offer similar analytical reliability without respect to the a priori fetal aneuploidy risk.

  15. Differential effect of platelet-rich plasma and fetal calf serum on bone marrow-derived human mesenchymal stromal cells expanded in vitro.

    Science.gov (United States)

    Goedecke, Anja; Wobus, Manja; Krech, Mathias; Münch, Nadine; Richter, Katja; Hölig, Kristina; Bornhauser, Martin

    2011-08-01

    Mesenchymal stromal cells (MSCs) derived from various sources have great potential for use in cell-based therapies. Since the proportion of primary MSCs contained in bone marrow or adipose tissue is low, plastic adherence and in vitro expansion are necessary to expand MSCs prior to clinical application. Human platelet-rich plasma has been introduced as an alternative serum source but functional differences have so far not been described. Here we cultured MSCs derived from human bone marrow in medium supplemented with either 10% fetal calf serum (FCS) or 5% and 10% platelet-rich plasma (PRP) until the first or second passage. Parameters under investigation were cell yield, clonogenicity, phenotype as well as migratory and differentiation potential. In addition, the secretion of SDF-1α and the induced migration of CD34(+) haematopoietic stem cells (HSCs) were investigated with regard to the different serum source. The use of PRP resulted in a significantly higher expansion rate and yield at passages 0 and 1. In addition, the level of secreted SDF-1α was significantly increased in the supernatant of MSCs cultured with FCS instead of human PRP. Consistent with this, the migration capacity of MSCs cultured with 10% FCS as well as their capability to induce the migration of CD34(+) haematopoietic progenitors in a transwell assay was higher. Our results demonstrate that human PRP can be seen as an alternative serum source to FCS for MSC cultivation. However, the requirements of the specific clinical application must be carefully considered before the respective serum source is selected. Copyright © 2010 John Wiley & Sons, Ltd.

  16. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Science.gov (United States)

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  17. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Haejin Lee

    Full Text Available Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%, APC-CC1+ oligodendrocytes (∼28%, and GFAP+ astrocytes (∼8%. Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest

  18. Cloning human fetal gamma globin and mouse alpha-type globin DNA: preparation and screening of shotgun collections.

    Science.gov (United States)

    Blattner, F R; Blechl, A E; Denniston-Thompson, K; Faber, H E; Richards, J E; Slightom, J L; Tucker, P W; Smithies, O

    1978-12-22

    Shotgun collections of Charon 3A bacteriophages containing Eco RI fragments of human and mouse DNA were constructed with the use of in vitro packaging. Plaques were screened by hybridization, and globin-specific clones were isolated from both human (Charon 3AHs51.1) and mouse (Charon 3AMm30.5). The fragments cloned were detected in unfractionated genomic DNA by the Southern method of hybridization.

  19. Fetal Alcohol Exposure: The Common Toll

    OpenAIRE

    Nakhoul, Marie R; Seif, Karl E; Haddad, Natasha; Haddad, Georges E

    2017-01-01

    Alcohol has always been present in human life, and currently it is estimated that 50% of women of childbearing age consume alcohol. It has become increasingly clear over the last years that alcohol exposure during fetal development can have detrimental effects on various organ systems, and these effects are exerted by alcohol through multiple means, including effects on free radical formation, cellular apoptosis, as well as gene expression. Fetal alcohol exposure can lead to a spectrum of sho...

  20. Novel isolation strategy to deliver pure fetal-origin and maternal-origin mesenchymal stem cell (MSC) populations from human term placenta.

    Science.gov (United States)

    Patel, J; Shafiee, A; Wang, W; Fisk, N M; Khosrotehrani, K

    2014-11-01

    The placenta is an abundant source of mesenchymal stem/stromal cells (MSC). Although presumed of translationally-advantageous fetal origin, the literature instead suggests a high incidence of either contaminating or pure maternal MSC. Despite definitional criteria that MSC are CD34-, increasing evidence suggests that fetal MSC may be CD34 positive in vivo. We flow sorted term placental digests based on CD34+ expression and exploited differential culture media to isolate separately pure fetal and maternal MSC populations. This method has considerable translational implications, in particular to clinical trials underway with "placental" MSC of uncertain or decidual origin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Angiotensin II type 2 receptor is critical for the development of human fetal pancreatic progenitor cells into islet-like cell clusters and their potential for transplantation.

    Science.gov (United States)

    Leung, Kwan Keung; Liang, Juan; Ma, Man Ting; Leung, Po Sing

    2012-03-01

    Local renin-angiotensin systems (RASs) regulate the differentiation of tissue progenitors. However, it is not known whether such systems can regulate the development of pancreatic progenitor cells (PPCs). To address this issue, we characterized the expression profile of major RAS components in human fetal PPC preparations and examined their effects on the differentiation of PPCs into functional islet-like cell clusters (ICCs). We found that expression of RAS components was highly regulated throughout PPC differentiation and that locally generated angiotensin II (Ang II) maintained PPC growth and differentiation via Ang II type 1 and type 2 (AT(1) and AT(2)) receptors. In addition, we observed colocalization of AT(2) receptors with critical β-cell phenotype markers in PPCs/ICCs, as well as AT(2) receptor upregulation during differentiation, suggesting that these receptors may regulate β-cell development. In fact, we found that AT(2) , but not AT(1) , receptor was a key mediator of Ang II-induced upregulation of transcription factors important in β-cell development. Furthermore, lentivirus-mediated knockdown of AT(2) receptor suppressed the expression of these transcription factors in ICCs. Transplantation of AT(2) receptor-depleted ICCs into immune-privileged diabetic mice failed to ameliorate hyperglycemia, implying that AT(2) receptors are indispensable during ICC maturation in vivo. These data strongly indicate that a local RAS is involved in governing the functional maturation of pancreatic progenitors toward the endocrine lineage. Copyright © 2011 AlphaMed Press.

  2. Distribution and viability of fetal and adult human bone marrow stromal cells in a biaxial rotating vessel bioreactor after seeding on polymeric 3D additive manufactured scaffolds

    Directory of Open Access Journals (Sweden)

    Anne eLeferink

    2015-10-01

    Full Text Available One of the conventional approaches in tissue engineering is the use of scaffolds in combination with cells to obtain mechanically stable tissue constructs in vitro prior to implantation. Additive manufacturing by fused deposition modeling is a widely used technique to produce porous scaffolds with defined pore network, geometry, and therewith defined mechanical properties. Bone marrow derived mesenchymal stromal cells (MSCs are promising candidates for tissue engineering based cell therapies due to their multipotent character. One of the hurdles to overcome when combining additive manufactured scaffolds with MSCs is the resulting heterogeneous cell distribution and limited cell proliferation capacity. In this study, we show that the use of a biaxial rotating bioreactor, after static culture of human fetal MSCs (hfMSCs seeded on synthetic polymeric scaffolds, improved the homogeneity of cell and extracellular matrix (ECM distribution and increased the total cell number. Furthermore, we show that the relative mRNA expression levels of indicators for stemness and differentiation are not significantly changed upon this bioreactor culture, whereas static culture shows variations of several indicators for stemness and differentiation. The biaxial rotating bioreactor presented here offers a homogeneous distribution of hfMSCs, enabling studies on MSCs fate in additive manufactured scaffolds without inducing undesired differentiation.

  3. [Influence of puerarin on proliferative activity of human fetal scleral fibroblasts and expression of collagen type I and matrix metalloproteinase-2 in power frequency electromagnetic field].

    Science.gov (United States)

    Su, Q; Yang, L

    2016-06-20

    To investigate the influence of puerarin on the proliferative activity of human fetal scleral fibroblasts (HFSFs) and the expression of collagen type I and matrix metalloproteinase-2 (MMP-2) in HFSFs in the power frequency electromagnetic field. HFSFs were cultured and divided into four radiation groups (0.2 mT, 50 Hz) and control group. Puerarin at concentrations of 0.0, 1.0, 5.0, and 10.0 μmol/L was added to the four radiation groups, respectively. The methyl thiazolyl tetrazolium colorimetry was used to measure the influence on the proliferative activity of HFSFs, Western blot and RT-qPCR were used to measure the protein and mRNA expression of collagen type I and MMP-2 induced by puerarin in the power frequency electromagnetic field. The radiation groups and control group showed significant increases in the proliferative activity of HFSFs over the culture time (F= 959.472 and 279.468, both Ptype I and significantly higher protein expression of MMP-2 (t=7.917 and 7.831, both Ptype I and significant reductions in the protein expression of MMP-2 (all Ptype I and MMP-2 (t=17.293 and 16.378, both Ptype I and significant reductions in the mRNA expression of MMP-2 (Ptype I, downregulate the expression of MMP-2, and thus exert its protective effect.

  4. Comparative Evaluation of Human Mesenchymal Stem Cells of Fetal (Wharton's Jelly and Adult (Adipose Tissue Origin during Prolonged In Vitro Expansion: Considerations for Cytotherapy

    Directory of Open Access Journals (Sweden)

    I. Christodoulou

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are somatic cells with a dual capacity for self-renewal and differentiation, and diverse therapeutic applicability, both experimentally and in the clinic. These cells can be isolated from various human tissues that may differ anatomically or developmentally with relative ease. Heterogeneity due to biological origin or in vitro manipulation is, nevertheless, considerable and may equate to differences in qualitative and quantitative characteristics which can prove crucial for successful therapeutic use. With this in mind, in the present study we have evaluated the proliferation kinetics and phenotypic characteristics of MSCs derived from two abundant sources, that is, fetal umbilical cord matrix (Wharton's jelly and adult adipose tissue (termed WJSC and ADSC, resp. during prolonged in vitro expansion, a process necessary for obtaining cell numbers sufficient for clinical application. Our results show that WJSC are derived with relatively high efficiency and bear a substantially increased proliferation capacity whilst largely sustaining the expression of typical immunophenotypic markers, whereas ADSC exhibit a reduced proliferation potential showing typical signs of senescence at an early stage. By combining kinetic with phenotypic data we identify culture thresholds up to which both cell types maintain their stem properties, and we discuss the practical implications of their differences.

  5. Influence of basement membrane proteins and endothelial cell-derived factors on the morphology of human fetal-derived astrocytes in 2D.

    Directory of Open Access Journals (Sweden)

    Amanda F Levy

    Full Text Available Astrocytes are the most prevalent type of glial cell in the brain, participating in a variety of diverse functions from regulating cerebral blood flow to controlling synapse formation. Astrocytes and astrocyte-conditioned media are widely used in models of the blood-brain barrier (BBB, however, very little is known about astrocyte culture in 2D. To test the hypothesis that surface coating and soluble factors influence astrocyte morphology in 2D, we quantitatively analyzed the morphology of human fetal derived astrocytes on glass, matrigel, fibronectin, collagen IV, and collagen I, and after the addition soluble factors including platelet-derived growth factor (PDGF, laminin, basic fibroblast growth factor (bFGF, and leukemia inhibitory factor (LIF. Matrigel surface coatings, as well as addition of leukemia inhibitory factor (LIF to the media, were found to have the strongest effects on 2D astrocyte morphology, and may be important in improving existing BBB models. In addition, the novel set of quantitative parameters proposed in this paper provide a test for determining the influence of compounds on astrocyte morphology, both to screen for new endothelial cell-secreted factors that influence astrocytes, and to determine in a high-throughput way which factors are important for translation to more complex, 3D BBB models.

  6. Clinical Trial of Human Fetal Brain-Derived Neural Stem/Progenitor Cell Transplantation in Patients with Traumatic Cervical Spinal Cord Injury.

    Science.gov (United States)

    Shin, Ji Cheol; Kim, Keung Nyun; Yoo, Jeehyun; Kim, Il-Sun; Yun, Seokhwan; Lee, Hyejin; Jung, Kwangsoo; Hwang, Kyujin; Kim, Miri; Lee, Il-Shin; Shin, Jeong Eun; Park, Kook In

    2015-01-01

    In a phase I/IIa open-label and nonrandomized controlled clinical trial, we sought to assess the safety and neurological effects of human neural stem/progenitor cells (hNSPCs) transplanted into the injured cord after traumatic cervical spinal cord injury (SCI). Of 19 treated subjects, 17 were sensorimotor complete and 2 were motor complete and sensory incomplete. hNSPCs derived from the fetal telencephalon were grown as neurospheres and transplanted into the cord. In the control group, who did not receive cell implantation but were otherwise closely matched with the transplantation group, 15 patients with traumatic cervical SCI were included. At 1 year after cell transplantation, there was no evidence of cord damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity. The American Spinal Injury Association Impairment Scale (AIS) grade improved in 5 of 19 transplanted patients, 2 (A → C), 1 (A → B), and 2 (B → D), whereas only one patient in the control group showed improvement (A → B). Improvements included increased motor scores, recovery of motor levels, and responses to electrophysiological studies in the transplantation group. Therefore, the transplantation of hNSPCs into cervical SCI is safe and well-tolerated and is of modest neurological benefit up to 1 year after transplants. This trial is registered with Clinical Research Information Service (CRIS), Registration Number: KCT0000879.

  7. Clinical Trial of Human Fetal Brain-Derived Neural Stem/Progenitor Cell Transplantation in Patients with Traumatic Cervical Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Ji Cheol Shin

    2015-01-01

    Full Text Available In a phase I/IIa open-label and nonrandomized controlled clinical trial, we sought to assess the safety and neurological effects of human neural stem/progenitor cells (hNSPCs transplanted into the injured cord after traumatic cervical spinal cord injury (SCI. Of 19 treated subjects, 17 were sensorimotor complete and 2 were motor complete and sensory incomplete. hNSPCs derived from the fetal telencephalon were grown as neurospheres and transplanted into the cord. In the control group, who did not receive cell implantation but were otherwise closely matched with the transplantation group, 15 patients with traumatic cervical SCI were included. At 1 year after cell transplantation, there was no evidence of cord damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity. The American Spinal Injury Association Impairment Scale (AIS grade improved in 5 of 19 transplanted patients, 2 (A → C, 1 (A → B, and 2 (B → D, whereas only one patient in the control group showed improvement (A → B. Improvements included increased motor scores, recovery of motor levels, and responses to electrophysiological studies in the transplantation group. Therefore, the transplantation of hNSPCs into cervical SCI is safe and well-tolerated and is of modest neurological benefit up to 1 year after transplants. This trial is registered with Clinical Research Information Service (CRIS, Registration Number: KCT0000879.

  8. Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues

    NARCIS (Netherlands)

    Jokubaitis, Vanta J.; Sinka, Lidia; Driessen, Rebecca; Whitty, Genevieve; Haylock, David N.; Bertoncello, Ivan; Smith, Ian; Peault, Bruno; Tavian, Manuela; Simmons, Paul J.

    2008-01-01

    Previous studies revealed that mAb BB9 reacts with a subset of CD34(+) human BM cells with hematopoietic stem cell (HSC) characteristics. Here we map B89 expression throughout hernatopoietic development and show that the earliest definitive HSCs that arise at the ventral wall of the aorta and

  9. 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

  10. Human platelet lysate is a feasible candidate to replace fetal calf serum as medium supplement for blood vascular and lymphatic endothelial cells.

    Science.gov (United States)

    Hofbauer, Pablo; Riedl, Sabrina; Witzeneder, Karin; Hildner, Florian; Wolbank, Susanne; Groeger, Marion; Gabriel, Christian; Redl, Heinz; Holnthoner, Wolfgang

    2014-09-01

    As angiogenic and lymphangiogenic key players, endothelial cells (ECs) are promising candidates for vascular regenerative therapies. To culture ECs in vitro, fetal calf serum (FCS) is most often used. However, some critical aspects of FCS usage, such as possible internalization of xenogeneic proteins and prions, must be considered. Therefore, the aim of this project was to determine if human platelet lysate (hPL) is a suitable alternative to FCS as medium supplement for the culture of blood vascular and lymphatic endothelial cells. The usability of hPL was tested by analysis of endothelial surface marker expression, metabolic activity and vasculogenic potential of outgrowth ECs (OECs), human umbilical vein ECs (HUVECs), and lymphatic ECs (LECs). Expression of EC markers CD31, VEGFR2, VE-cadherin and CD146 did not differ significantly between the EC types cultured in FCS or hPL. In addition, OECs, HUVECs and LECs formed tube-like structures on Matrigel when cultured in hPL and FCS. With the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid assays, we found that the metabolic activity of OECs and LECs was slightly decreased when hPL was used. However, HUVECs and LECs did not show a significant decrease in metabolic activity, and HUVECs showed a slightly higher activity at low seeding densities. The use of hPL on different EC types did not reveal any substantial negative effects on EC behavior. Thus, hPL appears to be a favorable candidate to replace FCS as a medium supplement in the culture of ECs. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  11. Immortalized human fetal bone marrow-derived mesenchymal stromal cell expressing suicide gene for anti-tumor therapy in vitro and in vivo.

    Science.gov (United States)

    Lee, Wayne Y W; Zhang, Ting; Lau, Carol P Y; Wang, C C; Chan, Kai-Ming; Li, Gang

    2013-12-01

    Cancer is one of the greatest health challenges facing the world today with >10 million new cases of cancer every year. The self-renewal, tumor-homing ability and low immunogenicity of mesenchymal stromal cells (MSCs) make them potential delivery candidates for suicide genes for anti-tumor therapy. However, unstable supply and short life span of adult MSCs in vitro have limited this therapeutic potential. In this study, we aimed to evaluate if immortalization of human fetal bone marrow-derived mesenchymal stromal cells by simian virus 40 (SV40-hfBMSCs) could be a stable source of MSCs for clinical application of suicide gene therapy. Transduction of SV40 and herpes simplex virus thymidine kinase-IRES-green fluorescent protein (TK-GFP) did not cause significant change in the stem cell properties of hfBMSCs. The anti-tumor effect of SV40-TK-hfBMSCs in the presence of the prodrug ganciclovir was demonstrated in vitro and in nude mice bearing human prostate cancer cells, DU145 and PC3, which had been transduced with luciferase and GFP for imaging evaluation by an in vivo live imaging system (IVIS 200 imaging system; Caliper Life Sciences). Repeated injection of low doses (1 × 10(6) cells/kg) of SV40-TK-hfBMSCs was as effective as previously reported and did not cause observable harmful side effects in multiple organs. Mixed lymphocyte reaction showed that SV40-TK-hfBMSCs did not induce significant proliferation of lymphocytes isolated from healthy adults. Taken together, immortalized hfBMSCs represent a reliable and safe source of MSCs for further clinical translational study. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  12. In vitro study of the proliferation and growth of human fetal osteoblasts on Mg and Si co-substituted tricalcium phosphate ceramics.

    Science.gov (United States)

    Parra, Juan; García Páez, Ismael H; De Aza, Antonio H; Baudin, Carmen; Rocío Martín, M; Pena, Pilar

    2017-08-01

    The objective of this work was to study the feasibility of the solid state sintering, a conventional ceramic processing method, to obtain Mg and Si co-substituted tricalcium phosphate bioceramics and composites containing diopside. A series of new Ca3 (PO4 )2 based ceramics has been prepared from attrition milled mixtures of synthetic Ca3 (PO4 )2 and CaMg(SiO3 )2 powders, isostatically pressed and sintered at 1250-1300°C. Materials containing 0, 1, and 5 wt % of CaMg(SiO3 )2 were constituted by β + α - Ca3 (PO4 )2 solid solutions while the material containing 60 wt % of CaMg(SiO3 )2 was a constituted by β- Ca3 (PO4 )2 and CaMg(SiO3 )2 . The biological responses of the developed ceramics were studied in vitro using human fetal osteoblast cultures. Culture times ranged from 1 to 21 days. The new family of materials promotes the adhesion and proliferation of human osteoblasts cultured onto their surface forming a monolayer and showing a normal morphology. The results of the MTT and Alamar Blue assays showed that the soluble components extracted from the Mg/Si- co-substituted Ca3 (PO4 )2 and the Ca3 (PO4 )2 -CaMg(SiO3 )2 composite were noncytotoxic. The specimens with diopside exhibited a better in vitro behavior which is attributed to the release of Si and Mg ions to the culture medium, enhancing the activity of cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2266-2275, 2017. © 2017 Wiley Periodicals, Inc.

  13. Shells and Bones: A Forensic Medicine Study of the Association of Terrestrial Snail Allopeas micra with Buried Human Remains in Brazil.

    Science.gov (United States)

    Galvão, Malthus Fonseca; Pujol-Luz, José Roberto; de Assis Pujol-Luz, Cristiane Vieira; de Rosa, Cássio Thyone Almeida; Simone, Luiz Ricardo L; Báo, Sônia Nair; Barros-Cordeiro, Karine Brenda; Pessoa, Larissa; Bissacot, Giovanna

    2015-09-01

    Little is known regarding the scavenger fauna associated with buried human corpses, particularly in clandestine burials. We report the presence of 20 shells of the terrestrial snail Allopeas micra, within hollow bones of human remains buried for 5 years, during the process of collecting DNA material. The fact that a large number of shells of A. micra had been found in the corpse and in the crime scene supports the assumption that there was no attempt to remove the corpse from the area where the crime occurred. Despite this, our observations cannot be used to estimate the postmortem interval because there is no precise knowledge about the development of this species. This is the first record of a terrestrial snail associated with a human corpse and its role in this forensic medicine case. © 2015 American Academy of Forensic Sciences.

  14. In vitro assessment of mouse fetal abdominal aortic vascular function

    OpenAIRE

    Renshall, Lewis J.; Dilworth, Mark R.; Greenwood, Susan L.; Sibley, Colin P.; Wareing, Mark

    2014-01-01

    Fetal growth restriction (FGR) affects 3?8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivit...

  15. Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation.

    Science.gov (United States)

    Rose, Destanie R; Careaga, Milo; Van de Water, Judy; McAllister, Kim; Bauman, Melissa D; Ashwood, Paul

    2017-07-01

    Infection during pregnancy can lead to activation of the maternal immune system and has been associated with an increased risk of having an offspring later diagnosed with a neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD) or schizophrenia (SZ). Most maternal immune activation (MIA) studies to date have been in rodents and usually involve the use of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C). However, since NDD are based on behavioral changes, a model of MIA in non-human primates could potentially provide data that helps illuminate complex behavioral and immune outputs in human NDD. In this study twenty-one pregnant rhesus macaques were either given three injections over 72 hours of poly I:C-LC, a double stranded RNA analog (viral mimic), or saline as a control. Injections were given near the end of the first trimester or near the end of the second trimester to determine if there were differences in immune output due to the timing of MIA.An additional three non-treated animals were used as controls. The offspring were followed until 4 years of age, with blood collected at the end of their first (year 1) and fourth (year 4) years to assess dynamic cellular immune function. Induced responses from peripheral immune cells were measured using multiplex assays.At one year of age, MIA exposed offspring displayed elevated production of innate inflammatory cytokines including: interleukin (IL)-1β, IL-6, IL-12p40, and tumor necrosis factor (TNF)α at baseline and following stimulation. At four years of age, the MIA exposed offspring continued to display elevated IL-1β, and there was also a pattern of an increased production of T-cell helper type (TH)-2 cytokines, IL-4 and IL-13. Throughout this time period, the offspring of MIA treated dams exhibited altered behavioral phenotypes including increased stereotyped behaviors. During the first two years, stereotyped behaviors were associated with innate cytokine production

  16. MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaoou [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Liu, Lian [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Wen, Fuqiang, E-mail: wenfuqiang.scu@gmail.com [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China)

    2014-11-28

    Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.

  17. Critical closing pressure in the fetal vessel of the human placenta in vitro. II. Compared effects of a beta adrenergic substance, Salbutamol, on the critical closing pressure and vascular resistance.

    Science.gov (United States)

    Benedetti, W L; González-Panizza, V H; Alvarez, H

    1976-01-01

    Salbutamol effects upon the fetal vessels of the human placenta were studied in vitro, comparing the changes induced upon the critical closing pressure (CCP) and viscous resistance (R). Four normal full-term placentas were used. In each of them, 4 cotyledonary areas were perfused, thus obtaining a total of 16 measurements for the observation of spontaneous variations (blank), by perfusion with Krebs solution, and the same amount for the variations due to Salbutamol. The concentration used was 10 microgram/ml, with a 4.25 ml/min flow. The relative effect of Salbutamol upon CCP was its decrease--30.4% against a relative spontaneous variation of --3.6%. The mean relative effect upon R was much lower, --9.4%. against a mean relative spontaneous variation of + 3.3%. The advantages of using CCP instead of R as a parameter of vascular contractility are discussed. Furthermore, Salbutamol is suggested to be useful in improving fetal placental circulation.

  18. Accounting for Fetal Origins

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan Lars; Hansen, Casper Worm; Strulik, Holger

    2017-01-01

    The Fetal Origins hypothesis has received considerable empirical support, both within epidemiology and economics. The present study compares the ability of two rival theoretical frameworks in accounting for the kind of path dependence implied by the Fetal Origins Hypothesis. We argue that while...

  19. 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 ...

  20. Long-term alterations to DNA methylation as a biomarker of prenatal alcohol exposure: From mouse models to human children with fetal alcohol spectrum disorders.

    Science.gov (United States)

    Laufer, Benjamin I; Chater-Diehl, Eric J; Kapalanga, Joachim; Singh, Shiva M

    2017-05-01

    Rodent models of Fetal Alcohol Spectrum Disorders (FASD) have revealed that prenatal alcohol exposure (PAE) results in differential DNA cytosine methylation in the developing brain. The resulting genome-wide methylation changes are enriched in genes with neurodevelopmental functions. The profile of differential methylation is dynamic and present in some form for life. The methylation changes are transmitted across subsequent mitotic divisions, where they are maintained and further modified over time. More recent follow up has identified a profile of the differential methylation in the buccal swabs of young children born with FASD. While distinct from the profile observed in brain tissue from rodent models, there are similarities. These include changes in genes belonging to a number of neurodevelopmental and behavioral pathways. Specifically, there is increased methylation at the clustered protocadherin genes and deregulation of genomically imprinted genes, even though no single gene is affected in all patients studied to date. These novel results suggest further development of a methylation based strategy could enable early and accurate diagnostics and therapeutics, which have remained a challenge in FASD research. There are two aspects of this challenge that must be addressed in the immediate future: First, the long-term differential methylomics observed in rodent models must be functionally confirmed. Second, the similarities in differential methylation must be further established in humans at a methylomic level and overcome a number of technical limitations. While a cure for FASD is challenging, there is an opportunity for the development of early diagnostics and attenuations towards a higher quality of life. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  1. Electronic fetal heart rate monitoring: where are we now?

    Science.gov (United States)

    Chez, Bonnie Flood; Baird, Suzanne McMurtry

    2011-01-01

    Electronic fetal heart rate monitoring (EFM) continues to be the primary method utilized for fetal assessment in the United States. Standardization of nomenclature associated with this perinatal technology has evolved over the past 40 years such that the current nomenclature recommended by the National Institute of Child Health and Human Development (NICHD) has been adopted by professional perinatal organizations as the agreed-upon method for professional communication and documentation. Current research continues to focus on the optimal management of intrapartum fetal heart rate tracings. The clinical controversies and challenges related to electronic fetal heart rate monitoring continue to evolve.

  2. Fetal stem cell transplantation: Past, present, and future.

    Science.gov (United States)

    Ishii, Tetsuya; Eto, Koji

    2014-09-26

    Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson's disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem (ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements.

  3. Epidemiology of fetal death in Latin America.

    Science.gov (United States)

    Conde-Agudelo, A; Belizán, J M; Díaz-Rossello, J L

    2000-05-01

    To identify risk factors associated with fetal death, and to measure the rate and the risk of fetal death in a large cohort of Latin American women. We analyzed 837,232 singleton births recorded in the Perinatal Information System Database of the Latin American Center for Perinatology and Human Development (CLAP) between 1985 and 1997. The risk factors analyzed included fetal factors and maternal sociodemographic, obstetric, and clinical characteristics. Adjusted relative risks were obtained, after adjustment for potential confounding factors, through multiple logistic regression models based on the method of generalized estimating equations. There were 14,713 fetal deaths (rate=17.6 per 1000 births). The fetal death risk increased exponentially as pregnancy advanced. Thirty-seven percent of all fetal deaths occurred at term, and 64% were antepartum. The main risk factors associated with fetal death were lack of antenatal care (adjusted relative risk [aRR]=4.26; 95% confidence interval, 3.84-4.71) and small for gestational age (aRR=3.26; 95% CI, 3.13-3.40). In addition, the risk of death during the intrapartum period was almost tenfold higher for fetuses in noncephalic presentations. Other risk factors associated with stillbirth were: third trimester bleeding, eclampsia, chronic hypertension, preeclampsia, syphilis, gestational diabetes mellitus, Rh isoimmunization, interpregnancy interval or =4, maternal age > or =35 years, illiteracy, premature rupture of membranes, body mass index > or =29.0, maternal anemia, previous abortion, and previous adverse perinatal outcomes. There are several preventable factors that should be dealt with in order to reduce the gap in fetal mortality between Latin America and developed countries.

  4. [Human placental mesenchymal stem cells of fetal origin relieves mouse pulmonary fibrosis via downregulating MyD88 and TGF-β signaling pathway].

    Science.gov (United States)

    Tao, Jin; Li, Qinglun; Ma, Xiaowei; Han, Fei; Liu, Xiaoming; Wei, Jun; Zhu, Yongzhao

    2016-10-01

    Objective To investigate the therapeutic effect and mechanism of human placental mesenchymal stem cells of fetal origin (hfPMSCs) cultured in serum-free medium on mouse pulmonary fibrosis induced by bleomycin treatment. Methods Human hfPMSCs were cultured and identified by flow cytometry. Fifteen 6-week-old male SPF C57BL/6J mice were divided into 3 groups: bleomycin treatment group, hfPMSCs transplantation group and negative control group. Pulmonary fibrosis model was induced in the mice of bleomycin treatment group and hfPMSCs transplantation group with bleomycin (1 μg/L, 50 μL) via intratracheal instillation. The mice in negative control group were instilled with PBS (50 μL) through the same manner of the other two groups. Three days post-modelling, 200 μL containing 5×10(5) hfPMSCs were injected into hfPMSCs transplantation group via tail vein. All the mice were sacrificed at day 21 after modeling in batch. Lung tissues were collected for analyzing the pathological changes by HE staining and Masson staining as well as detecting collagen content. The total protein of lung tissues was extracted for observing the expressions of myeloid differentiation factor 88 (MyD88) and transforming growth factor-β (TGF-β); the level of TGF-β in sera was determined by Western blotting. Results The hfPMSCs possessed the morphology of mesenchymal stem cells and expressed the surface markers CD73, CD90 and CD105, but did not express CD14, CD34 and CD45. HE and Masson staining showed that hfPMSCs transplantation significantly reduced the degree of pulmonary fibrosis compared with bleomycin treatment group. The collagen content and the expression levels of MyD88 and TGF-β in bleomycin treatment group were obviously higher than those in hfPMSCs transplantation group and negative control group. Conclusion hfPMSCs possess the capability of alleviating pulmonary fibrosis by down-regulating the expressions of MyD88 and TGF-β.

  5. Bibliography on Fetal Alcohol Syndrome and Related Issues. Second Edition.

    Science.gov (United States)

    All Indian Pueblo Council, Albuquerque, NM.

    The bibliography on Fetal Alcohol Syndrome presents 312 unannotated journal articles for use by professionals working with American Indian people and is designed to serve as a vital source of knowledge on alcohol and child health. The bibliography is intended to list articles on Fetal Alcohol Syndrome and humans, and only highlight a minimal…

  6. [The coordination of the forensic medical service with the medical criminology subdivisions of internal affairs organs in the personal identification of unidentified corpses].

    Science.gov (United States)

    Pashinian, G A; Tuchik, E S

    1997-01-01

    In order to improve the cooperation between medical criminology departments of the organs of home affairs and forensic medical service in personality identification of unidentified corpses, the authors propose amendments to the routine procedure regulated by documents of the Ministry of Home Affairs of the Russian Federation, for these documents are in need of serious correction and revision, so that they conform to the judicial legislation and other documents.

  7. Fetal heart rate monitoring.

    Science.gov (United States)

    Nageotte, Michael P

    2015-06-01

    Electronic fetal heart rate monitoring is a widely utilized means of assessment of fetal status during labor. Whereas little evidence exists regarding efficacy, this modality continues to be used extensively in every modern labor and delivery unit in developed countries. It is of importance that all providers of health care to the woman in labor and her newborn have a clear understanding of the basic pathophysiology of fetal heart rate monitoring and an appreciation for labor course and concerns as they arise in order to optimize outcomes and patient safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Individual human serum differs in the amount of antibodies with affinity for pig fetal ventral mesencephalic cells and the ability to lyse these cells by complement activation

    NARCIS (Netherlands)

    Koopmans, J; de Haan, A; Bruin, E; van der Gun, Ieneke; van Dijk, H; Rozing, J; de Leij, L; Staal, M

    2004-01-01

    Xenografting pig fetal ventral mesencephalic (pfVM) cells to repair the dopamine deficit in patients with Parkinson's disease is the focus of both experimental and clinical investigations. Although there have been marked advances in the experimental and even clinical application of these xenogeneic

  9. Angiogenic growth factors and their receptors in first-trimester human decidua of pregnancies further complicated by preeclampsia or fetal growth restriction

    NARCIS (Netherlands)

    Plaisier, M.; Streefland, E.; Koolwijk, P.; van Hinsbergh, V. W. M.; Helmerhorst, F. M.; Erwich, J. J. H. M.

    Disturbances in decidual and placental vascular development may play a role in the pathogenesis of pregnancy complications. This study focused on the role of angiogenic factors in the first trimester in the pathogenesis of preeeclampsia (PF) and/or fetal growth restriction (FGR). First-trimester

  10. Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans

    National Research Council Canada - National Science Library

    Sakamoto, Norihisa; Tsuji, Kazuhide; Muul, Linda M; Lawler, Ann M; Petricoin, Emanuel F; Candotti, Fabio; Metcalf, Julia A; Tavel, Jorge A; Lane, H Clifford; Urba, Walter J; Fox, Bernard A; Varki, Ajit; Lunney, Joan K; Rosenberg, Amy S

    2007-01-01

    ... on the cell surface and is internalized. Here we show that in the majority of patients administered 3 different types of cell-based therapies using cells grown in fetal calf serum-containing media, an antibody response to bovine apolipoprotein B-100 develops after the second infusion and is the dominant specificity. The known and potential clinical effects of such antibodies are discussed.

  11. 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

  12. Fetal Alcohol Spectrum Disorders

    Science.gov (United States)

    Alcohol can harm your baby at any stage during a pregnancy. That includes the earliest stages, before ... can cause a group of conditions called fetal alcohol spectrum disorders (FASDs). Children who are born with ...

  13. Challenge of Fetal Mortality

    Science.gov (United States)

    ... Ordering Information Printed Publications Birth, Death, Marriage and Divorce Certificates Government Printing Office Bookstore How to Order ... this page Key findings What is the impact of fetal mortality on U.S. families? What is ...

  14. Fetal-juvenile origins of point mutations in the adult human tracheal-bronchial epithelium: Absence of detectable effects of age, gender or smoking status

    Energy Technology Data Exchange (ETDEWEB)

    Sudo, Hiroko [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Toray Industries, Inc., New Frontiers Research Laboratories 10-1, Tebiro 6-chome, Kamakura, Kanagawa 248-8555 (Japan); Li-Sucholeiki, Xiao-Cheng [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Agencourt Bioscience Corp., 500 Cummings Center, Suite 2450, Beverly, MA 01915 (United States); Marcelino, Luisa A. [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Biomedical Engineering Department, Northwestern University, 633 Clark Street, Evanston, IL 60208 (United States); Gruhl, Amanda N. [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); Herrero-Jimenez, Pablo [Massachusetts Institute of Technology, Department of Biological Engineering, 21 Ames St., 16-743 Cambridge, MA 02139 (United States); SLC Ontario, 690 Dorval Drive, Suite 200, Oakville, Ontario L6K 3W7 Canada (Canada); Zarbl, Helmut [UMDNJ-Robert Wood Johnson Medical School, Environmental and Occupational Health Sciences Institute, 170 Freylinghuysen Road, Room 426, Piscataway, NJ 08854 (United States); Willey, James C. [Medical College of Ohio, 3120 Glendale Avenue, Room 12, Toledo, OH 43614 (United States); Furth, Emma E. [University of Pennsylvania Medical Center, Department of Pathology, 3400 Spruce Street, 6 Founders Building, Philadelphia, PA 19104 (United States); Morgenthaler, Stephan [Institute of Applied Mathematics, Swiss Federal Institute of Technology (EPFL), SB/IMA, 1015 Lausanne (Switzerland)] (and others)

    2008-11-10

    Allele-specific mismatch amplification mutation assays (MAMA) of anatomically distinct sectors of the upper bronchial tracts of nine nonsmokers revealed many numerically dispersed clusters of the point mutations C742T, G746T, G747T of the TP53 gene, G35T of the KRAS gene and G508A of the HPRT1 gene. Assays of these five mutations in six smokers have yielded quantitatively similar results. One hundred and eighty four micro-anatomical sectors of 0.5-6 x 10{sup 6} tracheal-bronchial epithelial cells represented en toto the equivalent of approximately 1.7 human smokers' bronchial trees to the fifth bifurcation. Statistically significant mutant copy numbers above the 95% upper confidence limits of historical background controls were found in 198 of 425 sector assays. No significant differences (P = 0.1) for negative sector fractions, mutant fractions, distributions of mutant cluster size or anatomical positions were observed for smoking status, gender or age (38-76 year). Based on the modal cluster size of mitochondrial point mutants, the size of the adult bronchial epithelial maintenance turnover unit was estimated to be about 32 cells. When data from all 15 lungs were combined the log 2 of nuclear mutant cluster size plotted against log 2 of the number of clusters of a given cluster size displayed a slope of {approx}1.1 over a range of cluster sizes from {approx}2{sup 6} to 2{sup 15} mutant copies. A parsimonious interpretation of these nuclear and previously reported data for lung epithelial mitochondrial point mutant clusters is that they arose from mutations in stem cells at a high but constant rate per stem cell doubling during at least ten stem cell doublings of the later fetal-juvenile period. The upper and lower decile range of summed point mutant fractions among lungs was about 7.5-fold, suggesting an important source of stratification in the population with regard to risk of tumor initiation.

  15. Fetal and neonatal thyrotoxicosis

    Directory of Open Access Journals (Sweden)

    Chandar Mohan Batra

    2013-01-01

    Full Text Available 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 20 th week of pregnancy and reaches its maximum by 30 th 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.

  16. The hidden maternal-fetal interface: events involving the lymphoid organs in maternal-fetal tolerance

    Science.gov (United States)

    Taglauer, Elizabeth S.; Adams Waldorf, Kristina M.; Petroff, Margaret G.

    2010-01-01

    The genetic disparity between the mother and fetus has long enticed immunologists to search for mechanisms of maternal tolerance to fetal antigens. The study of antigen-specific tolerance in murine and human pregnancy has gained new momentum in recent years through the focus on antigen-presenting cells, uterine lymphatics and fetal antigen-specific maternal T cell responses. In mice, we now know that these responses occur within the secondary lymphoid structures as they can be conveniently tracked through the use of defined, often transgenic fetal antigens and maternal T cell receptors. Although the secondary lymphoid organs are sites of both immunization and tolerization to antigens, the immunological processes that occur in response to fetal antigens during the healthy pregnancy must invariably lead to tolerance. The molecular properties of these maternal-fetal tolerogenic interactions are still being unraveled, and are likely to be greatly influenced by tissue-specific microenvironments and the hormonal milieu of pregnancy. In this article, we discuss the events leading to antigen-specific maternal tolerance, including the trafficking of fetal antigens to secondary lymphoid organs, the properties of the antigen-presenting cells that display them to maternal T lymphocytes, and the nature of the ensuing tolerogenic response. Experimental data generated from human biological specimens as well as murine transgenic models are considered. PMID:19876825

  17. Fetal assessment for anesthesiologists: are you evaluating the other patient?

    Science.gov (United States)

    Moaveni, Daria M; Birnbach, David J; Ranasinghe, J Sudharma; Yasin, Salih Y

    2013-06-01

    Suboptimal communication between anesthesiologists and obstetricians can be associated with unintended poor maternal and neonatal outcomes, especially for emergency cesarean deliveries. Obstetricians use the results of antepartum and intrapartum fetal assessments to assess fetal well-being and to make decisions about the timing and method of delivery. Because abnormal results may lead to the need for urgent or emergency cesarean deliveries, these decisions may directly impact anesthetic care. Lack of familiarity with fetal assessments and the significance of the results may thus hinder the communication necessary for optimal patient care. In this review article, we discuss the current antepartum and intrapartum fetal assessment modalities, including the nonstress test, biophysical profile, Doppler velocimetry, electronic fetal heart rate monitoring, fetal electrocardiogram (STAN-ST waveform analysis), and fetal pulse oximetry. The physiologic basis behind these modalities and the available evidence regarding their utility in clinical practice are also reviewed. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring categories, which are incorporated into the American College of Obstetricians and Gynecologists guidelines for intrapartum care, is examined. The implications of test interpretation to the practice of obstetric anesthesiology is also discussed. Anesthesia provider understanding of fetal assessment modalities is essential in improving communication with obstetricians and improving the planning of cesarean deliveries for high-risk obstetric patients.

  18. Genetic variations and normal fetal growth.

    Science.gov (United States)

    Dunger, D B; Petry, C J; Ong, K K

    2006-01-01

    Size at birth is said to be a highly heritable trait, with an estimated 30-70% of the variability a result of genetics. Data from family studies may be confounded, however, by potential interactions between fetal genes and the maternal uterine environment. Overall, the maternal environment tends to restrain fetal growth, and this is most evident in first pregnancies. Restraint of fetal growth appears to be inherited through the maternal line. Potential genetic candidates include the mitochondrial DNA 16189 variant, and common variants of exclusively maternally expressed genes, such as H19, which have been associated with size at birth. Maternal blood glucose levels and blood pressure are also correlated with size at birth, but the degree to which these changes relate to genetic variation in the mother is unclear. Elegant studies in mouse knockout models and rare genetic variants in humans have highlighted the importance of insulin-like growth factor I (IGF-I), IGF-II, insulin and their respective receptors in determining fetal growth. However, data linking common variation in the genes that regulate these proteins and receptors with size at birth are few and inconsistent. Interestingly, common variation in the insulin gene (INS) variable number tandem repeats, which regulates the transcription of insulin and IGF-II, has been associated with size at birth, largely in second and subsequent pregnancies, where maternal restraint is least evident. This suggests that fetal genes, and in particular paternally expressed genes, may have significant effects on fetal growth during pregnancies where maternal restraint of fetal growth is less evident. Copyright 2006 S. Karger AG, Basel.

  19. STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.

    Science.gov (United States)

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

    2015-09-01

    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 electrodrmal activity and fetal heartrate, 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 physio-logical 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

  20. Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

    Science.gov (United States)

    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

  1. Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer.

    Science.gov (United States)

    Katoh, Yuriko; Katoh, Masaru

    2007-03-01

    Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate FGF20, JAG1, DKK1, WISP1, CCND1 and MYC genes for cell-fate determination, while non-canonical WNT signals are transduced through FZD family receptor and ROR2/PTK7/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NLK and NFAT signaling cascades for the regulation of tissue polarity, cell movement, and adhesion. We previously reported molecular cloning and characterization of human FZD5, which showed six amino-acid substitutions with human Hfz5. FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology. Here, comparative integromics analyses on FZD5 orthologs were performed by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD5 and cow Fzd5 genes were identified within NW_104292.1 and AC166656.2 genome sequences, respectively. FZD5 orthologs were seven-transmembrane proteins with extracellular Frizzled domain, leucine zipper motif around the 5th transmembrane domain, and cytoplasmic DVL- and PDZ-binding motifs. Ser523 and Ser529 around the DVL-binding motif of FZD5 orthologs were putative aPKC phosphorylation sites. POU5F1 (OCT4)-binding site linked to SP1-binding site within the 5'-promoter region of human FZD5 gene was evolutionarily conserved among mammalian FZD5 orthologs. POU5F1 was more related to POU2F and POU3F subfamily members. POU5F1 was preferentially expressed in undifferentiated human embryonic stem (ES) cells, pancreatic islet, and diffuse-type gastric cancer. POU2F1 (OCT1) was expressed in ES cells, fetal liver/spleen, adult colon, POU2F2 in ES cells, fetal liver/spleen, and POU2F3 in diffuse-type gastric cancer. Multiple SP1/KLF family members, other than KLF2 or KLF4, were expressed in undifferentiated human ES cells. Together, these facts indicate that POU5F1 and POU2F subfamily members

  2. Fetal fluid and protein dynamics

    NARCIS (Netherlands)

    Pasman, Suzanne

    2010-01-01

    In this thesis fetal fluid and protein dynamics are investigated to gain insight in fetal (patho-)physiology. Studies were performed in fetuses with severe anemia and/or hydrops fetalis. Measurements were performed in fetal blood or amniotic fluid, obtained before or during intrauterine

  3. Fluoxetine during pregnancy: impact on fetal development.

    Science.gov (United States)

    Morrison, Janna L; Riggs, K Wayne; Rurak, Dan W

    2005-01-01

    increases the magnitude of the prepartum rise in fetal cortisol concentrations in sheep. Fetal FX exposure does not alter fetal circadian rhythms in melatonin or prolactin. Studies of the effects of FX exposure on fetal development in the sheep are important in defining possible physiological mechanisms that explain human clinical studies of birth outcomes after FX exposure. To date, there have been insufficient longer-term follow-up studies in any precocial species of offspring exposed to SSRIs in utero. Thus, further investigation of the long-term consequences of in utero exposure to FX and other SSRIs, as well as the mechanisms involved, are required for a complete understanding of the impact of these agents on development. This should involve studies in both humans and appropriate animal models.

  4. 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.

    Science.gov (United States)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter V; Kirchhoff, Maria; Mathiasen, Anders Bruun; Elberg, Jens Jørgen; Andersen, Peter Stemann; Drzewiecki, Krzysztof Tadeusz; Fischer-Nielsen, Anne

    2013-09-01

    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)). ASCs from four healthy donors were cultured in either DMEM(pHPL) or DMEM(FBS), and the population doubling time (PDT) was calculated. ASCs from two of the donors were expanded in DMEM(pHPL) or DMEM(FBS) and cultured for the final week before harvesting with or without the addition of vascular endothelial growth factor. We assessed the chromosomal stability (through the use of array comparative genomic hybridization), the expression of ASC and endothelial surface markers and the differentiation and angiogenic potential of these cells. The ASCs that were cultured in pHPL exhibited a significantly shorter PDT of 29.6 h (95% confidence interval, 22.3-41.9 h) compared with those cultured in FBS, for which the PDT was 123.9 h (95% confidence interval, 95.6-176.2 h). Comparative genomic hybridization analyses revealed no chromosomal aberrations. Cell differentiation, capillary structure formation and cell-surface marker expression were generally unaffected by the type of medium supplement that was used or by the addition of vascular endothelial growth factor. We observed that the use of pHPL as a growth supplement for ASCs facilitated a significantly higher proliferation rate compared with FBS without compromising genomic stability or differentiation capacity. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. Fetal Alcohol Exposure

    Science.gov (United States)

    ... categories: 4 » Fetal Alcohol Syndrome (FAS) » Partial FAS (pFAS) » Alcohol-Related Neurodevelopmental Disorder (ARND) » Alcohol-Related Birth ... either prenatally, after birth, or both Partial FAS (pFAS) Partial FAS (pFAS) involves prenatal alcohol exposure, and ...

  6. Fetal Alcohol Syndrome.

    Science.gov (United States)

    Zerrer, Peggy

    The paper reviews Fetal Alcohol Syndrome (FAS), a series of effects seen in children whose mothers drink alcohol to excess during pregnancy. The identification of FAS and its recognition as a major health problem in need of prevention are traced. Characteristics of children with FAS are described and resultant growth retardation, abnormal physical…

  7. Intrapartum fetal surveillance : Monitoring fetal oxygenation with fetal blood sampling and umbilical cord blood analysis

    NARCIS (Netherlands)

    van den Berg, P; Slager, E; Fauser, B; VanGeijn, H; Brolmann, H; Vervest, H

    2005-01-01

    Although electronic fetal heart rate monitoring remains the most popular technique for fetal surveillance during labour, there is much concern about the ever rising Caesarean section rate, probably partly due to this practice. Fetal blood sampling is still the gold standard when it comes to

  8. Expression of ZNF804A in human brain and alterations in schizophrenia, bipolar disorder, and major depressive disorder: a novel transcript fetally regulated by the psychosis risk variant rs1344706.

    Science.gov (United States)

    Tao, Ran; Cousijn, Helena; Jaffe, Andrew E; Burnet, Philip W J; Edwards, Freya; Eastwood, Sharon L; Shin, Joo Heon; Lane, Tracy A; Walker, Mary A; Maher, Brady J; Weinberger, Daniel R; Harrison, Paul J; Hyde, Thomas M; Kleinman, Joel E

    2014-10-01

    The single-nucleotide polymorphism rs1344706 in the zinc finger protein 804A gene (ZNF804A) shows genome-wide association with schizophrenia and bipolar disorder. Little is known regarding the expression of ZNF804A and the functionality of rs1344706. To characterize ZNF804A expression in human brain and to investigate how it changes across the life span and how it is affected by rs1344706, schizophrenia, bipolar disorder, and major depressive disorder. Molecular and immunochemical methods were used to study ZNF804A messenger RNA (mRNA) and ZNF804A protein, respectively. ZNF804A transcripts were investigated using next-generation sequencing and polymerase chain reaction-based methods, and ZNF804A protein was investigated using Western blots and immunohistochemistry. Samples of dorsolateral prefrontal cortex and inferior parietal lobe tissue were interrogated from 697 participants between 14 weeks' gestational age and age 85 years, including patients with schizophrenia, bipolar disorder, or major depressive disorder. Quantitative measurements of ZNF804A mRNA and immunoreactivity, and the effect of diagnosis and rs1344706 genotype. ZNF804A was expressed across the life span, with highest expression prenatally. An abundant and developmentally regulated truncated ZNF804A transcript was identified, missing exons 1 and 2 (ZNF804AE3E4) and predicted to encode a protein lacking the zinc finger domain. rs1344706 influenced expression of ZNF804AE3E4 mRNA in fetal brain (P = .02). In contrast, full-length ZNF804A showed no association with genotype (P > .05). ZNF804AE3E4 mRNA expression was decreased in patients with schizophrenia (P = .006) and increased in those with major depressive disorder (P disorder (P = .002). ZNF804A immunoreactivity was detected in fetal and adult human cerebral cortex. It was localized primarily to pyramidal neurons, with cytoplasmic as well as dendritic and nuclear staining. No differences in ZNF804A-immunoreactive neurons were

  9. Stillbirth and fetal growth restriction.

    Science.gov (United States)

    Bukowski, Radek

    2010-09-01

    The association between stillbirth and fetal growth restriction is strong and supported by a large body of evidence and clinically employed for the stillbirth prediction. However, although assessment of fetal growth is a basis of clinical practice, it is not trivial. Essentially, fetal growth is a result of the genetic growth potential of the fetus and placental function. The growth potential is the driving force of fetal growth, whereas the placenta as the sole source of nutrients and oxygen might become the rate limiting element of fetal growth if its function is impaired. Thus, placental dysfunction may prevent the fetus from reaching its full genetically determined growth potential. In this sense fetal growth and its aberration provides an insight into placental function. Fetal growth is a proxy for the test of the effectiveness of placenta, whose function is otherwise obscured during pregnancy.

  10. Fetal surgery for myelomeningocele: trials and tribulations. Isabella Forshall Lecture.

    Science.gov (United States)

    Adzick, N Scott

    2012-02-01

    The rationale for in utero repair of myelomeningocele (MMC) in the context of pathologic observations, animal models, and outcomes from the initial experience with human fetal MMC repair is presented. This has now culminated in a randomized trial, Management of Myelomeningocele Study, the findings of which are listed. The story is focused on the milestone contributions of members of the Center for Fetal Diagnosis and Treatment at the Children's Hospital of Philadelphia on the road to successful fetal surgery for spina bifida. This is now performed in selected patients and presents an additional therapeutic alternative for expectant mothers carrying a fetus with MMC. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Fetal alcohol exposure and development of the integument

    Directory of Open Access Journals (Sweden)

    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

  12. Forensic medical examination of the corpse of General Władysław Sikorski, a putative victim of assassination in 1943.

    Science.gov (United States)

    Konopka, Tomasz; Gross, Adam; Woźniak, Krzysztof; Kłys, Małgorzata

    2010-10-10

    The Krakow Department of Forensic Medicine was granted a unique opportunity to examine the body of a historical figure, i.e. General Władysław Sikorski, the Prime Minister of the Polish government in exile, deceased in 1943. General Sikorski died in the crash of a Liberator aircraft at Gibraltar, and the British commission investigating the crash decided it had been an accident. In the past several decades, doubts have been repeatedly expressed as to the circumstances of the General's death and the theory of assassination has become very popular. On November 25, 2008, the General's corpse buried in the cathedral of the Royal Castle on Wawel Hill in Krakow was exhumed and the body was thoroughly examined. The examinations demonstrated numerous fractures of the cranium, spine and extremities, the character of which corresponded to effects of an air crash. Based on corpse examination alone it was impossible to establish whether the air crash had been an effect of sabotage or an ill-fated accident. Although no typical evidence of intravitality was found, such as bruises or fat embolisms, yet the character of some fractures suggested that they had been incurred intravitally. These were represented by a spiral fracture of the femoral bone shaft, a fracture of the sustentaculum tali of the calcaneal bone and fractures of the transverse processes of the lumbar vertebrae. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Beyond The Anticipatory Corpse: Medicine, Power, and the Care of the Dying: A Theoretical and Methodological Intervention into the Sociology of Brain Implant Surgery.

    Science.gov (United States)

    Hancock, Black Hawk; Morrison, Daniel R

    2016-12-01

    Drawing on and extending the Foucaultian philosophical framework that Jeffrey Bishop develops in his masterful book, The Anticipatory Corpse: Medicine, Power, and the Care of the Dying, we undertake a sociological analysis of the neurological procedure-deep brain stimulation (DBS)-which implants electrodes in the brain, powered by a pacemaker-like device, for the treatment of movement disorders. Following Bishop's work, we carry out this analysis through a two-fold strategy. First, we examine how a multidisciplinary team evaluates candidates for this implant at a major medical center. We present excerpts from an ethnographic study of the "case conference" where disease entities are presented, contested, ratified, and made objects for intervention with this technology. The case conference becomes the key site in the transition from "person-with-illness" to "person-with-brain-implant" as a team of health professionals determines a plan of action by interpreting both statistical and "quality of life" data regarding their patients. Second, this article explores these decision-making processes through Bishop's conceptualization of evidence-based medicine, which relies on statistical approaches as the ultimate authority in knowledge production and medical decisions. We then reflect on Bishop's critique of the social sciences and the methodological, analytical, and substantive ramifications that The Anticipatory Corpse can offer future sociological work. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. 45 CFR 46.206 - Research involving, after delivery, the placenta, the dead fetus or fetal material.

    Science.gov (United States)

    2010-10-01

    ..., the dead fetus or fetal material. 46.206 Section 46.206 Public Welfare DEPARTMENT OF HEALTH AND HUMAN... placenta, the dead fetus or fetal material. (a) Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, shall be...

  15. Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans.

    Science.gov (United States)

    Sakamoto, Norihisa; Tsuji, Kazuhide; Muul, Linda M; Lawler, Ann M; Petricoin, Emanuel F; Candotti, Fabio; Metcalf, Julia A; Tavel, Jorge A; Lane, H Clifford; Urba, Walter J; Fox, Bernard A; Varki, Ajit; Lunney, Joan K; Rosenberg, Amy S

    2007-07-15

    Recent studies have demonstrated that cell populations intended for therapeutic purposes that are cultured in heterologous animal products can acquire xenoantigens, potentially limiting their utility. In investigations of the immune response to murine embryonic stem cells, we found that a strong antibody response was generated after the second infusion. Both polyclonal and monoclonal antibody responses, derived from immunized mice, were found to be specific for bovine apolipoprotein B-100, which binds to abundant low-density lipoprotein receptors on the cell surface and is internalized. Here we show that in the majority of patients administered 3 different types of cell-based therapies using cells grown in fetal calf serum-containing media, an antibody response to bovine apolipoprotein B-100 develops after the second infusion and is the dominant specificity. The known and potential clinical effects of such antibodies are discussed.

  16. Fetal drug therapy.

    OpenAIRE

    Evans, M I; Pryde, P G; Reichler, A; Bardicef, M; Johnson, M P

    1993-01-01

    Fetal drug therapy encompasses several areas, including the prevention of external genital masculinization in 21-hydroxylase deficiency syndrome (congenital adrenal hyperplasia), biochemical amelioration of methylmalonic acidemia, and biotin-responsive multiple carboxylase deficiency. The correction of cardiac arrhythmias has become relatively commonplace, and a reduction in the risks of neural tube defects is now possible with the use of preconceptual and early conceptual folic acid. Similar...

  17. Intrapartum fetal monitoring.

    Science.gov (United States)

    Cahill, Alison G; Spain, Janine

    2015-06-01

    Intrapartum fetal monitoring to assess fetal well-being during the labor and delivery process has been a central component of intrapartum care for decades. Today, electronic fetal monitoring (EFM) is the most common method used to assess the fetus during labor without substantial evidence to suggest a benefit. A Cochrane review of 13 trials, which included over 37,000 women, found that continuous EFM provided no significant improvement in perinatal death rate [risk ratio (RR) 0.86; 95% confidence interval (CI), 0.59-1.23] or cerebral palsy rate (RR 1.75; 95% CI, 0.84-3.63) as compared with intermittent auscultation; however, there was a significant decrease in neonatal seizures (RR 0.50; 95% CI, 0.31-0.80). In addition, there was a significant increase in cesarean delivery (RR 1.63; 95% CI, 1.29-2.07) and operative vaginal delivery (RR 1.15; 95% CI, 1.01-1.33). Despite the lack of scientific support to suggest that EFM reduces adverse neonatal outcomes, its use is almost universal in the hospital setting and very likely has contributed to the rise in cesarean rate.

  18. Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. Copyright © 2015 by the American Academy of Pediatrics.

  19. 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.

  20. Fetal vibroacoustic stimulation for facilitation of tests of fetal wellbeing.

    Science.gov (United States)

    Tan, Kelvin H; Smyth, Rebecca M D; Wei, Xing

    2013-12-07

    Acoustic stimulation of the fetus has been suggested to improve the efficiency of antepartum fetal heart rate testing. To assess the advantages and disadvantages of the use of fetal vibroacoustic stimulation in conjunction with tests of fetal wellbeing. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2013). All published and unpublished randomised controlled trials assessing the merits of the use of fetal vibroacoustic stimulation in conjunction with tests of fetal wellbeing. All review authors independently extracted data and assessed trial quality. Authors of published and unpublished trials were contacted for further information. Altogether 12 trials with a total of 6822 participants were included. Fetal vibroacoustic stimulation reduced the incidence of non-reactive antenatal cardiotocography test (nine trials; average risk ratio (RR) 0.62, 95% confidence interval (CI) 0.48 to 0.81). Vibroacoustic stimulation compared with mock stimulation evoked significantly more fetal movements when used in conjunction with fetal heart rate testing (one trial, RR 0.23, 95% CI 0.18 to 0.29). Vibroacoustic stimulation offers benefits by decreasing the incidence of non-reactive cardiotocography and reducing the testing time. Further randomised trials should be encouraged to determine not only the optimum intensity, frequency, duration and position of the vibroacoustic stimulation, but also to evaluate the efficacy, predictive reliability, safety and perinatal outcome of these stimuli with cardiotocography and other tests of fetal wellbeing.

  1. Cirugía fetal

    Directory of Open Access Journals (Sweden)

    DR. B. Juan Luis Leiva

    2014-11-01

    Full Text Available El campo de la cirugía fetal es de reciente comienzo y rápida evolución. Con el avance en las herramientas de diagnóstico antenatal, la capacidad de diagnóstico de condiciones fetales susceptibles de ser tratadas in utero ha dado paso a una serie de procedimientos destinados a dar solución a situaciones que, de no ser por estas intervenciones, terminarían en un resultado adverso perinatal. Las técnicas descritas para la terapia fetal incluyen procedimientos percutáneos guiados por ultrasonido, cirugía fetal abierta y cirugía mínimamente invasiva. En este artículo se presentan las diversas condiciones fetales tributarias de cirugía fetal y se discuten las opciones terapéuticas actuales para cada una.

  2. Hypoxia and Fetal Heart Development

    OpenAIRE

    Patterson, A.J.; Zhang, L

    2010-01-01

    Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not th...

  3. MRI of the fetal spine

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Erin M. [Departement of Radiology, Children' s Hospital of Philadelphia, PA (United States)

    2004-09-01

    Magnetic resonance imaging of the fetal spine is a vital complement to fetal sonographic examination. Assessing the wide spectrum of spinal dysraphism, as well as spinal neoplasia, allows for more correct prenatal diagnoses, patient care planning, and patient counselling. Proper appraisal of the value of experimental procedures, such as fetal myelomeningocoele repair, requires a high level of diagnostic accuracy for the selection and follow-up of appropriate candidates. (orig.)

  4. 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.

  5. Novel functions for the RNA-binding protein ETR-1 in Caenorhabditis elegans reproduction and engulfment of germline apoptotic cell corpses.

    Science.gov (United States)

    Boateng, Ruby; Nguyen, Ken C Q; Hall, David H; Golden, Andy; Allen, Anna K

    2017-09-01

    RNA-binding proteins (RBPs) are essential regulators of gene expression that act through a variety of mechanisms to ensure the proper post-transcriptional regulation of their target RNAs. RBPs in multiple species have been identified as playing crucial roles during development and as having important functions in various adult organ systems, including the heart, nervous, muscle, and reproductive systems. ETR-1, a highly conserved ELAV-Type RNA-binding protein belonging to the CELF/Bruno protein family, has been previously reported to be involved in C. elegans muscle development. Animals depleted of ETR-1 have been previously characterized as arresting at the two-fold stage of embryogenesis. In this study, we show that ETR-1 is expressed in the hermaphrodite somatic gonad and germ line, and that reduction of ETR-1 via RNA interference (RNAi) results in reduced hermaphrodite fecundity. Detailed characterization of this fertility defect indicates that ETR-1 is required in both the somatic tissue and the germ line to ensure wild-type reproductive levels. Additionally, the ability of ETR-1 depletion to suppress the published WEE-1.3-depletion infertility phenotype is dependent on ETR-1 being reduced in the soma. Within the germline of etr-1(RNAi) hermaphrodite animals, we observe a decrease in average oocyte size and an increase in the number of germline apoptotic cell corpses as evident by an increased number of CED-1::GFP and acridine orange positive apoptotic germ cells. Transmission Electron Microscopy (TEM) studies confirm the significant increase in apoptotic cells in ETR-1-depleted animals, and reveal a failure of the somatic gonadal sheath cells to properly engulf dying germ cells in etr-1(RNAi) animals. Through investigation of an established engulfment pathway in C. elegans, we demonstrate that co-depletion of CED-1 and ETR-1 suppresses both the reduced fecundity and the increase in the number of apoptotic cell corpses observed in etr-1(RNAi) animals. Combined

  6. A cGMP-applicable expansion method for aggregates of human neural stem and progenitor cells derived from pluripotent stem cells or fetal brain tissue.

    Science.gov (United States)

    Shelley, Brandon C; Gowing, Geneviève; Svendsen, Clive N

    2014-06-15

    A cell expansion technique to amass large numbers of cells from a single specimen for research experiments and clinical trials would greatly benefit the stem cell community. Many current expansion methods are laborious and costly, and those involving complete dissociation may cause several stem and progenitor cell types to undergo differentiation or early senescence. To overcome these problems, we have developed an automated mechanical passaging method referred to as "chopping" that is simple and inexpensive. This technique avoids chemical or enzymatic dissociation into single cells and instead allows for the large-scale expansion of suspended, spheroid cultures that maintain constant cell/cell contact. The chopping method has primarily been used for fetal brain-derived neural progenitor cells or neurospheres, and has recently been published for use with neural stem cells derived from embryonic and induced pluripotent stem cells. The procedure involves seeding neurospheres onto a tissue culture Petri dish and subsequently passing a sharp, sterile blade through the cells effectively automating the tedious process of manually mechanically dissociating each sphere. Suspending cells in culture provides a favorable surface area-to-volume ratio; as over 500,000 cells can be grown within a single neurosphere of less than 0.5 mm in diameter. In one T175 flask, over 50 million cells can grow in suspension cultures compared to only 15 million in adherent cultures. Importantly, the chopping procedure has been used under current good manufacturing practice (cGMP), permitting mass quantity production of clinical-grade cell products.

  7. Germline Melanocortin-1-Receptor Genotype Is Associated with Severity of Cutaneous Phenotype in Congenital Melanocytic Nevi: A Role for MC1R in Human Fetal Development

    Science.gov (United States)

    Kinsler, Veronica A; Abu-Amero, Sayeda; Budd, Peter; Jackson, Ian J; Ring, Susan M; Northstone, Kate; Atherton, David J; Bulstrode, Neil W; Stanier, Philip; Hennekam, Raoul C; Sebire, Neil J; Moore, Gudrun E; Healy, Eugene

    2012-01-01

    Congenital melanocytic nevi (CMN) are pigmented birthmarks that affect up to 80% of the skin surface area. The increased frequency of CMN in families of severely affected individuals is suggestive of a predisposing germline genotype. We noted a high prevalence of red hair in affected families, and considered a role for MC1R in this condition. A cohort of 166 CMN subjects underwent pigmentary phenotyping, with MC1R genotyping in 113. Results were compared with a local control group of 60 unrelated children and with 300 UK children without CMN. CMN subjects had higher prevalences of red hair and a red-haired parent than local controls and had a higher rate of compound heterozygosity and homozygosity for MC1R variants. The presence of a V92M or R allele (D84E, R151C, R160W, D294H) was associated with increasing size of the CMN, implying a growth-promoting effect of these alleles. Unexpectedly, the V92M and R151C alleles were also strongly associated with birth weight in the CMN cohort, a finding confirmed in the control group. The effect of germline MC1R genotype on development and severity of CMN led us to investigate potential broader effects on growth, revealing a role for MC1R in normal fetal development. PMID:22572819

  8. Fetal heart rate variation after corticosteroids for fetal maturation

    NARCIS (Netherlands)

    Knaven, Olga; Ganzevoort, Wessel; de Boer, Marjon; Wolf, Hans

    2017-01-01

    Introduction: Several studies report a decrease of fetal heart rate (FHR) short-term variation (STV) after corticosteroids for improvement of fetal maturity and advice not to deliver a fetus for low STV within 2-3 days after corticosteroids. However, literature is not unanimous in this respect. This

  9. Effect of fetal breathing movements on fetal cardiac hemodynamics

    NARCIS (Netherlands)

    K. van der Mooren (K.); J.W. Wladimiroff (Juriy); Th. Stijnen (Theo)

    1991-01-01

    markdownabstract__Abstract__ Maximum flow velocity waveforms were studied at atrioventricular and outflow tract level in 12 cases during fetal breathing activity and in 12 cases during fetal apnea matched for maternal and gestational age and maternal parity. Gestational age ranged between 27 and

  10. 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…

  11. Fetal Tachyarrhythmia - Part II: Treatment

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    Martijn A. Oudijk

    2004-10-01

    Full Text Available The decision to initiate pharmacological intervention in case of fetal tachycardia depends on several factors and must be weighed against possible maternal and/or fetal adverse effects inherent to the use of antiarrhythmics. First, the seriousness of the fetal condition must be recognized. Many studies have shown that in case of fetal tachycardia, there is a significant predisposition to congestive heart failure and subsequent development of fetal hydrops and even sudden cardiac death1,2,3 Secondly, predictors of congestive heart failure have been suggested in several studies, such as the percentage of time that the tachycardia is present, the gestational age at which the tachycardia occurs4, the ventricular rate5 and the site of origin of the tachycardia6. However, the sensitivity of these predictors is low and they are therefore clinically not very useful. In addition, hemodynamic compromise may occur in less than 24 - 48 hours as has been shown in the fetal lamb7 and in tachycardic fetuses8,9. On the other hand, spontaneous resolution of the tachycardia has also been described10. Thirdly, transplacental management of fetuses with tricuspid regurgitation11, congestive heart failure or fetal hydrops is difficult12,13, probably as a result of limited transplacental transfer of the antiarrhythmic drug14,15. In case of fetal hydrops, conversion rates are decreased and time to conversion is increased13. Treatment of sustained fetal tachycardia is therefore to be preferred above expectant management, although some centers oppose this regimen and suggest that in cases with (intermittent fetal SVT not complicated by congestive heart failure or fetal hydrops, conservative management and close surveillance might be a reasonable alternative16,17,18.

  12. HEPATITIS ALOINMUNE FETAL

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    Fernando Álvarez C., Dr.

    2015-07-01

    Full Text Available La hepatitis aloinmune fetal, conocida anteriormente como hemocromatosis neonatal, ha demostrado en los últimos años ser una enfermedad completamente distinta a la hemocromatosis del adulto, tanto en su etiología como en su la fisiopatología. Este conocimiento abre nuevas perspectivas tanto en la prevención de la enfermedad en futuros embarazos, así como en el tratamiento con inmunoglobulina endovenosa en la madre durante el embarazo y eventualmente el tratamiento postnatal, en el que el trasplante de hígado juega un rol primordial.

  13. 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.

  14. The Criminal Corpse, Anatomists and the Criminal Law: Parliamentary Attempts to Extend the Dissection of Offenders in Late Eighteenth-Century England.

    Science.gov (United States)

    Ward, Richard M

    2015-01-01

    In the later eighteenth century two schemes were introduced in Parliament for extending the practice of handing over the bodies of executed offenders to anatomists for dissection. Both measures were motivated by the needs of anatomy - including the improvement of surgical skill, the development of medical teaching in the provinces, and for conducting public anatomical demonstrations. Yet both failed to pass into law due to concerns about the possibly damaging effects in terms of criminal justice. Through a detailed analysis of the origins and progress of these two parliamentary measures - a moment when the competing claims of anatomy and criminal justice vied for supremacy over the criminal corpse - the following article sheds light on judicial attitudes to dissection as a method of punishment and adds to our understanding of why the dread of dissection would come to fall upon the dead poor (rather than executed offenders) in the nineteenth century.

  15. The Criminal Corpse, Anatomists and the Criminal Law: Parliamentary Attempts to Extend the Dissection of Offenders in Late Eighteenth-Century England

    Science.gov (United States)

    Ward, Richard M.

    2015-01-01

    In the later eighteenth century two schemes were introduced in Parliament for extending the practice of handing over the bodies of executed offenders to anatomists for dissection. Both measures were motivated by the needs of anatomy — including the improvement of surgical skill, the development of medical teaching in the provinces, and for conducting public anatomical demonstrations. Yet both failed to pass into law due to concerns about the possibly damaging effects in terms of criminal justice. Through a detailed analysis of the origins and progress of these two parliamentary measures — a moment when the competing claims of anatomy and criminal justice vied for supremacy over the criminal corpse — the following article sheds light on judicial attitudes to dissection as a method of punishment and adds to our understanding of why the dread of dissection would come to fall upon the dead poor (rather than executed offenders) in the nineteenth century. PMID:25821241

  16. Effects of experience on fetal voice recognition.

    Science.gov (United States)

    Kisilevsky, Barbara S; Hains, Sylvia M J; Lee, Kang; Xie, Xing; Huang, Hefeng; Ye, Hai Hui; Zhang, Ke; Wang, Zengping

    2003-05-01

    The ability of human fetuses to recognize their own mother's voice was examined. Sixty term fetuses were assigned to one of two conditions during which they were exposed to a tape recording of their mother or a female stranger reading a passage. Voice stimuli were delivered through a loudspeaker held approximately 10 cm above the maternal abdomen and played at an average of 95 dB SPL. Each condition consisted of three 2-min periods: no stimulus, voice (mother or stranger), and no stimulus. Fetal heart rate increased in response to the mother's voice and decreased in response to the stranger's; both responses were sustained for 4 min. The finding of differential behavior in response to a familiar versus a novel voice provides evidence that experience influences fetal voice processing. It supports an epigenetic model of speech perception, presuming an interaction between genetic expression of neural development and species-specific experience.

  17. 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

  18. Conceptual Design and Simulation of a Semi-Automatic Cell for the Washing and Preparation of a Corpse Prior to an Islamic Burial

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    A. Meghdari

    2012-07-01

    Full Text Available Washing the corpse and dressing the body prior to burial is an act of love and necessity in many religions. Applying robotics and automation technologies for the washing and preparation of a deceased Muslim in accordance with the Islamic Shari'at laws has been the challenging foundation of this research. With an increasing annual population growth resulting in an increase in the number of deaths (historically and/or immediately after a national disaster, automating part of this procedure to increase the speed of operation, reducing the health risks to the personnel of washing rooms “Ghassalkhaneh” at the cemeteries and enhancing their quality of life have been the primary objectives of this project. We have named and patented this semi-automated corpse preparation machine as the “PaakShooy” or “پاک شوی” in Persian (Farsi which means purifying the deceased. The whole process is composed of three operational units lined up in a series; the automatic washing chamber, drying cell and the semi-automatic shrouding table. This paper covers an introductory concept of the subject in Islam, a conceptual design of various machines and mechanisms to automate the important tasks in accordance with Islamic laws, and the final detailed design, graphic simulation and animation of the PaakShooy machine. In doing so, consultation with Islamic scholars has been a priority from the beginning of the project to the end and a few Fatwa have been issued by some high ranking Ayatollahs in support of the project. With a few modifications, the semi-automated PaakShooy machine may now be updated to conform to other religions/customs.

  19. Seasonal blowfly distribution and abundance in fragmented landscapes. Is it useful in forensic inference about where a corpse has been decaying?

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    Jabi Zabala

    Full Text Available Blowflies are insects of forensic interest as they may indicate characteristics of the environment where a body has been laying prior to the discovery. In order to estimate changes in community related to landscape and to assess if blowfly species can be used as indicators of the landscape where a corpse has been decaying, we studied the blowfly community and how it is affected by landscape in a 7,000 km2 region during a whole year. Using baited traps deployed monthly we collected 28,507 individuals of 10 calliphorid species, 7 of them well represented and distributed in the study area. Multiple Analysis of Variance found changes in abundance between seasons in the 7 analyzed species, and changes related to land use in 4 of them (Calliphora vomitoria, Lucilia ampullacea, L. caesar and L. illustris. Generalised Linear Model analyses of abundance of these species compared with landscape descriptors at different scales found only a clear significant relationship between summer abundance of C. vomitoria and distance to urban areas and degree of urbanisation. This relationship explained more deviance when considering the landscape composition at larger geographical scales (up to 2,500 m around sampling site. For the other species, no clear relationship between land uses and abundance was found, and therefore observed changes in their abundance patterns could be the result of other variables, probably small changes in temperature. Our results suggest that blowfly community composition cannot be used to infer in what kind of landscape a corpse has decayed, at least in highly fragmented habitats, the only exception being the summer abundance of C. vomitoria.

  20. Clinical implications of fetal magnetocardiography

    NARCIS (Netherlands)

    Quartero, H.W.P.; Stinstra, J.G.; Golbach, E.G.M.; Meijboom, E.J.; Peters, M.J.

    2002-01-01

    Objectives To test the usefulness and reliability of fetal magnetocardiography as a diagnostic or screening tool, both for fetuses with arrhythmias as well as for fetuses with a congenital heart defect. Methods We describe 21 women with either a fetal arrhythmia or a congenital heart defect

  1. Fetal and embryonic hemoglobins in erythroblasts from fetal blood and fetal cells enriched from maternal blood in fetal anemia.

    Science.gov (United States)

    Al-Mufti, R; Hambley, H; Farzaneh, F; Nicolaides, K H

    2001-12-01

    To determine whether there is a delay or reversal in switch mechanisms from embryonic (e and z) to fetal (g) hemoglobins accompanying the erythroblastosis of anemic fetuses and whether an increased erythroblast count in fetal blood is associated with an increase in feto-maternal cell trafficking. Fetal and maternal blood samples were obtained from 10 cases with rhesus isoimmunization and 2 cases with maternal Parvo-B19 virus at 19-33 weeks' gestation. Blood samples were also taken as controls from 61 fetuses and 86 mothers. Fetal erythroblasts were isolated by triple density gradient centrifugation and magnetic cell sorting with CD71 antibody. Fluorescent antibodies were used to immuno-stain for zeta (z), epsilon (e) and gamma (g) hemoglobin chains. In the maternal samples, fluorescence in situ hybridization (FISH) for X and Y chromosomes was also carried out to confirm the presence and proportion of the enriched fetal cells from maternal blood. In both fetal and maternal blood the percentage of erythroblasts positive for g-globin chain was significantly higher in the anemic fetuses compared to the controls (fetal blood, pmaternal blood, pmaternal samples of anemic fetuses compared to normal controls (pfetal hemoglobin chains. Severe fetal anemia is associated with an increase in feto-maternal cell trafficking.

  2. Arterial supply to the thyroid gland and the relationship between the recurrent laryngeal nerve and the inferior thyroid artery in human fetal cadavers.

    Science.gov (United States)

    Ozgüner, G; Sulak, O

    2014-11-01

    The aim of this study was to identify the arterial supply to the thyroid gland and the relationship between the inferior thyroid artery (ITA) and the recurrent laryngeal nerve (RLN) in fetal cadavers using anatomical dissection. The anterior necks of 200 fetuses were dissected. The origins of the superior thyroid artery (STA) and the ITA and location of the ITA in relation to the entrance of the thyroid lobe were examined. The relationship between the ITA and the RLN was determined. The origins of the STA were classified as: external carotid artery, common carotid artery (CCA), and the thyrolingual trunk. The origins of the ITA were the thyrocervical trunk and the CCA. The ITA was absent on the left side in two cases. The relationship of the RLN to the ITA fell into seven different types. Type 1: the RLN lay posterior to the artery; right (42.5%), left (65%). Type 2: the RLN lay anterior to the artery; right (40.5%), left (22.5%). Type 3: the RLN lay parallel to the artery; right (11.5%), left (7%). Type 4: the RLN lay between the two branches of the artery; right (1%), left (3.5%). Type 5: The extralaryngeal branch of the RLN was detected before it crossed the ITA; right (4.5%), left (0%). Type 6: the ITA lay between the two branches of the RLN; right (0%), left (0.5%). Type 7: the branches of the RLN lay among the branches of the ITA; right (0%), left (0.5%). The results from this study would be useful in future thyroid surgeries. © 2014 Wiley Periodicals, Inc.

  3. Impact of fetal echocardiography

    Directory of Open Access Journals (Sweden)

    Simpson John

    2009-01-01

    Full Text Available Prenatal diagnosis of congenital heart disease is now well established for a wide range of cardiac anomalies. Diagnosis of congenital heart disease during fetal life not only identifies the cardiac lesion but may also lead to detection of associated abnormalities. This information allows a detailed discussion of the prognosis with parents. For continuing pregnancies, appropriate preparation can be made to optimize the postnatal outcome. Reduced morbidity and mortality, following antenatal diagnosis, has been reported for coarctation of the aorta, hypoplastic left heart syndrome, and transposition of the great arteries. With regard to screening policy, most affected fetuses are in the "low risk" population, emphasizing the importance of appropriate training for those who undertake such obstetric anomaly scans. As a minimum, the four chamber view of the fetal heart should be incorporated into midtrimester anomaly scans, and where feasible, views of the outflow tracts should also be included, to increase the diagnostic yield. Newer screening techniques, such as measurement of nuchal translucency, may contribute to identification of fetuses at high risk for congenital heart disease and prompt referral for detailed cardiac assessment.

  4. Fetal habituation to vibroacoustic stimulation in relation to fetal states and fetal heart rate parameters.

    Science.gov (United States)

    van Heteren, C F; Boekkooi, P F; Jongsma, H W; Nijhuis, J G

    2001-03-01

    Fetal habituation to repeated stimulation has the potential to become a tool in the assessment of fetal condition and of the function of the fetal central nervous system (CNS). However, the influence of fetal quiescence and activity on habituation remains to be clarified. We studied habituation and the influence of fetal state and fetal heart rate (FHR) parameters on habituation in healthy term fetuses. We studied habituation in 37 healthy fetuses in two tests with an interval of 10 min. The vibroacoustic stimuli were applied to the maternal abdomen above the fetal legs for a period of 1 s every 30 s. A fetal trunk movement within 1 s after stimulation was defined as a positive response. Habituation rate is defined as the number of stimuli applied before an observed non-response to four consecutive stimuli. The FHR patterns (FHRP) of the 10 min observation period before and after the tests were visually classified. Fetal states were defined according to the FHRP. Baseline FHR, FHR variability and the number of accelerations were calculated in a subgroup of 25 fetuses. Of the 32 fetuses that responded normally during the first test, 26 habituated and six had persistent responses. The median habituation rate decreased significantly in the second test (P=0.001). There was no difference in habituation rate between fetuses that where initially in a quiet state and those in an active state. The FHR parameters before the first test and the difference between these FHR parameters before and after the test did not correlate with the habituation rate. Although the majority of healthy fetuses was able to habituate, the interfetal variability in habituation performance is such that testing of habituation seems not to be a sensitive tool for the assessment of the fetal CNS. This variability is neither the result of differences in fetal state nor of the various FHR parameters before testing, nor of the difference in change of FHR parameters arising from stimulation.

  5. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC(+) CD127(+) natural killer-like cells

    NARCIS (Netherlands)

    Cupedo, Tom; Crellin, Natasha K.; Papazian, Natalie; Rombouts, Elwin J.; Weijer, Kees; Grogan, Jane L.; Fibbe, Willem E.; Cornelissen, Jan J.; Spits, Hergen

    2009-01-01

    The human body contains over 500 individual lymph nodes, yet the biology of their formation is poorly understood. Here we identify human lymphoid tissue-inducer cells (LTi cells) as lineage-negative RORC(+) CD127(+) cells with the functional ability to interact with mesenchymal cells through

  6. Fetal and Maternal Outcomes in Pregnancies Complicated with Fetal Macrosomia

    Science.gov (United States)

    Alsammani, Mohamed Alkahatim; Ahmed, Salah Roshdy

    2012-01-01

    Background: Fetal macrosomia remains a considerable challenge in current obstetrics due to the fetal and maternal complications associated with this condition. Aim: This study was designed to determine the prevalence of fetal macrosomia and associated fetal and maternal morbidity and mortality in the Al Qassim Region of Saudi Arabia. Materials and Methods: This register-based study was conducted from January 1, 2011 through December 30, 2011 at the Maternity and Child Hospital, Qassim, Saudi Arabia. Macrosomia was defined as birth weight of 4 kg or greater. Malformed babies and those born dead were excluded. Results: The total number of babies delivered was 9241; of these, 418 were macrosomic. Thus, the prevalence of fetal macrosomia was 4.5%. The most common maternal complications were postpartum hemorrhage (5 cases, 1.2%), perineal tear (7 cases, 1.7%), cervical lacerations (3 cases, 0.7%), and shoulder dystocia (40 cases, 9.6%) that resulted in 4 cases of Erb's palsy (0.96%), and 6 cases of bone fractures (1.4%). The rate of cesarean section among women delivering macrosomic babies was 47.6% (199), while 52.4% (219) delivered vaginally. Conclusion: Despite extensive efforts to reduce fetal and maternal complications associated with macrosomia, considerable fetal and maternal morbidity remain associated with this condition. PMID:22754881

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

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    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.

  8. Maternal-fetal interactions in fetal cardiac surgery.

    Science.gov (United States)

    Eghtesady, Pirooz; Sedgwick, Joseph A; Schenbeck, Jennifer L; Lam, Christopher; Lombardi, John; Ferguson, Robert; Gardner, Aimee; McNamara, Jerri; Manning, Peter

    2006-01-01

    We examined potential maternal-fetal interactions during fetal cardiopulmonary bypass. these interactions, not previously described, may significantly influence attempts at fetal cardiac surgery. Eight fetal sheep underwent cardiopulmonary bypass (5 singletons, 3 twins; 100-109 days) for 60 minutes using a centrifugal microcircuit (20 mL prime), and the placenta as oxygenator. We measured maternal hemodynamics, arterial blood gases, and changes in blood flow to the gravid uterus using bilateral uterine artery flow probes. Maternal measurements were correlated to fetal hemodynamics, blood gases, and umbilical blood flows. After bypass, fetuses were followed for 60 minutes. Decreases in uterine blood flow occurred without changes in maternal hemodynamics or arterial blood gases, but were associated with worsening fetal arterial blood gases (pH decreased from 7.2 +/- 0.2 to 7.0 +/- 0.1, partial pressure of