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Fetal thymus

J Man, J C Hutchinson, M Ashworth, I Jeffrey, A E Heazell, N J Sebire
OBJECTIVES: The postmortem fetal brain:liver weight ratio is commonly used as a marker of nutrition for diagnosis of fetal growth restriction (FGR). However, there are limited data regarding the effects of intrauterine retention, fetal maceration and postmortem interval on organ weights and their ratios at autopsy. Our aims were to examine the relationships between gestational-age-adjusted and sex-adjusted fetal organ weights at autopsy, cause of intrauterine death and effects of intrauterine retention, and to determine whether the brain:liver weight ratio is a reliable marker of FGR in intrauterine death...
October 25, 2016: Ultrasound in Obstetrics & Gynecology
J Man, J C Hutchinson, M Ashworth, L Judge-Kronis, S Levine, N J Sebire
OBJECTIVES: Guidelines for the investigation of intrauterine death and sudden unexpected death in infancy (SUDI) recommend, based on expert opinion, autopsy procedures and tissue sampling strategies for histological analysis. Although stillbirth is much more common than SUDI, there have been no large-scale studies published which evaluate the usefulness of histological evaluation of specific organs in stillbirth for determining cause of death. Our aim was to evaluate the use of macroscopic and microscopic assessment of internal organs to determine cause of intrauterine death...
October 25, 2016: Ultrasound in Obstetrics & Gynecology
Tiago C Luis, Sidinh Luc, Takuo Mizukami, Hanane Boukarabila, Supat Thongjuea, Petter S Woll, Emanuele Azzoni, Alice Giustacchini, Michael Lutteropp, Tiphaine Bouriez-Jones, Harsh Vaidya, Adam J Mead, Deborah Atkinson, Charlotta Böiers, Joana Carrelha, Iain C Macaulay, Roger Patient, Frederic Geissmann, Claus Nerlov, Rickard Sandberg, Marella F T R de Bruijn, C Clare Blackburn, Isabelle Godin, Sten Eirik W Jacobsen
The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell-restricted progenitors...
October 3, 2016: Nature Immunology
Ashley R Hoover, Igor Dozmorov, Jessica MacLeod, Qiumei Du, M Teresa de la Morena, Joseph Forbess, Kristine Guleserian, Ondine B Cleaver, Nicolai S C van Oers
The thymus, an organ responsible for T cell development, is one of the more stress sensitive tissues in the body. Stress, in the form of infections, radiation exposure, and steroids, impairs thymic epithelial cell (TEC) functions and induces the programmed cell death of immature thymocytes. MicroRNAs are small noncoding RNAs involved in tissue repair and homeostasis, with several supporting T cell development. We report that miR-205, an epithelial-specific miR, maintains thymopoiesis following inflammatory perturbations...
September 19, 2016: Journal of Biological Chemistry
Xiaoyan Fan, Yan Li, Yulong Zhang, Meixiang Sang, Jianhui Cai, Qiaoxia Li, Toshinori Ozaki, Tetsuya Ono, Dongwei He
To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1-deficient lacZ-transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged. In addition, mutations that were found in brain, liver, spleen, small intestine and thymus showed similar levels and no statistically significant difference was found. The molecular nature of mutations at 12...
September 19, 2016: Radiation Research
Drake J Smith, Levina J Lin, Heesung Moon, Alexander T Pham, Xi Wang, Siyuan Liu, Sunjong Ji, Valerie Rezek, Saki Shimizu, Marlene Ruiz, Jennifer Lam, Deanna M Janzen, Sanaz Memarzadeh, Donald B Kohn, Jerome A Zack, Scott G Kitchen, Dong Sung An, Lili Yang
The humanized bone marrow-liver-thymus (BLT) mouse model harbors a nearly complete human immune system, therefore providing a powerful tool to study human immunology and immunotherapy. However, its application is greatly limited by the restricted supply of human CD34(+) hematopoietic stem cells and fetal thymus tissues that are needed to generate these mice. The restriction is especially significant for the study of human immune systems with special genetic traits, such as certain human leukocyte antigen (HLA) haplotypes or monogene deficiencies...
October 18, 2016: Stem Cells and Development
Yasuyuki Saito, Jana M Ellegast, Anahita Rafiei, Yuanbin Song, Daniel Kull, Mathias Heikenwalder, Anthony Rongvaux, Stephanie Halene, Richard A Flavell, Markus G Manz
Human CD34(+) hematopoietic stem and progenitor cells (HSPCs) can reconstitute a human hemato-lymphoid system when transplanted into immunocompromised mice. While fetal liver- and cord blood-derived CD34(+) cells lead to high engraftment levels, engraftment of mobilized, adult donor-derived CD34(+) cells has remained poor. We generated so-called MSTRG and MISTRG hu-manized mice on a Rag2(-/-)Il2rg(-/-) background carrying a transgene for human SIRPα and human homologues of the cytokines macrophage-colony stimulating factor, thrombopoietin, with or without interleukin-3 and granulocyte-macrophage colony stimulating factor under murine promotors...
August 19, 2016: Blood
Christina N Banti, Constantina Papatriantafyllopoulou, Maria Manoli, Anastasios J Tasiopoulos, Sotiris K Hadjikakou
Novel silver(I) metallo-drugs of the nonsteroidal anti-inflammatory drug nimesulide (nim) and the mitochondriotropic triaryl derivatives of pnictogen ligands (tpE, E = P (tpp, tptp, or totp), As (tpAs), Sb (tpSb)) with the formulas {[Ag(nim) (tpp)2]DMF} (1), [Ag(nim) (tptp)2] (2), [Ag(nim) (totp)] (3), [Ag(nim) (tpAs)2] (4), and [Ag(nim) (tpSb)3] (5) ((tpp = triphenyphosphine, tptp = tri(p-tolyl)phosphine, totp = tri(o-tolyl)phosphine, tpAs = triphenylarsine, tpSb = triphenylantimony, and DMF = dimethylformamide) were synthesized and characterized by melting point, vibrational spectroscopy (mid-Fourier transform IR), (1)H NMR, UV-visible spectroscopic techniques, and X-ray crystallography...
September 6, 2016: Inorganic Chemistry
A T Gotardo, V V Dipe, I M Hueza, S L Górniak
Studies have revealed that impairment of the pregnant body weight reduces the fetal body weight and causes minor changes in skeletal development. The aim of the present study was to assess the effects of maternal feed restriction during pregnancy in offspring immune system development. Pregnant Wistar rats were distributed into 5 groups: 1 control in which dams received food ad libitum and 4 experimental groups in which dams were fed restricted amounts of rodent ration (16, 12, 9, or 6 g/rat/day) from the 6th to 17th gestation day...
August 5, 2016: Human & Experimental Toxicology
Predrag Novakovic, John C S Harding, Andrea Ladinig, Ahmad N Al-Dissi, Daniel J MacPhee, Susan E Detmer
Several routes of porcine reproductive and respiratory virus PRRSV transmission across the porcine diffuse epitheliochorial placentation have been proposed, but none have been proven. The objectives of this study were to investigate associations between numbers of CD163 and CD169 positive macrophages, cathepsin positive areolae, and type 2 PRRSV load at the maternal-fetal interface in order to examine important factors related to transplacental infection. On gestation day 85 ± 1, naïve pregnant gilts were inoculated with PRRSV (n = 114) or were sham inoculated (n = 19)...
2016: Veterinary Research
Wei An, Bhopal C Mohapatra, Neha Zutshi, Timothy A Bielecki, Benjamin T Goez, Haitao Luan, Fany Iseka, Insha Mushtaq, Matthew D Storck, Vimla Band, Hamid Band
CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals...
July 16, 2016: Oncotarget
Michael L Dourson, Bernard K Gadagbui, Rod B Thompson, Edward J Pfau, John Lowe
A method for determining a safety range for non-cancer risks is proposed, similar in concept to the range used for cancer in the management of waste sites. This safety range brings transparency to the chemical specific Reference Dose or Concentration by replacing their "order of magnitude" definitions with a scientifically-based range. EPA's multiple RfCs for trichloroethylene (TCE) were evaluated as a case study. For TCE, a multi-endpoint safety range was judged to be 3 μg/m(3) to 30 μg/m,(3) based on a review of kidney effects found in NTP (1988), thymus effects found in Keil et al...
October 2016: Regulatory Toxicology and Pharmacology: RTP
Esra Bahar Gur, Mehmet Serkan Gur, Ozlem Ince, Esin Kasap, Mine Genc, Sumeyra Tatar, Sultan Bugday, Guluzar Arzu Turan, Serkan Guclu
OBJECTIVES: The aim of our study was to evaluate the association of vitamin D deficiency (VDD) during pregnancy with thymus size in full-term fetuses. MATERIAL AND METHODS: In this prospective study, we evaluated mid-pregnancy serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations. The fetal thymus size was measured by ultrasound in the third trimester. Neonatal 25(OH)D3 levels were evaluated by umbilical cord blood sampling. Correlation of maternal and neonatal vitamin D levels and association between thymus size and both, maternal and neonatal vitamin D concentrations were investigated...
2016: Ginekologia Polska
Magdalena B Rother, Marco W J Schreurs, Roel Kroek, Sophinus J W Bartol, Jacques J M van Dongen, Menno C van Zelm
The human thymus has been shown to host B cells, which have been implicated in presentation of autoantigens for negative selection of T cell progenitors. Although these Ags are thought to be taken up through their surface Igs, data on thymic Ig gene repertoires are limited and reactivity to autoantigens has not been demonstrated. We therefore studied the Ig gene repertoires and reactivity to autoantigens of single-sorted B cells from pediatric thymus, and compared these with mature B cells from fetal and pediatric bone marrow...
July 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Terkild Brink Buus, Jonas Damgård Schmidt, Charlotte Menné Bonefeld, Carsten Geisler, Jens Peter Holst Lauritsen
Co-stimulation is an integral part of T cell signaling involved in almost all facets of T cell biology. While much is known about co-stimulation in differentiation and function of conventional αβ T cells, less is known about how co-stimulation affects the development and programming of γδ T cells. In this study, we have investigated the role of inducible T cell co-stimulator (ICOS) on the development of γδ T cells. We show that ICOS is expressed by a population of immature Vγ2+CD45RBlow γδ T cells predisposed to interleukin-17 (IL-17) production...
April 12, 2016: Oncotarget
Ting Chen, Han-Xiao Liu, Hui-Yi Yan, Dong-Mei Wu, Jie Ping
Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the 'developmental programming' and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring...
August 2016: Molecular Human Reproduction
David A Clark
Natural Foxp3(+) regulatory T cells (nTregs) defined by expression of the Foxp3 marker generated in the thymus against self autoantigens prevent systemic autoimmune and inflammatory disease. A second population of Tregs induced by exogenous antigens in the periphery (iTregs) are currently thought to play a key role in preventing infertility, recurrent pregnancy loss (occult and clinically-evident), pre-eclampsia, fetal growth restriction, and premature birth in outbred matings where the father is histoincompatible with the mother...
August 2016: Journal of Reproductive Immunology
Martti Laan, Uku Haljasorg, Kai Kisand, Andres Salumets, Pärt Peterson
During normal pregnancy, the thymus undergoes a severe reduction in size and thymocyte output, which may contribute to maternal-fetal tolerance. It is presently unknown whether the pregnancy-induced thymic involution also affects nonlymphoid thymic cell populations and whether these changes in stromal cells play a role in the reduction in thymocyte numbers. Here, we characterize the changes in thymic lymphoid and nonlymphoid cells and show that pregnancy results in a reduction of all major thymic lymphoid cell populations, including the early T-lymphoid progenitors (TLPs) and thymic regulatory T cells...
August 2016: European Journal of Immunology
Richa Gupta, Tulika Gupta, Harjeet Kaur, Shobha Sehgal, Anjali Aggarwal, Kanchan Kapoor, Anshu Sharma, Daisy Sahni, Suhalika Singla
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...
September 2016: Clinical Anatomy
Jamie M Wilkinson, Hua Bao, Andrea Ladinig, Linjun Hong, Paul Stothard, Joan K Lunney, Graham S Plastow, John C S Harding
BACKGROUND: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant pigs can result in congenital infection and ultimately fetal death. Little is known about immune responses to infection at the maternal-fetal interface and in the fetus itself, or the molecular events behind virus transmission and disease progression in the fetus. To investigate these processes, RNA-sequencing of two sites, uterine endothelium with adherent placental tissue and fetal thymus, was performed 21 days post-challenge on four groups of fetuses selected from a large PRRSV challenge experiment of pregnant gilts: control (CON), uninfected (UNINF), infected (INF), and meconium-stained (MEC) (n = 12/group)...
2016: BMC Genomics
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