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Sample records for human fetal thymus

  1. 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...

  2. Thymus

    Indian Academy of Sciences (India)

    The removal of thymus of mice at birth before the leukemia virus was injected ..... finger proteins which mediate the differentiation of erythroid, myeloid, and lymphoid .... thymus undergoes an acute loss in thymic architecture and cellu- larity.

  3. CD34+CD38dim cells in the human thymus can differentiate into T, natural killer, and dendritic cells but are distinct from pluripotent stem cells

    NARCIS (Netherlands)

    Res, P.; Martínez-Cáceres, E.; Cristina Jaleco, A.; Staal, F.; Noteboom, E.; Weijer, K.; Spits, H.

    1996-01-01

    Recently we reported that the human thymus contains a minute population of CD34+CD38dim cells that do not express the T-cell lineage markers CD2 and CD5. The phenotype of this population resembled that of CD34+CD38dim cells present in fetal liver, umbilical cord blood, and bone marrow known to be

  4. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model.

    Directory of Open Access Journals (Sweden)

    Matthew B Greenblatt

    Full Text Available Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice. The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc(-/- delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

  5. Irradiated fetal thymus transplantation in a patient with combined immunodeficiency with predominant T cell defect

    International Nuclear Information System (INIS)

    Higuchi, Shigenori; Yanabe, Yasuhide; Tsuchiya, Hiroyuki; Akahoshi, Izumi; Migita, Masahiro; Matsuda, Ichiro; Udaka, Keiji.

    1993-01-01

    A 6 month old boy was diagnosed as a case of combined immunodeficiency (with predominant T cell defect by previous classification). His T cell count was decreased, his B cell count in peripheral blood was increased, his serum IgG level was decreased, his serum IgM level was normal and the thymus was not evident on CT scans and magnetic resonance imaging. Administration of the thymus hormone, thymosin, led to a partial recovery of T cell function without normalization of the T cell count. At age 26 months the patient received an irradiated thymus transplantation from a 16 week old female fetus. After the transplantation, the T cell count (mainly CD4 + cells) increased by 50-70%. A mild graft-versus-host reaction (GVHR) occurred and several immunosuppressants were prescribed. Chromosome analysis showed that the T cells have both 46 XY and 46 XX karyotypes while the B cells have the 46 XY karyotype alone. His cellular immunity (skin tests, DNA synthesis, mixed lymphocyte reaction, cytotoxic activity and natural killer cell function) and his serum IgG level remained low. However, being on regular γ-globulin therapy and oral anti-fungal drugs, he is now living normally with almost no trouble at age 6 years and 3 months. This case showed that irradiated thymus transplantation might be a useful method when an adequate donor for bone marrow transplantation is not available. The unexpected observation that the increased T cells were mainly CD4 may be related to the mild GVHR and the clinical improvement. (author)

  6. Effects of Intrauterine Growth Restriction During Late Pregnancy on the Development of the Ovine Fetal Thymus and the T-Lymphocyte Subpopulation.

    Science.gov (United States)

    Liu, Yingchun; He, Shan; Zhang, Yuan; Xia, Wei; Li, Ming; Zhang, Chongzhi; Gao, Feng

    2015-07-01

    The retarded development of fetal thymus in intrauterine growth restriction (IUGR) from maternal undernutrition during late pregnancy destroys the tridimensional structure and modifies the development of fetal T lymphocytes. The mechanisms, however, remain unclear. The objective of this study was to investigate the effect of IUGR during late pregnancy on the development of the ovine fetal thymus and the T-lymphocyte subpopulation. Eighteen time-mated ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/BW(0.75) /day, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW(0.75) /day, n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/BW(0.75) /day, n = 6). Fetuses were recovered at slaughter on day 140. Fetuses in RG1 exhibited decreased (P restricted groups. In addition, there was reduced mRNA expression (P < 0.05) of T-cell receptor, apoptosis antigen 1 ligand, and RAG2 in the RG1 group. In contrast, increases in glutathione peroxidase, malondialdehyde, caspase-3, Cytochrome c, and CD4(+) T cells were observed (P < 0.05), and higher mRNA expressions (P < 0.05) of protein 53, Bcl-2 associated X protein (Bax), and apoptosis antigen 1 (Fas) were found in RG1 fetuses; and thymuses of RG2 fetuses had increased caspase-3, and expression of Fas and Bax (P < 0.05), relative to control fetuses. These results indicate that reduced cell proliferation, oxidative stress, and increased cell apoptosis were the potential mechanisms for impaired development and microenvironment of IUGR fetal thymus, and for modifying the maturation of CD4(+) CD8(+) thymocytes underlying their reduced numbers . © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Human fetal anatomy: MR imaging.

    Science.gov (United States)

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

    1985-12-01

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

  8. Thymus Cancer

    Science.gov (United States)

    ... cell. These cells help protect you from infections. Cancer of the thymus is rare. You are more ... Sometimes there are no symptoms. Other times, thymus cancer can cause A cough that doesn't go ...

  9. Quantitation of human thymus/leukemia-associated antigen by radioimmunoassay in different forms of leukemia.

    Science.gov (United States)

    Chechik, B E; Jason, J; Shore, A; Baker, M; Dosch, H M; Gelfand, E W

    1979-12-01

    Using a radioimmunoassay, increased levels of a human thymus/leukemia-associated antigen (HThy-L) have been detected in leukemic cells and plasma from most patients with E-rosette-positive acute lymphoblastic leukemia (ALL) and a number of patients with E-rosette-negative ALL, acute myeloblastic leukemia (AML), acute monomyelocytic leukemia (AMML), and acute undifferentiated leukemia (AVL). Low levels of HThy-L have been demonstrated in white cells from patients with chronic myelocytic leukemia (stable phase) and in mononuclear cells from patients with chronic lymphatic leukemia. The relationship between HThy-L and differentiation of hematopoietic cells is discussed.

  10. Metabolism of lipoproteins by human fetal hepatocytes

    International Nuclear Information System (INIS)

    Carr, B.R.

    1987-01-01

    The rate of clearance of lipoproteins from plasma appears to play a role in the development of atherogenesis. The liver may account for as much as two thirds of the removal of low-density lipoprotein and one third of the clearance of high-density lipoprotein in certain animal species and humans, mainly by receptor-mediated pathways. The purpose of the present investigation was to determine if human fetal hepatocytes maintained in vitro take up and degrade lipoproteins. We first determined that the maximal binding capacity of iodine 125-iodo-LDL was approximately 300 ng of low-density lipoprotein protein/mg of membrane protein and an apparent dissociation constant of approximately 60 micrograms low-density lipoprotein protein/ml in membranes prepared from human fetal liver. We found that the maximal uptake of [ 125 I]iodo-LDL and [ 125 I]iodo-HDL by fetal hepatocytes occurred after 12 hours of incubation. Low-density lipoprotein uptake preceded the appearance of degradation products by 4 hours, and thereafter the degradation of low-density lipoprotein increased linearly for at least 24 hours. In contrast, high-density lipoprotein was not degraded to any extent by fetal hepatocytes. [ 125 I]Iodo-LDL uptake and degradation were inhibited more than 75% by preincubation with low-density lipoprotein but not significantly by high-density lipoprotein, whereas [ 125 I]iodo-HDL uptake was inhibited 70% by preincubation with high-density lipoprotein but not by low-density lipoprotein. In summary, human fetal hepatocytes take up and degrade low-density lipoprotein by a receptor-mediated process similar to that described for human extrahepatic tissues

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

    Science.gov (United States)

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

    1985-01-01

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

  12. Distribution of melatonin receptor in human fetal brain

    Institute of Scientific and Technical Information of China (English)

    WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

    2001-01-01

    Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

  13. Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

    Science.gov (United States)

    Melamed, Nir; Whittle, Wendy; Kelly, Edmond N; Windrim, Rory; Seaward, P Gareth R; Keunen, Johannes; Keating, Sarah; Ryan, Greg

    2015-06-01

    Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (B19 infection. A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT. Copyright © 2015. Published by Elsevier Inc.

  14. Fetal magnetic resonance imaging and human genetics

    International Nuclear Information System (INIS)

    Hengstschlaeger, Markus

    2006-01-01

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

  15. Fetal magnetic resonance imaging and human genetics

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-02-15

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

  16. Cholesterol synthesis by human fetal hepatocytes: effect of lipoproteins

    International Nuclear Information System (INIS)

    Carr, B.R.; Simpson, E.R.

    1984-01-01

    The purpose of the present investigation was to determine the effect of various lipoproteins on the rate of cholesterol synthesis of human fetal liver cells maintained in culture. This was accomplished by measuring the rate of incorporation of tritium from tritiated water or carbon 14-labeled acetate into cholesterol in human fetal liver cells. Optimal conditions for each assay were determined. When human fetal liver cells were maintained in the presence of low-density lipoprotein, cholesterol synthesis was inhibited in a concentration-dependent fashion. Intermediate--density lipoprotein and very-low-density lipoprotein also suppressed cholesterol synthesis in human fetal liver cells. In contrast, high-density lipoprotein stimulated cholesterol synthesis in human fetal liver cells. The results of the present as well as our previous investigations suggest that multiple interrelationships exist between fetal liver cholesterol synthesis and lipoprotein-cholesterol utilization by the human fetal adrenal gland and that these processes serve to regulate the lipoprotein-cholesterol levels in fetal plasma

  17. Thymus Gland Anatomy

    Science.gov (United States)

    ... historical Searches are case-insensitive Thymus Gland, Adult, Anatomy Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Thymus Gland, Adult, Anatomy Description: Anatomy of the thymus gland; drawing shows ...

  18. O6-methylguanine DNA methyltransferase in human fetal tissues: fetal and maternal factors

    International Nuclear Information System (INIS)

    D'Ambrosio, S.M.; Samuel, M.J.; Dutta-Choudhury, T.A.; Wani, A.A.

    1986-01-01

    O 6 -Methylguanine methyltransferase (O 6 -MT) was measured and compared in extracts of 7 human fetal tissues obtained from 21 different fetal specimens as a function of fetal age and race, and maternal smoking and drug usage. Activity was determined from the proteinase-K solubilized radioactivity transferred from the DNA to the O 6 -MT. S9 homogenates were incubated with a heat depurinated [ 3 H]-methylnitrosourea alkylated DNA. Liver exhibited the highest activity followed by kidney, lung, small intestine, large intestine, skin and brain. Each of the tissues exhibited a 3- to 5-fold level of interindividual variation of O 6 -MT. There did not appear to be any significant difference of O 6 -MT in the tissues obtained from mothers who smoked cigarettes during pregnancy. Also, fetal race and age did not appear to account for the level of variation of O 6 -MT. The fetal tissues obtained from an individual using phenobarbital and smoking exhibited 4-fold increases in O 6 -MT activity. The tissues obtained from another individual on kidney dialysis were 2- to 3-fold higher than the normal population. These data suggest that the variation in human O 6 -MT can not be explained by racial or smoking factors, but may be modulated by certain drugs

  19. Cross-hemispheric functional connectivity in the human fetal brain.

    Science.gov (United States)

    Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

    2013-02-20

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

  20. Histochemical and radioautographic studies of normal human fetal colon

    International Nuclear Information System (INIS)

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

    1974-01-01

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

  1. Mathematical models of human cerebellar development in the fetal period.

    Science.gov (United States)

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

    2018-04-01

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

  2. Distinct functional programming of human fetal and adult monocytes.

    Science.gov (United States)

    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.

  3. Anti-inflammatory Elafin in human fetal membranes.

    Science.gov (United States)

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

    2017-02-01

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

  4. Sphingosine-1-phosphate/sphingosine-1-phosphate receptor 1 signaling is required for migration of naive human T cells from the thymus to the periphery

    NARCIS (Netherlands)

    Resop, Rachel S.; Douaisi, Marc; Craft, Joshua; Jachimowski, Loes C. M.; Blom, Bianca; Uittenbogaart, Christel H.

    2016-01-01

    The mechanisms that govern the egress of mature thymocytes from the human thymus to the periphery remain understudied yet are of utmost importance to the field of basic immunology, as well as T-cell reconstitution in various immunodeficiencies. We examined the expression and function of

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

    Science.gov (United States)

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

    2013-10-01

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

  6. Proapoptotic and Antiproliferative Effects of Thymus caramanicus on Human Breast Cancer Cell Line (MCF-7 and Its Interaction with Anticancer Drug Vincristine

    Directory of Open Access Journals (Sweden)

    Saeed Esmaeili-Mahani

    2014-01-01

    Full Text Available Thymus caramanicus Jalas is one of the species of thymus that grows in the wild in different regions of Iran. Traditionally, leaves of this plant are used in the treatment of diabetes, arthritis, and cancerous situation. Therefore, the present study was designed to investigate the selective cytotoxic and antiproliferative properties of Thymus caramanicus extract (TCE. MCF-7 human breast cancer cells were used in this study. Cytotoxicity of the extract was determined using MTT and neutral red assays. Biochemical markers of apoptosis (caspase 3, Bax, and Bcl-2 and cell proliferation (cyclin D1 were evaluated by immunoblotting. Vincristine was used as anticancer control drug in extract combination therapy. The data showed that incubation of cells with TCE (200 and 250 μg/mL significantly increased cell damage, activated caspase 3 and Bax/Bcl2 ratio. In addition, cyclin D1 was significantly decreased in TCE-treated cells. Furthermore, concomitant treatment of cells with extract and anticancer drug produced a significant cytotoxic effect as compared to extract or drugs alone. In conclusion, thymus extract has a potential proapoptotic/antiproliferative property against human breast cancer cells and its combination with chemotherapeutic agent vincristine may induce cell death effectively and be a potent modality to treat this type of cancer.

  7. Radiation and host factors in human thyroid tumors following thymus irradiation

    International Nuclear Information System (INIS)

    Shore, R.E.; Pasternack, B.S.; Woodard, E.D.; Hempelmann, L.H.

    1980-01-01

    Thyroid tumor data from the 1971 survey of the Rochester, New York thymus irradiated population are further analyzed to study radiobiological and host factors. The analyses were based on the approx. 2650 irradiated subjects and 4800 sibling controls who had 5 or more years of follow-up. Twenty-four thyroid cancers and 52 thyroid adenomas were found in the irradiated group, and O thyroid cancers and 6 adenomas among the controls. The overall risk estimates were 3.8 thyroid cancers/10 6 persons/yr/rad and 4.5 thyroid adenomas/10 6 persons/yr/rad. The dose-response data (thyroid dose range of 5 to > 1000 rad) for thyroid cancer indicate both a linear and a dose-squared component, but no dose-squared component is evident for thyroid adenomas. At lower total doses (< 400 rad) there was a suggestion that dose fractionation diminished the thyroid cancer response, but a similar fractionation effect was not found for thyroid adenomas. The temporal pattern of tumors suggested an extended plateau of excess tumor production, rather than a wavelike temporal pattern. There was no evidence for an inverse relationship between thyroid radiation dose and thyroid cancer latency. Female and Jewish subjects had a higher risk of radiation-induced thyroid cancer than did their respective counterparts. The additive and multiplicative models of radiation effects were compared with respect to sex differences; neither model provided a superior fit to the data. The tentative nature of the conclusions is stressed because of the relatively small number of thyroid cancers. (author)

  8. APOPTOSIS DURING HUMAN FETAL KIDNEY DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2014-01-01

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

  10. The size of the thymus: an important immunological diagnostic tool?

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth

    2003-01-01

    of the thymus relevant to its function and could measurement of the thymus be a useful immunological diagnostic tool in the investigation of thymic function in humans with a depressed immune system? Conclusion: Studies using the size of the thymus as an immunological diagnostic tool should be encouraged....

  11. Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

    Directory of Open Access Journals (Sweden)

    Predrag Novakovic

    Full Text Available The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114 or sham inoculated (n = 19 at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391. Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both, but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both. The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both. Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection.

  12. Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts

    Science.gov (United States)

    Novakovic, Predrag; Harding, John C. S.; Al-Dissi, Ahmad N.; Ladinig, Andrea; Detmer, Susan E.

    2016-01-01

    The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection. PMID:26963101

  13. DNA Methylation Landscapes of Human Fetal Development

    NARCIS (Netherlands)

    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

  14. Immunohistochemical distribution of regulatory peptides in the human fetal adenohypophysis

    Science.gov (United States)

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

    2008-01-01

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

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  16. A radiographic study of the human fetal spine

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  17. Quaternary structure and spin state of human fetal methemoglobin

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  18. STEREOLOGICAL STUDIES ON FETAL VASCULAR DEVELOPMENT IN HUMAN PLACENTAL VILLI

    Directory of Open Access Journals (Sweden)

    Terry M Mayhew

    2011-05-01

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

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

    International Nuclear Information System (INIS)

    Roedler, H.D.

    1987-01-01

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

  20. A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

    Directory of Open Access Journals (Sweden)

    Matthew E. Brown

    2018-04-01

    Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus

  1. Human fetal growth is constrained below optimal for perinatal survival

    NARCIS (Netherlands)

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

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

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

    Directory of Open Access Journals (Sweden)

    Andrew J Childs

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

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

    Science.gov (United States)

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

    2011-01-01

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

  4. 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

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

    OpenAIRE

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2010-09-01

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

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

    Science.gov (United States)

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

    2018-05-13

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  10. 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...... acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease....

  11. Variation in ovarian follicle density during human fetal development.

    Science.gov (United States)

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

    2012-09-01

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

  12. 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.

  13. Thymus dependent immune competence

    International Nuclear Information System (INIS)

    Kruisbeek, A.M.

    1978-01-01

    Studies are described which are concerned with changes in cellular immunocompetance in ageing and tumour-bearing animals. The possible therapeutical application of thymic humoral factors in restoration of diminished T cell functions initiated the more fundamental studies on the humoral function of the thymus are also described. Irradiated mice and rats were used. (Auth.)

  14. Thymus function in drug-induced lupus.

    Science.gov (United States)

    Rubin, R L; Salomon, D R; Guerrero, R S

    2001-01-01

    Autoimmunity develops when a lupus-inducing drug is introduced into the thymus of normal mice, but the relevance of this model to the human disorder is unclear in part because it is widely assumed that the thymus is non-functional in the adult. We compared thymus function in 10 patients with symptomatic procainamide-induced lupus to that in 13 asymptomatic patients who only developed drug-induced autoantibodies. T cell output from the thymus was quantified using a competitive polymerase chain reaction that detects T cell receptor DNA excision circles in peripheral blood lymphocytes. Despite the advanced age of the patient population under study, newly generated T cells were detected in all subjects. Although there was no overall quantitative difference between the symptomatic and asymptomatic patients, we found a positive correlation between the level of T cell receptor excision circles in peripheral lymphocytes and serum IgG anti-chromatin antibody activity in patients with drug-induced lupus. The association between autoantibodies and nascent peripheral T cells supports the requirement for T cells in autoantibody production. Our observations are consistent with findings in mice in which autoreactive T cells derived from drug-induced abnormalities in T cell development in the thymus.

  15. Effects of UV Rays and Thymol/Thymus vulgaris L. Extract in an ex vivo Human Skin Model: Morphological and Genotoxicological Assessment.

    Science.gov (United States)

    Cornaghi, Laura; Arnaboldi, Francesca; Calò, Rossella; Landoni, Federica; Baruffaldi Preis, William Franz; Marabini, Laura; Donetti, Elena

    2016-01-01

    Ultraviolet (UV) radiation is the major environmental factor affecting functions of the skin. Compounds rich in polyphenols, such as Thymus vulgaris leaf extract and thymol, have been proposed for the prevention of UV-induced skin damage. We compared the acute effects induced by UVA and UVB rays on epidermal morphology and proliferation, cytotoxicity, and genotoxicity. Normal human skin explants were obtained from young healthy women (n = 7) after informed consent and cultured at the air-liquid interface overnight. After 24 h, the samples were divided in 2 groups: the former exposed to UVA (16 or 24 J/cm2) and the latter irradiated with UVB (0.24 or 0.72 J/cm2). One hour after the end of irradiation, supernatants were collected for evaluation of the lactate dehydrogenase activity. Twenty-four hours after UVB exposure, biopsies were processed for light and transmission electron microscopy analysis, proliferation, cytotoxicity, and genotoxicity. UVB and UVA rays induced early inhibition of cell proliferation and DNA damage compared to controls. In particular, UVB rays were always more cytotoxic and genotoxic than UVA ones. For this reason, we evaluated the effect of either T. vulgaris L. extract (1.82 µg/ml) or thymol (1 µg/ml) on all samples treated for 1 h before UVB irradiation. While Thymus had a protective action for all of the endpoints evaluated, the action of the extract was less pronounced on epidermal proliferation and morphological features. The results presented in this study could be the basis for investigating the mechanism of thymol and T. vulgaris L. extract against the damage induced by UV radiation. © 2016 S. Karger AG, Basel.

  16. 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.

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

    Science.gov (United States)

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

    2009-01-01

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

  18. 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.

  19. Radiation absorbed dose to the human fetal thyroid

    International Nuclear Information System (INIS)

    Watson, E.E.

    1992-01-01

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

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  1. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    Science.gov (United States)

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    1961-01-01

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

  4. 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.

  5. Fetal- and uterine-specific antigens in human amniotic fluid.

    Science.gov (United States)

    Sutcliffe, R G; Brock, D J; Nicholson, L V; Dunn, E

    1978-09-01

    Removal of the major maternal serum proteins from second trimester amniotic fluid by antibody affinity chromatography revealed various soluble tissue antigens, of which two were fetal-specific skin proteins and another, of alpha2-mobility, was specific to the uterus, and was therefore designated alpha-uterine protein (AUP). These proteins could not be detected in maternal serum by antibody-antigen crossed electrophoresis. The concentration of AUP in amniotic fluid reached a maximum between 10 and 20 weeks of gestation, suggesting that there is an influx of uterine protein into the amniotic fluid at this stage of pregnancy.

  6. 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

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

    International Nuclear Information System (INIS)

    Kong Weiwei; Teng Gaojun

    2004-01-01

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

  8. Ionizing radiation and the thymus

    International Nuclear Information System (INIS)

    Huiskamp, R.

    1986-01-01

    In this thesis the effects of whole body irradiation with fast fission neutrons and X-rays on the murine thymus are studied. Young adult CBA mice were exposed to whole body irradiation with either fast fission neutrons or X-rays. The results of the investigation of short- and long-term effects of the irradiation on the thymus showed a biphasic regeneration pattern followed by a marked decrease in relative thymus weight and cellularity which lasted up to at least 250 days. This late effect is attributed to possible loss of pluripotent stem cells and residual damage in the surviving stem cells in the bone marrow. The immunohistology of T cell subpopulations in the thymus of normal CBA/H mice was analyzed in order to describe the T cell composition of the irradiated thymus. The effects of irradiation with fast fission neutrons on the stromal cells of the thymus are studied in order to investigate whether the thymic stromal cells are involved in the regeneration process. The effect of graded doses of fission neutrons or X-rays on the lymphoid compartment on the thymus are studied in order to investigate the radiosensitivity of thymocyte subpopulations for these radiation types. Also the effects on the stromal compartment of the thymus are investigated. (Auth.)

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

    Science.gov (United States)

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

    2010-08-01

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

  10. 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,

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  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. 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...

  14. Construction of Thymus Organoids from Decellularized Thymus Scaffolds.

    Science.gov (United States)

    Tajima, Asako; Pradhan, Isha; Geng, Xuehui; Trucco, Massimo; Fan, Yong

    2016-10-12

    One of the hallmarks of modern medicine is the development of therapeutics that can modulate immune responses, especially the adaptive arm of immunity, for disease intervention and prevention. While tremendous progress has been made in the past decades, manipulating the thymus, the primary lymphoid organ responsible for the development and education of T lymphocytes, remains a challenge. One of the major obstacles is the difficulty to reproduce its unique extracellular matrix (ECM) microenvironment that is essential for maintaining the function and survival of thymic epithelial cells (TECs), the predominant population of cells in the thymic stroma. Here, we describe the construction of functional thymus organoids from decellularized thymus scaffolds repopulated with isolated TECs. Thymus decellularization was achieved by freeze-thaw cycles to induce intracellular ice crystal formation, followed by detergent-induced cell lysis. Cellular debris was removed with extensive wash. The decellularized thymus scaffolds can largely retain the 3D extracellular matrix (ECM) microenvironment that can support the recolonization of TECs. When transplanted into athymic nude mice, the reconstructed thymus organoids can effectively promote the homing of bone marrow-derived lymphocyte progenitors and support the development of a diverse and functional T cell repertoire. Bioengineering of thymus organoids can be a promising approach to rejuvenate/modulate the function of T-cell mediated adaptive immunity in regenerative medicine.

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

    Science.gov (United States)

    Hui, Lisa; Bianchi, Diana W

    2013-02-01

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

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

    Science.gov (United States)

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

    1999-05-01

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

  17. Discovery and Characterization of piRNAs in the Human Fetal Ovary

    Directory of Open Access Journals (Sweden)

    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.

  18. Effect Of Small Doses On THE Thymus In Pediatric Chest X - Ray

    International Nuclear Information System (INIS)

    Milkovic, Dj.; Ranogajec-Komor, M.; Anzic, S. A.; Zagar, I.

    2015-01-01

    The thymus, pyramid-shaped lymphoid organ is immediately beneath the breastbone at the level of the heart, therefore chest X-ray covers the position of thymus. The thymus is divided into two lobes, lying on either side of the midline of the body. Unlike most other lymphoid structures, the thymus grows rapidly and attains its greatest size relative to the rest of the body during fetal life and the first years after birth. The thymus is a specialized organ of the immune system. It has big responsibility helping the body protect itself against autoimmunity diseases. It is well known from literature data that thymus size reduced at radiotherapy irradiation. After many years of experience in X-ray chest diagnostics with children a fairly regular thymus size reduction after exposure to diagnostic low doses was noticed. Therefore it was analysed at what percentage of children patients their control radiograms would exhibit a thymus shade decrease compared to the primary image taken at the illness out-set. In the Children Hospital Srebrnjak in one year 1972 children in the age group 0 - 5 years underwent X-ray exam. In our earlier study at PA and profile projections of lung examinations of this age group 0.15 mSv and 0.11 mSv average doses were measured on the back and on the chest, respectively. From this group the radiograms of those 119 children were analysed who were exposed, according to medical indication, to control examinations. 58 of the investigated patients showed enlarged thymus at the first exam. It could be seen from the control radiogram that 52 children of these 58 patients had significant or discrete decrease in size of thymus. Taking into account that thymus has very important role in maturity of T-lymphocytes and development of immunology tolerance these empiric statements are important for radiation protection of children in X-ray diagnostic of chest. (author).

  19. 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.

  20. 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.

  1. 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

  2. Phenotypic characterization of early events of thymus repopulation in radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Sharrow, S.O.; Singer, A.; Hammerling, U.; Mathieson, B.J.

    1983-01-01

    The phenotype of murine thymocytes repopulating the thymus of radiation bone marrow chimeras shortly after irradiation and bone marrow reconstitution was analyzed by immunofluorescence and flow microfluorometry. Thymuses in these chimeras, while essentially devoid of lymphoid cells at day 7, were repopulated by days 10 to 12 after irradiation. It was found that this initial repopulation arose from a radioresistant intrathymic precursor that expanded to an almost complete complement of host-type thymocytes. However, these host-derived thymocytes were unusual in that they were relatively deficient in Lyt 1+2- and peanut agglutinin ''dull'' cells as compared with normal thymocytes. Donor bone-marrow-derived cells first appeared in the irradiated chimeric thymuses between days 12 and 15 after irradiation and bone marrow transfer. By day 19, chimeric thymuses contained more than 98% donor cells. This course was identical for three chimeric combinations, each made across different genetic barriers. In contrast to the cells that populate the fetal thymus during normal ontogeny, the first donor bone-marrow-derived cells that can be detected within the irradiated chimeric thymuses already expressed phenotypically normal adult T cell subpopulations in that they contained significant numbers both of Lyt 1+2- and of Lyt 1+2+ thymocytes. Thus, the Lyt phenotype of donor cells that initially repopulate an adult thymus after irradiation is markedly different from the Lyt phenotype of cells that initially populate the fetal thymus. The differences between adult and fetal thymic development that are observed in radiation bone marrow chimeras may be important in our understanding of T cell differentiation in these animals

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

    Science.gov (United States)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  5. 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...

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Vincent Muczynski

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

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

    Czech Academy of Sciences Publication Activity Database

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

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

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

    Science.gov (United States)

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

    1989-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-11-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  12. Lymphocyte development in irradiated thymuses: dynamics of colonization by progenitor cells and regeneration of resident cells

    International Nuclear Information System (INIS)

    Mehr, R.; Fridkis-Hareli, M.; Abel, L.; Segel, L.; Globerson, A.

    1995-01-01

    Lymphocyte development in irradiated thymuses was analyzed using two complementary strategies: an in vitro experimental model and computer simulations. In the in vitro model, fetal thymus lobes were irradiated and the regeneration of cells that survived irradiation were examined, with the results compared to those of reconstitution of the thymus by donor bone marrow cells and their competition with the thymic resident cells. In vitro measurements of resident cell kinetics showed that cell proliferation is slowed down significantly after a relatively low (10Gy) irradiation dose. Although the number of thymocytes that survived irradiation remained low for several days post-irradiation, further colonization by donor cells was not possible, unless performed within 6 h after irradiation. These experimental results, coupled with the analysis by computer simulations, suggest that bone marrow cell engraftment in the irradiated thymus may be limited by the presence of radiation-surviving thymic resident cells and the reduced availability of seeding niches. (Author)

  13. 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.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

    Guillot, Pascale V

    2016-02-01

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

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

    Science.gov (United States)

    Milos, N; Bamforth, S; Bagnall, K

    1999-04-01

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

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

    Science.gov (United States)

    Bajoria, R; Fisk, N M

    1998-05-01

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

  18. Discarded human fetal tissue and cell cultures for transplantation research

    International Nuclear Information System (INIS)

    Hay, R.J.; Phillips, T.; Thompson, A.; Vilner, L.; Cleland, M.; Tchaw-ren Chen; Zabrenetzky, V.

    1999-01-01

    A feasibility study has been performed to explore the utility of various tissues from discarded human abortuses for transplantation and related research. Specifically, aborted fetuses plus parental blood samples and all relevant clinical data were obtained through a local hospital complex. Whenever possible, pancreas, skin and skeletal muscle, heart, liver, kidney, cartilage and lung tissues were removed, dissociated and subfractionated for cryopreservation, characterization and cultivation trials in vitro. Existing protocols for these manipulations were compared and improved upon as required. Clonal culture, cell aggregate maintenance techniques and use of feeder cell populations have been utilized where appropriate to develop quantitative comparative data. Histological and biochemical assays were applied both to evaluate separation/cultivation methods and to identify optimal culture conditions for maintaining functional cells. Immunochemical and molecular biological procedures were applied to study expression of Major Histocompatibility Vomplex (MHC) class 1 and 11 molecules on cell lines derived. Tissue and cell culture populations were examined for infections with bacteria, ftingi, mycoplasma, HIV, CMV, hepatitis B and other viruses. Only 1% of the abortuses tested were virally infected. Cytogenetic analyses confin-ned the normal diploid status in the vast majority (>98%) of lines tested. A total of over 250 abortuses have been obtained and processed. Only 25 were found to be contaminated with bacteria or fungi and unsuitable for further cultivation trials. A total of over 200 cell populations were isolated, characterized and cryopreserved for further study. Included were kidney, lung, liver and epidermal epithelia: cartilage-derived cells from the spine and epiphyses plus myogenic myoblasts. Selected lines have been immortalized using HPV I 6E6/E7 sequences. Epithelia from the liver and pancreas and cardiac myocytes were the most problematic in that initial

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

    Science.gov (United States)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona; Husain, Nuzhat; Srivastava, Savita; Rathore, Ram K.S.; Sarma, Manoj K.; Malik, Gyanendra K.; Das, Vinita; Pradhan, Mandakini; Pandey, Chandra M.; Narayana, Ponnada A.

    2009-01-01

    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.)

  1. 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.)

  2. Chemical composition of essential oils of Thymus and Mentha species and their antifungal activities.

    NARCIS (Netherlands)

    Sokovic, M.D.; Vukojevic, J.; Marin, P.D.; Brkic, D.D.; Vajs, V.; Griensven, van L.J.L.D.

    2009-01-01

    The potential antifungal effects of Thymus vulgaris L., Thymus tosevii L., Mentha spicata L., and Mentha piperita L. (Labiatae) essential oils and their components against 17 micromycetal food poisoning, plant, animal and human pathogens are presented. The essential oils were obtained by

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. Isolation and characterization of neural stem cells from human fetal striatum

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2004-07-30

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Venu Jain

    2013-05-01

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

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

    Science.gov (United States)

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

    2015-05-01

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

  10. 3H-cyclosporine internalization and secretion by human fetal pancreatic islets

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  11. 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.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Science.gov (United States)

    Bryan, Jeffrey N

    2015-05-01

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

  15. 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.

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

    Science.gov (United States)

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

    2011-06-01

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

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

    OpenAIRE

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

    2015-01-01

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

  18. R5 strains of human immunodeficiency virus type 1 from rapid progressors lacking X4 strains do not possess X4-type pathogenicity in human thymus

    NARCIS (Netherlands)

    Berkowitz, R. D.; van't Wout, A. B.; Kootstra, N. A.; Moreno, M. E.; Linquist-Stepps, V. D.; Bare, C.; Stoddart, C. A.; Schuitemaker, H.; McCune, J. M.

    1999-01-01

    Some individuals infected with only R5 strains of human immunodeficiency virus type 1 progress to AIDS as quickly as individuals harboring X4 strains. We determined that three R5 viruses were much less pathogenic than an X4 virus in SCID-hu Thy/Liv mice, suggesting that R5 virus-mediated rapid

  19. 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...

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

    Science.gov (United States)

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

    2018-04-01

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

  1. de Thymus fontanesii Boiss & Reut

    African Journals Online (AJOL)

    AKA BOKO

    Les huiles essentielles sont conservées à 4°C et à l'abri de la lumière. 2-3. Analyse physicochimique de l'huile essentielle du. Thymus fontanesii. Ces analyses sont faites en conformité aux normes A.F.N.O.R [4] Nous avons déterminé les: Caractères physiques : densité, indice de réfraction, pouvoir rotatoire, solubilité dans.

  2. Use of fetal tissues for immunoreconstitution in horses with severe combined immunodeficiency

    International Nuclear Information System (INIS)

    Perryman, L.E.

    1980-01-01

    The authors have initiated studies designed to identify and characterize those parameters which must be considered in order to optimize immunoreconstitution following fetal tissue transplantation. The objectives of the first phase of experiments were to define ontogeny of lymphocyte function in equine fetal tissues and to determine if fetal liver and thymus, in combination, would immunologically reconstitute horses with combined immunodeficiency. (Auth.)

  3. Fetal cardiology

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

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

    Science.gov (United States)

    Heyden, E L; Wimalawansa, S J

    2018-06-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Stacy Zamudio

    2010-01-01

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

  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. Thymus transplantation and disease prevention in the diabetes-prone Bio-Breeding rat

    International Nuclear Information System (INIS)

    Georgiou, H.M.; Bellgrau, D.

    1989-01-01

    Bio-Breeding rat T lymphocytes proliferate poorly in response to alloantigen. Transplantation of Bio-Breeding rats with fetal thymus tissue from diabetes resistant rats leads to an improvement in the T cell proliferative response, but only if the thymus contains bone marrow-derived, radiation-resistant thymic antigen presenting cells of the diabetes-resistant phenotype. The current study provides evidence that thymus transplantation leading to the restoration of Bio-Breeding T cell proliferative function can also significantly reduce the incidence of insulitis and prevent the development of diabetes. It appears that a defect in the bone marrow-derived thymic APC population contributes to an abnormal maturation of Bio-Breeding T lymphocytes which in turn predisposes animals to insulitis and diabetic disease

  11. 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

    study. EXPERIMENTAL DESIGN: Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental......-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...

  12. Human fetal antehypophysis in vitro. Immunocytological study and radioimmunoassay of LH and FSH

    International Nuclear Information System (INIS)

    Li, J.Y.; Begeot, M.; Dubois, P.M.; Claustrat, B.

    1977-01-01

    Human fetal antehypophysis (16 males, 16 females and 4 unknown sex) were cultivated during several weeks. By immunocytochemistry LH gonadotroph cells were determined with anti-hTSH and anti-pLH serum. The release in vitro of LH and FSH was studied by radioimmunoassay. At the first medium change, the quantity of LH and FSH release was related to the gestational age and sex. A rapid decline of both LH and FSH occured over the 10 first days. There after, a basal release of LH was maintained during several months; the release of FSH was generally maintained at the lower limit of the assay. After 1 month in vitro, the level of LH could not be related to the sex. Release of LH was stimulated by synthetic LRF. A significant increase was observed independently of the sex and age of the fetuses studied [fr

  13. Regenerating computer model of the thymus

    International Nuclear Information System (INIS)

    Lumb, J.R.

    1975-01-01

    This computer model simulates the cell population kinetics of the development and later degeneration of the thymus. Nutritional factors are taken into account by the growth of blood vessels in the simulated thymus. The stem cell population is kept at its maximum by allowing some stem cells to divide into two stem cells until the population reaches its maximum, thus regenerating the thymus after an insult such as irradiation. After a given number of population doublings the maximum allowed stem cell population is gradually decreased in order to simulate the degeneration of the thymus. Results show that the simulated thymus develops and degenerates in a pattern similar to that of the natural thymus. This simulation is used to evaluate cellular kinetic data for the the thymus. The results from testing the internal consistency of available data are reported. The number of generations which most represents the natural thymus includes seven dividing generations of lymphocytes and one mature, nondividing generation of small lymphocytes. The size of the resulting developed thymus can be controlled without affecting other variables by changing the maximum stem cell population allowed. In addition, recovery from irradiation is simulated

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

    NARCIS (Netherlands)

    Favorito, LA; Sampaio, FJB

    1998-01-01

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

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

    Science.gov (United States)

    Li, Jingting; He, Fan; Pei, Ming

    2011-09-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Irmgard Tegeder

    2016-12-01

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

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

    Science.gov (United States)

    Tegeder, Irmgard

    2016-12-01

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

  19. CT findings of the thymus

    International Nuclear Information System (INIS)

    Kang, Eun Young; Kim, Yun Hwan; Seol, Hae Young; Chung, Woun Kyun; Suh, Won Hyuck

    1987-01-01

    In 14 cases of normal and abnormal thymus proved surgically and histopathologically in korea University Hae Wha Hospital during recent 6 years, the clinical and CT findings were analyzed. 1. Of 14 cases, 2 cases were normal thymus, 5 cases were thymic hyperplasia, 4 cases were benign thymoma, 2 case were malignant thymoma and 1 case was thymic cyst. 2. Of 14 cases, 10 cases were associated with myasthenia gravis, and 7 of these 10 cases were 3rd to 5th decades females. Among 10 cases with myasthenia gravis. 5 cases were thymic hyperplasia, 1 case was benign thymoma, 2 cases were malignant thymoma, and 2 cases were normal thymus. 3. All 5 thymic hyperplasia were associated with myasthenia gravis. CT findings of thymic hyperplasia were normal in 4 cases and increased lobe thickness in 1 case. 4. Of 4 cases of benign thymoma, only 1 case was associated with myasthenia gravis, and all 4 cases were positive findings in CT scan. CT findings of benign thymoma were round or oval soft tissue mass in anterior mediastinum, and 1 case had punctuate calcifications. 5. Of 2 cases of malignant thymoma, all 2 cases were associated with myasthenia gravis and positive findings in CT scan. CT findings of malignant thymoma were anterior mediastinal soft tissue mass with obliteration of the normal fat planes surrounding great vessels. SVC compression, and pleural tumor implants. 6. CT yielded significant diagnostic information of differential diagnosis between thymoma and thymoma hyperplasia in myasthenia gravis patients. Also CT was highly sensitive test in detection of thymoma and determined the extent and invasiveness of thymoma.

  20. CT findings of the thymus

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Young; Kim, Yun Hwan; Seol, Hae Young; Chung, Woun Kyun; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of)

    1987-02-15

    In 14 cases of normal and abnormal thymus proved surgically and histopathologically in korea University Hae Wha Hospital during recent 6 years, the clinical and CT findings were analyzed. 1. Of 14 cases, 2 cases were normal thymus, 5 cases were thymic hyperplasia, 4 cases were benign thymoma, 2 case were malignant thymoma and 1 case was thymic cyst. 2. Of 14 cases, 10 cases were associated with myasthenia gravis, and 7 of these 10 cases were 3rd to 5th decades females. Among 10 cases with myasthenia gravis. 5 cases were thymic hyperplasia, 1 case was benign thymoma, 2 cases were malignant thymoma, and 2 cases were normal thymus. 3. All 5 thymic hyperplasia were associated with myasthenia gravis. CT findings of thymic hyperplasia were normal in 4 cases and increased lobe thickness in 1 case. 4. Of 4 cases of benign thymoma, only 1 case was associated with myasthenia gravis, and all 4 cases were positive findings in CT scan. CT findings of benign thymoma were round or oval soft tissue mass in anterior mediastinum, and 1 case had punctuate calcifications. 5. Of 2 cases of malignant thymoma, all 2 cases were associated with myasthenia gravis and positive findings in CT scan. CT findings of malignant thymoma were anterior mediastinal soft tissue mass with obliteration of the normal fat planes surrounding great vessels. SVC compression, and pleural tumor implants. 6. CT yielded significant diagnostic information of differential diagnosis between thymoma and thymoma hyperplasia in myasthenia gravis patients. Also CT was highly sensitive test in detection of thymoma and determined the extent and invasiveness of thymoma.

  1. 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.

  2. /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.

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

    Science.gov (United States)

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

    1999-11-25

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

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

    Directory of Open Access Journals (Sweden)

    Gu Bin

    2011-12-01

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

  5. 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.

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

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    Andras eJakab

    2014-10-01

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

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

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

    2014-01-01

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

  8. 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.

  9. 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.

  10. 125I-human epidermal growth factor specific binding to placentas and fetal membranes from varoius pregnancy states

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

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

    2010-06-01

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

  12. 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.

  13. Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney.

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    Minuth, Will W

    2018-01-01

    While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies. Although they are born in a phase of active nephrogenesis, pathological findings illustrate that they evolve to a high incidence oligonephropathy and prematurity of renal parenchyma. Different extra- and intrauterine influences seem to be responsible, but independent from chemical nature, all of them culminate in the nephrogenic zone. One assumes that the marred development is caused either by an overshoot of metabolites, misleading signaling of morphogens, unbalanced synthesis of extracellular matrix or restricted contact between mesenchymal and epithelial stem cells. Even more surprising is that there is only a few vague morphological information of the nephrogenic zone in the human fetal kidney available and ultrastructural data is severely lacking. On this account, the first coordinates were determined by optical microscopy and morphometry. Without claiming to be complete, generated results made it possible to create schematic illustrations true to scale for orientation. It will help graduating students, young pediatricians, pathologists, and scientists working in the field of biomedicine to interpret professionally the nephrogenic zone and contained niches. © 2017 S. Karger AG, Basel.

  14. 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.

  15. 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

    2018-04-01

    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 three-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 eight 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 article thus demonstrated that formation of the membranous labyrinth, periotic space (labyrinth), and ossification of the OC occurs successively, according to an intricate timetable. Anat Rec, 301:563-570, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  16. Generation of human cortical neurons from a new immortal fetal neural stem cell line

    International Nuclear Information System (INIS)

    Cacci, E.; Villa, A.; Parmar, M.; Cavallaro, M.; Mandahl, N.; Lindvall, O.; Martinez-Serrano, A.; Kokaia, Z.

    2007-01-01

    Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology

  17. 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

  18. Effects of Thyme Extract Oils (from Thymus vulgaris, Thymus zygis, and Thymus hyemalis on Cytokine Production and Gene Expression of oxLDL-Stimulated THP-1-Macrophages

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    A. Ocaña

    2012-01-01

    Full Text Available Properties of thyme extracts from three different species (Thymus vulgaris, Thymus zygis, and Thymus hyemalis were examined. Two oil fractions from each species were obtained by CO2 supercritical fluid extraction. Main compounds presented in the supercritical extracts of the three thyme varieties were 1,8 cineole, thymol, camphor, borneol, and carvacrol. As a cellular model of inflammation/atherogenesis, we use human macrophages derived from THP-1 monocytes and activated by oxidized LDLs. These cells were incubated with the thyme fraction oils, and the productions and gene expressions of the inflammatory mediators TNF-α, IL-1B, IL-6, and IL-10 were determined. Thyme extracts significantly reduced production and gene expression of the proinflammatory mediators TNF-α, IL-1B, and IL-6 and highly increased these parameters on the anti-inflammatory IL-10 cytokine. Changes on production and gene expressions were dose dependent and according to the thyme content of each species. Taken together, these results may suggest that thyme extracts could have anti-inflammatory effects.

  19. 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.

  20. Fetal calf serum heat inactivation and lipopolysaccharide contamination influence the human T lymphoblast proteome and phosphoproteome

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    Rahman Hazir

    2011-11-01

    Full Text Available Abstract Background The effects of fetal calf serum (FCS heat inactivation and bacterial lipopolysaccharide (LPS contamination on cell physiology have been studied, but their effect on the proteome of cultured cells has yet to be described. This study was undertaken to investigate the effects of heat inactivation of FCS and LPS contamination on the human T lymphoblast proteome. Human T lymphoblastic leukaemia (CCRF-CEM cells were grown in FCS, either non-heated, or heat inactivated, having low ( Results A total of four proteins (EIF3M, PRS7, PSB4, and SNAPA were up-regulated when CCRF-CEM cells were grown in media supplemented with heat inactivated FCS (HE as compared to cells grown in media with non-heated FCS (NHE. Six proteins (TCPD, ACTA, NACA, TCTP, ACTB, and ICLN displayed a differential phosphorylation pattern between the NHE and HE groups. Compared to the low concentration LPS group, regular levels of LPS resulted in the up-regulation of three proteins (SYBF, QCR1, and SUCB1. Conclusion The present study provides new information regarding the effect of FCS heat inactivation and change in FCS-LPS concentration on cellular protein expression, and post-translational modification in human T lymphoblasts. Both heat inactivation and LPS contamination of FCS were shown to modulate the expression and phosphorylation of proteins involved in basic cellular functions, such as protein synthesis, cytoskeleton stability, oxidative stress regulation and apoptosis. Hence, the study emphasizes the need to consider both heat inactivation and LPS contamination of FCS as factors that can influence the T lymphoblast proteome.

  1. 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.

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

  4. Psidium guajava extract inhibits thymus and activation-regulated chemokine (TARC/CCL17) production in human keratinocytes by inducing heme oxygenase-1 and blocking NF-κB and STAT1 activation.

    Science.gov (United States)

    Han, Eun Hee; Hwang, Yong Pil; Choi, Jae Ho; Yang, Ji Hye; Seo, Jong Kwon; Chung, Young Chul; Jeong, Hye Gwang

    2011-09-01

    Psidium guajava (P. guajava) is a food and medicinal plant with antioxidant, anti-inflammatory, and anti-allergic activities that support its traditional uses. The aim of this study was to determine the effects of P. guajava ethyl acetate extract (PGEA) on atopic dermatitis and to investigate the possible mechanisms by which PGEA inhibits cytokine-induced Th2 chemokine expression in HaCaT human keratinocyte cells. We found that PGEA suppressed the IFN-γ/TNF-α-co-induced production of thymus and activation-regulated chemokine (TARC) protein and mRNA in HaCaT cells. Additionally, PGEA inhibited the TNF-α/IFN-γ-co-induced activation of NF-κB and STAT1 and increased the expression of heme oxygenase-1 (HO-1) protein and mRNA. HO-1 inhibitor enhanced the suppressive effects of PGEA on TNF-α/IFN-γ-co-induced TARC production and gene expression. Collectively, these data demonstrate that PGEA inhibits chemokine expression in keratinocytes by inducing HO-1 expression and it suggests a possible therapeutic application in atopic dermatitis and other inflammatory skin diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. KCC2a expression in a human fetal lens epithelial cell line.

    Science.gov (United States)

    Lauf, Peter K; Di Fulvio, Mauricio; Srivastava, Vinita; Sharma, Neelima; Adragna, Norma C

    2012-01-01

    The fetal human lens epithelial cell (LEC) line (FHL124) possesses all four K(+)Cl(-) (KCC) cotransporter isoforms, KCC1-4, despite KCC2 being typically considered a neuronal isoform. Since at least two spliced variants, KCC2a and KCC2b, are co-expressed in cells of the central nervous system, this study sought to define the KCC2 expression profile in FHL124 cells. KCC2a, but not KCC2b transcripts were detected by reverse transcriptase polymerase chain reaction (RT-PCR). Proteins of molecular weights ranging from 95 to 135 kDa were found by Western blotting using non-variant specific anti-KCC2 antibodies directed against two different regions of the KCC2 proteins, and by biotinylation suggesting membrane expression. Immunofluorescence revealed membrane and punctate cytoplasmic staining for KCC2. Low levels of cytosolic αA and αB crystallines, and neuron-specific enolase were also detected contrasting with the strong membrane immunofluorescence staining for the Na/K ATPase α1 subunit. Since the lack of neuron-specific expression of the KCC2b variant in non-neuronal tissues has been proposed under control of a neuron-restrictive silencing element in the KCC2 gene, we hypothesize that this control may be lifted for the KCC2a variant in the FHL124 epithelial cell culture, a non-neuronal tissue of ectodermal origin. Copyright © 2012 S. Karger AG, Basel.

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

    International Nuclear Information System (INIS)

    Saito, Chikara; Nakano, Yoko; Shigematsu, Shiro

    1999-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-06-01

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    DEFF Research Database (Denmark)

    Hod, Moshe; Damm, Peter; Kaaja, Risto

    2008-01-01

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

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

    Science.gov (United States)

    Raeside, James I

    2017-09-01

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

  14. Asymmetry of radial and symmetry of tangential neuronal migration pathways in developing human fetal brains

    Directory of Open Access Journals (Sweden)

    Yuta eMiyazaki

    2016-01-01

    Full Text Available AbstractThe 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. Thus, little evidence is available about their three-dimensional 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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Keith M Godfrey

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  18. Hedgehog Signalling in the Embryonic Mouse Thymus

    Directory of Open Access Journals (Sweden)

    Alessandro Barbarulo

    2016-07-01

    Full Text Available T cells develop in the thymus, which provides an essential environment for T cell fate specification, and for the differentiation of multipotent progenitor cells into major histocompatibility complex (MHC-restricted, non-autoreactive T cells. Here we review the role of the Hedgehog signalling pathway in T cell development, thymic epithelial cell (TEC development, and thymocyte–TEC cross-talk in the embryonic mouse thymus during the last week of gestation.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  1. CT evaluation of thymus in myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Guk Hee [Insung Hospital, Chuncheon (Korea, Republic of); Kang, Eun Young; Lee, Nam Joon; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    The relationship between myasthenia gravis and the thymus was well establish and myasthenia gravis occurs in the presence of thymic hyperplasia or thymoma or occasionally in histologically normal thymus. Since not every patients with myasthenia gravis is a candidate for thymectomy, unless a thymoma is present, the differentiation of normal and hyperplastic thymus from thymoma becomes important. Authors reviewed retrospectively clinical records and chest CT scans of 18 patients with myasthenia gravis who underwent thymectomy during recent 5 years, to evaluate the role of CT scan. The results were as follows. 1 Of total 18 cases, 5 cases had normal thymus, 6 cases had thymic hyperplasia, 4 cases had benign thymoma and 3 cases had malignant thymoma. 2. Of 5 cases of normal thymus, no false positive cases were noted in CT scan. 3. Of 6 cases of thymic hyperplasia, CT findings were normal except 1 cases of thickened left thymic lobe. 4. Of 7 cases of thymoma, no false negative cases were noted in CT scan. 5. CT findings of benign thymoma were round or oval shaped, discrete, slightly enhancing soft tissue mass in anterior mediastinum. 6. CT findings of malignant thymoma were lobulated contoured, infiltrative, soft tissue mass lesion in anterior mediastinum with calcifications, pleural tumor implants, and SVC compression. CT yielded valuable information on differential diagnosis of thymoma, thymic hyperplasia and normal thymus. Also CT was a highly sensitive method in the detection of thymoma and determining the extent and invasiveness.

  2. CT evaluation of thymus in myasthenia gravis

    International Nuclear Information System (INIS)

    Kim, Guk Hee; Kang, Eun Young; Lee, Nam Joon; Suh, Won Hyuck

    1989-01-01

    The relationship between myasthenia gravis and the thymus was well establish and myasthenia gravis occurs in the presence of thymic hyperplasia or thymoma or occasionally in histologically normal thymus. Since not every patients with myasthenia gravis is a candidate for thymectomy, unless a thymoma is present, the differentiation of normal and hyperplastic thymus from thymoma becomes important. Authors reviewed retrospectively clinical records and chest CT scans of 18 patients with myasthenia gravis who underwent thymectomy during recent 5 years, to evaluate the role of CT scan. The results were as follows. 1 Of total 18 cases, 5 cases had normal thymus, 6 cases had thymic hyperplasia, 4 cases had benign thymoma and 3 cases had malignant thymoma. 2. Of 5 cases of normal thymus, no false positive cases were noted in CT scan. 3. Of 6 cases of thymic hyperplasia, CT findings were normal except 1 cases of thickened left thymic lobe. 4. Of 7 cases of thymoma, no false negative cases were noted in CT scan. 5. CT findings of benign thymoma were round or oval shaped, discrete, slightly enhancing soft tissue mass in anterior mediastinum. 6. CT findings of malignant thymoma were lobulated contoured, infiltrative, soft tissue mass lesion in anterior mediastinum with calcifications, pleural tumor implants, and SVC compression. CT yielded valuable information on differential diagnosis of thymoma, thymic hyperplasia and normal thymus. Also CT was a highly sensitive method in the detection of thymoma and determining the extent and invasiveness

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

    Science.gov (United States)

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

    1989-08-01

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

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  5. Fetal abdominal magnetic resonance imaging

    International Nuclear Information System (INIS)

    Brugger, Peter C.; Prayer, Daniela

    2006-01-01

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

  6. Fetal abdominal magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-02-15

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

  7. ROLE OF STEM CELL FACTOR IN THE REACTIVATION OF HUMAN FETAL HEMOGLOBIN

    Directory of Open Access Journals (Sweden)

    Ugo Testa

    2009-06-01

    Full Text Available

    In humans the switch from fetal to adult  hemoglobin (HbF→ HbA takes place in the perinatal and postnatal period, determining the progressive replacement of HbF with HbA synthesis ( i.e., the relative HbF content in red blood cells decreases from 80-90% to <1%. In spite of more than twenty years of intensive investigations on this classic model, the molecular mechanisms regulating the Hb switching, as well as HbF synthesis in adults, has been only in part elucidated. In adult life, the residual HbF, restricted to F cell compartment, may be reactivated up to 10-20% of total Hb synthesis in various conditions associated with “stress erythropoiesis”: this reactivation represented until now an interesting model of partial Hb switch reverse with important therapeutic implications in patients with hemoglobinopathies, and particularly in -thalassemia.
    In vitro and in vivo models have led to the identification of several chemical compounds able to reactivate HbF synthesis in adult erythroid cells. Although the impact of these HbF inducers, including hypomethylating agents, histone deacetylase inhibitors and hydroxyurea, was clear on the natural history of sickle cell anemia, the benefit on the clinical course of -thalassemia was only limited: particularly, the toxicity and the modest increase in γ-globin reactivation indicated the need for improved agents able to induce higher levels of HbF.
    In the present review we describe the biologic properties of Stem Cell Factor (SCF, a cytokine sustaining the survival and proliferation of erythroid cells, that at pharmacological doses acts as a potent stimulator of HbF synthesis in adult erythroid cells.

  8. Transient HEXA expression in a transformed human fetal Tay-Sachs disease neuroglial cell line

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, M.J.; Hechtman, P.; Kaplan, F. [McGill Univ., Quebec (Canada)] [and others

    1994-09-01

    Tay-Sachs disease (TSD) is a severe neurodegenerative disorder characterized by the accumulation of GM{sub 2} ganglioside in the neurons of the central cortex. The recessively inherited disorder results from deficiency of hexosaminidase A (Hex A), a heterodimer of an {alpha} and {beta} subunit encoded by the HEXA and HEXB genes. Expression of HEXA mutations in COS cells has several disadvantages including high endogenous hexosaminidase activity. We report a new transient expression system with very low endogenous Hex A activity. An SV40-transformed fetal TSD neuroglial cell line was assessed for transient expression of the HEXA gene. pCMV{alpha}, a vector incorporating the cytomegalovirus promoter with the human {alpha}-subunit cDNA insert, proved to be the most efficient expression vector. Transfection of 4x10{sup 6} cells with 5-20 {mu}g of plasmid resulted in 100 to 500-fold Hex A activity (4MUGS hydrolysis) relative to mock-transfected cells. Use of pCMV{beta}-Gal as a control for transfection efficiency indicated that 10-20% of cells were transfected. Hex A specific activity increased for at least 72 h post-transfection. This new transient expression system should greatly improve the characterization of mutations in which low levels of HEXA expression result in milder clinical phenotypes and permit studies on enzymatic properties of mutant forms of Hex A. Since the cells used are of CNS origin and synthesize gangliosides, it should also be possible to study, in culture, the metabolic phenotype associated with TSD.

  9. Chondrocyte heterogeneity: immunohistologically defined variation of integrin expression at different sites in human fetal knees.

    Science.gov (United States)

    Salter, D M; Godolphin, J L; Gourlay, M S

    1995-04-01

    During development and at maturity different forms of cartilage vary in morphology and macromolecular content. This reflects heterogeneity of chondrocyte activity, in part involving differential interactions with the adjacent extracellular matrix via specialized cell surface receptors such as integrins. We undertook an immunohistological study on a series of human fetal knee joints to assess variation in the expression of integrins by chondrocytes and potential matrix ligands in articular, epiphyseal, growth plate, and meniscal cartilage. The results show that articular chondrocytes (beta 1+, beta 5 alpha V+, alpha 1+, alpha 2+/-, alpha 5+, weakly alpha 6+, alpha V+) differed from epiphyseal (beta 1+, beta 5 alpha V+, alpha 1+/-, alpha 2+/-, alpha 5+, alpha 6+, alpha V+) growth plate (beta 1+, beta 5 alpha V+, alpha 1-, alpha 2-, alpha 5+, alpha 6+, alpha V+), and meniscal cells (beta 1+, beta 5 alpha V+, alpha 1+, strongly alpha 2+, alpha 5+, alpha 6+, alpha V+ in expression of integrin subunits. There was no expression of beta 3, beta 4, beta 6, or alpha 3 by chondrocytes. These results differ from previous reports on the expression of integrins by adult articular cartilage, where alpha 2 and alpha 6 are not seen. Variation in distribution of matrix ligands was also seen. Fibronectin, laminin and Type VI collagen were expressed in all cartilages but there was restricted expression of tenascin, ED-A and ED-B fibronectin isoforms (articular cartilage and meniscus), and vitronectin (absent from growth plate cartilage). Regulated expression of integrins by chondrocytes, associated with changes in the pericellular matrix composition, is of potential importance in control of cartilage differentiation and function in health and disease.

  10. Clonally Expanding Thymocytes Having Lineage Capability in Gamma-Ray-Induced Mouse Atrophic Thymus

    International Nuclear Information System (INIS)

    Yamamoto, Takashi; Morita, Shin-ichi; Go, Rieka; Obata, Miki; Katsuragi, Yoshinori; Fujita, Yukari; Maeda, Yoshitaka; Yokoyama, Minesuke; Aoyagi, Yutaka; Ichikawa, Hitoshi; Mishima, Yukio; Kominami, Ryo

    2010-01-01

    Purpose: To characterize, in the setting of γ-ray-induced atrophic thymus, probable prelymphoma cells showing clonal growth and changes in signaling, including DNA damage checkpoint. Methods and Materials: A total of 111 and 45 mouse atrophic thymuses at 40 and 80 days, respectively, after γ-irradiation were analyzed with polymerase chain reaction for D-J rearrangements at the TCRβ locus, flow cytometry for cell cycle, and Western blotting for the activation of DNA damage checkpoints. Results: Limited D-J rearrangement patterns distinct from normal thymus were detected at high frequencies (43 of 111 for 40-day thymus and 21 of 45 for 80-day thymus). Those clonally expanded thymocytes mostly consisted of CD4 + CD8 + double-positive cells, indicating the retention of lineage capability. They exhibited pausing at a late G1 phase of cell cycle progression but did not show the activation of DNA damage checkpoints such as γH2AX, Chk1/2, or p53. Of interest is that 17 of the 52 thymuses showing normal D-J rearrangement patterns at 40 days after irradiation showed allelic loss at the Bcl11b tumor suppressor locus, also indicating clonal expansion. Conclusion: The thymocytes of clonal growth detected resemble human chronic myeloid leukemia in possessing self-renewal and lineage capability, and therefore they can be a candidate of the lymphoma-initiating cells.

  11. Expression of preprotachykinin-A and neuropeptide-Y messenger RNA in the thymus.

    Science.gov (United States)

    Ericsson, A; Geenen, V; Robert, F; Legros, J J; Vrindts-Gevaert, Y; Franchimont, P; Brene, S; Persson, H

    1990-08-01

    The preprotachykinin-A gene, the common gene of mRNAs encoding both substance-P (SP) and neurokinin-A (NKA), was shown to be expressed in Sprague-Dawley rat thymus by detection of specific mRNA in gel-blot analyses. In situ hybridization revealed dispersed PPT-A-labeled cells in sections from rat thymus, with a concentration of grains over a subpopulation of cells in the thymic medulla. Also, neuropeptide-Y mRNA-expressing cells were found in the rat thymus, primarily in the thymic medulla. Rat thymic extracts contained SP-like immunoreactivity (SP-LI), and the major part of the immunoreactivity coeluted with authentic SP and SP sulfoxide standards. SP-LI was also detected in human thymus, which contained between 0.09-0.88 ng SP-LI/g wet wt. Evidence for translation of preprotachykinin-A mRNA in the rat thymus was obtained from the demonstration of NKA-LI in thymic cells with an epithelial-like cell morphology. Combined with previous observations on the immunoregulatory roles of tachykinin peptides and the existence of specific receptors on immunocompetent cells, the demonstration of intrathymic synthesis of NKA suggests a role for NKA-LI peptides in T-cell differentiation in the thymus.

  12. Fetal MRI; Fetales MRT

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-02-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Fetal echocardiography

    International Nuclear Information System (INIS)

    Chaubal, Nitin G.; Chaubal, Jyoti

    2009-01-01

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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Soria Eladak

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

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

    Science.gov (United States)

    Giri, Shibashish; Bader, Augustinus

    2014-09-01

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

  18. Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

    International Nuclear Information System (INIS)

    Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

    2012-01-01

    Highlights: ► Estradiol induced stiffness changes of osteoblasts were quantified using AFM. ► Estradiol causes significant decrease in the stiffness of osteoblasts. ► Decreased stiffness was caused by decreased density of f-actin network. ► Stiffness changes were not associated with mineralized matrix of osteoblasts. ► Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E ∗ ) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with β-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E ∗ . The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E ∗ of osteoblasts significantly decreased by 43–46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness changes of osteoblasts were not associated with changes in the synthesized mineralized matrix of the cells. Thus, a decrease in osteoblast stiffness with estrogen treatment was

  19. Changes of the glomerular size during the human fetal kidney development

    Directory of Open Access Journals (Sweden)

    Daković-Bjelaković Marija

    2006-01-01

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

  20. Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

    Energy Technology Data Exchange (ETDEWEB)

    Muthukumaran, Padmalosini [Department of Bioengineering, National University of Singapore (Singapore); Lim, Chwee Teck [Department of Bioengineering, National University of Singapore (Singapore); Department of Mechanical Engineering, National University of Singapore (Singapore); Mechanobiology Institute, National University of Singapore (Singapore); Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore (Singapore); Lee, Taeyong, E-mail: bielt@nus.edu.sg [Department of Bioengineering, National University of Singapore (Singapore)

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

  1. Fetal echocardiography

    Science.gov (United States)

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

  2. Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques

    Directory of Open Access Journals (Sweden)

    Zhongjie Xu

    2016-06-01

    Full Text Available Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT exhibits significant antitumor activity. However, the mechanism of its pharmacological interaction with human serum albumin (HSA and DNA remains poorly understood. Here, we aimed to elucidate the interactions of Dp44mT with HSA and DNA using MTT assays, spectroscopic methods, and molecular docking analysis. Our results indicated that addition of HSA at a ratio of 1:1 did not alter the cytotoxicity of Dp44mT, but did affect the cytotoxicity of the Dp44mT-Cu complex. Data from fluorescence quenching and UV-VIS absorbance measurements demonstrated that Dp44mT could bind to HSA with a moderate affinity (Ka = approximately 104 M−1. CD spectra revealed that Dp44mT could slightly disrupt the secondary structure of HSA. Dp44mT could also interact with Ct-DNA, but had a moderate binding constant (KEB = approximately 104 M−1. Docking studies indicated that the IB site of HSA, but not the IIA and IIIA sites, could be favorable for Dp44mT and that binding of Dp44mT to HSA involved hydrogen bonds and hydrophobic force, consistent with thermodynamic results from spectral investigations. Thus, the moderate binding affinity of Dp44mT with HSA and DNA partially contributed to its antitumor activity and may be preferable in drug design approaches.

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

    Science.gov (United States)

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

    2015-06-16

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

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

    Science.gov (United States)

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

    1997-10-01

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

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

    Science.gov (United States)

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

    2010-06-01

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

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

    OpenAIRE

    Guillot, P. V.

    2016-01-01

    Pluripotency defines the ability of stem cells to differentiate into all the lineages of the three germ layers and self-renew indefinitely. Somatic cells can regain the developmental potential of embryonic stem cells following ectopic expression of a set of transcription factors or, in certain circumstances, via modulation of culture conditions and supplementation with small molecule, that is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal tissues for reprogramming, f...

  7. Inter-specific relationships among two Tunisian Thymus taxa ...

    African Journals Online (AJOL)

    Genetic relationships between two sympatric species Thymus capitatus Hoffm. et Link. and Thymus algeriensis Boiss. et Reut. (Thymus hirtus Willd. subsp. algeriensis Boiss. et Reut.) were assessed using random amplified polymorphic DNA (RAPD) markers. Eighteen natural populations from different geographical and ...

  8. Visualization of the thymus in myasthenia gravis

    International Nuclear Information System (INIS)

    Komatsu, Midori; Tanaka, Makoto; Morimatsu, Mitsunori; Hirai, Shunsaku; Heshiki, Atsuko

    1982-01-01

    We investigated whether CT had any advantage over pneumomediastinography (PMG) for the visualization of thymus in twenty-one patients with myasthenia gravis (MG). In two cases of thymoma which had been suspected with chest radiography, CT demonstrated an anterior mediastinal tumor distinguishable from other mediastinal organs, and for these cases PMG was not performed. Excluding three patients who were submitted to PMG only, CT of the anterior mediastinum was carried out in sixteen patients of MG, revealing thymic shadows in seven (44%). PMG followed by conventional tomography was done subsequently in three of these seven cases, for whom thymectomy was indicated because of uncontrollable myasthenic symptoms, and in all patients finger-like thymic shadows were disclosed. The vertical extension of thymus was more easily demonstrable by PMG than CT. PMG was carried out in six of nine patients in whom CT was negative, and in all cases thymic shadows were obvious with subsequent conventional tomography. Consequently, false negative rate of CT was at least 38% (6/16) with regard to the visualization of the nontumorous thymus. Although CT of the anterior mediastinum is useful as a screening method because of its non-invasiveness, its negative result does not rule out an absence of the pathologic thymus in view of its high false negative rate. In this regard, PMG is still necessary for the final determination of the thymic configuration in the MG patients. (J.P.N.)

  9. Gigantic enlargement of the thymus gland

    International Nuclear Information System (INIS)

    Regal, Mohamed A.

    2007-01-01

    True massive thymic hyperplasia is a very rare entity, characterized by an increase in the size and weight of the thymus gland without an apparent cause. Surgery has been required in patients with severe respiratory distress. We present an idiopathic true massive thymic hyperplasia in a 5-month-old boy. (author)

  10. Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select for Different Mesenchymal Stromal Cells.

    Science.gov (United States)

    Fernandez-Rebollo, Eduardo; Mentrup, Birgit; Ebert, Regina; Franzen, Julia; Abagnale, Giulio; Sieben, Torsten; Ostrowska, Alina; Hoffmann, Per; Roux, Pierre-François; Rath, Björn; Goodhardt, Michele; Lemaitre, Jean-Marc; Bischof, Oliver; Jakob, Franz; Wagner, Wolfgang

    2017-07-11

    Culture medium of mesenchymal stromal cells (MSCs) is usually supplemented with either human platelet lysate (HPL) or fetal calf serum (FCS). Many studies have demonstrated that proliferation and cellular morphology are affected by these supplements - it is therefore important to determine if they favor outgrowth of different subpopulations and thereby impact on the heterogeneous composition of MSCs. We have isolated and expanded human bone marrow-derived MSCs in parallel with HPL or FCS and demonstrated that HPL significantly increases proliferation and leads to dramatic differences in cellular morphology. Remarkably, global DNA-methylation profiles did not reveal any significant differences. Even at the transcriptomic level, there were only moderate changes in pairwise comparison. Furthermore, the effects on proliferation, cytoskeletal organization, and focal adhesions were reversible by interchanging to opposite culture conditions. These results indicate that cultivation of MSCs with HPL or FCS has no systematic bias for specific cell types.

  11. Characterization of death of human fetal bone marrow CD34+ cells after different dose of γ-irradiation

    International Nuclear Information System (INIS)

    Xiang Yingsong; Yang Rujun; Tang Gusheng

    2001-01-01

    Objective: To investigate the characterization of death of the human hematopoietic stem cells after irradiation. Methods: Human fetal bone marrow mononuclear cells were irradiated with different doses of 60 Co γ-rays at different high dose rates. Apoptosis and necrosis of CD34 + cells were analyzed by flow cytometry, following three-color labelling with PE-CD34/FITC-Annexin V/7AAD at different times after irradiation. Results: The death of CD34 + cells after 5 Gy and 8 Gy irradiation showed a continuous process of reproductive death during the first week,and the main death type was apoptosis. A majority of CD34 + cells died of necrosis during the first day after 10 Gy and 12 Gy irradiation, and all of them died within a week. Conclusion: Niches are continuously vacated every day within a week following irradiation and reproductive death of hematopoietic stem cells occurred

  12. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  14. Mutator/hypermutable fetal/juvenile metakaryotic stem cells and human colorectal carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Lohith G. Kini

    2013-10-01

    Full Text Available Adult age-specific colorectal cancer incidence rates increase exponentially from maturity, reach a maximum, then decline in extreme old age. Armitage and Doll (1957 postulated that the exponential increase resulted from n mutations occurring throughout adult life in normal cells at risk that initiated the growth of a preneoplastic colony in which subsequent m mutations promoted one of the preneoplastic cells at risk to form a lethal neoplasia. We have reported cytologic evidence that these cells at risk are fetal/juvenile organogenic, then preneoplastic metakaryotic stem cells. Metakaryotic cells display stem-like behaviors of both symmetric and asymmetric nuclear divisions and peculiarities such as bell shaped nuclei and amitotic nuclear fission that distinguish them from embryonic, eukaryotic stem cells. Analyses of mutant colony sizes and numbers in adult lung epithelia supported the inferences that the metakaryotic organogenic stem cells are constitutively mutator/hypermutable and that their contributions to cancer initiation are limited to the fetal/juvenile period. We have amended the two-stage model of Armitage and Doll and incorporated these several inferences in a computer program CancerFit v.5.0. We compared the expectations of the amended model to adult (15-104 yr age-specific colon cancer rates for European American males born 1890-99 and observed remarkable concordance. When estimates of normal colonic fetal/juvenile APC and OAT gene mutation rates (~2-5 x 10-5 per stem cell doubling and preneoplastic colonic gene loss rates (~ 8 x 10-3 were applied, the model was in accordance only for the values of n = 2 and m = 4 or 5.

  15. 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.

  16. Development of the Human Placenta and Fetal Heart: Synergic or Independent?

    Directory of Open Access Journals (Sweden)

    Graham J. Burton

    2018-04-01

    Full Text Available The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c. give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12–14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 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,...

  20. 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)

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

    2014-10-01

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

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

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

    International Nuclear Information System (INIS)

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

    1980-01-01

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

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  5. 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

  6. Temporal and spatial performance of vector velocity imaging in the human fetal heart.

    Science.gov (United States)

    Matsui, H; Germanakis, I; Kulinskaya, E; Gardiner, H M

    2011-02-01

    To assess the spatial and temporal performance of fetal myocardial speckle tracking, using high-frame-rate (HFR) storing and Lagrangian strain analysis. Dummy electrocardiographic signaling permitted DICOM HFR in 124 normal fetuses and paired low-frame-rate (LFR) video storing at 25 Hz in 93 of them. Vector velocity imaging (VVI) tracking co-ordinates were used to compare time and spatial domain measures. We compared tracking success, Lagrangian strain, peak diastolic velocity and positive strain rate values in HFR vs. LFR video storing. Further comparisons within an HFR subset included Lagrangian vs. natural strain, VVI vs. M-mode annular displacement, and VVI vs. pulsed-wave tissue Doppler imaging (TDI) peak velocities. HFR (average 79.4 Hz) tracking was more successful than LFR (86 vs. 76%, P = 0.024). Lagrangian and natural HFR strain correlated highly (left ventricle (LV): r = 0.883, P < 0.001; right ventricle (RV): r = 0.792, P < 0.001) but natural strain gave 20% lower values, suggesting reduced reliability of measurement. Lagrangian HFR strain was similar in LV and RV and decreased with gestation (P = 0.015 and P < 0.001, respectively). LV Lagrangian LFR strain was significantly lower than the values for the RV (P < 0.001) and those using paired LV-HFR recordings (P = 0.007). Annular displacement methods correlated highly (LV = 1.046, r = 0.90, P < 0.001; RV = 1.170, r = 0.88, P < 0.001). Early diastolic waves were visible in 95% of TDI, but in only 26% of HFR and 0% of LFR recordings, and HFR-VVI velocities were significantly lower than those for TDI (P < 0.001). Doppler estimation of velocities remains superior to VVI but image gating and use of original co-ordinates should improve offline VVI assessment of fetal myocardial function. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  7. Fetal MSCs

    Indian Academy of Sciences (India)

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

  8. 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......) or adipocytic markers (PPAR-gamma2, lipoprotein lipase (LPL), aP2), respectively. In order to test for the functional capacity of hMSC-TERT that have been maintained in long-term cultures in the presence of HuS vs. FBS, the cells were mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) and implanted...... subcutaneously in immune deficient mice. hMSC maintained in HuS vs. FBS formed comparable heterotopic bone. DISCUSSION: Human serum can support proliferation and differentiation of hMSC in vitro and can maintain their bone forming capacity in vivo. The use of human serum in cell cultures of hMSC intended...

  9. 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.

  10. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy.

    Science.gov (United States)

    Heusschen, Roy; Freitag, Nancy; Tirado-González, Irene; Barrientos, Gabriela; Moschansky, Petra; Muñoz-Fernández, Raquel; Leno-Durán, Ester; Klapp, Burghard F; Thijssen, Victor L J L; Blois, Sandra M

    2013-01-01

    Disruption of fetal-maternal tolerance mechanisms can contribute to pregnancy complications, including spontaneous abortion. Galectin-9 (LGALS9), a tandem repeat lectin associated with immune modulation, is expressed in the endometrium during the mid and late secretory phases and in decidua during human early pregnancy. However, the role of LGALS9 during pregnancy remains poorly understood. We used real-time PCR and immunohistochemical staining to analyze the expression of Lgals9/LGALS9 during mouse gestation as well as in human tissues obtained from normal pregnancy and spontaneous abortions. In mice, three Lgals9 splice variants were detected, the expression of which was differentially regulated during gestation. Furthermore, decidual Lgals9 expression was deregulated in a mouse model of spontaneous abortion, whereas placental levels did not change. We further found that the LGALS9 D5 isoform suppresses interferon gamma production by decidual natural killer cells. In human patients, six Lgals9 splice variants were detected, and a decrease in Lgals9 D5/10 was associated with spontaneous abortion. Altogether, these results show a differential regulation of Lgals9 isoform expression during normal and pathological pregnancies and designate Lgals9 as a potential marker for adverse pregnancy outcomes.

  13. 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.

  14. Sequential appearance of thymocyte subpopulations and T cell antigen receptor gene messages in the mouse thymus after sublethal irradiation

    International Nuclear Information System (INIS)

    Tomooka, S.; Matsuzaki, G.; Kishihara, K.; Tanaka, K.; Yoshikai, Y.; Taniguchi, K.; Himeno, K.; Nomoto, K.

    1987-01-01

    The sequential differentiation patterns of thymocyte were observed with cell surface phenotypes and the expression of T cell antigen receptor in 800 rad irradiated adult mice. Thymus was severely reduced in size and cell number by day 5 after whole body irradiation and rapidly recovered from day 7 to day 14. Surface marker analysis on day 5 after irradiation showed thymocytes with Thy-1low L3T4+/Lyt-2- dominantly existed and suggested that these cells were radioresistant-survived cells. On the other hand, thymocytes on day 7 were composed of a large number of Thy-1high L3T4+/Lyt-2+ blast-like cells and a relatively high proportion of Thy-1high L3T4-/Lyt-2- cells which expressed a large amount of gamma-chain gene messages but scarcely any alpha- and beta-chain gene messages similar to the fetal thymocytes. On day 14, thymocytes were composed mostly of Thy-1high H-2low L3T4+/Lyt-2+ subpopulation which expressed a remarkably low level of gamma-chain gene messages, and high levels of alpha- and beta-chain transcripts analogous to those of normal adult thymus. Taken together, intrathymic radioresistent stem cells for T thymocytes seem to proliferate and differentiate after irradiation with the same pattern as was seen in a fetal thymus development

  15. Computed tomography of the thymus in myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Tanimura, Shigeo; Sakaguchi, Kozo; Tomoyasu, Hiroshi; Banba, Jiro; Masaki, Mikio; Kurosaki, Atsuko; Matsushita, Hisashi [Toranomon Hospital, Tokyo (Japan)

    1995-01-01

    Comparison of preoperative CT diagnosis and histopathological diagnosis for the thymus were studied in 39 patients with myasthenia gravis. The patients consisted of 10 patients with thymoma and 29 without thymoma confirmed at the operation. CT diagnosis was 11 thymomas, 18 thymic hyperplasias and 10 normal thymuses. Eleven thymomas revealed histopathologically 9 thymomas, one follicular lymphoid hyperplasia (FLH) and one involved thymus. Out of 18 thymic hyperplasias 15 cases were FLH and 3 involved thymus. There were 5 involved thymuses, 4 FLHs and one thymoma in the 10 normal thymuses on CT. The finding of `reticular pattern`, many small nodules scattered reticularly in the thymus, in computed tomography could be regarded as a sign suggesting FLH of the thymus. The accuracy of this finding of CT was 83% for FLH. The finding of thymoma on CT revealed 82% of the accuracy. Therefore, CT was very useful in the diagnosis of the localization of the thymoma but not for the diagnosis of FLH of the thymus. Nevertheless the finding of `reticular pattern` on CT was helpful in the diagnosis of FLH. (author).

  16. Computed tomography of the thymus in myasthenia gravis

    International Nuclear Information System (INIS)

    Tanimura, Shigeo; Sakaguchi, Kozo; Tomoyasu, Hiroshi; Banba, Jiro; Masaki, Mikio; Kurosaki, Atsuko; Matsushita, Hisashi

    1995-01-01

    Comparison of preoperative CT diagnosis and histopathological diagnosis for the thymus were studied in 39 patients with myasthenia gravis. The patients consisted of 10 patients with thymoma and 29 without thymoma confirmed at the operation. CT diagnosis was 11 thymomas, 18 thymic hyperplasias and 10 normal thymuses. Eleven thymomas revealed histopathologically 9 thymomas, one follicular lymphoid hyperplasia (FLH) and one involved thymus. Out of 18 thymic hyperplasias 15 cases were FLH and 3 involved thymus. There were 5 involved thymuses, 4 FLHs and one thymoma in the 10 normal thymuses on CT. The finding of 'reticular pattern', many small nodules scattered reticularly in the thymus, in computed tomography could be regarded as a sign suggesting FLH of the thymus. The accuracy of this finding of CT was 83% for FLH. The finding of thymoma on CT revealed 82% of the accuracy. Therefore, CT was very useful in the diagnosis of the localization of the thymoma but not for the diagnosis of FLH of the thymus. Nevertheless the finding of 'reticular pattern' on CT was helpful in the diagnosis of FLH. (author)

  17. Fetal Ultrasound

    Science.gov (United States)

    ... isn't recommended simply to determine a baby's sex. Similarly, fetal ultrasound isn't recommended solely for the purpose of producing keepsake videos or pictures. If your health care provider doesn' ...

  18. Fetal Macrosomia

    Science.gov (United States)

    ... re more likely to have a large baby. Maternal obesity. Fetal macrosomia is more likely if you're ... is more likely to be a result of maternal diabetes, obesity or weight gain during pregnancy than other causes. ...

  19. The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth

    NARCIS (Netherlands)

    Salavati, Nastaran; Sovio, U.; Mayo, R. Plitman; Charnock-Jones, D. S.; Smith, G. C. S.

    Introduction: Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and

  20. 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.

  1. Fatty acid oxidation in the human fetus: implications for fetal and adult disease

    NARCIS (Netherlands)

    Oey, Nadia A.; Ruiter, Jos P. N.; Attié-Bitach, Tania; Ijlst, Lodewijk; Wanders, Ronald J. A.; Wijburg, Frits A.

    2006-01-01

    Studies in the last few years have shown a remarkably high activity of fatty acid oxidation (FAO) enzymes in human placenta. We have recently shown mRNA expression as well as enzymatic activity of long-chain FAO enzymes in the human embryo and fetus. In this study we show activity of the FAO enzymes

  2. Development of interleukin-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymus

    DEFF Research Database (Denmark)

    Buus, Terkild Brink; Schmidt, Jonas Damgård; Bonefeld, Charlotte Menné

    2016-01-01

    . 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. We found that treatment with ICOS specific antibodies...... drastically reduces fetal development of IL-17-producing γδ T cells by agonistic actions, and that ICOS deficient mice have a significant increase in the population of IL-17-producing Vγ2+ γδ T cells in the thymus, spleen, lymph nodes and skin and exhibit exacerbated sensitization responses to 2......,4-dinitrofluorobenzene. In conclusion, this study demonstrates that development of IL-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymus....

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

    Directory of Open Access Journals (Sweden)

    Seed Mike

    2012-11-01

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

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

    Science.gov (United States)

    Lim, R; Barker, G; Lappas, M

    2015-04-01

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

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

    Science.gov (United States)

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

    2012-11-26

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

  6. 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.

  7. 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.

  8. 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.

  9. Thymus species in Ethiopia: Distribution, medicinal value, economic ...

    African Journals Online (AJOL)

    The plant specimens from these localities were authenticated by experts in the National Herbarium of Addis Ababa University as Thymus serrulatus and Thymus schimperi. The plants were rated by local informants as treatments for ailments like blood pressure (30.7%), general pain syndrome (10%), influenza (10%), ...

  10. Thymus transplantation for complete DiGeorge syndrome

    DEFF Research Database (Denmark)

    Davies, E Graham; Cheung, Melissa; Gilmour, Kimberly

    2017-01-01

    BACKGROUND: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). METHODS: Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus. OBJECTIVE: We sought to confirm and extend the results previously obtained in a ...

  11. Thymus: The site for Development of Cellular Immunity

    Indian Academy of Sciences (India)

    The immune system protects our bodies against infectionsand cancers. This review introduce readers to the thymus. – a primary lymphoid organ – which is the site of developmentand maturation of functional T lymphocytes. Progenitorstem cells arise from the bone marrow and undergo sequentialdevelopment in the thymus ...

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

    Science.gov (United States)

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

    2017-01-01

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

  13. High activity of fatty acid oxidation enzymes in human placenta: implications for fetal-maternal disease

    NARCIS (Netherlands)

    Oey, N. A.; den Boer, M. E. J.; Ruiter, J. P. N.; Wanders, R. J. A.; Duran, M.; Waterham, H. R.; Boer, K.; van der Post, J. A. M.; Wijburg, F. A.

    2003-01-01

    As the human fetus and placenta are considered to be primarily dependent on glucose oxidation for energy metabolism, the cause of the remarkable association between severe maternal pregnancy complications and the carriage of a fetus with an inborn error of mitochondrial long-chain fatty acid

  14. 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...... 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......PL MoM values was carried out for each pregnancy to find the slope of the line (hPL-slope); at least 3 serum hPL values were required. The estimated fetal weight and weight-for-age at birth was expressed in Z-scores. The individual intrauterine growth velocity was calculated by regression analysis...

  15. Chemical Composition of Essential Oilsof Thymus and Mentha Speciesand Their Antifungal Activities

    Directory of Open Access Journals (Sweden)

    Leo J. L. D. van Griensven

    2009-01-01

    Full Text Available The potential antifungal effects of Thymus vulgaris L., Thymus tosevii L., Mentha spicata L., and Mentha piperita L. (Labiatae essential oils and their components against 17 micromycetal food poisoning, plant, animal and human pathogens are presented. The essential oils were obtained by hydrodestillation of dried plant material. Their composition was determined by GC-MS. Identification of individual constituents was made by comparison with analytical standards, and by computer matching mass spectral data with those of the Wiley/NBS Library of Mass Spectra. MIC’s and MFC’s of the oils and their components were determined by dilution assays. Thymol (48.9% and p-cymene (19.0% were the main components of T. vulgaris, while carvacrol (12.8%, a-terpinyl acetate (12.3%, cis-myrtanol (11.2% and thymol (10.4% were dominant in T. tosevii. Both Thymus species showed very strong antifungal activities. In M. piperita oil menthol (37.4%, menthyl acetate (17.4% and menthone (12.7% were the main components, whereas those of M. spicata oil were carvone (69.5% and menthone (21.9%. Mentha sp. showed strong antifungal activities, however lower than Thymus sp. The commercial fungicide, bifonazole, used as a control, had much lower antifungal activity than the oils and components investigated. It is concluded that essential oils of Thymus and Mentha species possess great antifungal potential and could be used as natural preservatives and fungicides.

  16. Transcriptome dynamics of human pluripotent stem cell-derived contracting cardiomyocytes using an embryoid body model with fetal bovine serum.

    Science.gov (United States)

    Jung, Kwang Bo; Son, Ye Seul; Lee, Hana; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

    2017-07-25

    Cardiomyocyte (CM) differentiation techniques for generating adult-like mature CMs remain imperfect, and the plausible underlying mechanisms remain unclear; however, there are a number of current protocols available. Here, to explore the mechanisms controlling cardiac differentiation, we analyzed the genome-wide transcription dynamics occurring during the differentiation of human pluripotent stem cells (hPSCs) into CMs using embryoid body (EB) formation. We optimized and updated the protocol to efficiently generate contracting CMs from hPSCs by adding fetal bovine serum (FBS) as a medium supplement, which could have a significant impact on the efficiency of cardiac differentiation. To identify genes, biological processes, and pathways involved in the cardiac differentiation of hPSCs, integrative and comparative analyses of the transcriptome profiles of differentiated CMs from hPSCs and of control CMs of the adult human heart (CM-AHH) were performed using gene ontology, functional annotation clustering, and pathway analyses. Several genes commonly regulated in the differentiated CMs and CM-AHH were enriched in pathways related to cell cycle and nucleotide metabolism. Strikingly, we found that current differentiation protocols did not promote sufficient expression of genes involved in oxidative phosphorylation to differentiate CMs from hPSCs compared to the expression levels in CM-AHH. Therefore, to obtain mature CMs similar to CM-AHH, these deficient pathways in CM differentiation, such as energy-related pathways, must be augmented prior to use for in vitro and in vivo applications. This approach opens up new avenues for facilitating the utilization of hPSC-derived CMs in biomedical research, drug evaluation, and clinical applications for patients with cardiac failure.

  17. 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

  18. Fetal MRI

    International Nuclear Information System (INIS)

    Prayer, D.; Brugger, P.C.

    2004-01-01

    New, ultrafast sequences have made it possible to obtain MR images of the fetus without maternal sedation or immobilization of the fetus itself. While fetal MRI began as an adjunct to ultrasound, it has now been shown that MRI can provide additional information that may change prognosis, the management of pregnancy, or the treatment of the newborn child. It is of particular value in the assessment of malformations of the central nervous system. The steady development and adaptation of MR-sequences to the needs of fetal imaging has led to new indications that can support prognostic and therapeutic decisions. (orig.)

  19. Fetal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Prayer, D.; Brugger, P.C. [University Hospital of Vienna (Austria). Division of Neuroradiology

    2004-07-01

    New, ultrafast sequences have made it possible to obtain MR images of the fetus without maternal sedation or immobilization of the fetus itself. While fetal MRI began as an adjunct to ultrasound, it has now been shown that MRI can provide additional information that may change prognosis, the management of pregnancy, or the treatment of the newborn child. It is of particular value in the assessment of malformations of the central nervous system. The steady development and adaptation of MR-sequences to the needs of fetal imaging has led to new indications that can support prognostic and therapeutic decisions. (orig.)

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

    OpenAIRE

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

    2014-01-01

    The functional connectivity architecture of the adult human brain enables complex cognitive processes, and exhibits a remarkably complex structure shared across individuals. We are only beginning to understand its heterogeneous structure, ranging from a strongly hierarchical organization in sensorimotor areas to widely distributed networks in areas such as the parieto-frontal cortex. Our study relied on the functional magnetic resonance imaging (fMRI) data of 32 fetuses with no detectable mor...

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

    Directory of Open Access Journals (Sweden)

    Franziska Fettke

    2016-12-01

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

  2. 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.

  3. 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

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

    Science.gov (United States)

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

    2014-01-01

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

  5. 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),

  6. 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

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  8. Computer tomographic examination of the thymus

    International Nuclear Information System (INIS)

    Weiss, C.; Dinkel, E.; Wimmer, B.; Grosser, G.; Schildge, J.

    1987-01-01

    The diagnostic value of CT in follicular thymic hyperplasia and in thymomas in 8 patients with myasthenia gravis and in 12 patients without myasthenia gravis suffering from thymic tumors was evaluated by correlating CT-findings to surgical results and pathological-histological findings. Thymic size of the six patients with histologically proven follicular hyperplasia were scattered within the normal range, but half of them were at the upper limit. Thymic tumors were differentiated between invasive and non invasive tumors by CT staging. Solid tumors with different histology could not be further classified; the attenuation values ranging from 15-55 HU were the same in tumors, follicular hyperplasia and normal thymus. (orig.) [de

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

    OpenAIRE

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

    2011-01-01

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

  10. Normal CT characteristics of the thymus in adults

    Energy Technology Data Exchange (ETDEWEB)

    Simanovsky, Natalia, E-mail: natalias@hadassah.org.il [Department of Medical Imaging, Hadassah - Hebrew University Medical Center, Jerusalem (Israel); Hiller, Nurith; Loubashevsky, Natali; Rozovsky, Katya [Department of Medical Imaging, Hadassah - Hebrew University Medical Center, Jerusalem (Israel)

    2012-11-15

    Background: The thymus changes with age. Its shape and the proportion of solid tissue and fat vary between individuals, yet there is no comprehensive work describing the size and morphology of the normal thymus on CT. As a result, many adults with some preserved soft tissue in the thymus may undergo extensive work-up to exclude mediastinal tumor. Our aim was to quantify CT characteristics of the normal thymus in an adult population. Methods: CT chest scans of 194 trauma patients aged 14-78 years (mean 52.6 years), were retrospectively reviewed. The density, volume, shape and predominant side of the thymus were recorded for 56 patients in whom some solid tissue was preserved. Statistical analysis of these characteristics according to the patient age and gender was performed. Results: Thymic density and volume decreased progressively with age. No solid tissue component was seen in the thymus in patients older than 54 years. In the majority of patients, the thymus had an arrowhead shape, with middle position. However, great variability in thymic shape and border were noted. There was a highly significant relationship between density and patient age (p < 0.0001). Conclusion: We hope that our work will help in the definition of normal thymic CT parameters in adults, help to prevent unnecessary and expensive imaging procedures, and reduce patient exposure to ionizing radiation.

  11. Normal CT characteristics of the thymus in adults

    International Nuclear Information System (INIS)

    Simanovsky, Natalia; Hiller, Nurith; Loubashevsky, Natali; Rozovsky, Katya

    2012-01-01

    Background: The thymus changes with age. Its shape and the proportion of solid tissue and fat vary between individuals, yet there is no comprehensive work describing the size and morphology of the normal thymus on CT. As a result, many adults with some preserved soft tissue in the thymus may undergo extensive work-up to exclude mediastinal tumor. Our aim was to quantify CT characteristics of the normal thymus in an adult population. Methods: CT chest scans of 194 trauma patients aged 14–78 years (mean 52.6 years), were retrospectively reviewed. The density, volume, shape and predominant side of the thymus were recorded for 56 patients in whom some solid tissue was preserved. Statistical analysis of these characteristics according to the patient age and gender was performed. Results: Thymic density and volume decreased progressively with age. No solid tissue component was seen in the thymus in patients older than 54 years. In the majority of patients, the thymus had an arrowhead shape, with middle position. However, great variability in thymic shape and border were noted. There was a highly significant relationship between density and patient age (p < 0.0001). Conclusion: We hope that our work will help in the definition of normal thymic CT parameters in adults, help to prevent unnecessary and expensive imaging procedures, and reduce patient exposure to ionizing radiation.

  12. Senescence and quiescence in adipose-derived stromal cells: Effects of human platelet lysate, fetal bovine serum and hypoxia.

    Science.gov (United States)

    Søndergaard, Rebekka Harary; Follin, Bjarke; Lund, Lisbeth Drozd; Juhl, Morten; Ekblond, Annette; Kastrup, Jens; Haack-Sørensen, Mandana

    2017-01-01

    Adipose-derived stromal cells (ASCs) are attractive sources for cell-based therapies. The hypoxic niche of ASCs in vivo implies that cells will benefit from hypoxia during in vitro expansion. Human platelet lysate (hPL) enhances ASC proliferation rates, compared with fetal bovine serum (FBS) at normoxia. However, the low proliferation rates of FBS-expanded ASCs could be signs of senescence or quiescence. We aimed to determine the effects of hypoxia and hPL on the expansion of ASCs and whether FBS-expanded ASCs are senescent or quiescent. ASCs expanded in FBS or hPL at normoxia or hypoxia until passage 7 (P7), or in FBS until P5 followed by culture in hPL until P7, were evaluated by proliferation rates, cell cycle analyses, gene expression and β-galactosidase activity. hPL at normoxia and hypoxia enhanced proliferation rates and expression of cyclins, and decreased G0/G1 fractions and expression of p21 and p27, compared with FBS. The shift from FBS to hPL enhanced cyclin levels, decreased p21 and p27 levels and tended to decrease G0/G1 fractions. Hypoxia does not add to the effect of hPL during ASC expansion with regard to proliferation, cell cycle regulation and expression of cyclins, p21 and p27. hPL rejuvenates FBS-expanded ASCs with regard to cell cycle regulation and expression of cyclins, p21 and p27. This indicates a reversible arrest. Therefore, we conclude that ASCs expanded until P7 are not senescent regardless of culture conditions. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. Multilineage Potential and Self-Renewal Define an Epithelial Progenitor Cell Population in the Adult Thymus

    Directory of Open Access Journals (Sweden)

    Kahlia Wong

    2014-08-01

    Full Text Available Thymic epithelial cells (TECs are critical for T cell development and self-tolerance but are gradually lost with age. The existence of thymic epithelial progenitors (TEPCs in the postnatal thymus has been inferred, but their identity has remained enigmatic. Here, we assessed the entire adult TEC compartment in order to reveal progenitor capacity is retained exclusively within a subset of immature thymic epithelium displaying several hallmark features of stem/progenitor function. These adult TEPCs generate mature cortical and medullary lineages in a stepwise fashion, including Aire+ TEC, within fetal thymus reaggregate grafts. Although relatively quiescent in vivo, adult TEPCs demonstrate significant in vitro colony formation and self-renewal. Importantly, 3D-cultured TEPCs retain their capacity to differentiate into cortical and medullary TEC lineages when returned to an in vivo thymic microenvironment. No other postnatal TEC subset exhibits this combination of properties. The characterization of adult TEPC will enable progress in understanding TEC biology in aging and regeneration.

  14. In Vitro Large Scale Production of Human Mature Red Blood Cells from Hematopoietic Stem Cells by Coculturing with Human Fetal Liver Stromal Cells

    Directory of Open Access Journals (Sweden)

    Jiafei Xi

    2013-01-01

    Full Text Available In vitro models of human erythropoiesis are useful in studying the mechanisms of erythroid differentiation in normal and pathological conditions. Here we describe an erythroid liquid culture system starting from cord blood derived hematopoietic stem cells (HSCs. HSCs were cultured for more than 50 days in erythroid differentiation conditions and resulted in a more than 109-fold expansion within 50 days under optimal conditions. Homogeneous erythroid cells were characterized by cell morphology, flow cytometry, and hematopoietic colony assays. Furthermore, terminal erythroid maturation was improved by cosculturing with human fetal liver stromal cells. Cocultured erythroid cells underwent multiple maturation events, including decrease in size, increase in glycophorin A expression, and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to 80% of the cells. Importantly, they possessed the capacity to express the adult definitive β-globin chain upon further maturation. We also show that the oxygen equilibrium curves of the cord blood-differentiated red blood cells (RBCs are comparable to normal RBCs. The large number and purity of erythroid cells and RBCs produced from cord blood make this method useful for fundamental research in erythroid development, and they also provide a basis for future production of available RBCs for transfusion.

  15. Propagating Humanized BLT Mice for the Study of Human Immunology and Immunotherapy.

    Science.gov (United States)

    Smith, Drake J; Lin, Levina J; Moon, Heesung; Pham, Alexander T; Wang, Xi; Liu, Siyuan; Ji, Sunjong; Rezek, Valerie; Shimizu, Saki; Ruiz, Marlene; Lam, Jennifer; Janzen, Deanna M; Memarzadeh, Sanaz; Kohn, Donald B; Zack, Jerome A; Kitchen, Scott G; An, Dong Sung; Yang, Lili

    2016-12-15

    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. To circumvent this critical limitation, we have developed a method to quickly propagate established BLT mice. Through secondary transfer of bone marrow cells and human thymus implants from BLT mice into NSG (NOD/SCID/IL-2Rγ -/- ) recipient mice, we were able to expand one primary BLT mouse into a colony of 4-5 proBLT (propagated BLT) mice in 6-8 weeks. These proBLT mice reconstituted human immune cells, including T cells, at levels comparable to those of their primary BLT donor mouse. They also faithfully inherited the human immune cell genetic traits from their donor BLT mouse, such as the HLA-A2 haplotype that is of special interest for studying HLA-A2-restricted human T cell immunotherapies. Moreover, an EGFP reporter gene engineered into the human immune system was stably passed from BLT to proBLT mice, making proBLT mice suitable for studying human immune cell gene therapy. This method provides an opportunity to overcome a critical hurdle to utilizing the BLT humanized mouse model and enables its more widespread use as a valuable preclinical research tool.

  16. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    International Nuclear Information System (INIS)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation

  17. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    Energy Technology Data Exchange (ETDEWEB)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation.

  18. 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 approaches depend on a 3D volume reconstruction step during the slice alignment. This is both computationally expensive and makes the convergence of the registration process poorly defined. In this paper our key contribution is a new approach which considers the collective alignment of all slices directly...... of the approach applied to simulated data and clinically acquired fetal images....

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

    Science.gov (United States)

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

    2012-11-01

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

  20. 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

  1. 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.

  2. 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.

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

    Science.gov (United States)

    Nicholas, Christina L.

    2016-01-01

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

  4. Neuro-immune modulation of the thymus microenvironment (review).

    Science.gov (United States)

    Mignini, Fiorenzo; Sabbatini, Maurizio; Mattioli, Laura; Cosenza, Monica; Artico, Marco; Cavallotti, Carlo

    2014-06-01

    The thymus is the primary site for T-cell lympho-poiesis. Its function includes the maturation and selection of antigen specific T cells and selective release of these cells to the periphery. These highly complex processes require precise parenchymal organization and compartmentation where a plethora of signalling pathways occur, performing strict control on the maturation and selection processes of T lymphocytes. In this review, the main morphological characteristics of the thymus microenvironment, with particular emphasis on nerve fibers and neuropeptides were assessed, as both are responsible for neuro-immune‑modulation functions. Among several neurotransmitters that affect thymus function, we highlight the dopaminergic system as only recently has its importance on thymus function and lymphocyte physiology come to light.

  5. 81-92, 2015 81 Thymus species in Ethiopia

    African Journals Online (AJOL)

    Figure 1: Data/Sample Collection Sites of Thymus species for the present study ..... ly reduced level of Systolic Atrial Pressure (SAP) and ... T. schimperi is a big challenge owing to their suitabil- .... of Local Hybrid Maize Seed Production and.

  6. 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.

  7. The relationship between human placental morphometry and ultrasonic measurements of utero-placental blood flow and fetal growth.

    Science.gov (United States)

    Salavati, N; Sovio, U; Mayo, R Plitman; Charnock-Jones, D S; Smith, G C S

    2016-02-01

    Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and arterial Doppler flow velocimetry have not previously been studied in relation to postnatal placental morphometry in detail. We conducted a prospective cohort study of nulliparous women in The Rosie Hospital, Cambridge (UK). We studied a group of 2120 women who had complete data on uterine and umbilical Doppler velocimetry and fetal biometry at 20, 28 and 36 weeks' gestational age, digital images of the placenta available, and delivered a liveborn infant at term. Associations were expressed as the difference in the standard deviation (SD) score of the gestational age adjusted ultrasound measurement (z-score) comparing the lowest and highest decile of the given placental morphometric measurement. The lowest decile of placental surface area was associated with 0.87 SD higher uterine artery Doppler mean pulsatility index (PI) at 20 weeks (95% CI: 0.68 to 1.07, P flow, respectively, and both are associated with fetal growth rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. The roles of the cyclo-oxygenases types one and two in prostaglandin synthesis in human fetal membranes at term.

    Science.gov (United States)

    Sawdy, R J; Slater, D M; Dennes, W J; Sullivan, M H; Bennett, P R

    2000-01-01

    The aim of this study was to determine the relative contributions of cyclo-oxygenase (COX) types 1 and 2 to prostaglandin synthesis at term. Fetal membranes were collected from 6 pregnancies after elective caesarean section at term, prior to labour. The presence of COX-1 and COX-2 protein was determined using Western analysis. The relative contributions of the two isoforms of COX to prostaglandin synthesis were determined by incubation of fetal membrane discs with either a COX-2 selective inhibitor, SC236, or a COX-1 selective inhibitor, SC560, and measurement of prostaglandin release during 24 h using enzyme-linked immuno-sorbent assay (ELISA). Both COX-1 and COX-2 protein were demonstrated in amnion and chorion-decidua. The COX-2 selective inhibitor, SC-236, significantly reduced prostaglandin synthesis, both in its COX-2 specific and higher, non-specific concentration ranges. The COX-1 selective inhibitor, SC-560, had no effect upon prostaglandin synthesis in its COX-1 specific concentration range, but did significantly reduce prostaglandin synthesis at higher, non-selective concentrations. Fetal membranes contain both COX-1 and COX-2 at term, but only COX-2 contributes towards prostaglandin synthesis. COX-2 selective NSAI drugs will be as effective as non-selective agents in inhibition of fetal membrane prostaglandin synthesis and may represent a new strategy for tocolysis. Copyright 2000 Harcourt Publishers Ltd.

  9. Characterization of human mucin (MUC15) and identification of ovine and caprine orthologs

    DEFF Research Database (Denmark)

    Pallesen, Lone Tjener; Pedersen, Lise Refstrup Linnebjerg; Petersen, Torben Ellebæk

    2008-01-01

    expression in placenta, salivary gland, thyroid gland, trachea, esophagus, kidney, testis, and the leukemia K-562 cell line. Furthermore, moderate expression was seen in the pancreas, adult and fetal lung, fetal kidney, lymph node, adult and fetal thymus, and parietal lobe. Structural motifs for interactions...

  10. 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)

    Patrikoski, Mimmi; 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.

  11. Sonographic evaluation of normal thymus in infants and children

    Energy Technology Data Exchange (ETDEWEB)

    Lemaitre, L.; Marconi, V.; Remy, J.; Avni, F.

    1987-05-01

    Sonography has been used to evaluate 50 'asymptomatic' infants (aged from birth up to two years) with typical appearing thymus on chest X-ray. The ultrasonic features of the normal gland are described. Moreover, the contribution of ultrasound is illustrated by five cases of partially ectopic thymus and by one case of prominent gland in a teenager. Ultrasound may help in differentiating normal gland from mediastinal masses by defining echogenicity, location and extension.

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Xu, Long; Ge, Jingjing; Huo, Xia; Zhang, Yuling; Lau, Andy T.Y.; Xu, Xijin

    2016-01-01

    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.

  15. Radiographical diagnosis of the thymus in myasthenia gravis

    International Nuclear Information System (INIS)

    Tanimura, Shigeo; Banba, Jiro; Masaki, Mikio; Irimoto, Masahiro; Matsushita, Akira

    1987-01-01

    Comparison of radiographical findings of the thymus between pneumomediastinography and computed tomography were studied in 35 patients with myasthenia gravis. The patients consisted of 10 patients with thymoma and 25 without thymoma confirmed at the operations. Pneumomediastinography was very useful to discern whether the thymoma was invasive or noninvasive, but not contributory to know whether the thymus was composed of folicular lymphoid hyperplasia or normal thyimic tissues. Computed tomography was also useful to dertermine the localization and the invasiveness of the thymoma, but not helpful to know whether the thymus was of follicular lymphoid hyperplasia or normal tissues. However, the finding of ''reticular pattern''-many small nodules scattered resicularly in the thymus-in computed tomography could be regarded as a sign suggesting follicular lymphoid hyperplasia of the thymus. Therfore, both pneumomediastinography and computed tomography were very useful in the diagnosis of the localization and the invasiveness of the thymoma but not for the diagnosis of follicular lymphoid hyperplasia of the thymus. Neverethless the finding of ''reticular pattern'' computred tomography was helpful in the diagnosis of follicular lymphoid hyperplasia. (author)

  16. Effect of TCDD on the fate of epithelial cells isolated from human fetal palatal shelves (hFPECs)

    International Nuclear Information System (INIS)

    Gao, Zhan; Bu, Yongjun; Zhang, Guofu; Liu, Xiaozhuan; Wang, Xugang; Ding, Shibin; Wang, Erhui; Shi, Ruling; Li, Qiaoyun; Fu, Jianhong; Yu, Zengli

    2016-01-01

    Cleft palate is caused by the failure of palatal midline epithelial cells to disintegrate, which is necessary for palatal mesenchymal confluence. Although 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure is linked to cleft palate at a high rate, the mechanism remains to be elucidated. The present study was designed to determine the effects of TCDD on the fate of epithelial cell isolated from human fetal palatal shelves (hFPECs). We demonstrate that TCDD increased cell proliferation and promoted the progression of cells from G1 to S phase as well as increased the number of cells entering the G2/M phase. We found that TCDD has no measurable effect on apoptosis of hFPECs. The protein level assays revealed that TCDD increased cyclin-dependent kinases 4 (cdk4), cyclin D1, cyclin E and p21 (Waf1/Cip1) but not cdk2, bcl-2, cyclin B1 and cyclin A. Furthermore, TCDD activated PI3K/AKT signaling, and the PI3K inhibitor, LY294002, partially abrogated TCDD-induced cell proliferation and gene modulations. TCDD treatment increased CYP1A1 mRNA and protein levels, which indicated the activation of AhR signaling. Knockdown of the AhR with siRNA suppressed TCDD-induced cell proliferation and PI3K/AKT signaling activation. Taken together, these data demonstrated that TCDD is able to promote growth of hFPECs through AhR-dependent activation of the PI3K/AKT pathway, which may account for the underlying mechanism by which TCDD causes a failure of palatal fusion. - Highlights: • TCDD promoted the cell growth with a character of significant accumulation of cells in G2/M. • TCDD treatment induced a various profile of cell cycle regulatory proteins. • PI3K/AKT pathway was involved in TCDD-induced cell proliferation and gene modifications. • AhR knockdown blocked TCDD-induced cell proliferation and PI3K/Akt signaling activation.

  17. Human Umbilical Cord Blood Serum Has Higher Potential in Inducing Proliferation of Fibroblast than Fetal Bovine Serum

    Directory of Open Access Journals (Sweden)

    Ferry Sandra

    2017-09-01

    Full Text Available Background: Cytokines and growth factors were reported to play an important role in stimulating fibroblast proliferation. In vitro culture, fibroblast is mostly culture in medium containing fetal bovine serum (FBS.  Human umbilical cord blood (hUCB has been reported to have low immunogenic property and potential in wound healing, so therefore hUCB serum (hUCBS could be potential and were investigated in current study. Materials and Methods: Five hUCBs were collected from healthy volunteers with normal delivering procedure. hUCB was ex utero immediately collected from umbilical vein in vacutainers and processed. NIH3T3 cells were cultured in DMEM with 10% FBS or 5-20% hUCBS for 48 hours. Cells were then quantified using MTT assay. Protein concentration of FBS and hUCBS were quantified using Bradford assay. Results: NIH3T3 cells density grown in DMEM with 10% FBS was the lowest. NIH3T3 cells densities were increased along with the increment of hUCBS concentrations. MTT results showed that average number of NIH3T3 cells grown in DMEM with 10% FBS was 6,185±1,243. Meanwhile average numbers of NIH3T3 cells grown in DMEM with 5%, 10% and 20% hUCBS were 8,126±628, 9,685±313 and 12,200±304, respectively. Average numbers of NIH3T3 cells grown in DMEM with 5% hUCBS were significantly higher than the ones with 10% FBS (p=0.000. Bradford results showed that concentration of hUCBS was significantly higher than the one of FBS (p=0.000. Conclusion: hUCBS could induce higher proliferation rate of NIH3T3 cells than FBS. Hence hUCBS could be suggested as an alternate of FBS in inducing fibroblast. Keywords: NIH3T3, fibroblast, UCB, serum, FBS, proliferation

  18. Effect of TCDD on the fate of epithelial cells isolated from human fetal palatal shelves (hFPECs)

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Zhan [School of Public Health, Xinxiang Medical University, 453003 (China); The Fifth Affiliated Hospital, Zhengzhou University, 450052 (China); Bu, Yongjun; Zhang, Guofu [School of Public Health, Xinxiang Medical University, 453003 (China); Liu, Xiaozhuan [Medical College, Henan University of Science & Technology, 471023 (China); Wang, Xugang; Ding, Shibin; Wang, Erhui; Shi, Ruling [School of Public Health, Xinxiang Medical University, 453003 (China); Li, Qiaoyun; Fu, Jianhong [The Fifth Affiliated Hospital, Zhengzhou University, 450052 (China); Yu, Zengli, E-mail: zly@zzu.edu.cn [School of Public Health, Xinxiang Medical University, 453003 (China); Public Health College, Zhengzhou University, 450001 (China)

    2016-08-15

    Cleft palate is caused by the failure of palatal midline epithelial cells to disintegrate, which is necessary for palatal mesenchymal confluence. Although 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure is linked to cleft palate at a high rate, the mechanism remains to be elucidated. The present study was designed to determine the effects of TCDD on the fate of epithelial cell isolated from human fetal palatal shelves (hFPECs). We demonstrate that TCDD increased cell proliferation and promoted the progression of cells from G1 to S phase as well as increased the number of cells entering the G2/M phase. We found that TCDD has no measurable effect on apoptosis of hFPECs. The protein level assays revealed that TCDD increased cyclin-dependent kinases 4 (cdk4), cyclin D1, cyclin E and p21 (Waf1/Cip1) but not cdk2, bcl-2, cyclin B1 and cyclin A. Furthermore, TCDD activated PI3K/AKT signaling, and the PI3K inhibitor, LY294002, partially abrogated TCDD-induced cell proliferation and gene modulations. TCDD treatment increased CYP1A1 mRNA and protein levels, which indicated the activation of AhR signaling. Knockdown of the AhR with siRNA suppressed TCDD-induced cell proliferation and PI3K/AKT signaling activation. Taken together, these data demonstrated that TCDD is able to promote growth of hFPECs through AhR-dependent activation of the PI3K/AKT pathway, which may account for the underlying mechanism by which TCDD causes a failure of palatal fusion. - Highlights: • TCDD promoted the cell growth with a character of significant accumulation of cells in G2/M. • TCDD treatment induced a various profile of cell cycle regulatory proteins. • PI3K/AKT pathway was involved in TCDD-induced cell proliferation and gene modifications. • AhR knockdown blocked TCDD-induced cell proliferation and PI3K/Akt signaling activation.

  19. A Transcriptomic and Epigenomic Comparison of Fetal and Adult Human Cardiac Fibroblasts Reveals Novel Key Transcription Factors in Adult Cardiac Fibroblasts

    Directory of Open Access Journals (Sweden)

    Malin K.B. Jonsson, PhD

    2016-12-01

    Full Text Available Cardiovascular disease remains the number one global cause of death and presents as multiple phenotypes in which the interplay between cardiomyocytes and cardiac fibroblasts (CFs has become increasingly highlighted. Fetal and adult CFs influence neighboring cardiomyocytes in different ways. Thus far, a detailed comparison between the two is lacking. Using a genome-wide approach, we identified and validated 2 crucial players for maintaining the adult primary human CF phenotype. Knockdown of these factors induced significant phenotypical changes, including senescence and reduced collagen gene expression. These may now represent novel therapeutic targets against deleterious functions of CFs in adult cardiovascular disease.

  20. Histological investigations on thymus of male rats prenatally exposed to bisphenol A.

    Science.gov (United States)

    Aydemir, Işıl; Kum, Şadiye; Tuğlu, Mehmet İbrahim

    2018-04-27

    Bisphenol A is called as a endocrine-distrupting chemical because of the its steroid-like activity and it used in the construction of plastic containing materials. It is indicated that bisphenol A can pass the human serum, urine, follicular fluid, placenta and umblical cord as a result of the use of substances containing this agent. In this study, we aimed to investigate the effects of bisphenol A on the development of the thymus, a primary lymphoid organ which plays an important role in the specific immunity. The adult pregnant female rats were administered orally with bisphenol A (for 21 days) and postnatal thymus samples were obtained on day 21, 45 and 90 and were performed for histochemical and immunohistochemical staining for CD3, CD4, CD8 and CD79a and TUNEL assay for the apoptotic cells. Evaluation of all groups, CD3, CD4, CD8 and CD79a stainings were decreased in the experimental groups compared with control group. The apoptotic cells were determined in the all groups on day 90 as a result of the thymus involution. It is noted that there was not any histological and morphological damages in the rats prenatally exposed the bisphenol A. The effect of the bisphenol A is unknown in the future, but there is no problem in the adult rats. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. The localization of primary efferent sympathetic neurons innervating the porcine thymus – a retrograde tracing study

    Directory of Open Access Journals (Sweden)

    Paweł Kulik

    2017-01-01

    Full Text Available The autonomic nervous system is a sophisticated and independent structure composed of two antagonistic (opposing divisions (sympathetic and parasympathetic that control many vital functions including: homeostasis maintenance, heart rate, blood circulation, secretion, etc. Thymus is one of the most important primary lymphoid organs playing a role in the developing of a juvenile’s immune system mainly by maturation, development, and migration of T-cells (T lymphocytes. In the last decades, several studies identifying sources of the thymic autonomic supply have been undertaken in humans and several laboratory rodents but not in higher mammals such as the pig. Therefore, in the present work, retrograde tracing technique of Fast Blue and DiI was used to investigate the sources of sympathetic efferent supply to the porcine thymus. After Fast Blue injection into the right lobe of the thymus, the presence of Fast Blue-positive neurons was found in the unilateral cranial cervical ganglion (82.8 ± 3.0% of total Fast Blue-positive neurons as well as in the middle cervical ganglion (17.2 ± 3.0%. Injection of DiI resulted in the presence of retrograde tracer in neurons of the cranial cervical ganglion (80.4 ± 2.3% of total amount of DiI-labelled neurons, the middle cervical ganglion (18.4 ± 1.9%, and the cervicothoracic ganglion (1.2 ± 0.8%. The present report provides the first data describing in details the localization of primary efferent sympathetic neurons innervating the porcine thymus.

  2. 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 (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 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.

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

    Science.gov (United States)

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

    2014-10-01

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

  4. [Fetal urology].

    Science.gov (United States)

    Jakobovits, Akos; Jakobovits, Antal

    2009-06-14

    Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

  5. 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))....

  6. [Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

    Science.gov (United States)

    Sevost'ianova, N N; Trofimov, A V; Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

    2010-01-01

    The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

  7. Studies on the termination of immunological tolerance in the mouse thymus cell population after irradiation

    International Nuclear Information System (INIS)

    Amagai, Takashi

    1981-01-01

    Immunological tolerance in the mouse thymus cell population induced by the intravenous injection of deaggregated bovine gamma globulin was terminated by whole body irradiation. After irradiation, the weight of the thymus recovered biphasically, and the termination of tolerance occurred as early as in the first phase. Both Thy-1 antigen expression and helper activity of the thymus cell population in irradiated mice recovered in parallel with the recovery of the thymus weight. Sensitivity of the regenerating thymus cells to the tolerogen was not different from that of the normal thymus cells. The first phase of thymus regeneration may be caused by the proliferation and differentiation of relatively radioresistant and tolerogen insensitive precursors residing in the thymus. Tolerogen and/or immunogen reactive thymus cells may originate from the precursor. (author)

  8. The entry of the prothymocyte into the thymus after lethal irradiation and bone marrow transplantation. 2

    International Nuclear Information System (INIS)

    Mulder, A.H.; Visser, J.W.M.; Zoetelief, J.; Bekkum, D.W. van

    1988-01-01

    The time of entry of prothymocytes into the thymus after lethal irradiation and bone marrow transplantation (BMT) was determined by exposing the thymus only or the whole body with the thymus shielded to a second irradiation after different intervals. The repopulation of the thymus by donor type cells was determined by a thymus repopulation assay using donor specific markers. Reirradiation of the thymus kills the prothymocytes that have entered the thymus during the interval. It was found that reirradiation of the thymus from 48 hours after BMT onwards increasingly delayed thymus regeneration. This shows that donor prothymocytes do not enter the thymus until about 2 days after BMT and that they continue to do so during at least 3 subsequent days. In the second reirradiation protocol thymus regeneration occurred earlier in the shielded thymus than in thymuses of whole body irradiated mice. Earlier thymus regeneration was not seen in mice that were reirradiated at 24 hours after BMT, but occurred only when irradiation took place at 48 hours and later. These data are consistent with those obtained in the first protocol. The results are in contradiction with results of direct homing experiments, which showed entrance of donor cells within 3 hours after BMT. A functional assay demonstrated that the early appearing cells cannot be prothymocytes. In retransplantation experiments it was shown that the bone marrow may indeed be the initial homing site of prothymocytes. 14 refs.; 5 figs.; 1 table

  9. Effects of proteolysis on the adenosinetriphosphatase activities of thymus myosin

    International Nuclear Information System (INIS)

    Vu, N.D.; Wagner, P.D.

    1987-01-01

    Limited proteolysis was used to identify regions on the heavy chains of calf thymus myosin which may be involved in ATP and actin binding. Assignments of the various proteolytic fragments to different parts of the myosin heavy chain were based on solubility, gel filtration, electron microscopy, and binding of 32 P-labeled regulatory light chains. Chymotrypsin rapidly cleaved within the head of thymus myosin to give a 70,000-dalton N-terminal fragment and a 140,000-dalton C-terminal fragment. These two fragments did not dissociate under nondenaturing conditions. Cleavage within the myosin tail to give heavy meromyosin occurred more slowly. Cleavage at the site 70,000 daltons from the N-terminus of the heavy chain caused about a 30-fold decrease in the actin concentration required to achieve half-maximal stimulation of the magnesium-adenosinetriphosphatase (Mg-ATPase) activity of unphosphorylated thymus myosin. The actin-activated ATPase activity of this digested myosin was only slightly affected by light chain phosphorylation. Actin inhibited the cleavage at this site by chymotrypsin. In the presence of ATP, chymotrypsin rapidly cleaved the thymus myosin heavy chain at an additional site about 4000 daltons from the N-terminus. Cleavage at this site caused a 2-fold increase in the ethylenediaminetetraacetic acid-ATPase activity and 3-fold decreases in the Ca 2+ - and Mg-ATPase activities of thymus myosin. Thus, cleavage at the N-terminus of thymus myosin was affected by ATP, and this cleavage altered ATPase activity. Papain cleaved the thymus myosin heavy chain about 94,000 daltons from the N-terminus to give subfragment 1. Although this subfragment 1 contained intact light chains, its actin-activated ATPase activity was not affected by light chain phosphorylation

  10. 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].

  11. Human Platelet Lysate as a Xeno Free Alternative of Fetal Bovine Serum for the In Vitro Expansion of Human Mesenchymal Stromal Cells.

    Science.gov (United States)

    Mohammadi, Saeed; Nikbakht, Mohsen; Malek Mohammadi, Ashraf; Zahed Panah, Mahdi; Ostadali, Mohammad Reza; Nasiri, Hajar; Ghavamzadeh, Ardeshir

    2016-07-01

    Mesenchymal stromal cells (MSCs) are employed in various different clinical settings in order to modulate immune response. Human autologous and allogeneic supplements including platelet derivatives such as platelet lysate (PL), platelet-released factors (PRF) and serum are assessed in clinical studies to replace fetal bovine serum (FBS). The immunosuppressive activity and multi-potential characteristic of MSCs appear to be maintained when the cells are expanded in platelet derivatives. Platelet-rich plasma was collected from umbrical cord blood (UCB). Platelet-derived growth factors obtained by freeze and thaw methods. CD62P expression was determined by flow cytometry. The concentration of PDGF-BB and PDGF-AB was detemined by ELISA. We tested the ability of a different concentration of PL-supplemented medium to support the ex vivo expansion of Wharton's jelly derived MSCs. We also investigated the biological/functional properties of expanded MSCs in presence of different concentration of PL. The conventional karyotyping was performed in order to study the chromosomal stability. The gene expression of Collagen I and II aggrecan and SOX-9 in the presence of different concentrations of PL was evaluated by Real-time PCR. We observed 5% and 10% PL, causing greater effects on proliferation of MSCs .These cells exhibited typical morphology, immunophenotype and differentiation capacity. The genetic stability of these derivative cells from Wharton's jelly was demonstrated by a normal karyotype. Furthermore, the results of Real-time PCR analysis showed that the expression of chondrocyte specific genes was higher in MSCs in the presence of 5% and 10% PL, compared with FBS supplement. We demonstrated that PL could be used as an alternative safe source of growth factors for expansion of MSCs and also maintained similar growing potential and phenotype without any effect on chromosomal stability.

  12. 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.

  13. 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.

  14. 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.

  15. Adrenergic nerve fibres and mast cells: correlation in rat thymus.

    Science.gov (United States)

    Artico, Marco; Cavallotti, Carlo; Cavallotti, Daniela

    2002-10-21

    The interactions between adrenergic nerve fibres and mast cells (MCs) were studied in the thymus of adult and old rats by morphological methods and by quantitative analysis of images (QAIs). The whole thymus was drawn in adult (12 months old) rats: normal, sympathectomized or electrostimulated. Thymuses from the above-mentioned animals were weighed, measured and dissected. Thymic slices were stained with eosin orange for detection of microanatomical details and with Bodian's method for identification of the whole nerve fibres. Thymic MCs were stained with Astrablau. Histofluorescence microscopy was used for staining of adrenergic nerve fibres. Finally, all morphological results were submitted to the QAIs and statistical analysis of data. Our results suggest that after surgical sympathectomy, the greater part of adrenergic nerve fibres disappear while related MCs appear to show less evident fluorescence and few granules. On the contrary, electrostimulation of the cervical superior ganglion induced an increase in the fluorescence of adrenergic nerve fibres and of related MCs.

  16. Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

    Science.gov (United States)

    Alvarez-Nava, Francisco; Soto, Marisol; Lanes, Roberto; Pons, Hector; Morales-Machin, Alisandra; Bracho, Ana

    2015-12-01

    The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P Turner syndrome pregnancies with the highest risk of fetal death. © 2015 Japan Society of Obstetrics and Gynecology.

  17. 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,

  18. 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,

  19. Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers.

    Science.gov (United States)

    Mori, Chisato; Nakamura, Noriko; Todaka, Emiko; Fujisaki, Takeyoshi; Matsuno, Yoshiharu; Nakaoka, Hiroko; Hanazato, Masamichi

    2014-11-01

    Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. 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.

  1. T cell progenitors in the mouse fetal liver

    International Nuclear Information System (INIS)

    Rabinowich, H.; Umiel, T.; Globerson, A.

    1983-01-01

    Fourteen-day mouse fetal liver was found to contain cells capable of giving rise to T as well as B cell functions. The experimental system consisted of congenic C3H/DiSn and (C3H/DiSn X C3H.SW)F1 lethally irradiated (900 R) mice reconstituted with C3H/DiSn fetal liver or bone marrow cells. Assays included thyroid allograft rejection as well as in vitro measurement of reactivity to phytohemagglutinin (PHA) and concanavalin A (Con A) and in a mixed lymphocyte culture (MLC) system in spleen, lymph node, and thymus cells. The fetal liver chimeras were found to become as capable as the bone marrow chimeras in responding in these various assays. The T cell responses lagged behind the responses to the B cell mitogens dextran sulfate (DXS) and lipopolysaccharide (LPS) (30 days after reconstitution, as compared with 14 days for DXS and 21 for LPS). The reacting cells were of the donor genotype, as revealed after treatment with C3H/DiSn (H-2k) anti-C3H.SW (H-2b) congenic sera. T cell responses were not manifest in thymectomized (TX) chimeras. Hence, the liver seems to contain cells capable of developing into T cell lineages in a thymus-dependent process

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

    International Nuclear Information System (INIS)

    Zhang, Shaojie; Patel, Ananddeep; Chu, Chun; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-01-01

    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

  3. 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

  4. Thymus size at 6 months of age and subsequent child mortality

    DEFF Research Database (Denmark)

    Garly, M.L.; Trautner, S.L.; Marx, C.

    2008-01-01

    OBJECTIVE: To examine determinants of thymus size at age 6 months and investigate whether thymus size at this age is a determinant of subsequent mortality. STUDY DESIGN: Thymus size was measured by transsternal sonography in 923 6-month-old children participating in a measles vaccination trial...... in Guinea-Bissau. RESULTS: Thymus size was strongly associated with anthropometric measurements. Boys had larger thymuses than girls, controlling for anthropometry. Crying during sonography made the thymus appear smaller. Children who were not vaccinated with Bacille Calmette-Guerin (BCG) or were vaccinated...... thymus size remained a strong and independent risk factor for mortality (hazard ratio = 0.31; 95% confidence interval = 0.18 to 0.52). CONCLUSIONS: Small thymus size at age 6 months is a strong risk factor for mortality. To prevent unnecessary deaths, it is important to identify preventable factors...

  5. ALTERED HISTOLOGY OF THE THYMUS AND SPLEEN IN CONTAMINANT-EXPOSED JUVENILE AMERICAN ALLIGATORS

    Science.gov (United States)

    Morphological difference in spleen and thymus are closely related to functional immune differences. Hormonal regulation of the immune system has been demonstrated in reptilian splenic and thymic tissue. Spleens and thymus were obtained from juvenile alligators at two reference si...

  6. Measurement of the capability of DNA synthesis of human fetal liver cells by the assay of 3H-TdR incorporation

    International Nuclear Information System (INIS)

    Wang Tao; Ma Xiangrui; Wang Hongyun; Cao Xia

    1987-01-01

    The fetal liver is one of the major sites of hematopoiesis during gestation. Under erythropoietin (EPO) stimulation, in erythroid precusor cells of fetal liver, proliferation and differentiation occurred and function of metabolism was enhanced. The technique of 3 H-TdR incorporation was used to measure the function of fetal liver cellular DNA synthesis. As EPO concentration at the range of approximately 20 ∼ 100 mU/ml, the counts of 3 H-TdR incorporation into fetal liver cells increased. As the concentration of EPO increased, however, its incorporation counts are lower than that in bone marrow of either the fetal or the adult. It suggested that precusors of erythrocyte of fetal liver has differentiated to later phases with the progressive accumulation of mature cells, therefore, both proliferation and function of metabolism are more or less decreased respectively. Under EPO stimulation, however, precusor of erythroid of fetal liver can greatly increase potential effects on DNA synthesis

  7. 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

  8. Thymus size at 6 months of age and subsequent child mortality.

    Science.gov (United States)

    Garly, May-Lill; Trautner, Sisse Lecanda; Marx, Charlotte; Danebod, Kamilla; Nielsen, Jens; Ravn, Henrik; Martins, Cesário Lourenco; Balé, Carlito; Aaby, Peter; Lisse, Ida Maria

    2008-11-01

    To examine determinants of thymus size at age 6 months and investigate whether thymus size at this age is a determinant of subsequent mortality. Thymus size was measured by transsternal sonography in 923 6-month-old children participating in a measles vaccination trial in Guinea-Bissau. Thymus size was strongly associated with anthropometric measurements. Boys had larger thymuses than girls, controlling for anthropometry. Crying during sonography made the thymus appear smaller. Children who were not vaccinated with Bacille Calmette-Guérin (BCG) or were vaccinated with BCG in the preceding 4 weeks before inclusion into the study had larger thymuses. Children who had malaria or had been treated with chloroquine or Quinimax in the previous week before inclusion had smaller thymuses. Controlled for background factors associated with thymus size and mortality, small thymus size remained a strong and independent risk factor for mortality (hazard ratio = 0.31; 95% confidence interval = 0.18 to 0.52). Small thymus size at age 6 months is a strong risk factor for mortality. To prevent unnecessary deaths, it is important to identify preventable factors predisposing to small thymus size.

  9. Effect of Euphorbia hirta and Thymus vulgaris powders on ...

    African Journals Online (AJOL)

    The ban placed on the long term use of commercial antibiotics at subtherapeutic levels for diseases control and growth promotion in livestock production necessitated a worldwide search for available, cost effective and efficacious alternatives. Accordingly, the effects of Euphorbia hirta (EH) and Thymus vulgaris (TV) ...

  10. The size of the thymus: an important immunological diagnostic tool?

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth

    2003-01-01

    The report on the influence of seasonal factors on thymic size in early life describes a pattern of ultrasonographically measured thymic growth in Gambian infants including the finding of a smaller thymus in the hungry season. These factors raise a number of important questions: Is the size...

  11. Structural changes in the regenerating rat thymus after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Tetsuo; Wang, Yu-Hsueh; Hashimoto, Noriko; Tokuda, Nobuko; Sawada, Tomoo [Yamaguchi Univ., Ube (Japan). School of Medicine

    1999-11-01

    The structural changes of the rat thymus after irradiation were examined. Thymocytes regenerate rapidly after irradiation and the mechanism responsible for this rapid regeneration was examined analyzing vascular and immunohistochemical changes in the thymus. Following results were obtained: Vascular fine mesh works in the cortex were destroyed on day 3 after 6 Gy irradiation, while on day 5 these changes appeared to be restored to almost normal. Massive macrophage accumulations were observed in the cortex on day 3-5 after irradiation. This may be due to clean up the damaged thymocytes, although other possibility, as production of cytokines which may contribute to the rapid proliferation must be intensively examined. Immunohistochemical staining with anti MHC class II molecule showed relatively strong staining in the medulla compared to the cortex in the normal thymus, while this finding was reversed and cortex stained heavily compared to the medulla on day 5-7 after irradiation suggesting the importance of the cortical MHC class II positive thymic epithelial cells in regeneration of thymocytes. Anti FTS antibody stained relatively strongly in the irradiated and recovering thymus compared to the normal. These results may partly explain the abrupt proliferation of thymocytes after irradiation and further studies on cytokine message changes and thymic epithelial characterization responsible to produce the cytokines for the effective thymocyte proliteration are on the way of analysis. (author)

  12. Effects of Thymus vulgaris and Mentha pulegium on colour, nutrients ...

    African Journals Online (AJOL)

    This study was designed to investigate the effects of Thymus vulgaris (thyme) and Mentha pulegium (mentha) powders on meat colour, nutrient composition and malondialdehyde (MDA) where broiler chickens were under heat stress. Two hundred one-day-old male chicks were used in a completely randomized design with ...

  13. Dark reticular cells in the thymus of mice

    Energy Technology Data Exchange (ETDEWEB)

    Jaerplid, B [Foersvarets Forskningsanstalt, Stockholm (Sweden)

    1974-01-01

    The morphology and distribution of dark reticular cells in the thymus of normal mice, of irradiated mice, and of mice with thymic lymphoma are described. It is concluded that dark cells are epithelial reticular cells and the hypothesis is suggested that dark and light epithelial reticular cells may be different modes of expression of the same cell type. (auth)

  14. Updates in MRI characterization of the thymus in myasthenic patients.

    Science.gov (United States)

    Popa, G A; Preda, E M; Scheau, C; Vilciu, C; Lupescu, I G

    2012-06-12

    To evaluate the imaging appearance of the thymus in the myasthenic patients by using chemical shift magnetic resonance imaging, and, to correlate the chemical shift ratio (CSR) with pathologic findings after surgical excision. In the past year, a total of 11 myasthenic patients (4 males, 7 females; age range of 26-65 years), have been investigated by MRI centered at the thymic lodge. Our protocol included a Dual-Echo technique, T1-weighted In-phase/Opposed-phase MR images in all patients. A chemical shift ratio (CSR) was calculated by comparing the signal intensity of the thymus gland with that of the chest wall muscle for quantitative analysis. For this purpose, we have used standard region-of-interest electronic cursors at a slice level of the maximum axial surface of the thymus. We have identified two patients groups: a thymic hyperplasia group and a thymic tumoral group. With the decrease in the signal intensity of the thymus gland at chemical shift, the MR imaging was evident only in the hyperplasia group. The mean CSR in the hyperplasia group was considerably lower than that in the tumor group, 0,4964 ± 0,1841, compared with 1,0398 ± 0,0244. The difference in CSR between the hyperplasia and tumor groups was statistically significant (P=0,0028). MR imaging using T1-weighted In-phase/Opposed-phase images could be a useful diagnostic tool in the preoperative assessment of the thymic lodge and may help differentiate thymic hyperplasia from tumors of the thymus gland.

  15. Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

    International Nuclear Information System (INIS)

    Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit Kumar; Maturu, Paramahamsa; Moorthy, Bhagavatula; Shivanna, Binoy

    2016-01-01

    Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC. OM induced HO-1 mRNA and protein expression in a dose-dependent manner. siRNA-mediated knockdown of AhR failed to abrogate, whereas knockdown of Nrf2 abrogated HO-1 induction by OM. To identify the underlying molecular mechanisms, we determined the effects of OM on cellular hydrogen peroxide (H 2 O 2 ) levels since oxidative stress mediated by the latter is known to activate Nrf2. Interestingly, the concentration at which OM induced HO-1 also increased H 2 O 2 levels. Furthermore, H 2 O 2 independently augmented HO-1 expression. Although N-acetyl cysteine (NAC) significantly decreased H 2 O 2 levels in OM-treated cells, we observed that OM further increased HO-1 mRNA and protein expression in NAC-pretreated compared to vehicle-pretreated cells, suggesting that OM induces HO-1 via H 2 O 2 -independent mechanisms. In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H 2 O 2 - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. - Highlights: • Omeprazole induces HO-1 in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of HO-1. • Nrf2 knockdown abrogates omeprazole-mediated HO-1 induction in human lung cells. • Hydrogen peroxide depletion augments omeprazole-mediated induction of HO-1.

  16. Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit Kumar; Maturu, Paramahamsa; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2016-11-15

    Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC. OM induced HO-1 mRNA and protein expression in a dose-dependent manner. siRNA-mediated knockdown of AhR failed to abrogate, whereas knockdown of Nrf2 abrogated HO-1 induction by OM. To identify the underlying molecular mechanisms, we determined the effects of OM on cellular hydrogen peroxide (H{sub 2}O{sub 2}) levels since oxidative stress mediated by the latter is known to activate Nrf2. Interestingly, the concentration at which OM induced HO-1 also increased H{sub 2}O{sub 2} levels. Furthermore, H{sub 2}O{sub 2} independently augmented HO-1 expression. Although N-acetyl cysteine (NAC) significantly decreased H{sub 2}O{sub 2} levels in OM-treated cells, we observed that OM further increased HO-1 mRNA and protein expression in NAC-pretreated compared to vehicle-pretreated cells, suggesting that OM induces HO-1 via H{sub 2}O{sub 2}-independent mechanisms. In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H{sub 2}O{sub 2} - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. - Highlights: • Omeprazole induces HO-1 in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of HO-1. • Nrf2 knockdown abrogates omeprazole-mediated HO-1 induction in human lung cells. • Hydrogen peroxide depletion augments

  17. Value of radiologic imaging of the thymus gland in myasthenia gravis

    International Nuclear Information System (INIS)

    Glathe, S.; Neufang, K.F.R.; Haupt, F.W.

    1989-01-01

    Radiologic imaging in myasthenia gravis is used for the evaluation of pathologic changes of the thymus gland. Computed tomography can demonstrate tumors of the anterior mediastinum in nearly 90% and is therefore superior to conventional radiography.Because of the variety of size and shape of the normal thymus gland, differentiation between normal thymus, follicular hyperplasia and thymoma is rarely possible especially in younger patients. In elderly patients with myasthenia gravis and involution of the thymus gland tumors of the thymus are reliably detected by computed tomography, whereas the ability of computed tomography to predict the histological diagnosis is poor even with intravenous administration of contrast media. (orig.) [de

  18. Migration of bone marrow cells to the thymus in sublethally irradiated mice

    International Nuclear Information System (INIS)

    Varlet, Andree; Lenaerts, Patrick; Houben-Defresne, M.P.; Boniver, Jacques

    1982-01-01

    In sublethally irradiated mice, thymus repopulation is due first to the proliferation of surviving thymocytes followed by the multiplication of bone marrow derived prothymocytes. The migration of bone marrow cells to the thymus after a single sublethal whole-body X irradiation was studied by using fluorescein isothiocyanate as a cell marker. Irradiation increases the permissiveness of the thymus to the immigration of bone marrow cells. Furthermore, the post-Rx regenerating bone marrow cells exhibit migration capacities greater than the normal ones. The radiation induced changes in the bone marrow thymus interaction might play an important role in thymus regeneration after sublethal irradiation [fr

  19. In vitro secretion profiles of interleukin (IL-1beta, IL-6, IL-8, IL-10, and TNF alpha after selective infection with Escherichia coli in human fetal membranes

    Directory of Open Access Journals (Sweden)

    Maida-Claros Rolando

    2007-12-01

    Full Text Available Abstract Background Chorioamniotic membranes infection is a pathologic condition in which an abnormal secretion of proinflammatory cytokines halts fetal immune tolerance. The aim of the present study was to evaluate the functional response of human chorioamniotic membranes, as well as the individual contribution of the amnion and choriodecidua after stimulation with Escherichia coli, a pathogen associated with preterm labor. Methods Explants of chorioamniotic membranes from 10 women (37–40 weeks of gestation were mounted and cultured in a Transwell system, which allowed us to test the amnion and choriodecidua compartments independently. Escherichia coli (1 × 10 6 CFU/mL was added to either the amniotic or the choriodecidual regions or both; after a 24-h incubation, the secretion of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10 in both compartments was measured using a specific ELISA. Data were analyzed by Kruskal-Wallis one-way analysis of variance. Results After stimulation with Escherichia coli, the choriodecidua compartment showed an increase in the secretion of IL-1beta (21-fold, IL-6 (2-fold, IL-8 (6-fold, and IL-10 (37-fold, regardless of which side of the membrane was stimulated; TNFalpha secretion augmented (22-fold also but only when the stimulus was applied simultaneously to both sides. When the amnion was stimulated directly, the level of IL-1beta (13-fold rose significantly; however, the increase in IL-8 secretion was larger (20-fold, regardless of the primary site of infection. TNFalpha secretion in the amnion compartment rose markedly only when Escherichia coli was simultaneously applied to both sides. Conclusion Selective stimulation of fetal membranes with Escherichia coli results in a differential production of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10. These tissues were less responsive when the amnion side was stimulated. This is in agreement with the hypothesis that the choriodecidua may play a primary role during an ascending

  20. Fetal behavioral teratology.

    Science.gov (United States)

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

    2010-10-01

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

  1. Air pollution and the fetal origin of disease: A systematic review of the molecular signatures of air pollution exposure in human placenta.

    Science.gov (United States)

    Luyten, Leen J; Saenen, Nelly D; Janssen, Bram G; Vrijens, Karen; Plusquin, Michelle; Roels, Harry A; Debacq-Chainiaux, Florence; Nawrot, Tim S

    2018-06-13

    Fetal development is a crucial window of susceptibility in which exposure-related alterations can be induced on the molecular level, leading to potential changes in metabolism and development. The placenta serves as a gatekeeper between mother and fetus, and is in contact with environmental stressors throughout pregnancy. This makes the placenta as a temporary organ an informative non-invasive matrix suitable to investigate omics-related aberrations in association with in utero exposures such as ambient air pollution. To summarize and discuss the current evidence and define the gaps of knowledge concerning human placental -omics markers in association with prenatal exposure to ambient air pollution. Two investigators independently searched the PubMed, ScienceDirect, and Scopus databases to identify all studies published until January 2017 with an emphasis on epidemiological research on prenatal exposure to ambient air pollution and the effect on placental -omics signatures. From the initial 386 articles, 25 were retained following an a priori set inclusion and exclusion criteria. We identified eleven studies on the genome, two on the transcriptome, five on the epigenome, five on the proteome category, one study with both genomic and proteomic topics, and one study with both genomic and transcriptomic topics. Six studies discussed the triple relationship between exposure to air pollution during pregnancy, the associated placental -omics marker(s), and the potential effect on disease development later in life. So far, no metabolomic or exposomic data discussing associations between the placenta and prenatal exposure to air pollution have been published. Integration of placental biomarkers in an environmental epidemiological context enables researchers to address fundamental questions essential in unraveling the fetal origin of disease and helps to better define the pregnancy exposome of air pollution. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Neuroendocrine cells during human prostate development: does neuroendocrine cell density remain constant during fetal as well as postnatal life?

    NARCIS (Netherlands)

    Xue, Y.; van der Laak, J.; Smedts, F.; Schoots, C.; Verhofstad, A.; de la Rosette, J.; Schalken, J.

    2000-01-01

    Knowledge concerning differentiation of neuroendocrine (NE) cells during development of the human prostate is rather fragmentary. Using immunohistochemistry combined with a morphometric method, we investigated the distribution and density of NE cells in the developing human prostate, with special

  3. Metabolism of progesterone-4-14C in organ cultures of fetal adrenal glands in the human being

    International Nuclear Information System (INIS)

    Weber, S.

    1979-01-01

    1. In 72 hours of incubation in two subsequent cultures, progesterone-4- 14 C was converted into different corticosteroids and androgenes by using explants of the adrenal glands in organ cultures, which were taken from a male fetus with a crown-to-rump length of 8.5 cm. In the most cases the water-dilutable metabolites are steroidsulfates. 2. The following individual progesterone metabolites were found: 17α-hydroxyprogesterone-4- 14 C, 16α-hydroxyprogesterone-4- 14 C, corticosterone-4- 14 C, cortisole-4- 14 C, cortisone-4- 14 C, androstendione-4- 14 C, and 11β-hydroxyandrostendione-4- 14 C. 3. These steroides let appear possible the presence and efficacy of the following enzyme systems: 17α-hydroxylase, 16α-hydroxylase, 21-hydroxylase, 11β-hydroxylase, 11β-hydroxysteroide-dehydrogenase, and Csub(17-20) desmolase. 4. Calculations of our dates by the analogue computer, which are present by now, apparently seem to render possible the kinetic of the corticosteroide biosynthesis in the tissue of fetal adrenal glands by organ cultures, because under the present conditions incubations can be carried out for considerably longer periods than by cell fractions, cell homogenates, and organ sections. (orig.) [de

  4. 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

  5. [Proliferative capacity of mesenchymal stem cells from human fetal bone marrow and their ability to differentiate into the derivative cell types of three embryonic germ layers].

    Science.gov (United States)

    Wang, Yue-Chun; Zhang, Yuan

    2008-06-25

    Strong proliferative capacity and the ability to differentiate into the derivative cell types of three embryonic germ layers are the two important characteristics of embryonic stem cells. To study whether the mesenchymal stem cells from human fetal bone marrow (hfBM-MSCs) possess these embryonic stem cell-like biological characteristics, hfBM-MSCs were isolated from bone barrows and further purified according to the different adherence of different kinds of cells to the wall of culture flask. The cell cycle of hfBM-MSCs and MSC-specific surface markers such as CD29, CD44, etc were identified using flow cytometry. The expressions of human telomerase reverse transcriptase (hTERT), the embryonic stem cell-specific antigens, such as Oct4 and SSEA-4 were detected with immunocytochemistry at the protein level and were also tested by RT-PCR at the mRNA level. Then, hfBM-MSCs were induced to differentiate toward neuron cells, adipose cells, and islet B cells under certain conditions. It was found that 92.3% passage-4 hfBM-MSCs and 96.1% passage-5 hfBM-MSCs were at G(0)/G(1) phase respectively. hfBM-MSCs expressed CD44, CD106 and adhesion molecule CD29, but not antigens of hematopoietic cells CD34 and CD45, and almost not antigens related to graft-versus-host disease (GVHD), such as HLA-DR, CD40 and CD80. hfBM-MSCs expressed the embryonic stem cell-specific antigens such as Oct4, SSEA-4, and also hTERT. Exposure of these cells to various inductive agents resulted in morphological changes towards neuron-like cells, adipose-like cells, and islet B-like cells and they were tested to be positive for related characteristic markers. These results suggest that there are plenty of MSCs in human fetal bone marrow, and hfBM-MSCs possess the embryonic stem cell-like biological characteristics, moreover, they have a lower immunogenic nature. Thus, hfBM-MSCs provide an ideal source for tissue engineering and cellular therapeutics.

  6. Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues.

    Science.gov (United States)

    Cohen, Shahar; Leshansky, Lucy; Zussman, Eyal; Burman, Michael; Srouji, Samer; Livne, Erella; Abramov, Natalie; Itskovitz-Eldor, Joseph

    2010-10-01

    The use of stem cells for tissue engineering (TE) encourages scientists to design new platforms in the field of regenerative and reconstructive medicine. Human embryonic stem cells (hESC) have been proposed to be an important cell source for cell-based TE applications as well as an exciting tool for investigating the fundamentals of human development. Here, we describe the efficient derivation of connective tissue progenitors (CTPs) from hESC lines and fetal tissues. The CTPs were significantly expanded and induced to generate tendon tissues in vitro, with ultrastructural characteristics and biomechanical properties typical of mature tendons. We describe a simple method for engineering tendon grafts that can successfully repair injured Achilles tendons and restore the ankle joint extension movement in mice. We also show the CTP's ability to differentiate into bone, cartilage, and fat both in vitro and in vivo. This study offers evidence for the possibility of using stem cell-derived engineered grafts to replace missing tissues, and sets a basic platform for future cell-based TE applications in the fields of orthopedics and reconstructive surgery.

  7. 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)

    2012-01-01

    Introduction 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. Methods 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. Results 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. Conclusions 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. PMID:22333342

  8. CARBOXYLIC ACIDS OF HERB OF THYMUS CRETACEUS KLOK. ET SCHOST

    Directory of Open Access Journals (Sweden)

    V. N. Bubenchikova

    2014-01-01

    Full Text Available We have studied carboxylic acids of the herb of Thymus cretaceus Klok. et Schost which is widespread on a territory of some regions (Belgorod, Voronezh. The study was carried out using gas-liquid chromatography at Agilent Technologies 6890 chromatographer with massspectrometric detector 5973 N. Acids concentration was calculated by means of inner standard.We have established that carboxylic acids of Thymus cretaceus are represented by 34 compounds. Palmitic (1779.02 mg/kg, behenic (1084.15 mg/kg, levulinic (986.24 mg/kg and linoleic acids (678.82 mg/kg predominate among fatty acids; citric (9835.14 mg/kg, malonic (447.91 mg/kg and oxalic acids (388.32 mg/kg predominate among organic acids; andferulic acid predominate amongphenolcarbonic acids.

  9. Gap junction modulation by extracellular signaling molecules: the thymus model

    Directory of Open Access Journals (Sweden)

    Alves L.A.

    2000-01-01

    Full Text Available Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

  10. Effect of Interleukin 1b on rat thymus microenvironment

    Directory of Open Access Journals (Sweden)

    M Artico

    2009-12-01

    Full Text Available The effect of interleukin 1b on the thymus of control and chemically sympathectomized adult and aged rats was studied with the aim of assessing the importance of adrenergic nerve fibres (ANF in the regulation of some immunological functions.The whole thymus was removed from normal, sympathectomized (with the neurotoxin 6-OH-dopamine and treated (interleukin 1b rats. Thymic slices were stained with eosin orange (for the recognition of microanatomical details of the thymic microenvironment and with Bodian’s method for staining of nerve fibres. Histofluorescence microscopy was employed for staining ANF and immunofluorescence was used for detecting NPY-like immunoreactivity. All images were submitted to quantitative morphometrical analysis and statistical analysis of data. Moreover, the amount of proteins and noradrenaline was measured on thymic homogenates. The results indicate that in normal conditions the formation of the thymic nerve plexi in the rat is complex: the majority of ANF are destroyed after chemical sympathectomy with 6-OH-dopamine and do not change after treatment with interleukin 1b; on the contrary, treatment with interleukin 1b induces substantial changes in the fresh weight of the thymus, the thymic microenvironment, thymic nerve fibers, ANF, NPY-like positive nerve fibres, and on the total amount of proteins and noradrenaline in rat thymic tissue homogenates.Immunostimulation with interleukin 1b induces substantial changes in the whole thymus, in its microenvironment and in ANF and NPY-like nerve fibres. After chemical sympathectomy, no significant immune response was evoked by interleukin 1b, since the majority of ANF was destroyed by chemical sympathectomy.

  11. Quantitative analysis of thymus lymphoid cells during murine radioleukemogenesis

    International Nuclear Information System (INIS)

    Boniver, J.; Simar, L.J.; Courtoy, R.; Betz, E.H.

    1978-01-01

    Fractionated irradiation by four doses of 150 R leads to the development of lymphoma in the thymus of C57BL mice, after a long latent period (4 to 12 months) during which thymic subcapsular blast cells undergo neoplastic transformation. Electron microscope studies on this blast cell population have revealed several types that are distinguishable on the basis of nuclear ultrastructure and activity in the cell cycle. These blast cells are lymphoblasts, ring-shaped nucleolus cells, and x-cells. A stereological analysis demonstrates that the result of the irradiations is not an increase of the thymic blast cell number during the preleukemic period, as generally thought before, but important modifications in the relative proportion of the three cell types forming the blastic population. X-cells, which essentially appear in S phase, are more numerous after the third and fourth doses of radiation. They might be more ''sensitive'' to the action of the leukemogenic virus and facilitate the leukemogenic process. In contrast, in the preleukemic atrophic thymus just before the appearance of the lymphoma, x-cells are scarce, and ring-shaped nucleolus cells are more frequent than in the controls, suggesting important changes in thymus cell kinetics. The only modification detected in the blast cells at any time after irradiation concerns the surface of Golgi membranes, which decreases in x-cells and ring-shaped nucleolus cells of the atrophic thymus. Because the same change is observed later on in the lymphomatous cells, it is suggested that the change might be related to the transformation of the thymic blast cells into cancerous cells

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  13. Prognosis of thymectomy in myasthenia gravis patients with thymus hyperplasia.

    Science.gov (United States)

    Yang, Jing; Liu, Chanchan; Li, Tao; Li, Chengyan

    2017-09-01

    To compare the post-thymectomy prognosis in different conditions of myasthenia gravis (MG) patients with thymus hyperplasia. Collecting medical record and carrying out the follow-up study of 123 myasthenia gravis patients with thymus hyperplasia who have underwent thymectomy during the period between 2003 and 2013. Dividing into different groups based on gender, age of onset, duration of disease and Myasthenia Gravis Association of America (MGFA) clinical classification to analyze different prognosis in different groups. Complete stable remission (CSR) was achieved in 71 of 123 patients (59.5%). There is no gender-related difference in achieving CSR. Patients with early onset of MG (≤40 years old) or disease duration less than 12 months had significantly higher CSR rates than those with late onset of MG (>40 years old) or disease duration more than 12 months respectively, while no difference was found in remission rate between MGFA clinical classification I and MGFA II. Myasthenia gravis patients with thymus hyperplasia who had thymectomy are proved to possess greater chance of achieving CSR. The onset age of disease and duration are the prognostic factors.

  14. 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

    -PAGE analysis gave an M(r) = 27 kDa under reducing and non-reducing conditions for both forms, whereas the exact M(r) determined by mass spectrometry was 14,343 +/- 3 Da. FA2 was N-terminally blocked and after tryptic digestion the amino acid composition and sequences of the peptides showed identity...... 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...... 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...

  15. Metabolism of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured human fetal aortic smooth muscle cells

    International Nuclear Information System (INIS)

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

    1979-01-01

    Cultured human fetal aortic smooth muscle cells derived from the abdominal aorta converted benzo[a]pyrene (BaP) and 7,12-dimethylbenz[a]anthracene (DMBA) via cytochrome P-450-dependent monooxygenation to metabolites detectable by both a highly sensitive radiometric assay and high pressure liquid chromatography (HPLC). Cells incubated with 3 H-BaP transformed this substrate primarily to phenols. 14 C-DMBA was converted to metabolites that cochromatographed with 12-hydroxymethyl-methylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, 7- 7,12-dihydroxymethylbenz[a]anthracene, and trans-8,9-dihydrodiol-7,12-DMBA. Exposure of cells in culture to 13 μM 1,2-benz[a]anthracene resulted in increased oxidative metabolism of both BaP and DMBA. In the case of BaP, total phenol formation was increased, while with DMBA all metabolites detected by HPLC were increased. Support for the potential role of metabolism of polycyclic aromatic hydrocarbons by aortic smooth muscle cells in the etiology of atherosclerosis was obtained

  16. 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.

  17. 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.

  18. 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.

  19. Radiation effects on regeneration and T-cell-inducing function of the thymus

    International Nuclear Information System (INIS)

    Hirokawa, K.; Sado, T.

    1984-01-01

    Radiation effects on regeneration and T-cell-inducing function of the thymus were studied in three sets of experiments. When TXB mice were grafted with 1-week-old thymus which had been previously irradiated at various doses, an exponential decrease was observed in the morphological regeneration of the thymus grafts and in their T-cell-inducing function at doses of 600 R and over, showing about 10% that of the control at 1500 R. When in situ thymus of adult mice was locally irradiated, the radiation effect on T-cell-inducing function was less pronounced as compared with the first experiment; i.e., about 40% of the control at 1797 R. When in situ thymus of 1-day-old newborn mice was locally irradiated, regeneration potential of 1-day-old newborn thymus was highly resistant to radiation exposure and no effect on immunological functions was observed even by local irradiation of 2000 R

  20. 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

  1. 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 ...

  2. EBV promotes human CD8 NKT cell development.

    Directory of Open Access Journals (Sweden)

    Yuling He

    2010-05-01

    Full Text Available The reports on the origin of human CD8(+ Valpha24(+ T-cell receptor (TCR natural killer T (NKT cells are controversial. The underlying mechanism that controls human CD4 versus CD8 NKT cell development is not well-characterized. In the present study, we have studied total 177 eligible patients and subjects including 128 healthy latent Epstein-Barr-virus(EBV-infected subjects, 17 newly-onset acute infectious mononucleosis patients, 16 newly-diagnosed EBV-associated Hodgkin lymphoma patients, and 16 EBV-negative normal control subjects. We have established human-thymus/liver-SCID chimera, reaggregated thymic organ culture, and fetal thymic organ culture. We here show that the average frequency of total and CD8(+ NKT cells in PBMCs from 128 healthy latent EBV-infected subjects is significantly higher than in 17 acute EBV infectious mononucleosis patients, 16 EBV-associated Hodgkin lymphoma patients, and 16 EBV-negative normal control subjects. However, the frequency of total and CD8(+ NKT cells is remarkably increased in the acute EBV infectious mononucleosis patients at year 1 post-onset. EBV-challenge promotes CD8(+ NKT cell development in the thymus of human-thymus/liver-SCID chimeras. The frequency of total (3% of thymic cells and CD8(+ NKT cells ( approximately 25% of NKT cells is significantly increased in EBV-challenged chimeras, compared to those in the unchallenged chimeras (<0.01% of thymic cells, CD8(+ NKT cells undetectable, respectively. The EBV-induced increase in thymic NKT cells is also reflected in the periphery, where there is an increase in total and CD8(+ NKT cells in liver and peripheral blood in EBV-challenged chimeras. EBV-induced thymic CD8(+ NKT cells display an activated memory phenotype (CD69(+CD45RO(hiCD161(+CD62L(lo. After EBV-challenge, a proportion of NKT precursors diverges from DP thymocytes, develops and differentiates into mature CD8(+ NKT cells in thymus in EBV-challenged human-thymus/liver-SCID chimeras or

  3. 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

  4. COMPARATIVE STUDY OF PIGMENTS ON REGENERANTS FROM IN VITRO AND SPONTANEOUS FLORA OF THYMUS sp.

    Directory of Open Access Journals (Sweden)

    ANA M. ROŞU

    2016-12-01

    Full Text Available This paper presents the quantitative determination of pigments extract of Thymus sp. from in vitro culture and spontaneous flora. For in vitro culture were used phytohormones (indoleacetic acid-IAA, indole-3-butyric acid-IBA and benzylaminopurine-BAP in order to obtain a high yield in development of Thymus sp. plants. The source of spontaneous flora of Thymus sp. was Bacau (Magura, Romania. The biochemical investigations realised on Thymus sp. using Thin Layer Chromatography and the UV-Vis spectrophotometry showed that the production of assimilating pigments is influenced by growth and lighting conditions of plants.

  5. 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.

  6. Sequence of interleukin-2 isolated from human placental poly A+ RNA: possible role in maintenance of fetal allograft.

    Science.gov (United States)

    Chernicky, C L; Tan, H; Burfeind, P; Ilan, J; Ilan, J

    1996-02-01

    There are several cell types within the placenta that produce cytokines which can contribute to the regulatory mechanisms that ensure normal pregnancy. The immunological milieu at the maternofetal interface is considered to be crucial for survival of the fetus. Interleukin-2 (IL-2) is expressed by the syncytiotrophoblast, the cell layer between the mother and the fetus. IL-2 appears to be a key factor in maintenance of pregnancy. Therefore, it was important to determine the sequence of human placental interleukin-2. Direct sequencing of human placental IL-2 cDNA was determined for the coding region. Subclone sequencing was carried out for the 5'- and 3'-untranslated regions (5'-UTR and 3'-UTR). The 5'-UTR for human placental IL-2 cDNA is 294 bp, which is 247 nucleotides longer than that reported for cDNA IL-2 derived from T cells. The sequence of the coding region is identical to that reported for T cell IL-2, while sequence analysis of the polymerase chain reaction (PCR) product showed that the cDNA from the 3' end was the same as that reported for cDNA from T cells. Human placental IL-2 cDNA is 1,028 base pairs (excluding the poly A tail), which is 247 bp longer at the 5' end than that reported for IL-2 T cell cDNA. Therefore, the extended 5'-UTR of the placental IL-2 cDNA may be a consequence of alternative promoter utilization in the placenta.

  7. Effects of Thymus vulgaris Essential Oil on Decay Resistance and Quality of Iranian Table Grape

    Directory of Open Access Journals (Sweden)

    Mahsa GERANSAYEH

    2012-11-01

    Full Text Available Because of greater consumer awareness and concern regarding synthetic chemical additives, foods preserved with natural additives have become popular. Medicinal plants have been used by human being since ages in traditional medicine due to their therapeutic potential and the search on medicinal plants have led the discovery of novel drug candidates used against diverse diseases. Therefore Thymus vulgaris essential oil was applied in Bidaneh Qermez grape cultivar at six concentrations (0, 100, 200, 300, 400 and 500 ?l/l in water. Quality characteristics (pH, decay, vitamin C, reducing sugars, weight loss, berry abscission, dehydration of rachis, berry cracking and sensory analyses were evaluated. The results showed that treated fruits with essential oil had lower decay percentage, dehydration of rachis, berry abscission, berry cracking and higher pH, reducing sugars and storage quality compared to control. As a general result, essential oil treatment caused lower decay incident and longer storability.

  8. Effects of Thymus vulgaris Essential Oil on Decay Resistance and Quality of Iranian Table Grape

    Directory of Open Access Journals (Sweden)

    Mahsa GERANSAYEH

    2012-11-01

    Full Text Available Because of greater consumer awareness and concern regarding synthetic chemical additives, foods preserved with natural additives have become popular. Medicinal plants have been used by human being since ages in traditional medicine due to their therapeutic potential and the search on medicinal plants have led the discovery of novel drug candidates used against diverse diseases. Therefore Thymus vulgaris essential oil was applied in �Bidaneh Qermez� grape cultivar at six concentrations (0, 100, 200, 300, 400 and 500 ?l/l in water. Quality characteristics (pH, decay, vitamin C, reducing sugars, weight loss, berry abscission, dehydration of rachis, berry cracking and sensory analyses were evaluated. The results showed that treated fruits with essential oil had lower decay percentage, dehydration of rachis, berry abscission, berry cracking and higher pH, reducing sugars and storage quality compared to control. As a general result, essential oil treatment caused lower decay incident and longer storability.

  9. Essential Oil of Thymus munbyanus subsp. coloratus from Algeria: Chemotypification and in vitro Biological Activities.

    Science.gov (United States)

    Bendif, Hamdi; Boudjeniba, Messaoud; Miara, Mohamed Djamel; Biqiku, Loreta; Bramucci, Massimo; Lupidi, Giulio; Quassinti, Luana; Vitali, Luca A; Maggi, Filippo

    2017-03-01

    Thymus munbyanus subsp. coloratus (Lamiaceae) is a small shrub endemic to Algeria and Morocco where is found in lawns, rockeries and mountainous regions. From a phytochemical point of view this taxon has never been characterized. In this work we have analysed the chemical compositions of the essential oils obtained from inflorescences and vegetative parts by GC/MS. A new chemotype, i.e. borneol-chemotype, was characterized for the first time in the species. Furthermore, we assessed the biological activities of essential oils, namely the antioxidant, antimicrobial and cytotoxicity on tumor cells that were evaluated by the DPPH, ABTS, and FRAP, disc diffusion, and MTT methods, respectively. Biological assays highlighted a moderate inhibitory effect on Staphylococcus aureus, Escherichia coli and Candida albicans (inhibition zone diameter in the range 9 - 10 mm), and noteworthy cytotoxicity on A375 human melanoma cells (IC 50 of 46.95 μg/ml). © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  10. Computer tomographic examination of the thymus. Normal and pathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, C.; Dinkel, E.; Wimmer, B.; Grosser, G.; Schildge, J.

    1987-09-01

    The diagnostic value of CT in follicular thymic hyperplasia and in thymomas in 8 patients with myasthenia gravis and in 12 patients without myasthenia gravis suffering from thymic tumors was evaluated by correlating CT-findings to surgical results and pathological-histological findings. Thymic size of the six patients with histologically proven follicular hyperplasia were scattered within the normal range, but half of them were at the upper limit. Thymic tumors were differentiated between invasive and non invasive tumors by CT staging. Solid tumors with different histology could not be further classified; the attenuation values ranging from 15-55 HU were the same in tumors, follicular hyperplasia and normal thymus.

  11. Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery

    International Nuclear Information System (INIS)

    Brown, Nicole; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2006-01-01

    Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effects of DES on T-cell differentiation in the thymus using the HY-TCR transgenic (Tg) mouse model in which the female mice exhibit positive selection of T cells bearing the Tg TCR, while the male mice show negative selection of such T cells. In female HY-TCR-Tg mice, exposure to DES showed more pronounced decrease in thymic cellularity when compared to male mice. Additionally, female mice also showed a significant decrease in the proportion of double-positive (DP) T cells in the thymus and HY-TCR-specific CD8 + T cells in the periphery. Male mice exhibiting negative selection also showed decreased thymic cellularity following DES exposure. Moreover, the male mice showed increased proportion of double-negative (DN) T cells in the thymus and decreased proportion of CD8 + T cells. The density of expression of HY-TCR on CD8 + cells was increased following DES exposure in both females and males. Finally, the proliferative response of thymocytes to mitogens and peripheral lymph node T cells to male H-Y antigen was significantly altered in female and male mice following DES treatment. Taken together, these data suggest that DES alters T-cell differentiation in the thymus by interfering with positive and negative selection processes, which in turn modulates the T-cell repertoire in the periphery

  12. MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

    International Nuclear Information System (INIS)

    Li, Xiaoou; Liu, Lian; Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan; Wen, Fuqiang

    2014-01-01

    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

  13. 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.

  14. 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...

  15. 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...... expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens. METHODS AND RESULTS: We detected abundant expression of NANOG in CIS and in CIS-derived testicular tumours with marked differences...

  16. Effects of mesenchymal stem cells on thymus tissue injury induced by ionizing radiation in mice

    International Nuclear Information System (INIS)

    Wang Hongyan; Qi Yali; Gong Shouliang; Song Xiangfu; Liu Liping; Chen Yubing

    2009-01-01

    Objective: To observe the migration,colonization and repairing effects of marrow mesenchymal stem cells (MSCs) on thymus tissue injury induced by ionizing radiation in mice. Methods: MSCs of C57BL/6 mice were isolated, purified and cultivated in vitro. Their migration and colorization were observed with laser confocal microscopy 1, 5 and 10 d after DAPI labeled. MSCs were injected into the thymus tissue of mice through tail vein. The model of thymus tissue injury induced by whole-body X-irradiation was established. The mice were divided into four groups: normal, irradiation, irradiation+saline, and irradiation+MSCs groups. The apoptosis was detected by flow cytometry and the repairing effect of MSCs on thymus tissue injury was observed by histological method 3 months later. Results: The occurrence of MSCs in the thymus was observed 1 d after MSCs injection, the diffusion of MSCs in the thymus appeared 5 d later, and widely dispersed 10 d later. The apoptotic rate of thymocytes in irradiation group was higher than that in normal (P<0.05) and was lower than that in MSCs group (P<0.05). The structures of cortex and medulla of thymus were clear in mice in normal group, there were a large number of lymphocytes in the cortex and small number of lymphocytes in the medulla. The structures of cortex and medulla of thymus were unclear in mice in both irradiation, irradiation and saline groups. The lymphocytes in thymus showed extensive coagulation necrosis. There were remnants or newborn lymphoid tissue in the cortex and medulla in mice in irradiation+MSCs groups. Conclusion: MSCs can be rapidly enriched in thymus tissue and promote regeneration and repair of damaged thymus. (authors)

  17. 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 ...

  18. An EG-VEGF-dependent decrease in homeobox gene NKX3.1 contributes to cytotrophoblast dysfunction: a possible mechanism in human fetal growth restriction.

    Science.gov (United States)

    Murthi, P; Brouillet, S; Pratt, A; Borg, Aj; Kalionis, B; Goffin, F; Tsatsaris, V; Munaut, C; Feige, Jj; Benharouga, M; Fournier, T; Alfaidy, N

    2015-07-21

    Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that EG-VEGF (endocrine gland derived-vascular endothelial growth factor), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesise that EG-VEGF-dependent change in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a Homeobox gene cDNA array on placental explants of 8-12 weeks' gestation after stimulation with EG-VEGF in vitro for 24 hours. The Homeobox gene array identified a >5-fold increase in HOXA9, HOXC8, HOXC10, HOXD1, HOXD8, HOXD9 and HOXD11, while NKX 3.1 showed a >2 fold-decrease in mRNA expression compared to untreated controls. Homeobox gene NKX3.1 was selected as a candidate because it is a downstream target of EG-VEGF and its expression and functional role are largely unknown in control and idiopathic FGR-affected placentae. Real-time PCR and immunoblotting showed a significant decrease in NKX3.1 mRNA and protein levels, respectively, in placentae from FGR compared to control pregnancies. Gene inactivation in vitro using short-interference RNA specific for NKX3.1 demonstrated an increase in BeWo cell differentiation and a decrease in HTR8-SVneo proliferation. We conclude that the decreased expression of homeobox gene NKX3.1 down-stream of EG-VEGF may contribute to the trophoblast dysfunction associated with idiopathic FGR pregnancies.

  19. Fetal development of deep back muscles in the human thoracic region with a focus on transversospinalis muscles and the medial branch of the spinal nerve posterior ramus

    Science.gov (United States)

    Sato, Tatsuo; Koizumi, Masahiro; Kim, Ji Hyun; Kim, Jeong Hyun; Wang, Bao Jian; Murakami, Gen; Cho, Baik Hwan

    2011-01-01

    Fetal development of human deep back muscles has not yet been fully described, possibly because of the difficulty in identifying muscle bundle directions in horizontal sections. Here, we prepared near-frontal sections along the thoracic back skin (eight fetuses) as well as horizontal sections (six fetuses) from 14 mid-term fetuses at 9–15 weeks of gestation. In the deep side of the trapezius and rhomboideus muscles, the CD34-positive thoracolumbar fascia was evident even at 9 weeks. Desmin-reactivity was strong and homogeneous in the superficial muscle fibers in contrast to the spotty expression in the deep fibers. Thus, in back muscles, formation of the myotendinous junction may start from the superficial muscles and advance to the deep muscles. The fact that developing intramuscular tendons were desmin-negative suggested little possibility of a secondary change from the muscle fibers to tendons. We found no prospective spinalis muscle or its tendinous connections with other muscles. Instead, abundant CD68-positive macrophages along the spinous process at 15 weeks suggested a change in muscle attachment, an event that may result in a later formation of the spinalis muscle. S100-positive intramuscular nerves exhibited downward courses from the multifidus longus muscle in the original segment to the rotatores brevis muscles in the inferiorly adjacent level. The medial cutaneous nerve had already reached the thoracolumbar fascia at 9 weeks, but by 15 weeks the nerve could not penetrate the trapezius muscle. Finally, we propose a folded myotomal model of the primitive transversospinalis muscle that seems to explain a fact that the roofing tile-like configuration of nerve twigs in the semispinalis muscle is reversed in the multifidus and rotatores muscles. PMID:21954879

  20. Características morfométricas do desenvolvimento do timo em cães Morphometric characteristics of thymus development in dogs

    Directory of Open Access Journals (Sweden)

    Fernanda R. Agreste

    2007-06-01

    Full Text Available O timo é um órgão de grande importância imunológica durante a vida fetal e o período neonatal. Ele é o precursor da linfopoiese e apresenta alta atividade linfopoiética, sendo também o maior órgão linfóide durante a vida intrauterina e até o nascimento. Neste estudo, os aspectoso morfológicos do desenvolvimento prenatal de timos de cães foram descritos em fetos de diferentes idades e sexos. Vinte e quatro fetos de cães domésticos, sem raça definida, machos e fêmeas, foram divididos em 4 grupos etários. O timo apresentou-se composto por dois lobos unidos por um tecido de conexão, com coloração rósea, localizados no espaço mediastinal cranial. A porção cranial estendeu-se pouco além do primeiro par de costelas. As células que formavam o parênquima do timo estavam bem organizadas. Agrega dos concêntricos chamados Corpúsculos de Hassal foram observados, envolvidos por uma delgada cápsula de tecido conjuntivo que é espessada por tecido adiposo. O tamanho dos vasos aumentou gradativamente com a idade dos fetos, sendo maior nos animais próximos ao nascimento. Os timos das fêmeas apresentaram maior volume (Vref e dimensões de tamanho que nos machos.The thymus is an organ with great immunological relevance during foetus life and neonatal period, It is the predecessor of lymphopoiesis and shows high lymphopoietic activity, being also the largest lymphoid organ during intrauterine life and at birth. In this study, the morphological aspects of the prenatal development of dog thymus were described in foetus of different ages and sexes. Twenty-four foetus of mongrel domestic dogs, males and females, were divided into four age groups. The thymus presented two lobes linked by a rose-colored tissue connection that was localized in the cranial mediastinal space. The cranial portion protrudes slightly beyond the first pair of ribs. The cells that formed the thymus parenchyma were well organized. Concentric aggregates named

  1. Melatonin regulates PARP1 to control the senescence-associated secretory phenotype (SASP) in human fetal lung fibroblast cells.

    Science.gov (United States)

    Yu, Songtao; Wang, Xiaojiao; Geng, Peiliang; Tang, Xudong; Xiang, Lisha; Lu, Xin; Li, Jianjun; Ruan, Zhihua; Chen, Jianfang; Xie, Ganfeng; Wang, Zhe; Ou, Juanjuan; Peng, Yuan; Luo, Xi; Zhang, Xuan; Dong, Yan; Pang, Xueli; Miao, Hongming; Chen, Hongshan; Liang, Houjie

    2017-08-01

    Cellular senescence is an important tumor-suppressive mechanism. However, acquisition of a senescence-associated secretory phenotype (SASP) in senescent cells has deleterious effects on the tissue microenvironment and, paradoxically, promotes tumor progression. In a drug screen, we identified melatonin as a novel SASP suppressor in human cells. Strikingly, melatonin blunts global SASP gene expression upon oncogene-induced senescence (OIS). Moreover, poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, was identified as a new melatonin-dependent regulator of SASP gene induction upon OIS. Here, we report two different but potentially coherent epigenetic strategies for melatonin regulation of SASP. The interaction between the telomeric repeat-containing RNA (TERRA) and PARP-1 stimulates the SASP, which was attenuated by 67.9% (illustrated by the case of IL8) by treatment with melatonin. Through binding to macroH2A1.1, PARP-1 recruits CREB-binding protein (CBP) to mediate acetylation of H2BK120, which positively regulates the expression of target SASP genes, and this process is interrupted by melatonin. Consequently, the findings provide novel insight into melatonin's epigenetic role via modulating PARP-1 in suppression of SASP gene expression in OIS-induced senescent cells. Our studies identify melatonin as a novel anti-SASP molecule, define PARP-1 as a new target by which melatonin regulates SASP, and establish a new epigenetic paradigm for a pharmacological mechanism by which melatonin interrupts PARP-1 interaction with the telomeric long noncoding RNA(lncRNA) or chromatin. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. T cell precursor migration towards beta 2-microglobulin is involved in thymus colonization of chicken embryos

    DEFF Research Database (Denmark)

    Dunon, D; Kaufman, J; Salomonsen, J

    1990-01-01

    beta 2-microglobulin (beta 2m) attracts hemopoietic precursors from chicken bone marrow cells in vitro. The cell population responding to beta 2m increases during the second period of thymus colonization, which takes place at days 12-14 of incubation. The precursors from 13.5 day old embryos were...... isolated after migration towards beta 2m in vitro and shown to be able to colonize a 13 day old thymus in ovo, where they subsequently acquire thymocyte markers. In contrast these beta 2m responsive precursors did not colonize embryonic bursa, i.e. differentiate into B lymphocytes. During chicken...... embryogenesis, peaks of beta 2m transcripts and of free beta 2m synthesis can only be detected in the thymus. The peak of free beta 2m synthesis in the thymus and the increase of beta 2m responding bone marrow cells both occur concomitantly with the second wave of thymus colonization in chicken embryo, facts...

  3. Diagnostic potentialities of pneumomediastinography and selective phlebography in the evaluation of thymus evolution in myasthenia

    Energy Technology Data Exchange (ETDEWEB)

    Vasil' ev, V.N.; Bel' chikova, N.S.; Kuksinskij, V.E. (Leningradskij Inst. Usovershenstvovaniya Vrachej (USSR))

    1983-01-01

    Based on an analysis of X-ray, intraoperative and histological findings in 124 operated on patients (thymectomy) with myasthenia the authors describe potentialities of pneumomediastinography (PMG) (pheumomediastinotomography-PMTG) in the determination of its main variants (hyperplasia, involution, tumor). Clear knowledge of the variants of x-ray image of the normal anatomical structures of the anterior mediastinum and age peculiarities of the thymus for correct interpretation of pneumomediastinograms is necessary. The importance of selective phlebography of the thymus for differential diagnosis of thymomas and nodular indurations of the fatty tissue in the anterior mediastinum, thymomas and fatty involution of the thymus, residual thymus and zones of fibrous-adipose tissue in the mediastinum is stressed. Selective phlebography is a simple and safe method that adds to PMG (PMTG) potentialities in the evaluation of thymus evolution in myasthenia.

  4. Diagnostic potentialities of pneumomediastinography and selective phlebography in the evaluation of thymus evolution in myasthenia

    International Nuclear Information System (INIS)

    Vasil'ev, V.N.; Bel'chikova, N.S.; Kuksinskij, V.E.

    1983-01-01

    Basing on an analysis of X-ray, intraoperative and histological findings in 124 operated on patients (thymectomy) with myasthenia the authors describe potentialities of pneumomediastinography (PMG) (pheumomediastinotomography-PMTG) in the determination of its main variants (hyperplasia, involUtion, tumor). Clear knowledge of the variants of x-ray image of the normal anatomical structures of the anterior mediastinum and age peculiarities of the thymus for correct interpretation of pneumomediastinograms is necessary. The importance of selective phlebography of the thymus for differential diagnosis of thymomas and nodular indurations of the fatty tissue in the anterior mediastinum, thymomas and fatty involution of the thymus, residual thymus and zones of fibrous-adipose tissue in the mediastinum is stressed. Selective phlebography is a simple and safe method that adds to PMG (PMTG) potentialities in the evaluation of thymus evolution in myasthenia

  5. Adhesion of thymus lymphocytes to aortic endothelial cells in rats irradiated with sup 60 Co-. gamma. -rays

    Energy Technology Data Exchange (ETDEWEB)

    Yongjian, Geng; Zijun, Mao; Zhiwei, Yin [Suzhou Medical Coll., JS (China)

    1990-03-01

    Adhesion of thymus lymphocytes to aortic endothelial cells in Wistar rats irradiated with {sup 60}Co-{gamma}-rays was preliminarily investigated with a stereological method. The results of experiments suggest that the number of lymphocytes of thymus which adhered to aortic endothelial cells significantly (p < 0.01) decreased after irradiation at doses of 2 and 8 Gy. However, when both thymus and aorta were irradiated, there were more lymphocytes adhering to endothelial cells than that when only thymus was irradiated.

  6. Fetal Echocardiography and Indications

    Directory of Open Access Journals (Sweden)

    Melih Atahan Güven

    2008-09-01

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

  7. Contribution of aquaporin 9 and multidrug resistance-associated protein 2 to differential sensitivity to arsenite between primary cultured chorion and amnion cells prepared from human fetal membranes

    Energy Technology Data Exchange (ETDEWEB)

    Yoshino, Yuta [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Yuan, Bo, E-mail: yuanbo@toyaku.ac.jp [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1550 4th St, RH584E Box 2911 San Francisco, CA 94158-2911 (United States); Kaise, Toshikazu [Laboratory of Environmental Chemodynamics, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Takeichi, Makoto [Yoneyama Maternity Hospital, 2-12 Shin-machi, Hachioji, Tokyo 192-0065 (Japan); Tanaka, Sachiko; Hirano, Toshihiko [Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Kroetz, Deanna L. [Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1550 4th St, RH584E Box 2911 San Francisco, CA 94158-2911 (United States); Toyoda, Hiroo [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan)

    2011-12-15

    Arsenic trioxide (arsenite, As{sup III}) has shown a remarkable clinical efficacy, whereas its side effects are still a serious concern. Therefore, it is critical to understand the effects of As{sup III} on human-derived normal cells for revealing the mechanisms underlying these side effects. We examined the effects of As{sup III} on primary cultured chorion (C) and amnion (A) cells prepared from human fetal membranes. A significant dose-dependent As{sup III}-mediated cytotoxicity was observed in the C-cells accompanied with an increase of lactate dehydrogenase (LDH) release. Higher concentrations of As{sup III} were required for the A-cells to show cytotoxicity and LDH release, suggesting that the C-cells were more sensitive to As{sup III} than the A-cells. The expression levels of aquaporin 9 (AQP9) were approximately 2 times higher in the C-cells than those in the A-cells. Both intracellular arsenic accumulation and its cytotoxicity in the C-cells were significantly abrogated by sorbitol, a competitive AQP9 inhibitor, in a dose-dependent manner. The protein expression levels of multidrug resistance-associated protein (MRP) 2 were downregulated by As{sup III} in the C-cells, but not in the A-cells. No significant differences in the expression levels of MRP1 were observed between C- and A-cells. The protein expression of P-glycoprotein (P-gp) was hardly detected in both cells, although a detectable amount of its mRNA was observed. Cyclosporine A, a broad-spectrum inhibitor for ABC transporters, and MK571, a MRP inhibitor, but not PGP-4008, a P-gp specific inhibitor, potently sensitized both cells to As{sup III}-mediated cytotoxicity. These results suggest that AQP9 and MRP2 are involved in controlling arsenic accumulation in these normal cells, which then contribute to differential sensitivity to As{sup III} cytotoxicity between these cells. -- Highlights: Black-Right-Pointing-Pointer Examination of effect of As{sup III} on primary cultured chorion (C) and amnion

  8. Contribution of aquaporin 9 and multidrug resistance-associated protein 2 to differential sensitivity to arsenite between primary cultured chorion and amnion cells prepared from human fetal membranes

    International Nuclear Information System (INIS)

    Yoshino, Yuta; Yuan, Bo; Kaise, Toshikazu; Takeichi, Makoto; Tanaka, Sachiko; Hirano, Toshihiko; Kroetz, Deanna L.; Toyoda, Hiroo

    2011-01-01

    Arsenic trioxide (arsenite, As III ) has shown a remarkable clinical efficacy, whereas its side effects are still a serious concern. Therefore, it is critical to understand the effects of As III on human-derived normal cells for revealing the mechanisms underlying these side effects. We examined the effects of As III on primary cultured chorion (C) and amnion (A) cells prepared from human fetal membranes. A significant dose-dependent As III -mediated cytotoxicity was observed in the C-cells accompanied with an increase of lactate dehydrogenase (LDH) release. Higher concentrations of As III were required for the A-cells to show cytotoxicity and LDH release, suggesting that the C-cells were more sensitive to As III than the A-cells. The expression levels of aquaporin 9 (AQP9) were approximately 2 times higher in the C-cells than those in the A-cells. Both intracellular arsenic accumulation and its cytotoxicity in the C-cells were significantly abrogated by sorbitol, a competitive AQP9 inhibitor, in a dose-dependent manner. The protein expression levels of multidrug resistance-associated protein (MRP) 2 were downregulated by As III in the C-cells, but not in the A-cells. No significant differences in the expression levels of MRP1 were observed between C- and A-cells. The protein expression of P-glycoprotein (P-gp) was hardly detected in both cells, although a detectable amount of its mRNA was observed. Cyclosporine A, a broad-spectrum inhibitor for ABC transporters, and MK571, a MRP inhibitor, but not PGP-4008, a P-gp specific inhibitor, potently sensitized both cells to As III -mediated cytotoxicity. These results suggest that AQP9 and MRP2 are involved in controlling arsenic accumulation in these normal cells, which then contribute to differential sensitivity to As III cytotoxicity between these cells. -- Highlights: ► Examination of effect of As III on primary cultured chorion (C) and amnion (A) cells. ► Dose-dependent As III -mediated cytotoxicity in C

  9. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Science.gov (United States)

    2010-04-01

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

  10. Fetal tachycardia : diagnosis and treatment

    NARCIS (Netherlands)

    Oudijk, Martijn Alexander

    2003-01-01

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

  11. Fetal body movement monitoring.

    Science.gov (United States)

    Rayburn, W F

    1990-03-01

    Recording fetal activity serves as an indirect measure of central nervous system integrity and function. The coordination of whole body movement, which requires complex neurologic control, is likely similar to that of the newborn infant. Short-term observations of the fetus are best performed using real-time ultrasound imaging. Monitoring fetal motion has been shown to be clinically worthwhile in predicting impending death or compromise, especially when placental insufficiency is longstanding. The presence of a vigorous fetus is reassuring. Perceived inactivity requires a reassessment of any underlying antepartum complication and a more precise evaluation by fetal heart rate testing or real-time ultrasonography before delivery is contemplated.

  12. Fetal blood drawing.

    Science.gov (United States)

    Hobbins, J C; Mahoney, M J

    1975-07-19

    A small sample of fetal blood suitable for studies of haemoglobin synthesis was obtained from a placental vessel under endoscopic visualisation in 23 of 26 patients in whom the procedure was attempted prior to second-trimester abortion. Fetal blood loss, calculated in 23 cases, was between 0-2 ml. and 2-5 ml., and fetal blood-volume depletion varied from 0-5% to 15%. No short-term ill-effects were demonstrated in mother or fetus in any of 16 patients in whom the injection of aborti-facient was postponed for between 16 and 24 hours after the procedure.

  13. Stepwise development of MAIT cells in mouse and human.

    Directory of Open Access Journals (Sweden)

    Emmanuel Martin

    2009-03-01

    Full Text Available Mucosal-associated invariant T (MAIT cells display two evolutionarily conserved features: an invariant T cell receptor (TCRalpha (iTCRalpha chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC molecule, MHC-related molecule 1 (MR1. MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanValpha7.2 antibody and MAIT cell-specific iTCRalpha and TCRbeta transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRalpha and TCRbeta transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%-4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the

  14. Thymus development and infant and child mortality in rural Bangladesh.

    Science.gov (United States)

    Moore, Sophie E; Fulford, Anthony J C; Wagatsuma, Yukiko; Persson, Lars Å; Arifeen, Shams E; Prentice, Andrew M

    2014-02-01

    Data from West Africa indicate that a small thymus at birth and at 6 months of age is a strong and independent risk factor for infection-related mortality up to 24 and 36 months of age, respectively. We investigated the association between thymus size (thymic index, TI) in infancy and subsequent infant and child survival in a contemporary South Asian population. The study focused on the follow-up of a randomized trial of prenatal nutritional interventions in rural Bangladesh (ISRCTN16581394), with TI measured longitudinally in infancy (at birth and weeks 8, 24 and 52 of age) and accurate recording of mortality up to 5 years of age. A total of 3267 infants were born into the Maternal and Infant Nutrition Interventions, Matlab study; data on TI were available for 1168 infants at birth, increasing to 2094 infants by 52 weeks of age. TI in relation to body size was largest at birth, decreasing through infancy. For infants with at least one measure of TI available, there were a total of 99 deaths up to the age of 5 years. No association was observed between TI and subsequent mortality when TI was measured at birth. However, an association with mortality was observed with TI at 8 weeks of age [odds ratio (OR) for change in mortality risk associated with 1 standard deviation change in TI: all deaths: OR = 0.64, 95% confidence interval (CI) 0.41, 0.98; P = 0.038; and infection-related deaths only: OR = 0.32, 95% CI 0.14, 0.74; P = 0.008]. For TI when measured at 24 and 52 weeks of age, the numbers of infection-related deaths were too few (3 and 1, respectively) for any meaningful association to be observed. These results confirm that thymus size in early infancy predicts subsequent survival in a lower mortality setting than West Africa. The absence of an effect at birth and its appearance at 8 weeks of age suggests early postnatal influences such as breast milk trophic factors.

  15. Preventing an identity crisis: unexpected co-expression of class III beta-tubulin and glial fibrillary acidic protein in human fetal astrocytes in culture

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Dráberová, Eduarda; Del Valle, L.; Bertrand, L.; Agamanolis, D.P.; de Chadarévian, J.-P.; Legido, A.; Dráber, Pavel

    2007-01-01

    Roč. 26, č. 11 (2007), s. 107-107 ISSN 0364-5134 R&D Projects: GA MŠk LC545; GA ČR GA204/05/2375 Institutional research plan: CEZ:AV0Z50520514 Keywords : class III beta-tubulin * fetal glia Subject RIV: EB - Genetics ; Molecular Biology

  16. 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 ...

  17. Fetal and neonatal thyrotoxicosis

    Science.gov (United States)

    Batra, Chandar Mohan

    2013-01-01

    Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20th week of pregnancy and reaches its maximum by 30th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

  18. 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

  19. Towards a new era in fetal medicine in the Nordic countries

    DEFF Research Database (Denmark)

    Sitras, Vasilis; Brodszki, Jana; Carlsson, Ylva

    2016-01-01

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

  20. New medium used in the differentiation of human pluripotent stem cells to retinal cells is comparable to fetal human eye tissue.

    Science.gov (United States)

    Wang, Xiaobing; Xiong, Kai; Lin, Cong; Lv, Lei; Chen, Jing; Xu, Chongchong; Wang, Songtao; Gu, Dandan; Zheng, Hua; Yu, Hurong; Li, Yan; Xiao, Honglei; Zhou, Guomin

    2015-06-01

    Human pluripotent stem cells (hPSCs) have the potential to differentiate along the retinal lineage. However, most induction systems are dependent on multiple small molecular compounds such as Dkk-1, Lefty-A, and retinoic acid. In the present study, we efficiently differentiated hPSCs into retinal cells using a retinal differentiation medium (RDM) without the use of small molecular compounds. This novel differentiation system recapitulates retinal morphogenesis in humans, i.e. hPSCs gradually differentiate into optic vesicle-shaped spheres, followed by optic cup-shaped spheres and, lastly, retinal progenitor cells. Furthermore, at different stages, hPSC-derived retinal cells mirror the transcription factor expression profiles seen in their counterparts during human embryogenesis. Most importantly, hinge epithelium was found between the hPSC-derived neural retina (NR) and retinal pigment epithelium (RPE). These data suggest that our culture system provides a new method for generating hPSC-derived retinal cells that, for the first time, might be used in human transplantation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. 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.

  2. Antifungal and antimycotoxigenic activity of essential oils from Eucalyptus globulus, Thymus capitatus and Schinus molle

    Directory of Open Access Journals (Sweden)

    Ana Karenth LÓPEZ-MENESES

    2015-12-01

    Full Text Available Abstract Essential oils (EO of eucalyptus (Eucalyptus globulus L., thymus (Thymus capitatus L. pirul (Schinus molle L. were evaluated for their efficacy to control Aspergillus parasiticus and Fusarium moniliforme growth and their ability to produce mycotoxins. Data from kinetics radial growth was used to obtain the half maximal inhibitory concentration (IC50. The IC50 was used to evaluate spore germination kinetic and mycotoxin production. Also, spore viability was evaluated by the MTT assay. All EO had an effect on the radial growth of both species. After 96 h of incubation, thymus EO at concentrations of 1000 and 2500 µL L–1 totally inhibited the growth of F. moniliforme and A. parasiticus, respectively. Eucalyptus and thymus EO significantly reduced spore germination of A. parasiticus. Inhibition of spore germination of F. moniliforme was 84.6, 34.0, and 30.6% when exposed to eucalyptus, pirul, and thymus EO, respectively. Thymus and eucalyptus EO reduced aflatoxin (4% and fumonisin (31% production, respectively. Spore viability was affected when oils concentration increased, being the thymus EO the one that reduced proliferation of both fungi. Our findings suggest that EO affect F. moniliforme and A. parasiticus development and mycotoxin production.

  3. The usefulness of MRI for detection of the thymus gland in myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Hokezu, Youichi; Kaseda, Syun; Arimura, Kimiyoshi; Osame, Mitsuhiro; Baba, Kuniaki (Kagoshima Univ. (Japan). Faculty of Medicine); Ohkubo, Koichi; Hagiwara, Hiroshi

    1989-08-01

    Seven patients with myasthenia gravis (MG) were examined to find thymus or thymoma employing chest radiographs, computed tomography (CT), pneumomediastinography (PMG), computed tomography after pneumomediastinography (PMG-CT) and magnetic resonance imaging (MRI). X-ray CT examination could reveal thymus only in half out of 6 cases scanned. On the other hand, MRI confirmed thymus or thymoma in 6 out of 7 patients. PMG and PMG-CT confirmed thymus or thymoma clearly in all of the 4 cases studied. PMG and PMG-CT examinations revealed thymus or thymoma more clearly than MRI. MRI is, however, an examination causing no pain to the patients and also more superior to X-ray CT in distinguishing between a thymus and mediastinal fat or vascular structure. In addition, MRI could reveal even capsules in thymoma which were never revealed by X-ray CT. We concluded that MRI could be an alternative method to CT and PMG in detection of thymus or thymoma in MG. (author).

  4. The usefulness of MRI for detection of the thymus gland in myasthenia gravis

    International Nuclear Information System (INIS)

    Hokezu, Youichi; Kaseda, Syun; Arimura, Kimiyoshi; Osame, Mitsuhiro; Baba, Kuniaki; Ohkubo, Koichi; Hagiwara, Hiroshi.

    1989-01-01

    Seven patients with myasthenia gravis (MG) were examined to find thymus or thymoma employing chest radiographs, computed tomography (CT), pneumomediastinography (PMG), computed tomography after pneumomediastinography (PMG-CT) and magnetic resonance imaging (MRI). X-ray CT examination could reveal thymus only in half out of 6 cases scanned. On the other hand, MRI confirmed thymus or thymoma in 6 out of 7 patients. PMG and PMG-CT confirmed thymus or thymoma clearly in all of the 4 cases studied. PMG and PMG-CT examinations revealed thymus or thymoma more clearly than MRI. MRI is, however, an examination causing no pain to the patients and also more superior to X-ray CT in distinguishing between a thymus and mediastinal fat or vascular structure. In addition, MRI could reveal even capsules in thymoma which were never revealed by X-ray CT. We concluded that MRI could be an alternative method to CT and PMG in detection of thymus or thymoma in MG. (author)

  5. Cadmium content in Hypericum perforatum L. and Thymus serpyllum L. from localities of the mountains Rtanj and Ozren

    Directory of Open Access Journals (Sweden)

    Đukić-Ćosić Danijela

    2011-01-01

    Full Text Available Background/Aim. The beneficial effects of medicinal plants are well-known from the ancient times. However, expansion of phytopharmacy and phytotherapy occured during the last decades. Medicinal plants can absorb environmental contaminants from the ground and consequently may cause harmful effects on human health. Quality control usually comprises standard methodology which includes macroscopic identification and examination of active ingredients. Additionaly, there is a permanent need to control the level of pollutants in herbs, with a particular attention to the level of toxic metals. In this study we estimated the level of contamination by determining the content of cadmium (Cd in the herbs of Hypericum perforatum and Thymus serpyllum collected from the different localities of the mountains Rtanj and Ozren. Methods. Herbs of investigated plants were collected during July 2005 from various localities of Rtanj and Ozren mountains. After drying, homogenization and mineralization, Cd content was determined by atomic absorption spectrophotometry. Results. The obtained results show that Cd content varies significantly in Hypericum perforatum samples collected. The lowest Cd level was found in samples from the one of Rtanj localities (0.25 mg Cd/kg, while the highest was observed in Hypericum perforatum from Ozren locality (1.24 mg/kg. Levels of Cd in the three of four investigated localities were higher than pro posed by WHO (0.3 mg/kg dried herb material. In all investigated samples of Thymus serpyllum herbs Cd levels were below the limit of detection of analytical method (0.2 mg Cd/kg dried materials. Conclusion. This work contributes to the issue of Cd content in Hypericum perforatum and Thymus serpyllum grown in localities of Rtanj and Ozren, and implies the importance for systemic control of Cd content in Hypericum species in order to provide safety of their preparations. Furthermore, regarding Cd toxicity, maximal permissible level of Cd in

  6. Thymus is enlarged in children with current atopic dermatitis. A cross-sectional study

    DEFF Research Database (Denmark)

    Olesen, Anne Braae; Andersen, Gratien; Jeppesen, Dorthe

    2005-01-01

    Atopic dermatitis is a common skin disorder of unknown aetiology with peak incidence in early childhood. The disease is associated with peripheral T-cell accumulation in the skin. The thymus is a key organ of the cellular immune response early in life. We hypothesized that atopic dermatitis...... is associated with an unbalanced establishment of the peripheral T-lymphocyte system. This cross-sectional study was performed to compare thymus sizes in patients with atopic dermatitis and healthy controls. Thirty-seven children with current atopic dermatitis were enrolled and compared with 29 healthy controls...... of thymus is compatible with increased thymic activity and emission of T lymphocytes....

  7. 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

  8. Class III beta-tubulin is constitutively coexpressed with glial fibrillary acidic protein and nestin in midgestational human fetal astrocytes: implications for phenotypic identity

    Czech Academy of Sciences Publication Activity Database

    Dráberová, Eduarda; Del Valle, L.; Gordon, J.; Marková, Vladimíra; Šmejkalová, Barbora; Bertrand, L.; de Chadarévian, J.-P.; Agamanolis, D.P.; Legido, A.; Khalili, K.; Dráber, Pavel; Katsetos, C.D.

    2008-01-01

    Roč. 67, č. 4 (2008), s. 341-354 ISSN 0022-3069 R&D Projects: GA MŠk LC545; GA ČR GA204/05/2375 Institutional research plan: CEZ:AV0Z50520514 Keywords : astrocytes * class III beta-tubulin * fetal glia Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.140, year: 2008

  9. Involvement of placental/umbilical cord blood acid-base status and gas values on the radiosensitivity of human fetal/neonatal hematopoietic stem/progenitor cells

    International Nuclear Information System (INIS)

    Yamaguchi, Masaru; Ebina, Satoko; Kashiwakura, Ikuo

    2013-01-01

    Arterial cord blood (CB) acid-base status and gas values, such as pH, PCO 2 , PO 2 , HCO 3 - and base excess, provide useful information on the fetal and neonatal condition. However, it remains unknown whether these values affect the radiosensitivity of fetal/neonatal hematopoiesis. The present study evaluated the relationship between arterial CB acid-base status, gas values, and the radiosensitivity of CB hematopoietic stem/progenitor cells (HSPCs). A total of 25 CB units were collected. The arterial CB acid-base status and gas values were measured within 30 min of delivery. The CD34 + HSPCs obtained from CB were exposed to 2 Gy X-irradiation, and then assayed for colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid (BFU-E), and colony-forming unit-granulocyte erythroid, macrophage and megakaryocyte cells. Acid-base status and gas values for PCO 2 and HCO 3 - showed a statistically significant negative correlation with the surviving fraction of BFU-E. In addition, a significant positive correlation was observed between gestational age and PCO 2 . Moreover, the surviving fraction of BFU-E showed a significant negative correlation with gestational age. Thus, HSPCs obtained from CB with high PCO 2 /HCO 3 - levels were sensitive to X-irradiation, which suggests that the status of arterial PCO 2 /HCO 3 - influences the radiosensitivity of fetal/neonatal hematopoiesis, especially erythropoiesis. (author)

  10. Intrapartum fetal heart rate profiles with and without fetal asphyxia.

    Science.gov (United States)

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

    1977-04-01

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

  11. Carcinoma Showing Thymus-Like Differentiation (CASTLE of Thyroid: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Leong-Perng Chan

    2008-11-01

    Full Text Available Carcinoma showing thymus-like differentiation (CASTLE is a rare malignant neoplasm that occurs in the thyroid gland, or head and neck. This tumor arises from either ectopic thymus tissue or remnants of branchial pouches, which retain the potential to differentiate along the thymus line. Clinical presentation and imaging can be consistent with a malignant lesion such as thyroid cancer or thymic carcinoma. Immunohistochemical staining with CD5 can differentiate CASTLE from other malignant thyroid neoplasms. A 54-year-old male had initially presented with a painless, left neck mass for 3 months. He underwent left thyroid lobectomy via a median sternotomy approach. Carcinoma showing thymus-like differentiation was the final histopathologic diagnosis. After 36 months of follow-up, no evidence of recurrence was observed. A median sternotomy is an excellent approach for CASTLE with anterior mediastinum involvement. Complete resection is important to improve the long-term survival rate and the locoregional recurrence rate.

  12. NADPH-d activity in rat thymus after the application of retinoid acid

    Directory of Open Access Journals (Sweden)

    F. Dorko

    2012-02-01

    Full Text Available The aim of this work was to determine the localization of nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d activity as the marker for synthesis of nitric oxide synthase (NOS in the rat thymus after the application of retinoid acid (RA on 1st, 7th, 14th and 21st days of gestation. The given results can build the basis for understanding of the role of NOS in rat thymus. NADPH-d positive cells were represented with dark-blue color and were localized on corticomedullar junction of the thymus. These cells were of different intensity of coloring and were shaped in oval, circle or irregular forms. NADPH-d positive nerve fibers were observed in perivascular topography. They were marked more strongly in the case of control group. The result of application of RA to gravid rats was that the birth weights of newborn rats and their thymuses were smaller, but without statistically significance.

  13. Isolation of thymus gland fractions and the determination of their biological activity

    Directory of Open Access Journals (Sweden)

    MILENA RADETA

    2007-03-01

    Full Text Available A calf thymus extract was prepared and fractionated into lipid and non-lipid fractions. The non-lipid fraction was isolated from the calf thymus extract using the Folch method. The components isolated from the non-lipid fraction were characterized by IR, NMR, biuret and HPLC method. The results of the analyses indicated the presence of peptides. The lipid fraction contained phospholipids, glycolipids and neutral lipids. The biological activity of both the isolated lipid and peptide fractions was determined by the in vivo hemolytic plaques method in Wistar rats with an involuted thymus. The peptide and phospholipid fractions of the thymus extract showed a significant increase of hemolytic plaques. The glycolipid and neutral lipid fraction failed to express a significant immunological response.

  14. Ultrasonic prediction of fetal mass

    African Journals Online (AJOL)

    1983-02-19

    Feb 19, 1983 ... Summary. A clinically accurate method for estimating fetal. mass from fetal body parameters is reviewed. The abdominal circumference is first calculated from ... reliable clinical parameter is the impression of uterine volume,.

  15. Dysfunction of irradiated thymus for the development of helper T cells

    International Nuclear Information System (INIS)

    Amagai, T.; Kina, T.; Hirokawa, K.; Nishikawa, S.; Imanishi, J.; Katsura, Y.

    1987-01-01

    The development of cytotoxic T cells and helper T cells in an intact or irradiated thymus was investigated. C57BL/6 (H-2b, Thy-1.2) mice were whole body-irradiated, or were irradiated with shielding over either the thymus or right leg and tail, and were transferred with 1.5 X 10(7) bone marrow cells from B10.Thy-1.1 mice (H-2b, Thy-1.1). At various days after reconstitution, thymus cells from the recipient mice were harvested and a peanut agglutinin low-binding population was isolated. This population was further treated with anti-Thy-1.2 plus complement to remove host-derived cells and was assayed for the frequency of cytotoxic T cell precursors (CTLp) and for the activity of helper T cells (Th). In the thymus of thymus-shielded and irradiated mice, Th activity reached normal control level by day 25, whereas CTLp frequency remained at a very low level during these days. In the thymus of whole body-irradiated mice, generation of CTLp was highly accelerated while that of Th was retarded, the period required for reconstitution being 25 days and more than 42 days for CTLp and Th, respectively. Preferential development of CTLp was also seen in right leg- and tail-shielded (L-T-shielded) and irradiated recipients. Histological observation indicated that Ia+ nonlymphoid cells were well preserved in the thymus of thymus-shielded and irradiated recipients, whereas in L-T-shielded and irradiated recipients, such cells in the medulla were markedly reduced in number. These results suggest strongly that the generation of Th but not CTLp is dependent on radiosensitive thymic component(s), and that such components may represent Ia+ cells themselves in the medulla or some microenvironment related to Ia+ cells

  16. Unexplained fetal death

    OpenAIRE

    Sepúlveda, Janer; Quintero, Eliana Maribel

    2004-01-01

    El porcentaje de muertes fetales inexplicadas oscila entre un 21% a 50%; se define como la muerte que ocurre en fetos con edad gestacional mayor de 20 semanas o peso superior a 500 g, en la cual ni la autopsia ni el examen histológico del cordón umbilical, placenta y membranas, se logra identificar la causa. Los factores asociados con muerte fetal inexplicada son edad materna mayor de 35 años, sobrepeso, nivel educativo menor de 10 años, cigarrillo y bajo nivel socioeconómico, entre otros. La...

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

    Science.gov (United States)

    Wolff, H P

    1992-04-01

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

  18. SOME ASPECTS OF EARLY DEVELOPMENT OF THE THYMUS: EMBRYOLOGICAL BASIS FOR ECTOPIC THYMUS AND THYMOPHARYNGEAL DUCT CYST. Algunas observaciones acerca del temprano desarrollo del timo: bases embriológicas del timo ectópico y del quiste del conducto timofar

    Directory of Open Access Journals (Sweden)

    Ivan Varga

    2016-03-01

    Full Text Available Introducción. El objetivo principal de nuestro trabajo es el estudio histológico del desarrollo del timo humano entre la 5ª y la 8ª semana de gestación. Describimos varios términos embriológicos poco usados como: timo secundus, descensus thymi (la base embriológica para situar el timo en la garganta, ductus timicus (la base embriológica para el defecto innato llamado conducto timofaríngeo con posibilidad de formar un quiste. Material y método. Nuestras observaciones se basan en la investigación de 18 embriones humanos entre la 6ª y la 8ª semana de gestación. Resultados. La base del timo es común con la base de las glándulas paratiroideas. Es comparable con las bolsas faríngeas (saccus pharyngeus en los embriones largos de 8 a 9 mm. La proliferación endodermal del epitelio en el tercer foco faríngeo (focus faringeus 3 es muy visible. La parte craneal y la parte dorsal son la base de origen de las glándulas paratiroideas inferiores. La parte caudal y la parte ventral son la base para el timo. Hemos observado también la notable proliferación del epitelio en la segunda bolsa faríngea, llamado por algunos autores Timo secundus. En nuestra opinión, en el ser humano no se forma un timo funcional en este lugar y la proliferación del epitelio en la mayoría de los casos, se detiene pronto. Conclusión. En este trabajo ofrecemos una vista general sobre la importancia clínica del desarrollo del timo y la descripción de los defectos innatos más frecuentes del mismo. Introduction. The aim of our morphological study is to describe the development of human thymus from 5th up to 8th week after fertilization in the context of its phylogenesis. We explicate some of the “forgotten” embryological terms with respect to their functions in thymic development, such as “thymus secundus”, “descensus thymi” (an embryological basis for cervical thymus and “ductus thymicus” (an embryologic basis for a congenital anomaly called

  19. Preventing the first cesarean delivery: summary of a joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop.

    Science.gov (United States)

    Spong, Catherine Y; Berghella, Vincenzo; Wenstrom, Katharine D; Mercer, Brian M; Saade, George R

    2012-11-01

    With more than one third of pregnancies in the United States being delivered by cesarean and the growing knowledge of morbidities associated with repeat cesarean deliveries, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists convened a workshop to address the concept of preventing the first cesarean delivery. The available information on maternal and fetal factors, labor management and induction, and nonmedical factors leading to the first cesarean delivery was reviewed as well as the implications of the first cesarean delivery on future reproductive health. Key points were identified to assist with reduction in cesarean delivery rates including that labor induction should be performed primarily for medical indication; if done for nonmedical indications, the gestational age should be at least 39 weeks or more and the cervix should be favorable, especially in the nulliparous patient. Review of the current literature demonstrates the importance of adhering to appropriate definitions for failed induction and arrest of labor progress. The diagnosis of "failed induction" should only be made after an adequate attempt. Adequate time for normal latent and active phases of the first stage, and for the second stage, should be allowed as long as the maternal and fetal conditions permit. The adequate time for each of these stages appears to be longer than traditionally estimated. Operative vaginal delivery is an acceptable birth method when indicated and can safely prevent cesarean delivery. Given the progressively declining use, it is critical that training and experience in operative vaginal delivery are facilitated and encouraged. When discussing the first cesarean delivery with a patient, counseling should include its effect on future reproductive health.

  20. Preventing the First Cesarean Delivery: Summary of a Joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop

    Science.gov (United States)

    Spong, Catherine Y.; Berghella, Vincenzo; Wenstrom, Katharine D.; Mercer, Brian M.; Saade, George R.

    2012-01-01

    With over one-third of pregnancies in the United States being delivered by cesarean and the growing knowledge of morbidities associated with repeat cesarean deliveries, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists convened a workshop to address the concept of preventing the first cesarean. The available information on maternal and fetal factors, labor management and induction, and non-medical factors leading to the first cesarean were reviewed as well as the implications of the first cesarean on future reproductive health. Key points were identified to assist with reduction in cesarean rates including that labor induction should be performed primarily for medical indication; if done for non-medical indications, the gestational age should be at least 39 weeks or more and the cervix should be favorable, especially in the nulliparous patient. Review of the current literature demonstrates the importance of adhering to appropriate definitions for failed induction and arrest of labor progress. The diagnosis of “failed induction” should only be made after an adequate attempt. Adequate time for normal latent and active phases of the first stage, and for the second stage, should be allowed, as long as the maternal and fetal conditions permit. The adequate time for each of these stages appears to be longer than traditionally estimated. Operative vaginal delivery is an acceptable birth method when indicated, and can safely prevent cesarean delivery. Given the progressively declining use, it is critical that training and experience in operative vaginal delivery is facilitated and encouraged. When discussing the first cesarean with a patient, counseling should include its effect on future reproductive health. PMID:23090537

  1. Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking

    International Nuclear Information System (INIS)

    Araki, Tetsuro; Nishino, Mizuki; Hatabu, Hiroto; Gao, Wei; Dupuis, Josee; Hunninghake, Gary M.; Washko, George R.; Murakami, Takamichi; O'Connor, George T.

    2016-01-01

    To investigate CT appearance and size of the thymus in association with participant characteristics. 2540 supposedly healthy participants (mean age 58.9 years, 51 % female) were evaluated for the CT appearance of thymic glands with four-point scores (according to the ratio of fat and soft tissue), size and morphology. These were correlated with participants' age, sex, BMI and smoking history. Of 2540 participants, 1869 (74 %) showed complete fatty replacement of the thymus (Score 0), 463 (18 %) predominantly fatty attenuation (Score 1), 172 (7 %) half fatty and half soft-tissue attenuation (Score 2) and 36 (1 %) solid thymic gland with predominantly soft-tissue attenuation (Score 3). Female participants showed less fatty degeneration of the thymus with higher thymic scores within age 40-69 years (P < 0.001). Participants with lower thymic scores showed higher BMI (P < 0.001) and were more likely to be former smokers (P < 0.001) with higher pack-years (P = 0.04). Visual assessment with four-point thymic scores revealed a sex difference in the fatty degeneration of the thymus with age. Women show significantly higher thymic scores, suggesting less fat content of the thymus, during age 40-69 years. Cigarette smoking and high BMI are associated with advanced fatty replacement of the thymus. (orig.)

  2. Normal thymus in adults: appearance on CT and associations with age, sex, BMI and smoking

    Energy Technology Data Exchange (ETDEWEB)

    Araki, Tetsuro [Harvard Medical School, Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Boston, MA (United States); Kinki University Faculty of Medicine, Department of Radiology, Osaka-Sayama (Japan); Nishino, Mizuki; Hatabu, Hiroto [Harvard Medical School, Department of Radiology, Center for Pulmonary Functional Imaging, Brigham and Women' s Hospital, Boston, MA (United States); Gao, Wei [Boston University School of Public Health, Department of Biostatistics, Boston, MA (United States); Dupuis, Josee [Boston University School of Public Health, Department of Biostatistics, Boston, MA (United States); The National Heart Lung and Blood Institute' s Framingham Heart Study, Framingham, MA (United States); Hunninghake, Gary M.; Washko, George R. [Harvard Medical School, The Pulmonary and Critical Care Division, Brigham and Women' s Hospital, Boston, MA (United States); Murakami, Takamichi [Kinki University Faculty of Medicine, Department of Radiology, Osaka-Sayama (Japan); O' Connor, George T. [The National Heart Lung and Blood Institute' s Framingham Heart Study, Framingham, MA (United States); Boston University School of Medicine, Pulmonary Center and Department of Medicine, Boston, MA (United States)

    2016-01-15

    To investigate CT appearance and size of the thymus in association with participant characteristics. 2540 supposedly healthy participants (mean age 58.9 years, 51 % female) were evaluated for the CT appearance of thymic glands with four-point scores (according to the ratio of fat and soft tissue), size and morphology. These were correlated with participants' age, sex, BMI and smoking history. Of 2540 participants, 1869 (74 %) showed complete fatty replacement of the thymus (Score 0), 463 (18 %) predominantly fatty attenuation (Score 1), 172 (7 %) half fatty and half soft-tissue attenuation (Score 2) and 36 (1 %) solid thymic gland with predominantly soft-tissue attenuation (Score 3). Female participants showed less fatty degeneration of the thymus with higher thymic scores within age 40-69 years (P < 0.001). Participants with lower thymic scores showed higher BMI (P < 0.001) and were more likely to be former smokers (P < 0.001) with higher pack-years (P = 0.04). Visual assessment with four-point thymic scores revealed a sex difference in the fatty degeneration of the thymus with age. Women show significantly higher thymic scores, suggesting less fat content of the thymus, during age 40-69 years. Cigarette smoking and high BMI are associated with advanced fatty replacement of the thymus. (orig.)

  3. Radiographical diagnosis of the thymus in myasthenia gravis. Comparison of pneumomediastinography and computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Tanimura, Shigeo; Banba, Jiro; Masaki, Mikio; Irimoto, Masahiro; Matsushita, Akira

    1987-11-01

    Comparison of radiographical findings of the thymus between pneumomediastinography and computed tomography were studied in 35 patients with myasthenia gravis. The patients consisted of 10 patients with thymoma and 25 without thymoma confirmed at the operations. Pneumomediastinography was very useful to discern whether the thymoma was invasive or noninvasive, but not contributory to know whether the thymus was composed of folicular lymphoid hyperplasia or normal thyimic tissues. Computed tomography was also useful to dertermine the localization and the invasiveness of the thymoma, but not helpful to know whether the thymus was of follicular lymphoid hyperplasia or normal tissues. However, the finding of ''reticular pattern''-many small nodules scattered resicularly in the thymus-in computed tomography could be regarded as a sign suggesting follicular lymphoid hyperplasia of the thymus. Therfore, both pneumomediastinography and computed tomography were very useful in the diagnosis of the localization and the invasiveness of the thymoma but not for the diagnosis of follicular lymphoid hyperplasia of the thymus. Neverethless the finding of ''reticular pattern'' computred tomography was helpful in the diagnosis of follicular lymphoid hyperplasia.

  4. 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...... extends with minor corrections to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact...... to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating...

  5. Glandular Trichomes and Essential Oil of Thymus quinquecostatus

    Directory of Open Access Journals (Sweden)

    Ping Jia

    2013-01-01

    Full Text Available The distribution and types of glandular trichomes and essential oil chemistry of Thymus quinquecostatus were studied. The glandular trichomes are distributed on the surface of stem, leaf, rachis, calyx and corolla, except petiole, pistil and stamen. Three morphologically distinct types of glandular trichomes are described. Peltate trichomes, consisting of a basal cell, a stalk cell and a 12-celled head, are distributed on the stem, leaf, corolla and outer side of calyx. Capitate trichomes, consisting of a unicellular base, a 1–2-celled stalk and a unicellular head, are distributed more diffusely than peltate ones, existing on stem, leaf, rachis and calyx. Digitiform trichomes are just distributed on the outer side of corolla, consisting of 1 basal cell, 3 stalk cells and 1 head cell. All three types of glandular trichomes can secrete essential oil, and in small capitate trichomes of rachis, all peltate trichomes and digitiform trichomes, essential oil is stored in a large subcuticular space, released by cuticle rupture, whereas, in other capitate trichomes, essential oil crosses the thin cuticle. The essential oil of T. quinquecostatus is yellow, and its content is highest in the growth period. 68 constituents were identified in the essential oils. The main constituent is linalool.

  6. Essential Oils Composition and Antioxidant Properties of Three Thymus Species

    Directory of Open Access Journals (Sweden)

    Hamzeh Amiri

    2012-01-01

    Full Text Available The essential oils of three wild-growing Thymus species, collected from west of Iran during the flowering stage, were obtained by hydrodistillation and analyzed by gas chromatography (GC and gas chromatography/mass spectrometry (GC-MS. Under the optimum extraction and analysis conditions, 44, 38, and 38 constituents (mainly monoterpenes compounds were identified in T. kotschyanus Boiss. and Hohen, T. eriocalyx (Ronniger Jalas, and T. daenensis subsp lancifolius (Celak Jalas which represented 89.9%, 99.7%, and 95.8% of the oils, respectively. The main constituents were thymol (16.4–42.6%, carvacrol (7.6–52.3%, and γ-terpinene (3–11.4%. Antioxidant activity was employed by two complementary test systems, namely, 2,2-diphenyl-1-picrylhydrazyl (DPPH free-radical scavenging and β-carotene/linoleic acid systems. Antioxidant activity of polar subfraction of T. daenensis subsp lancifolius (Celak Jalas was found to be higher than those of the others in DPPH assay, while nonpolar subfraction of T. eriocalyx (Ronniger Jalas has most antioxidant activity in β-carotene/linoleic acid test (19.1±0.1 μg/mL and 96.1±0.8% inhibition rate, resp..

  7. Chemotaxonomic study on Thymus xtoletanus Ladero and its parental species

    Directory of Open Access Journals (Sweden)

    José B. Salas

    2011-01-01

    Full Text Available We analysed the essential oils of cultivated material of Thymus xtoletanus Ladero and its parents, Th. mastichina (L. L. and Th. villosus subsp. lusitanicus (Boiss. Coutinho, with seeds from the same locality in the centre of the Iberian Peninsula. The essential oil of Th. xtoletanus, which had not been analyzed previously, presented 1,8-cineole as the major component (25.5%, as was also the case for Th. mastichina (76.1%. Other components with a major presence in Th. xtoletanus and Th. villosus subsp. lusitanicus were [(Z-β-ocimene (8.1%; camphor (4.5%; sabinene (3.2%; α-pinene (2.8%], and [(Z-β-ocimene (4.1%, camphor (9.8%, sabinene (2.8%, α-pinene (7.1%], respectively. However, in the hybrid the components β-phelandrene (14.5%, limonene (6.9%, (E-γ-bisabolene (3.5%, and viridiflorol (3.3% stood out, inter alia, whereas their presence in the parents was limited. The study confirms the hybrid origin of Th. xtoletanus as intermediate between Th. mastichina and Th. villosus subsp. lusitanicus.

  8. Ovine fetal necrobacillosis

    DEFF Research Database (Denmark)

    Agerholm, J.S.; Boye, Mette; Aalbæk, B.

    2007-01-01

    were found in several tissues. Histologically, placental lesions were characterized by locally diffuse infiltration of neutrophils, closely associated with abundant small Gram-negative and FISH-positive rods, thrombosis and necrosis. Lesions in the fetal-maternal interface were multifocal and consisted...

  9. 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…

  10. 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 ...

  11. Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Nicole [Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 (United States); Nagarkatti, Mitzi [Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 (United States); Nagarkatti, Prakash S [Department of Pharmacology and Toxicology, PO Box 980613, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0613 (United States)

    2006-04-15

    Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effects of DES on T-cell differentiation in the thymus using the HY-TCR transgenic (Tg) mouse model in which the female mice exhibit positive selection of T cells bearing the Tg TCR, while the male mice show negative selection of such T cells. In female HY-TCR-Tg mice, exposure to DES showed more pronounced decrease in thymic cellularity when compared to male mice. Additionally, female mice also showed a significant decrease in the proportion of double-positive (DP) T cells in the thymus and HY-TCR-specific CD8{sup +} T cells in the periphery. Male mice exhibiting negative selection also showed decreased thymic cellularity following DES exposure. Moreover, the male mice showed increased proportion of double-negative (DN) T cells in the thymus and decreased proportion of CD8{sup +} T cells. The density of expression of HY-TCR on CD8{sup +} cells was increased following DES exposure in both females and males. Finally, the proliferative response of thymocytes to mitogens and peripheral lymph node T cells to male H-Y antigen was significantly altered in female and male mice following DES treatment. Taken together, these data suggest that DES alters T-cell differentiation in the thymus by interfering with positive and negative selection processes, which in turn modulates the T-cell repertoire in the periphery.

  12. 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.

  13. Application of PLE for the determination of essential oil components from Thymus vulgaris L.

    Science.gov (United States)

    Dawidowicz, Andrzej L; Rado, Ewelina; Wianowska, Dorota; Mardarowicz, Marek; Gawdzik, Jan

    2008-08-15

    Essential plants, due to their long presence in human history, their status in culinary arts, their use in medicine and perfume manufacture, belong to frequently examined stock materials in scientific and industrial laboratories. Because of a large number of freshly cut, dried or frozen plant samples requiring the determination of essential oil amount and composition, a fast, safe, simple, efficient and highly automatic sample preparation method is needed. Five sample preparation methods (steam distillation, extraction in the Soxhlet apparatus, supercritical fluid extraction, solid phase microextraction and pressurized liquid extraction) used for the isolation of aroma-active components from Thymus vulgaris L. are compared in the paper. The methods are mainly discussed with regard to the recovery of components which typically exist in essential oil isolated by steam distillation. According to the obtained data, PLE is the most efficient sample preparation method in determining the essential oil from the thyme herb. Although co-extraction of non-volatile ingredients is the main drawback of this method, it is characterized by the highest yield of essential oil components and the shortest extraction time required. Moreover, the relative peak amounts of essential components revealed by PLE are comparable with those obtained by steam distillation, which is recognized as standard sample preparation method for the analysis of essential oils in aromatic plants.

  14. Chemical Composition and Antimicrobial Activity of the Essential Oils from Two Species of Thymus Growing Wild in Southern Italy

    Directory of Open Access Journals (Sweden)

    Felice Senatore

    2009-11-01

    Full Text Available The volatile constituents of the aerial parts of two samples of Thymus longicaulis C. Presl, collected in Campania and in Sicily, and two samples of Thymus pulegioides L. from the same regions, were extracted by hydrodistillation and analyzed. Considering the four oils together, seventy-eight different compounds were identified: 57 for Thymus longicaulis from Sicily (91.1% of the total oil, 40 for Thymus longicaulis from Campania (91.5% of the oil, 39 for Thymus pulegioides from Sicily (92.5% of the oil and 29 for Thymus pulegioides from Campania (90.1% of the oil. The composition of the oils is different, although the most abundant components are identical in T. pulegioides. The essential oils showed antibacterial activity against eight selected microorganisms.

  15. Activité antifongique des huiles essentielles de Thymus bleicherianus Pomel et Thymus capitatus (L. Hoffm. & Link contre les champignons de pourriture du bois d'oeuvre

    Directory of Open Access Journals (Sweden)

    Amarti F.

    2008-01-01

    Full Text Available Antifungal activity of the Thymus bleicherianus Pomel and Thymus capitatus (L. Hoffm. & Link essential oils againstwood-decay fungi. Essential oils and their constituents have a long history of applications as antimicrobial agents, but theiruse as wood preservatives has rarely been reported. This study deals with the antifungal activity of two medicinal and aromaticplants essential oils of the Moroccan flora against four wood-decay fungi, in order to find new bioactive natural products. Thechemical composition of essential oils extracted by hydrodistillation from the aerial parts of Thymus bleicherianus Pomel andThymus capitatus (L. Hoffm. & Link was analyzed by GC and GC-MS. The major components of T. bleicherianus oil wereα-terpinene (42.2% and thymol (23.9%. Carvacrol (70.92% was the predominant constituent in the essence of T. capitatus.Minimal inhibitory concentrations of the essential oils added to malt agar medium in defined concentrations were determinedby a screening test with the agar dilution method. The oils, object of the survey, showed a strong antifungal activity againstall tested fungi.

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

    DEFF Research Database (Denmark)

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

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

  17. The effect of fetal sex on customized fetal growth charts.

    Science.gov (United States)

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

    2016-12-01

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

  18. Thoracic computer tomography for the evaluation of the thymus gland in cases of myasthenia gravis

    International Nuclear Information System (INIS)

    Druschky, K.F.; Stadler, H.W.; Daun, H.; Erlangen-Nuernberg Univ., Erlangen

    1981-01-01

    Hyperplasia of the thymus gland is observed in 65% of all patients with myasthenia gravis, while the incidence of thymus tumor is reported to be 8.5-28%. Conventional radiological techniques provide little information in the diagnosis of mediastinal lesions. Even a clearly developed thymus tumor can escape clinical detection. Since March 1978 thoracic computer tomography has been performed in addition to X-rays of the chest in a series of 19 patients with myasthenia ravis, 10 women and 9 men ranging in age from 15-71 years and in 3 patients with suspected thymomas but without myasthenia gravis. These examinations were carried out with a Somatom II (Siemens) since September 1979. On the average 15-20 scans were made at the level of the upper two-third of the sternum. The chest X-rays in 2 planes revealed signs of a thymus tumor in 3 female patients. Thoracic computer tomography showed definite signs of a space-occupying lesion in the anterior mediastinum in 11 cases. At thymectomy 6 patients were found to have hyperplasia of the thymus, 2 patients had a benign thymoma and 3 patients a malignant thymoma. In 6 cases computer tomography showed only slight changes and in 5 patients no pathological findings could be demonstrated in the thymus gland. Thoracic computer tomography is a relatively harmless diagnostic measure without any risk for the patient. It has a high resolution and great accuracy in the evaluation of the thymus gland and is therefore the method of choice for the diagnosis of patients with myasthenia gravis. (orig.) [de

  19. Thoracic computer tomography for the evaluation of the thymus gland in cases of myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Druschky, K.F.; Stadler, H.W.; Daun, H.

    1981-01-01

    Hyperplasia of the thymus gland is observed in 65% of all patients with myasthenia gravis, while the incidence of thymus tumor is reported to be 8.5-28%. Conventional radiological techniques provide little information in the diagnosis of mediastinal lesions. Even a clearly developed thymus tumor can escape clinical detection. Since March 1978 thoracic computer tomography has been performed in addition to X-rays of the chest in a series of 19 patients with myasthenia ravis, 10 women and 9 men ranging in age from 15-71 years and in 3 patients with suspected thymomas but without myasthenia gravis. These examinations were carried out with a Somatom II (Siemens) since September 1979. On the average 15-20 scans were made at the level of the upper two-third of the sternum. The chest X-rays in 2 planes revealed signs of a thymus tumor in 3 female patients. Thoracic computer tomography showed definite signs of a space-occupying lesion in the anterior mediastinum in 11 cases. At thymectomy 6 patients were found to have hyperplasia of the thymus, 2 patients had a benign thymoma and 3 patients a malignant thymoma. In 6 cases computer tomography showed only slight changes and in 5 patients no pathological findings could be demonstrated in the thymus gland. Thoracic computer tomography is a relatively harmless diagnostic measure without any risk for the patient. It has a high resolution and great accuracy in the evaluation of the thymus gland and is therefore the method of choice for the diagnosis of patients with myasthenia gravis.

  20. 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

  1. Melatonin modulates the fetal cardiovascular defense response to acute hypoxia.

    Science.gov (United States)

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

    2015-08-01

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

  2. Maternal exposure to hurricane destruction and fetal mortality.

    Science.gov (United States)

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

    2014-08-01

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

  3. In vitro Antimicrobial, Cytotoxic and Radical Scavenging Activities and Chemical Constituents of the Endemic Thymus laevigatus (Vahl

    Directory of Open Access Journals (Sweden)

    Mohamed Al-Fatimi

    2010-01-01

    Full Text Available The leaves of Thymus laevigatus (Vahl, Lamiaceae (Labiatae, an endemic species of Yemen, are traditionally used in the treatment of various disorders including stomach and respiratory system. In a first biological and chemical study of this endemic species we investigated antimicrobial, cytotoxic and antioxidant activities of different extracts of the leaves of this plant. The preliminary phytochemical screening of extracts composition was performed by TLC while the composition of the essential oil was determined by GC-MS. Twelve constituents were detected from the essential oil, which constituted 99.6 % of the total amount. The major constituents of the oil were: carvacrol (84.3 %, p-cymene (4.1 % p-mentha-1, 4-diene (4.0 % and trans-anethole (3.6%. The main active components were identified by TLC as carvacrol and anethole for dichloromethane extract and as non-volatile phenols and flavonoids for the methanol extract. The methanol, dichloromethane and aqueous extracts were tested for their antimicrobial activities against five bacteria strains and six human pathogenic fungi. Both methanol and dichloromethane showed strong activities against most human pathogenic strains. In the contrast, methanol extract showed broader and stronger antibacterial activities than the dichloromethane extract, especially against the Gram-negative bacterium Pseudomonas aeruginosa. The methanol extract showed the same strong radical scavenging activity in the DPPH assay (14.9mg/ml, when compared to the standard antioxidant, ascorbic acid. In contrast, the cytotoxic activity of the methanol against FL cells, a human amniotic epithelial cell line, was only moderate (IC50 298, 8 mg/ml. On the contrary, the water extract did not show any biological activity. Results presented here suggest that the essential oil and extracts of Thymus laevigatus possess strong antimicrobial and antioxidant properties, and therefore, they can be used as a natural preservative ingredient

  4. Correlates of thymus size and changes during treatment of children with severe acute malnutrition: a cohort study

    DEFF Research Database (Denmark)

    Rytter, Maren Johanne Heilskov; Namusoke, Hanifa; Ritz, Christian

    2017-01-01

    BACKGROUND: The impairment of immune functions associated with malnutrition may be one reason for the high mortality in children with severe acute malnutrition (SAM), and thymus atrophy has been proposed as a marker of this immunodeficiency. The aim of this study was to identify nutritional....... CONCLUSION: Malnutrition and inflammation are associated with thymus atrophy, and thymus area seems positively associated with plasma phosphate. Substituting therapeutic formula with unfortified rice porridge with the aim of alleviating diarrhea may impair regain of thymus size with nutritional...

  5. Fetal cardiac assessment

    International Nuclear Information System (INIS)

    Greene, K.R.

    1983-01-01

    The better understanding of fetal cardiovascular physiology coupled with improved technology for non-invasive study of the fetus now enable much more detailed assessment of fetal cardiac status than by heart rate alone. Even the latter, relatively simple, measurement contains much more information than was previously realized. It is also increasingly clear that no single measurement will provide the answer to all clinical dilemmas either on cardiac function or the welfare of the fetus as a whole. There are obvious clinical advantages in measuring several variables from one signal and the measurement of heart rate, heart rate variation and waveform from the ECG in labour is a potentially useful combination. Systolic time intervals or flow measurements could easily be added or used separately by combining real-time and Doppler ultrasound probes

  6. Fetal chromosome analysis

    DEFF Research Database (Denmark)

    Philip, J; Tabor, A; Bang, J

    1983-01-01

    The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...

  7. MRI manifestations of thymus in myasthenia gravis (MG) patients in various age groups

    International Nuclear Information System (INIS)

    Wang Ying; Peng Xi; Li Zhizhao; Jiang Kuiming; Song Ting; Dong Tianfa; Xiao Youcheng

    2003-01-01

    Objective: To study MRI findings of the thymus in patients with myasthenia gravis (MG) in different age groups and to analyze the relationship between the morphological changes of thymus and the MG. Methods: In total 90 patients with MG (male: female=43:47) received MR scan and were divided into four groups (group A, B, C and D) by age. Fourteen patients out of 90 received additional enhanced scan. Group A included 33 patients aged under 10 years (m:f=18:15); 27 patients aged 11-25 years were in group B (m:f=12:15); group C had 17 patients aged 26-50 years (m:f=6:11); and in group D there were 13 patients whose ages were over 51 years (m:f=7:6). And 30 Non-MG patients aged 8-75 years were selected as control group, in which the thickness, the fat collection, and glandulous atrophy of thymus was studied on CT. Results: 1) The thymus was unremarkable in 44 cases out of 90 (48.88%). 2) Enlarged thymus was shown in 42 cases out of 90 (46.66%), in which non-nodular enlargement was revealed in 34 cases and nodular enlargement in 8 cases. There were 27 cases with abnormality of thymus out of 33 (81.81%) in group A, 12 cases out of 27 (44.44%) in group B and 3 cases in group C, but no abnormality was found in group D. 3) Only 4/90 patients (4.44%) had thymic mass that respectively seen in one case of group B, two of group C and one of group D. No evidence of the involvement of the adjacent structure was found on MRI in the cases of thymic mass. No thymus enlargement was revealed in control group. Fat collection in thymus was seen in both study groups and control group. Conclusion: Intimate relationship between the abnormality of the thymus gland and MG exists in children and teenagers. While in the middle-aged patients or the seniors, further studies should be made to find out whether there is a correlation

  8. Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

    OpenAIRE

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

    2015-01-01

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

  9. Desoxyribonucleic acid (DNA) synthesis in vitro by thymus and spleen cells of the rat after hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Tempel, K.; Spath, A.

    1988-03-01

    The inhibition of the semiconservative and restorative DNA synthesis caused by hyperthermia (30 to 60 min, 43/sup 0/C) was significantly higher in spleen cells than in thymus cells. The DNA repair synthesis of thymus cells measured at 37/sup 0/C was increased by about two times the initial value after a pre-incubation of 30 to 90 min and 30 to 60 min, respectively, with 37 and 43/sup 0/C, respectively. Under the same conditions, the /sup 3/H-thymidine incorporation into the DNA of spleen cells diminished proportionally to the pre-incubation time after a pre-incubation of 30 and 45 min, respectively, with 43 and 37/sup 0/C, respectively. When hyperthermia and inhibitors of DNA synthesis or DNA repair (hydroxyurea, 1-..beta..-D-arabinofuranosylcytosine, 3', 5'-didesoxythymidine, and 3-aminobenzamide) were combined, overadditive effects - without cellspecific particularities - were seen only in the case of 3-aminobenzamide. Only in thymus cells, the inhibitor of DNA topoisomerase II novobiocin caused an overadditive reinforcement of the inhibition induced by hyperthermia of the semiconservative DNA synthesis. The stimulation of DNA repair synthesis in thymus cells caused by novobiocin with the aid of DNA polymerase ..beta.. could be compensated by hyperthermia. The sedimentation of thymus and spleen cell nucleoids was increased after hyperthermia. The results suggest a special importance of DNA topology and of the DNA polymerase ..beta.. activity for the cellular effect of hyperthermia.

  10. Thymus transcriptome reveals novel pathways in response to avian pathogenic Escherichia coli infection.

    Science.gov (United States)

    Sun, H; Liu, P; Nolan, L K; Lamont, S J

    2016-12-01

    Avian pathogenic Escherichia coli (APEC) can cause significant morbidity in chickens. The thymus provides the essential environment for T cell development; however, the thymus transcriptome has not been examined for gene expression in response to APEC infection. An improved understanding of the host genomic response to APEC infection could inform future breeding programs for disease resistance and APEC control. We therefore analyzed the transcriptome of the thymus of birds challenged with APEC, contrasting susceptible and resistant phenotypes. Thousands of genes were differentially expressed in birds of the 5-day post infection (dpi) challenged-susceptible group vs. 5 dpi non-challenged, in 5 dpi challenged-susceptible vs. 5 dpi challenged-resistant birds, as well as in 5 dpi vs. one dpi challenged-susceptible birds. The Toll-like receptor signaling pathway was the major innate immune response for birds to respond to APEC infection. Moreover, lysosome and cell adhesion molecules pathways were common mechanisms for chicken response to APEC infection. The T-cell receptor signaling pathway, cell cycle, and p53 signaling pathways were significantly activated in resistant birds to resist APEC infection. These results provide a comprehensive assessment of global gene networks and biological functionalities of differentially expressed genes in the thymus under APEC infection. These findings provide novel insights into key molecular genetic mechanisms that differentiate host resistance from susceptibility in this primary lymphoid tissue, the thymus. © The Author 2016. Published by Oxford University Press on behalf of Poultry Science Association.

  11. The Normal Fetal Pancreas.

    Science.gov (United States)

    Kivilevitch, Zvi; Achiron, Reuven; Perlman, Sharon; Gilboa, Yinon

    2017-10-01

    The aim of the study was to assess the sonographic feasibility of measuring the fetal pancreas and its normal development throughout pregnancy. We conducted a cross-sectional prospective study between 19 and 36 weeks' gestation. The study included singleton pregnancies with normal pregnancy follow-up. The pancreas circumference was measured. The first 90 cases were tested to assess feasibility. Two hundred ninety-seven fetuses of nondiabetic mothers were recruited during a 3-year period. The overall satisfactory visualization rate was 61.6%. The intraobserver and interobserver variability had high interclass correlation coefficients of of 0.964 and 0.967, respectively. A cubic polynomial regression described best the correlation of pancreas circumference with gestational age (r = 0.744; P pancreas circumference percentiles for each week of gestation were calculated. During the study period, we detected 2 cases with overgrowth syndrome and 1 case with an annular pancreas. In this study, we assessed the feasibility of sonography for measuring the fetal pancreas and established a normal reference range for the fetal pancreas circumference throughout pregnancy. This database can be helpful when investigating fetomaternal disorders that can involve its normal development. © 2017 by the American Institute of Ultrasound in Medicine.

  12. Role of melatonin in embryo fetal development

    OpenAIRE

    Voiculescu, SE; Zygouropoulos, N; Zahiu, CD; Zagrean, AM

    2014-01-01

    Melatonin is an indoleamine produced by the pineal gland and secreted in a circadian manner. In the past few decades, research over this topic has been enhanced. Melatonin has many important roles in the human physiology: regulator of the circadian rhythms, sleep inducer, antioxidant, anticarcinogenic. This paper reviews the involvement of melatonin in embryo fetal development. The pineal gland develops completely postpartum, so both the embryo and the fetus are dependent on the maternal mela...

  13. 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.

  14. Fetal magnetic resonance: technique applications and normal fetal anatomy

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  15. Hepatoprotective activity of Thymus vulgaris extract against Toxoplasma gondii infection

    Directory of Open Access Journals (Sweden)

    Nagwa Mostafa El-Sayed

    2017-05-01

    Full Text Available Objective: To evaluate the hepatoprotective activity of Thymus vulgaris (T. vulgaris extract against Toxoplasma gondii (T. gondii infection in experimentally infected mice. Methods: Sixty mice were divided into six groups (Group I–Group VI. Group I was normal control (non-infected, non-treated; Group II was non-infected and treated with T. vulgaris extract (500 mg/kg; Group III was T. gondii infected-non-immunosuppressed control; Group IV consisted of infected immunosuppressed mice; Group V was infected and treated with T. vulgaris extract; Group VI consisted of infected immunosuppressed mice treated with T. vulgaris extract. Hepatoprotective effect of T. vulgaris extract was evaluated by histopathological examination of tissue sections stained with hematoxylin and eosin, determination of liver function parameters (alanine aminotransaminase, aspartate aminotransaminase and alkaline phosphates, total bilirubin, total protein concentrations and assessment of hepatocytes genotoxicity by comet assay.Antigenotoxic effect of T. vulgaris was assessed by several comet assay parameters that were provided by the image analysis software, including % tailed cells, % of DNA in the tail, tail length, and tail moment. Results: Treatment with T. vulgaris in both Groups V and VI improved T. gondii induced pathological lesions in the infected liver that regressed to near the normal picture especially in Group V. Also, it restored the altered values of liver function parameters near to the normal levels significantly (P < 0.05 compared with Groups III and IV respectively. Regarding comet assay parameters, all of them were significantly increased (P < 0.05 after T. gondii infection (Group III and reached the greatest values in infected immunosuppressed group (Group IV compared to the normal controls (Group I. With treatment by T. vulgaris in Groups V and VI, there was a significant decrease (P < 0.05 in all values compared to Groups III and V respectively. The

  16. MRI of the fetal spine

    International Nuclear Information System (INIS)

    Simon, Erin M.

    2004-01-01

    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.)

  17. 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.)

  18. Arterial supply of the thoracic lobes of the thymus in dogs of the Great Dane race.

    Directory of Open Access Journals (Sweden)

    Rosana Marques Silva

    2007-09-01

    Full Text Available The origins, numbers and type of arterial branches responsible for the blood supply of thoracic lobes of the thymus were studied in 28 stillborn dogs of the Great Dane, of which 18 were males and 10 were females. The arterial systems of these animals were filled with aqueous solution of Neoprene Latex “450”, 50%. After, the specimens were fixed in 10% formaldehyde aqueous solution. The lobes of the thymus were supplied by direct or indirect arterial branches coming from the right and left internal thoracic arteries, pericardiacophrenicas arteries, right and left costocervicais trunks, and left subclavian artery. The left subclavian artery and brachiocephalic trunk emitted direct branches towards the left thoracic lobe of the thymus.

  19. Anatomical variations of the thymus in relation to the left brachiocephalic vein, findings of necropsia.

    Science.gov (United States)

    Plaza, Oscar Alonso; Moreno, Freddy

    2018-04-01

    Two cases of anatomical variations of the thymus are presented with respect to the anatomical relations with the left brachiocephalic vein and found during the necropsy process. Less than 2 days after birth with Noonan Syndrome, when the left brachiocephalic vein was scanning behind the upper thymus horns, there were other adjacent lesions consisting of three supernumerary spleens and three hepatic veins. The second case was an 8-year-old infant with child malpractice who died from urinary sepsis due to obstructive uropathy, in which case the upper lobes of the thymus were fused and formed a ring through which the left brachiocephalic vein passed. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Is the plant-associated microbiota of Thymus spp. adapted to plant essential oil?

    Science.gov (United States)

    Checcucci, Alice; Maida, Isabel; Bacci, Giovanni; Ninno, Cristina; Bilia, Anna Rita; Biffi, Sauro; Firenzuoli, Fabio; Flamini, Guido; Fani, Renato; Mengoni, Alessio

    2017-04-01

    We examined whether the microbiota of two related aromatic thyme species, Thymus vulgaris and Thymus citriodorus, differs in relation to the composition of the respective essential oil (EO). A total of 576 bacterial isolates were obtained from three districts (leaves, roots and rhizospheric soil). They were taxonomically characterized and inspected for tolerance to the EO from the two thyme species. A district-related taxonomic pattern was found. In particular, high taxonomic diversity among the isolates from leaves was detected. Moreover, data obtained revealed a differential pattern of resistance of the isolates to EOs extracted from T. vulgaris and T. citriodorus, which was interpreted in terms of differing chemical composition of the EO of their respective host plants. In conclusion, we suggest that bacterial colonization of leaves in Thymus spp. is influenced by the EO present in leaf glandular tissue as one of the selective forces shaping endophytic community composition. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  1. Thymus Atrophy and Double-Positive Escape Are Common Features in Infectious Diseases

    Directory of Open Access Journals (Sweden)

    Juliana de Meis

    2012-01-01

    Full Text Available The thymus is a primary lymphoid organ in which bone marrow-derived T-cell precursors undergo differentiation, leading to migration of positively selected thymocytes to the T-cell-dependent areas of secondary lymphoid organs. This organ can undergo atrophy, caused by several endogenous and exogenous factors such as ageing, hormone fluctuations, and infectious agents. This paper will focus on emerging data on the thymic atrophy caused by infectious agents. We present data on the dynamics of thymus lymphocytes during acute Trypanosoma cruzi infection, showing that the resulting thymus atrophy comprises the abnormal release of thymic-derived T cells and may have an impact on host immune response.

  2. Age-related changes in the thymus gland: CT-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Moore, A.V.; Korobkin, M.; Olanow, W.; Heaston, D.K.; Ram, P.C.; Dunnick, N.R.; Silverman, P.M.

    1983-08-01

    Recent reports suggest that computed tomography (CT) is useful for thymoma detection in patients with myasthenia gravis. However, that usefulness may be conditioned by the state of the normal thymus. To examine this concept, the CT findings in 64 consecutive patients with histologic confirmation of thymic status after thymectomy or thymic biopsy during mediastinal exploration were reviewed. The normal thymus has a bilobed, arrowhead-shaped cross section at all ages, with gradual focal or diffuse fatty infiltration of the parenchyma usually occurring between 20 and 40 years of age. A thymoma is usually a spherical or oval mass, often producing a focal, distinct bulge in the adjacent pleural reflection. The differentiation of thymoma from normal thymus should be possible in most patients if age-related changes in the normal gland are appreciated.

  3. Binding of /sup 125/I alpha-bungarotoxin to the thymus of mice

    Energy Technology Data Exchange (ETDEWEB)

    Ohshima, F.; Kondo, K.; Tsubaki, T.

    1978-01-01

    Alpha-bungarotoxin is known to bind with nicotinic acetylcholine receptors of skeletal muscle. Binding of iodine 125-labeled alpha bungarotoxin to the murine thymus, muscle, and liver was estimated. The toxin was bound to the muscle. The thymus was also capable of binding a considerable amount of the toxin, and the binding was obviously blocked by tubocurarine chloride. Binding to the liver, an organ containing no nicotinic acetylcholine receptor, was very slight. These results may indicate the presence of nicotinic acetylcholine receptors in the thymus, which could have implications in the pathogenesis of myasthenia gravis. Degenerating myoid cells and their receptors may represent autoantigens that induce an immunological cross-reaction with the receptors of skeletal muscles, giving rise to myasthenia gravis.

  4. Binding of 125I alpha-bungarotoxin to the thymus of mice

    International Nuclear Information System (INIS)

    Ohshima, F.; Kondo, K.; Tsubaki, T.

    1978-01-01

    Alpha-bungarotoxin is known to bind with nicotinic acetylcholine receptors of skeletal muscle. Binding of iodine 125-labeled alpha bungarotoxin to the murine thymus, muscle, and liver was estimated. The toxin was bound to the muscle. The thymus was also capable of binding a considerable amount of the toxin, and the binding was obviously blocked by tubocurarine chloride. Binding to the liver, an organ containing no nicotinic acetylcholine receptor, was very slight. These results may indicate the presence of nicotinic acetylcholine receptors in the thymus, which could have implications in the pathogenesis of myasthenia gravis. Degenerating myoid cells and their receptors may represent autoantigens that induce an immunological cross-reaction with the receptors of skeletal muscles, giving rise to myasthenia gravis

  5. Effect of low molecular fraction of thymus humoral factor on blood formation processes of irradiated mice

    International Nuclear Information System (INIS)

    Stolyarova, T.V.; Skobel'tsyna, E.S.; Grinberg, S.M.; Kruglikov, I.L.; Korotaev, G.K.; Tepelina, O.M.; Il'ina, T.I.

    1982-01-01

    The effect of low-molecular fraction of thymus humoral factor on blood formation in mice irradiated at 4 Gy was studied. It is shown that injection of low-molecular fraction of thymus hymoral factor to irradiated animals affects proliferative processes in spleen and bone marrow, however the degree of the effect depends on the injection scheme of the preparation. Application of mathematical planning methods of the experiment enables to analyze various injection schemes of low-molecular fraction of thymus humoral factor on the investigated indices. The optimal scheme of preparation injection is determined: 1st injection with the dose of 10 mkg/kg following 4 hour after irradiation, 2d injection - with the same dose in 7-21 days

  6. Age-related changes in the thymus gland: CT-pathologic correlation

    International Nuclear Information System (INIS)

    Moore, A.V.; Korobkin, M.; Olanow, W.; Heaston, D.K.; Ram, P.C.; Dunnick, N.R.; Silverman, P.M.

    1983-01-01

    Recent reports suggest that computed tomography (CT) is useful for thymoma detection in patients with myasthenia gravis. However, that usefulness may be conditioned by the state of the normal thymus. To examine this concept, the CT findings in 64 consecutive patients with histologic confirmation of thymic status after thymectomy or thymic biopsy during mediastinal exploration were reviewed. The normal thymus has a bilobed, arrowhead-shaped cross section at all ages, with gradual focal or diffuse fatty infiltration of the parenchyma usually occurring between 20 and 40 years of age. A thymoma is usually a spherical or oval mass, often producing a focal, distinct bulge in the adjacent pleural reflection. The differentiation of thymoma from normal thymus should be possible in most patients if age-related changes in the normal gland are appreciated

  7. Fetal Eye Movements on Magnetic Resonance Imaging

    Science.gov (United States)

    Woitek, Ramona; Kasprian, Gregor; Lindner, Christian; Stuhr, Fritz; Weber, Michael; Schöpf, Veronika; Brugger, Peter C.; Asenbaum, Ulrika; Furtner, Julia; Bettelheim, Dieter; Seidl, Rainer; Prayer, Daniela

    2013-01-01

    Objectives Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. Methods Dynamic SSFP sequences were acquired in 72 singleton fetuses (17–40 GW, three age groups [17–23 GW, 24–32 GW, 33–40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. Results In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3–45%. Conclusions In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations. PMID:24194885

  8. 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.

  9. Activation Kinetics and Off-Target Effects of Thymus-Initiated Cre Transgenes

    Science.gov (United States)

    Shi, Jianjun; Petrie, Howard T.

    2012-01-01

    The bacteriophage enzyme Cre is a site-specific recombinase widely used to delete loxP-flanked DNA sequences in lineage-specific fashion. Several mouse lines that direct Cre expression to lymphoid progenitors in the thymus have been established, but a side-by-side comparison of when they first become active, and/or their relative efficiency at various developmental stages, has been lacking. In this study, we evaluated these in four common Cre transgenic strains with thymus-initiated promoters (Lck, Cd2, or Cd4). We found that while all of them eventually labeled nearly all thymocytes, their kinetics were dramatically different, and other than Cd4[Cre], did not faithfully recapitulate the expression pattern of the corresponding endogenous gene. Perhaps even more importantly, while thymuses from some strains compared favorably to thymuses from control (Cre-negative) mice, we found that Cre expression could also result in off-target effects, including moderate to severe decreases in thymic cellularity. These effects occurred in the absence of loxP-flanked DNA target genes, and were dose and copy number dependent. Loss of cellularity was attributable to a specific decrease in CD4+8+ immature cells, and corresponds to an increased rate of programmed cell death. In addition to a comprehensive analysis of activation kinetics in thymus-initiated Cre transgenes, our data show that Cre is toxic to CD4+8+ cells in a dose-dependent fashion, and emphasize that the choice of thymus-initiated Cre strain is critically important for minimizing off-target effects of Cre. PMID:23049709

  10. Interplay of thymus and bone marrow regeneration in x-irradiated mice

    International Nuclear Information System (INIS)

    Hiesche, K.-D.

    1975-01-01

    aim of the prepresent investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed. (author)

  11. Interplay of thymus and bone marrow regeneration in x-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hiesche, K D

    1975-01-01

    The aim of the present investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed.

  12. Fascial relationship of the thymus: radiologic-pathologic correlation in neonatal pneumomediastinum

    International Nuclear Information System (INIS)

    Quattromani, F.L.; Foley, L.C.; Bowen, A.D.; Weisman, L.; Hernandez, J.

    1981-01-01

    The radiographic appearance of retrothymic pneumomediastinum is quite specific. The findings include elevation of the thymus away from other mediastinal structures with increased lucency beneath it, visualization of a radiodense line extending from the inferior pole of the thymus to the midportion of the heart, and tenting of the pericardium at the point of attachment of this line. This constellation of findings will aid in the differential diagnosis of medial anterior pneumothorax, pneumopericardium, and intrapulmonary cyst in the infant with air block. The paper details the mediastinal anatomy with special emphasis on a previously undescribed layer of connective tissue that accounts for this specific radiographic appearance

  13. Essential Oils from Thyme (Thymus vulgaris): Chemical Composition and Biological Effects in Mouse Model.

    Science.gov (United States)

    Vetvicka, Vaclav; Vetvickova, Jana

    2016-12-01

    Thymus species are popular spices and contain volatile oils as main chemical constituents. Recently, plant-derived essential oils are gaining significant attention due to their significant biological activities. Seven different thymus-derived essential oils were compared in our study. First, we focused on their chemical composition, which was followed up by testing their effects on phagocytosis, cytokine production, chemotaxis, edema inhibition, and liver protection. We found limited biological activities among tested oils, with no correlation between composition and biological effects. Similarly, no oils were effective in every reaction. Based on our data, the tested biological use of these essential oils is questionable.

  14. Importance of thymus and its humoral factors in radiation syndrome treatment

    International Nuclear Information System (INIS)

    Vavrova, J.

    1983-01-01

    The high radiosensitivity is emphasised of lymphoid tissues and of the immunological response of the organism. The red--uced immunity of the irradiated organism even after sublethal doses lasts for a number of months. The thymus is not only an important lymphoid organ but it also secerns hormones having lymph-stimulating effects. The shielding of the thymus during irradiation or the application of thymosine favourably affected in gamma or X-ray irradiated mice not only the regeneration of damaged lymphoid tissues and of immunological response but also the regeneration of blood formation. (A.K.)

  15. Fetal Echocardiography/Your Unborn Baby's Heart

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Fetal Echocardiography / Your Unborn Baby's Heart Updated:Oct 6,2016 ... Your Risk • Symptoms & Diagnosis Introduction Common Tests Fetal Echocardiography/Your Unborn Baby's Heart - Fetal Echocardiogram Test - Detection ...

  16. Antigen recognition by MHC-incompatible cells of a human mismatched chimera

    NARCIS (Netherlands)

    Roncarolo, M. G.; Yssel, H.; Touraine, J. L.; Bacchetta, R.; Gebuhrer, L.; de Vries, J. E.; Spits, H.

    1988-01-01

    Tetanus toxin (TT)-specific T cell clones of donor origin were obtained from a patient with severe combined immunodeficiency (SCID) successfully reconstituted by transplantation of allogeneic fetal liver and thymus cells from two different donors performed 10 yr ago. A series of these clones

  17. 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…

  18. Functional and structural microanatomy of the fetal sciatic nerve.

    Science.gov (United States)

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

    2017-10-01

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

  19. Fetal plasma erythropoietin concentration in severe growth retardation.

    Science.gov (United States)

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

    1993-02-01

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

  20. HEPATITIS ALOINMUNE FETAL

    Directory of Open Access Journals (Sweden)

    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.