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81.
Radek Bukowski Nellie I. Hansen Marian Willinger Uma M. Reddy Corette B. Parker Halit Pinar Robert M. Silver Donald J. Dudley Barbara J. Stoll George R. Saade Matthew A. Koch Carol J. Rowland Hogue Michael W. Varner Deborah L. Conway Donald Coustan Robert L. Goldenberg for the Eunice Kennedy Shriver National Institute of Child Health Human Development Stillbirth Collaborative Research Network 《PLoS medicine》2014,11(4)
Background
Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.Methods and Findings
We conducted a population-based case–control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.Conclusions
Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies. Please see later in the article for the Editors'' Summary 相似文献82.
Hongfei Ge Jonitha Gardner Xiaosu Wu Ingrid Rulifson Jinghong Wang Yumei Xiong Jingjing Ye Edward Belouski Ping Cao Jie Tang Ki Jeong Lee Suzanne Coberly Xinle Wu Jamila Gupte Lynn Miao Li Yang Natalie Nguyen Bei Shan Wen-Chen Yeh Murielle M. Véniant Yang Li Helene Baribault 《PloS one》2015,10(6)
Trefoil factor 3 (TFF3), also called intestinal trefoil factor or Itf, is a 59 amino acid peptide found as a homodimer predominantly along the gastrointestinal tract and in serum. TFF3 expression is elevated during gastrointestinal adenoma progression and has been shown to promote mucosal wound healing. Here we show that in contrast to other trefoil factor family members, TFF1 and TFF2, TFF3 is highly expressed in mouse duodenum, jejunum and ileum and that its expression is regulated by food intake. Overexpression of TFF3 using a recombinant adeno-associated virus (AAV) vector, or daily administration of recombinant TFF3 protein in vivo improved glucose tolerance in a diet-induced obesity mouse model. Body weight, fasting insulin, triglyceride, cholesterol and leptin levels were not affected by TFF3 treatment. Induction of mucinous metaplasia was observed in mice with AAV-mediated TFF3 overexpression, however, no such adverse histological effect was seen after the administration of recombinant TFF3 protein. Altogether these results suggest that the therapeutic potential of targeting TFF3 to treat T2D may be limited. 相似文献
83.
De Bandt M Ben Mahdi MH Ollivier V Grossin M Dupuis M Gaudry M Bohlen P Lipson KE Rice A Wu Y Gougerot-Pocidalo MA Pasquier C 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(9):4853-4859
It was recently shown that vascular endothelial growth factor (VEGF), a growth factor for endothelial cells, plays a pivotal role in rheumatoid arthritis. VEGF binds to specific receptors, known as VEGF-RI and VEGF-RII. We assessed the physical and histological effects of selective blockade of VEGF and its receptors in transgenic K/BxN mice, a model of rheumatoid arthritis very close to the human disease. Mice were treated with anti-mouse VEGF Ab, anti-mouse VEGF-RI and -RII Abs, and an inhibitor of VEGF-RI tyrosine kinase. Disease activity was monitored using clinical indexes and by histological examination. We found that synovial cells from arthritic joints express VEGF, VEGF-RI, and VEGF-RII. Treatment with anti-VEGF-RI strongly attenuated the disease throughout the study period, while anti-VEGF only transiently delayed disease onset. Treatment with anti-VEGF-RII had no effect. Anti-VEGF-RI reduced the intensity of clinical manifestations and, based on qualitative and semiquantitative histological analyses, prevented joint damage. Treatment with a VEGF-RI tyrosine kinase inhibitor almost abolished the disease. These results show that VEGF is a key factor in pannus development, acting through the VEGF-RI pathway. The observation that in vivo administration of specific inhibitors targeting the VEGF-RI pathway suppressed arthritis and prevented bone destruction opens up new possibilities for the treatment of rheumatoid arthritis. 相似文献
84.
Key role for cyclin-dependent kinases in the first and second meiotic divisions of rat spermatocytes 总被引:3,自引:0,他引:3
In all systems examined so far, the G2/M phase transition is controlled by the M-phase promoting factor (MPF), a complex of cdc2 (CDK1) and cyclin B1. Histone H1 kinase activity and MPF components are present in pachytene spermatocytes (PS). However, it has not been demonstrated yet that direct inhibition of MPF activity prevents the G2/M transition in these cells. When roscovitine, a potent inhibitor of CDK1, CDK2, and CDK5 activities, was added to cocultures of PS with Sertoli cells, the number of both secondary spermatocytes and round spermatids formed were lower than in control cultures, despite similar cell viability. This effect of roscovitine was reversible, did not involve the Sertoli cells, and was dependent on the concentration of the inhibitor. Roscovitine did not modify the amount of MPF in these germ cells but inhibited the CDK1- or CDK2-associated histone H1 kinase activity of PS. Hence a functional relationship between cyclin-dependent kinase activity and the spontaneous processing of the first meiotic division and, for the first time, of the second meiotic division of male germ cells is shown. 相似文献
85.
Wolff M Seemann M Tse Sum Bui B Frapart Y Tritsch D Garcia Estrabot A Rodríguez-Concepción M Boronat A Marquet A Rohmer M 《FEBS letters》2003,541(1-3):115-120
The last enzyme (LytB) of the methylerythritol phosphate pathway for isoprenoid biosynthesis catalyzes the reduction of (E)-4-hydroxy-3-methylbut-2-enyl diphosphate into isopentenyl diphosphate and dimethylallyl diphosphate. This enzyme possesses a dioxygen-sensitive [4Fe-4S] cluster. This prosthetic group was characterized in the Escherichia coli enzyme by UV/visible and electron paramagnetic resonance spectroscopy after reconstitution of the purified protein. Enzymatic activity required the presence of a reducing system such as flavodoxin/flavodoxin reductase/reduced nicotinamide adenine dinucleotide phosphate or the photoreduced deazaflavin radical. 相似文献
86.
Girard M Bisser S Courtioux B Vermot-Desroches C Bouteille B Wijdenes J Preud'homme JL Jauberteau MO 《International journal for parasitology》2003,33(7):713-720
In human African trypanosomiasis, trypanosomes first develop in the blood and lymph (Stage 1), then spread to the central nervous system (CNS) (Stage 2). Disruption of the blood-brain barrier of unknown mechanism occurs in Stage 2 disease. The hypothesis that cerebrospinal fluids (CSF) from African trypanosomiasis patients might contain factor(s) able to induce apoptosis in endothelial cells led us to evaluate this effect by two methods, the TdT-mediated dUTP nick end labelling (TUNEL) method and the measurement of soluble nucleosomes released by apoptotic cells in culture supernatant by ELISA. Apoptosis induction by CSF was also studied with microglial cells, the resident macrophages in the brain, which participate in the blood-brain barrier in the perivascular area. In contrast with control CSF, African trypanosomiasis patients' CSF induced apoptosis in both microglial and endothelial cells. The results obtained with the two methods correlated well, and showed that Stage 2 CSF induced apoptosis at higher levels in microglial cells, whereas the disease stage was not decisive for apoptosis induction in endothelial cells. We measured soluble Fas ligand (sFasL) and anti-Fas antibodies levels, two potent inducers of the Fas signalling pathway leading to apoptosis, in CSF from African trypanosomiasis patients and controls. CSF from African trypanosomiasis patients contained sFasL, and anti-Fas antibodies at higher levels than in controls. Stage 2 CSF contained more sFasL than Stage 1 CSF, and anti-Fas antibodies were detected only in Stage 2 CSF. Caspase-8 inhibitor effect and statistical data suggest that other pro-apoptotic factors may be involved in some CSF-induced apoptosis. Apoptosis induction may participate in the pathogenesis during African trypanosomiasis, and the presence of sFasL and anti-Fas antibodies may provide new tools for diagnosis and prognosis of the disease. 相似文献
87.
Rabiller-Baudry M Chaufer B 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,797(1-2):331-345
Ion binding is a term that assumes that the ion is included in the solvation sphere characterising the biomolecule. The binding forces are not clearly stated except for electrostatic attraction; weak forces (hydrogen bonds and Van der Waals forces) are likely involved. Many publications have dealt with ion binding to proteins and the consequences over the past 10 years, but only a few studies were performed using high-performance liquid chromatography (HPLC: ion exchange, reversed phase without the well-identified immobilised metal affinity chromatography) and capillary zone electrophoresis (CZE). This review focuses on the binding of proteins and DNAs mainly to the oxyanions (phosphate, borate, citrate) and amines used as buffers for both the HPLC eluent and the background electrolyte of CZE. Such specific ion adsorption on biomolecules is evidenced by physico-chemical characteristics such as the mobility or retention volume, closely associated with the net charge, which differ from the expected or experimental data obtained under the conditions of an indifferent electrolyte. It is shown that ion binding to proteins is a key parameter in the electrostatic repulsion between the free protein and a fouled membrane in the ultrafiltration separation of a protein mixture. 相似文献
88.
Isolation and culture of the three vascular cell types from a small vein biopsy sample 总被引:4,自引:0,他引:4
Grenier G Remy-Zolghadri M Guignard R Bergeron F Labbe R Auger FA Germain L 《In vitro cellular & developmental biology. Animal》2003,39(3-4):131-139
Summary The availability of small-diameter blood vessels remains a significant problem in vascular reconstruction. In small-diameter
blood vessels, synthetic grafts resulted in low patency; the addition of endothelial cells (EC) has clearly improved this
parameter, thereby proving the important contribution of the cellular component to the functionality of any construct. Because
the optimal source of cells should be autologous, the adaptation of existing methods for the isolation of all the vascular
cell types present in a single and small biopsy sample, thus reducing patient’s morbidity, is a first step toward future clinical
applications of any newly developed tissue-engineered blood vessel. This study describes such a cell-harvesting procedure
from vein biopsy samples of canine and human origin. For this purpose, we combined preexisting mechanical methods for the
isolation of the three vascular cell types: EC by scraping of the endothelium using a scalpel blade, vascular smooth muscle
cells (VSMC), and perivascular fibroblasts according to the explant method. Once in culture, cells rapidly grew with the high
level of enrichment. The morphological, phenotypical, and functional expected criteria were maintained: EC formed cobblestone
colonies, expressed the von Willebrand factor, and incorporated acetylated low-density lipoprotein (LDL); VSMC were elongated
and contracted when challenged by vasoactive agents; perivascular fibroblasts formed a mechanically resistant structure. Thus,
we demonstrated that an appropriate combination of preexisting harvesting methods is suitable to isolate simultaneously the
vascular cell types present in a single biopsy sample. Their functional characteristics indicated that they were suitable
for the cellularization of synthetic prosthesis or the reconstruction of functional multicellular autologous organs by tissue
engineering. 相似文献
89.
Rallu M Machold R Gaiano N Corbin JG McMahon AP Fishell G 《Development (Cambridge, England)》2002,129(21):4963-4974
Considerable data suggest that sonic hedgehog (Shh) is both necessary and sufficient for the specification of ventral pattern throughout the nervous system, including the telencephalon. We show that the regional markers induced by Shh in the E9.0 telencephalon are dependent on the dorsoventral and anteroposterior position of ectopic Shh expression. This suggests that by this point in development regional character in the telencephalon is established. To determine whether this prepattern is dependent on earlier Shh signaling, we examined the telencephalon in mice carrying either Shh- or Gli3-null mutant alleles. This analysis revealed that the expression of a subset of ventral telencephalic markers, including Dlx2 and Gsh2, although greatly diminished, persist in Shh(-/-) mutants, and that these same markers were expanded in Gli3(-/-) mutants. To understand further the genetic interaction between Shh and Gli3, we examined Shh/Gli3 and Smoothened/Gli3 double homozygous mutants. Notably, in animals carrying either of these genetic backgrounds, genes such as Gsh2 and Dlx2, which are expressed pan-ventrally, as well as Nkx2.1, which demarcates the ventral most aspect of the telencephalon, appear to be largely restored to their wild-type patterns of expression. These results suggest that normal patterning in the telencephalon depends on the ventral repression of Gli3 function by Shh and, conversely, on the dorsal repression of Shh signaling by Gli3. In addition these results support the idea that, in addition to hedgehog signaling, a Shh-independent pathways must act during development to pattern the telencephalon. 相似文献
90.
Derre L Corvaisier M Pandolfino MC Diez E Jotereau F Gervois N 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(10):4864-4870
NK cell receptors (NKRs) are expressed on a subset of human T cells, predominantly CD8(+), within which they can modulate TCR-mediated functions. In an attempt to identify the mechanisms leading to NKR expression, we analyzed the capacity of IL-12 to modulate the expression by T cells of the components of the CD94/NKG2-A inhibitory receptor, a member of the C-type lectin-like family of NKR. We show that IL-12 induces the expression of NKG2-A and/or CD94 by CD8(+) T cells in culture, and that this induction was mediated neither by IFN-gamma nor by IL-15. We also show, using the redirected killing assay, that IL-12-induced expression of both CD94 and NKG2-A led to the acquisition by T cells of a functional inhibitory receptor. Expression of the CD94/NKG2-A inhibitory receptor was also induced by IL-12 during T cell Ag stimulation so that in the presence of this cytokine a high proportion of melanoma-reactive CTL induced from PBL by melanoma peptide stimulation expressed this receptor. This study emphasizes the implication of IL-12 in the modulation of immune responses through NKR induction. 相似文献