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81.
Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture 总被引:3,自引:1,他引:3
We have recently shown using dansyl-L-lysine exclusion studies that the
release of human chorionic gonadotrophin (HCG) in conjunction with L-
lactate dehydrogenase (LDH) from first trimester villi during organ culture
is symptomatic of syncytiotrophoblast degeneration. The purpose of this
study was to examine chorionic villi at the ultrastructural level in order
to determine events occurring during organ culture. The tissue was sampled
after 0, 24, 48 and 120 h in culture and processed for electron microscopy.
In addition to confirming the previously recorded syncytial degeneration,
the electron micrographs showed clearly the generation of a new
syncytiotrophoblast layer. The new layer, derived from differentiating
cytotrophoblast cells, was largely formed by 48 h and was maintained for at
least 120 h in culture. This study demonstrates a model which provides an
opportunity to study the differentiation of cytotrophoblast cells whilst
they retain their anatomical relationships within the villous structure.
相似文献
82.
83.
Regulation of the efficacy of synaptic transmission by activity-dependent processes has been implicated in learning and memory as well as in developmental processes. We previously described transient potentiation of excitatory synapses onto layer 2/3 pyramidal neurons in the visual cortex that is induced by coincident presynaptic stimulation and postsynaptic depolarization. In the adult visual cortex, activation of N-methyl-d-aspartate (NMDA) glutamate receptors is necessary to induce this plasticity. These receptors act as coincidence detectors, sensing presynaptic glutamate release and postsynaptic depolarization, and cause an influx of Ca(2+) that is necessary for the potentiation. In the neurons of the neonatal visual cortex, on the other hand, coincident presynaptic stimulation and postsynaptic depolarization induce stable long-term potentiation (LTP). In addition, reduced but significant LTP can be induced in many neurons in the presence of the NMDA receptor (NMDAR) antagonist, 2-amino-5-phosphonovaleric acid despite the Ca(2+) requirement. Therefore there must be an alternative postsynaptic Ca(2+) source and coincidence detection mechanism linked to the LTP induction mechanism in the neonatal cortex operating in addition to NMDARs. In this study, we find that in layer 2/3 pyramidal neurons, release of Ca(2+) from inositol trisphosphate (InsP(3)) receptor-mediated intracellular stores and influx through voltage-gated Ca(2+) channels (VGCCs) provide alternative postsynaptic Ca(2+) sources. We hypothesize that InsP(3)Rs are coincidence detectors, sensing presynaptic glutamate release through linkage with group I metabotropic glutamate receptors (mGluRs), and depolarization, through VGCCs. We also find that the downstream protein kinases, PKA and PKC, have a role in potentiation in layer 2/3 pyramidal neurons of the neonatal visual cortex. 相似文献
84.
Matyas GR Friedlander AM Glenn GM Little S Yu J Alving CR 《Infection and immunity》2004,72(2):1181-1183
Three immunizations of mice with recombinant protective antigen (rPA) by transcutaneous immunization (TCI) induced long-term neutralizing antibody titers that were superior to those obtained with aluminum-adsorbed rPA. In addition, rPA alone exhibited adjuvant activity for TCI. Forty-six weeks after completion of TCI, 100% protection was observed against lethal anthrax challenge. 相似文献
85.
Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1) 总被引:10,自引:1,他引:10
Rousseau F; el Ghouzzi V; Delezoide AL; Legeai-Mallet L; Le Merrer M; Munnich A; Bonaventure J 《Human molecular genetics》1996,5(4):509-512
Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with
micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced
thoracic cavity. In the most common subtype (TD1), femurs are curved, while
in TD2, straight femurs are associated with cloverleaf skull. Mutations in
the fibroblast growth factor receptor 3 (FGFR3) gene were identified in
both subtypes. While TD2 was accounted for by a single recurrent mutation
in the tyrosine kinase 2 domain, TD1 resulted from either stop codon
mutations or missense mutations in the extracellular domain of the gene.
Here, we report the identification of FGFR3 mutations in 25/26 TD cases.
Two novel missense mutations (Y373C and G370C) were detected in 8/26 and
1/26 TD1 cases respectively. Both mutations created cysteine residues in
the juxta extramembrane domain of the receptor. Sixteen cases carried the
previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon
FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically
homogeneous condition and give additional support to the view that newly
created cysteine residues in the extracellular domain of the protein play a
key role in the severity of the disease.
相似文献
86.
KJ Champion C Bunag AL Estep JR Jones CH Bolt RC Rogers KA Rauen DB Everman 《Clinical genetics》2011,79(5):468-474
Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation. 相似文献
87.
H4 acetylation, XIST RNA and replication timing are coincident and define x;autosome boundaries in two abnormal X chromosomes 总被引:2,自引:1,他引:2
The inactive X (Xi) differs from its active homologue (Xa) in a number of
ways, including increased methylation of CpG islands, replication late in S
phase, underacetylation of histone H4 and association with XIST RNA. Global
changes in DNA methylation occur relatively late in development, but the
other properties all change during or shortly after the establishment of Xi
and may play a role in the mechanism by which an inactive chromatin
conformation spreads across most of the chromosome. In the present report,
we use two human X;autosome translocation chromosomes to study the
spreading of inactive X chromatin across X;autosome boundaries. In one of
these chromosomes, t(X;6), Xp distal to p11.2 is replaced by 6p21.1-6pter
and, in the other, ins(X;16), a small fragment derived from 16p13 is
inserted into the distal third of Xq. In lymphoid cells from patients
carrying these translocations in an unbalanced form, Xi was shown by HUMARA
assay to be derived exclusively [t(X:6)] or predominantly [ins (X;16)] from
the derived X chromosome. We used a combination of immunolabelling and
RNA/DNA fluorescence in situ hybridization to define the distribution of
XIST RNA, deacetylated H4 and late-replicating DNA across the two derived X
chromosomes in inactive form. Within the limits of the cytogenetic
techniques employed, the results show complete coincidence of these three
parameters, with all three being excluded from the autosomal component of
the derived X chromosome.
相似文献
88.
Protective efficacy of recombinant Yersinia outer proteins against bubonic plague caused by encapsulated and nonencapsulated Yersinia pestis 总被引:3,自引:0,他引:3 下载免费PDF全文
Andrews GP Strachan ST Benner GE Sample AK Anderson GW Adamovicz JJ Welkos SL Pullen JK Friedlander AM 《Infection and immunity》1999,67(3):1533-1537
To evaluate the role of Yersinia outer proteins (Yops) in conferring protective immunity against plague, six yop loci from Yersinia pestis were individually amplified by PCR, cloned, and expressed in Escherichia coli. The recombinant proteins were purified and injected into mice. Most Yop-vaccinated animals succumbed to infection with either wild-type encapsulated Y. pestis or a virulent, nonencapsulated isogenic variant. Vaccination with YpkA significantly prolonged mean survival time but did not increase overall survival of mice infected with the nonencapsulated strain. The only significant protection against death was observed in YopD-vaccinated mice challenged with the nonencapsulated strain. 相似文献
89.
Bacillus anthracis spores of the bclA mutant exhibit increased adherence to epithelial cells, fibroblasts, and endothelial cells but not to macrophages 下载免费PDF全文
Bozue J Moody KL Cote CK Stiles BG Friedlander AM Welkos SL Hale ML 《Infection and immunity》2007,75(9):4498-4505
Bacillus anthracis is the causative agent of anthrax, and the spore form of the bacterium represents the infectious particle introduced into a host. The spore is surrounded by an exosporium, a loose-fitting membrane composed of proteins and carbohydrates from which hair-like projections extend. These projections are composed mainly of BclA (Bacillus-collagen-like protein of B. anthracis). To date, exact roles of the exosporium structure and BclA protein remain undetermined. We examined differences in spore binding of wild-type Ames and a bclA mutant of B. anthracis to bronchial epithelial cells as well as to the following other epithelial cells: A549, CHO, and Caco-2 cells; the IMR-90 fibroblast line; and human umbilical vein vascular endothelium cells. The binding of wild-type Ames spores to bronchial epithelial cells appeared to be a dose-dependent, receptor-ligand-mediated event. There were similar findings for the bclA mutant, with an additional nonspecific binding component likely leading to significantly more adherence to all nonprofessional phagocytic cell types. In contrast, we detected no difference in adherence and uptake of spores by macrophages for either the wild-type Ames or the bclA mutant strain. These results suggest that one potential role of the BclA fibers may be to inhibit nonspecific interactions between B. anthracis spores with nonprofessional phagocytic cells and thus direct the spores towards uptake by macrophages during initiation of infection in mammals. 相似文献
90.
Janneke AL van Kempen Henk J Schers Anne Jacobs Sytse U Zuidema Franca Ruikes Sarah HM Robben René JF Melis Marcel GM Olde Rikkert 《The British journal of general practice》2013,63(608):e225-e231