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11.
12.
Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography 总被引:10,自引:17,他引:10
Payne D; Flaherty SP; Barry MF; Matthews CD 《Human reproduction (Oxford, England)》1997,12(3):532-541
In this study, we have used time-lapse video cinematography to study
fertilization in 50 human oocytes that had undergone intracytoplasmic sperm
injection (ICSI). Time-lapse recording commenced shortly after ICSI and
proceeded for 17-20 h. Oocytes were cultured in an environmental chamber
which was maintained under standard culture conditions. Overall, 38 oocytes
(76%) were fertilized normally, and the fertilization rate and embryo
quality were not significantly different from 487 sibling oocytes cultured
in a conventional incubator. Normal fertilization followed a defined course
of events, although the timing of these events varied markedly between
oocytes. In 35 of the 38 fertilized oocytes (92%), there were circular
waves of granulation within the ooplasm which had a periodicity of 20-53
min. The sperm head decondensed during this granulation phase. The second
polar body was then extruded, and this was followed by the central
formation of the male pronucleus. The female pronucleus formed in the
cytoplasm adjacent to the second polar body at the same time as, or
slightly after, the male pronucleus, and was subsequently drawn towards the
male pronucleus until the two abutted. Both pronuclei then increased in
size, the nucleoli moved around within the pronuclei and some nucleoli
coalesced. During pronuclear growth, the organelles contracted from the
cortex towards the centre of the oocyte, leaving a clear cortical zone. The
oocyte decreased in diameter from 112 to 106 microm (P < 0.0001) during
the course of the observation period. The female pronucleus was
significantly smaller in diameter than the male pronucleus (24.1 and 22.4
microm respectively, P = 0.008) and contained fewer nucleoli (4.2 and 7.0
respectively, P < 0.0001). After time-lapse recording, oocytes were
cultured for 48 h prior to embryo transfer or cryopreservation. Embryo
quality was related to fertilization events and periodicity of the
cytoplasmic wave, and it was found that good quality embryos arose from
oocytes that had more uniform timing from injection to pronuclear abuttal
and tended to have a longer cytoplasmic wave. In conclusion, we have shown
that time-lapse video cinematography is an excellent tool for studying
fertilization and early embryo development, and have demonstrated that
human fertilization comprises numerous complex dynamic events.
相似文献
13.
High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes 总被引:5,自引:0,他引:5
Shuber AP; Michalowsky LA; Nass GS; Skoletsky J; Hire LM; Kotsopoulos SK; Phipps MF; Barberio DM; Klinger KW 《Human molecular genetics》1997,6(3):337-347
As more mutations are identified in genes of known sequence, there is a
crucial need in the areas of medical genetics and genome analysis for
rapid, accurate and cost-effective methods of mutation detection. We have
developed a multiplex allele-specific diagnostic assay (MASDA) for analysis
of large numbers of samples (> 500) simultaneously for a large number of
known mutations (> 100) in a single assay. MASDA utilizes
oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA
samples are immobilized on a solid support and a single hybridization is
performed with a pool of allele-specific oligonucleotide (ASO) probes. Any
probes complementary to specific mutations present in a given sample are in
effect affinity purified from the pool by the target DNA. Sequence-specific
band patterns (fingerprints), generated by chemical or enzymatic sequencing
of the bound ASO(s), easily identify the specific mutation(s). Using this
design, in a single diagnostic assay, we tested samples for 66 cystic
fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell
anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations,
four mutations in Canavan disease, four mutations in Fanconi anemia, and
five mutations in BRCA1. Each mutation was correctly identified. Finally,
in a blinded study of 106 of these mutations in > 500 patients, all
mutations were properly identified. There were no false positives or false
negatives. The MASDA assay is capable of detecting point mutations as well
as small insertion or deletion mutations. This technology is amenable to
automation and is suitable for immediate utilization for high-throughput
genetic diagnostics in clinical and research laboratories.
相似文献
14.
Predominance of null mutations in ataxia-telangiectasia 总被引:15,自引:4,他引:15
Gilad S; Khosravi R; Shkedy D; Uziel T; Ziv Y; Savitsky K; Rotman G; Smith S; Chessa L; Jorgensen TJ; Harnik R; Frydman M; Sanal O; Portnoi S; Goldwicz Z; Jaspers NG; Gatti RA; Lenoir G; Lavin MF; Tatsumi K; Wegner RD; Shiloh Y; Bar-Shira A 《Human molecular genetics》1996,5(4):433-439
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving
cerebellar degeneration, immunodeficiency, chromosomal instability,
radiosensitivity and cancer predisposition. The responsible gene, ATM, was
recently identified by positional cloning and found to encode a putative
350 kDa protein with a Pl 3-kinase-like domain, presumably involved in
mediating cell cycle arrest in response to radiation-induced DNA damage.
The nature and location of A-T mutations should provide insight into the
function of the ATM protein and the molecular basis of this pleiotropic
disease. Of 44 A-T mutations identified by us to date, 39 (89%) are
expected to inactivate the ATM protein by truncating it, by abolishing
correct initiation or termination of translation, or by deleting large
segments. Additional mutations are four smaller in-frame deletions and
insertions, and one substitution of a highly conserved amino acid at the Pl
3-kinase domain. The emerging profile of mutations causing A-T is thus
dominated by those expected to completely inactivate the ATM protein. ATM
mutations with milder effects may result in phenotypes related, but not
identical, to A-T.
相似文献
15.
Mafee MF; Peyman GA; Grisolano JE; Fletcher ME; Spigos DG; Wehrli FW; Rasouli F; Capek V 《Radiology》1986,160(3):773-780
Twenty-one patients with intraocular disease were studied by magnetic resonance (MR) imaging and computed tomography (CT). In 13 cases, malignant uveal melanoma was considered the likely diagnosis. Both imaging methods were accurate in determining the location and size of uveal melanomas. MR imaging was superior for the assessment of possible associated retinal detachment, for assessment of vitreous change, and for differentiating uveal melanoma from choroidal hemangioma and choroidal detachment. A case of retinal gliosis could not be differentiated from uveal melanoma by either technique. Uveal melanomas appeared as hyperintense lesions on T1-weighted images and as hypointense lesions on T2-weighted images. High signal intensity of the vitreous was observed in patients with vitritis and in those who were thought to have protein leaking into the vitreous as a result of impairment of the retinal-blood barrier. 相似文献
16.
Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine 总被引:7,自引:2,他引:7
Torrealba-de Ron AT; Papayannopoulou T; Knapp MS; Fu MF; Knitter G; Stamatoyannopoulos G 《Blood》1984,63(1):201-210
In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma- globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment. 相似文献
17.
18.
19.
Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta 总被引:12,自引:0,他引:12
Farcet JP; Gaulard P; Marolleau JP; Le Couedic JP; Henni T; Gourdin MF; Divine M; Haioun C; Zafrani S; Goossens M 《Blood》1990,75(11):2213-2219
Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells. 相似文献
20.
Eva MF Brekke Tora S Morken Marius Wider?e Asta K H?berg Ann-Mari Brubakk Ursula Sonnewald 《Journal of cerebral blood flow and metabolism》2014,34(4):724-734
The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-13C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using 1H- and 13C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress. 相似文献