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排序方式: 共有731条查询结果,搜索用时 31 毫秒
31.
Amplification of genes encoding human myeloid membrane antigens after DNA-mediated gene transfer 总被引:2,自引:0,他引:2
Spontaneous amplification of genes encoding two different human myeloid surface antigens was observed after DNA-mediated gene transfer of cellular DNA from the human myeloid cell line HL-60 into NIH-3T3 mouse fibroblasts. Transformed recipient cells with highly amplified expression of either of two donor membrane polypeptides, gp150 or p67, were isolated with a fluorescence-activated cell sorter (FACS), using monoclonal antibodies specific for human myeloid cells. Immunoprecipitation of enzymatically radioiodinated polypeptides from the surface of transformed NIH-3T3 cells confirmed that expression of these proteins was amplified tenfold to 20-fold in comparison to their expression on human myeloid cell lines. The cellular DNA of cloned secondary and tertiary transformants expressing high levels of gp150 and p67 contained amplified sets of DNA restriction fragments that hybridized with human repetitive DNA sequences. Cytogenetic analysis of subclones overexpressing gp150 revealed extrachromosomal double minutes (DMs), whose presence correlated with the unstable expression of the membrane polypeptide. Human sequences in gp150-positive clones did not localize to chromosomes, consistent with their association with extrachromosomal DMs. By contrast, p67-positive subclones stably expressed the antigen, and in situ hybridization to metaphase spreads demonstrated that amplified human DNA sequences were integrated into a specific marker chromosome. Cytogenetic analysis of the parental NIH- 3T3 subclone used in these studies disclosed DMs in a low percentage of metaphases, suggesting that the recipient cells have a propensity for amplifying donor DNA. 相似文献
32.
Sebaceous carcinoma is a rare cutaneous malignancy, commonly affecting the eyelids. This case highlights a patient who presented with sebaceous carcinoma of the right upper lip with extensive involvement of the soft tissues of the head and neck. As part of the initial investigation, ultrasound was requested. This case demonstrates the ultrasound features of sebaceous carcinoma as well as revising the normal ultrasound anatomy of the upper lip and muscles of the cheek. 相似文献
33.
Elevated numbers of primitive Philadelphia chromosome-positive (Ph+) progenitors, including long-term culture-initiating cells (LTC-IC) as well as colony-forming cells (CFC), have been previously described in the blood of patients with chronic myeloid leukemia (CML) in chronic phase with high white blood cell counts. In the present study, which focused primarily on an analysis of circulating progenitors present in such patients at diagnosis, we discovered the frequent and occasionally exclusive presence of circulating normal (Ph-) LTC-IC, often at levels above those seen for LTC-IC in the blood of normal individuals. The presence of detectable numbers of circulating Ph- LTC-IC was independent of the fact that the same peripheral blood samples also contained elevated numbers of predominantly or exclusively Ph+ CFC. Interestingly, both the Ph+ and Ph- LTC-IC in these samples were CD34+CD71- and variably CD38- and Thy-1+, as previously documented for LTC-IC in normal marrow. Thus, neither CD38 nor Thy-1 expression was useful for discriminating between Ph+ and Ph- LTC-IC in mixed populations. Nevertheless, an association of these phenotypes with LTC- IC function did allow highly enriched (> 5% pure) suspensions of either Ph+ or Ph- LTC-IC to be obtained from selected samples of CML blood in which the initial LTC-IC population was either predominantly Ph+ or Ph- , respectively. These findings suggest that the mechanisms causing mobilization of leukemic stem cells in untreated CML patients may affect their normal counterparts. They also indicate a possible new source of autologous cells for the support of intensive therapy of CML patients. Finally, they provide a method for obtaining the most highly purified populations of Ph+ LTC-IC described to date. This method should be useful for further analyses of the molecular activities of these very primitive neoplastic cells. 相似文献
34.
Hermine A van Duyvenvoorde Julian C Lui Sarina G Kant Wilma Oostdijk Antoinet CJ Gijsbers Mari?tte JV Hoffer Marcel Karperien Marie JE Walenkamp Cees Noordam Paul G Voorhoeve Verónica Mericq Alberto M Pereira Hedi L Claahsen-van de Grinten Sandy A van Gool Martijn H Breuning Monique Losekoot Jeffrey Baron Claudia AL Ruivenkamp Jan M Wit 《European journal of human genetics : EJHG》2014,22(5):602-609
Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes. 相似文献
35.
Arjan PM de Brouwer Sander B Nabuurs Ingrid EC Verhaart Astrid R Oudakker Roel Hordijk Helger G Yntema Jannet M Hordijk-Hos Krysta Voesenek Bert BA de Vries Ton van Essen Wei Chen Hao Hu Jamel Chelly Johan T den Dunnen Vera M Kalscheuer Annemieke M Aartsma-Rus Ben CJ Hamel Hans van Bokhoven Tjitske Kleefstra 《European journal of human genetics : EJHG》2014,22(4):480-485
We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy. 相似文献
36.
37.
O'Malley CJ; Rasko JE; Basser RL; McGrath KM; Cebon J; Grigg AP; Hopkins W; Cohen B; O'Byrne J; Green MD; Fox RM; Berndt MC; Begley CG 《Blood》1996,88(9):3288-3298
This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status. 相似文献
38.
Tessa Timmers Rik Ossenkoppele Denise Visser Hayel Tuncel Emma E Wolters Sander CJ Verfaillie Wiesje M van der Flier Ronald Boellaard Sandeep SV Golla Bart NM van Berckel 《Journal of cerebral blood flow and metabolism》2020,40(12):2464
The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [18F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [18F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr80–100 and SUVr110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods. 相似文献
39.
KI Wheeler GM Schmölzer CJ Morley PG Davis 《Acta paediatrica (Oslo, Norway : 1992)》2011,100(1):67-70
Background: Ventilator frequency is one of the determinants of tidal volume delivery during high‐frequency ventilation. Clinicians increasingly use data on ventilator displays to inform their decisions. Aim: To measure the frequencies delivered by the Dräger Babylog 8000plus ventilator when used in high‐frequency mode. Methods: Ventilator waveforms using a test lung were recorded at the full range of settings 5–20 Hz using Spectra software at 1000 Hz. The changes in frequency produced by a 1‐ Hz change in set frequency were calculated. Actual and displayed frequencies were compared. Results: For settings up to 12 Hz, median (range) difference between set and delivered frequencies was 0 (?0.4 to +0.1) Hz. Above 12 Hz, delivered frequency varied by ?0.3 (?1.9 to +0.3) Hz. For 1‐ Hz changes in frequency settings, in the range 5–12 Hz, 1‐ Hz changes produced a change in delivered frequency of 1.0 (0.6–1.4) Hz. Above 12 Hz, the corresponding changes were 0.7 (0–2.9) Hz. The ventilator displays the set frequency during operation rather than the delivered frequency. Conclusion: At 12 Hz and below, the differences between set and delivered frequencies were relatively small compared with those at 13 Hz and higher. Above 13 Hz, the difference between set and delivered frequencies was up to 2.9 Hz. Some frequency setting changes did not result in a change in delivered frequency. 相似文献
40.
CJ Mitchell P Stephany 《Malawi medical journal : the journal of Medical Association of Malawi》2013,25(3):88-89
An outbreak of Tunga Penetrans (Jigger Flea) infestation affecting a number of villages near to a Central Hospital in Malawi is described. Due to the large number of affected individuals, high parasitic load, and extended duration of infection an alternative to the recommended approach of surgical removal of the flea was required. Benzyl benzoate paint and liquid paraffin had been used in local Primary Healthcare settings previously and topical treatment with antiparasitic agents has been advocated in the literature, particularly for severe infestation. Benzyl benzoate and liquid paraffin were applied topically to four adults with numerous jigger flea burrows, and their progress assessed regularly. After completion of 7 days of treatment patients noted that fleas were dislodging spontaneously, and that embedded parasites had not increased in size to the same extent that untreated fleas had in previous infestations. Following confirmation of the viability of its implementation in a resource-poor setting, this treatment regimen has subsequently been adopted by the local branch of the District Health Office for distribution to infected communities. 相似文献