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51.
52.
Gazitt Y; Tian E; Barlogie B; Reading CL; Vesole DH; Jagannath S; Schnell J; Hoffman R; Tricot G 《Blood》1996,87(2):805-811
Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are now widely used to support myeloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event- free and overall survival. Because tumor cells are present not only in bone marrow, but also in virtually all PBSC harvests, it is conceivable that autografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem cell contents were measured by multiparameter flow cytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg) within the first 2 days, whereas peak levels (percent and absolute numbers) of myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days of collection, mobilized tumor cells exhibited more frequently high labeling index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The differential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests. 相似文献
53.
Ann Iverson Larissa I. Stanberry Peter Tajti Ross Garberich Amber Antos M. Nicholas Burke Ivan Chavez Mario Gössl Timothy D. Henry Daniel Lips Michael Mooney Anil Poulose Paul Sorajja Jay Traverse Yale Wang Steven Bradley Emmanouil S. Brilakis 《Cardiovascular Revascularization Medicine》2019,20(4):289-292
Background/purpose
Patients and lesions at a higher procedural risk for percutaneous coronary intervention (PCI) are an understudied population. We examined the frequency, clinical characteristics, and outcomes of higher risk and non-higher risk PCIs at a large tertiary center.Methods/materials
The following procedures were considered higher risk: unprotected left main PCI, chronic total occlusion PCI, PCI requiring atherectomy, multivessel PCI, bifurcation PCI, PCI in prior coronary artery bypass graft surgery (CABG) patients, pre-PCI left ventricular ejection fraction ≤30%, or use of hemodynamic support.Results
Of the 1975 PCIs performed from 6/29/09 to 12/30/2016 in patients without acute coronary syndromes, 1230 (62%) were higher risk. Patients undergoing higher risk PCI were more likely to have a history of CABG, myocardial infarction, PCI, cerebrovascular disease, peripheral arterial disease, or congestive heart failure. Higher risk PCIs required more stents (2.0 vs. 1.0, p?<?0.001), and had longer median fluoroscopy times (17.3 vs. 8.5?min, p?<?0.001) and higher median contrast doses (160 vs. 120?mL, p?<?0.001). In higher risk PCIs, the risks for technical failure and periprocedural complications were 2.9 (95% CI 1.2–7.4) times and 2.2 (95% CI 0.9–5.4) times higher as compared with non-higher risk PCI procedures.Conclusions
In summary, over half of the PCIs performed in non-acute coronary syndrome patients were higher risk and were associated with lower odds of technical success and higher periprocedural complication rates as compared with non-higher risk PCIs.Summary
We examined the frequency, clinical characteristics, and outcomes of higher risk and non-higher risk PCIs at a large tertiary center. Higher risk PCI was associated with lower odds of technical and procedural success and higher odds of procedural complications as compared with non-higher risk PCI. However, the risk/benefit ratio may still be favorable for many of these higher-risk patients and should be estimated on a case by case basis. 相似文献54.
Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation 总被引:17,自引:0,他引:17
Nollen EA Garcia SM van Haaften G Kim S Chavez A Morimoto RI Plasterk RH 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(17):6403-6408
Protein misfolding and the formation of aggregates are increasingly recognized components of the pathology of human genetic disease and hallmarks of many neurodegenerative disorders. As exemplified by polyglutamine diseases, the propensity for protein misfolding is associated with the length of polyglutamine expansions and age-dependent changes in protein-folding homeostasis, suggesting a critical role for a protein homeostatic buffer. To identify the complement of protein factors that protects cells against the formation of protein aggregates, we tested transgenic Caenorhabditis elegans strains expressing polyglutamine expansion yellow fluorescent protein fusion proteins at the threshold length associated with the age-dependent appearance of protein aggregation. We used genome-wide RNA interference to identify genes that, when suppressed, resulted in the premature appearance of protein aggregates. Our screen identified 186 genes corresponding to five principal classes of polyglutamine regulators: genes involved in RNA metabolism, protein synthesis, protein folding, and protein degradation; and those involved in protein trafficking. We propose that each of these classes represents a molecular machine collectively comprising the protein homeostatic buffer that responds to the expression of damaged proteins to prevent their misfolding and aggregation. 相似文献
55.
Re-expansion pulmonary edema 总被引:2,自引:0,他引:2
56.
Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells. 相似文献
57.
Effect of 3'' flanking neighbors on kinetics of pairing of dCTP or dTTP opposite O6-methylguanine in a defined primed oligonucleotide when Escherichia coli DNA polymerase I is used. 总被引:7,自引:4,他引:7 下载免费PDF全文
B Singer F Chavez M F Goodman J M Essigmann M K Dosanjh 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(21):8271-8274
O6-Methylguanine (m6G) was incorporated site-specifically into two 25-base oligonucleotides differing only in the nucleotide on the 3' side of the modified base. Templates were primed with oligonucleotides terminating one or two bases prior to the site at which incorporation kinetics were to be investigated. Escherichia coli DNA polymerase I (Klenow fragment) was used to determine the apparent Km and relative Vmax of incorporation of either dCTP or dTTP opposite m6G or G. These data were used to calculate the relative frequency of incorporation opposite the m6G or the unmodified G. When the sequence was 3'-Cm6G-5', there was a 6- to 7-fold preference for formation of a m6G.T pair compared with m6G.C. The m6G.T frequency, based on Vmax/Km, was at least 50-fold greater than that of a G.T pair at the same site. Changing the sequence to 3'-Tm6G-5' had a marked effect on both Km and Vmax of pairs containing m6G and on the incorporation frequency of T opposite m6G, which was then only slightly favored over m6G.C. When replication was started directly opposite m6G, the kinetics appeared unaffected. These data indicate that the frequency of incorporation of C or T opposite m6G in a DNA template is dependent on the flanking neighbors and that a change of even a single base at the 3' position can have a major effect on mutagenic efficiency. Replication using Drosophila Pol alpha gave the same values for relative frequencies. Pairing of either C or T with m6G on the primer terminus did not significantly inhibit extension of the next normal base pair, in contrast to terminal mismatches of unmodified bases. It is concluded that, in the absence of repair, m6G can exhibit widely differing mutation frequencies which, in these experiments, can be as high as 85% of the replicated base. This variation in frequency of changed pairing could contribute to the occurrence of mutational "'hot spots" after replication of damaged DNA. 相似文献
58.
Nicole J. Cook Lucas Hollar Summer Chavez David L. Quinn Teina Phillips Michael DeLucca Lindsay Corrales 《Journal of cross-cultural gerontology》2014,29(4):405-415
Previous studies have gauged support for implementing smoke-free multi-unit housing (MUH) policies in the United States, but none have specifically examined attitudes among racially and ethnically diverse elders living in low-income MUH. We surveyed a convenience sample of elders 62 years of age and older (n?=?807) across 24 low-income housing properties in Broward County, Florida in order to assess residents’ smoking behaviors, exposure to second-hand smoke, and support for smoke-free policies. The study sample was ethnically and racially diverse with Hispanics comprising more than 61 % of the population, and 22 % identifying as Black or other races. Although close to 22 % of the sample were former smokers, only 9 % of residents reported being current smokers. The majority of residents surveyed supported no-smoking policies: 75 % support no-smoking policies for individual units; 77 % supported no-smoking policies in common areas; and, 68 % supported no-smoking policies in outdoor areas. Over 29 % of residents surveyed reported being exposed to secondhand smoke entering their units from elsewhere in their building. Residents who reported having a home smoking rule were more than twice as likely to support an indoor policy compared to residents who allowed smoking anywhere in their home (OR?=?2.36; 95%CI 1.25–4.43; p?≤?0.01), and nonsmoking residents were nearly three times as likely to support an indoor policy compared to smokers (OR?=?2.89; 95%CI 1.44–5.79; p?≤?0.01). Support for an indoor policy was not modified by age, gender, ethnicity or race. . This study demonstrates that elders living in low-income MUH properties overwhelmingly supported the implementation of smoke-free policies. 相似文献
59.
Helen E.D. Burchett Sandra Mounier-Jack Sergio Torres-Rueda Ulla K. Griffiths Pierre Ongolo-Zogo Stephen Rulisa Jean-Marie Edengue Enrique Chavez Yayehirad Kitaw Mitike Molla Mamadou Konate Lawrence Gelmon Washington Onyango-Ouma Mylene Lagarde Anne Mills 《Vaccine》2014
Objective
We aimed to explore the impacts of new vaccine introductions on immunization programmes and health systems in low- and middle-income countries.Methods
We conducted case studies of seven vaccine introductions in six countries (Cameroon, PCV; Ethiopia, PCV; Guatemala, rotavirus; Kenya, PCV; Mali, Meningitis A; Mali, PCV; Rwanda, HPV). Interviews were conducted with 261 national, regional and district key informants and questionnaires were completed with staff from 196 health facilities. Routine data from districts and health facilities were gathered on vaccination and antenatal service use. Data collection and analysis were structured around the World Health Organisation health system building blocks.Findings
The new vaccines were viewed positively and seemed to integrate well into existing health systems. The introductions were found to have had no impact on many elements within the building blocks framework. Despite many key informants and facility respondents perceiving that the new vaccine introductions had increased coverage of other vaccines, the routine data showed no change. Positive effects perceived included enhanced credibility of the immunisation programme and strengthened health workers’ skills through training. Negative effects reported included an increase in workload and stock outs of the new vaccine, which created a perception in the community that all vaccines were out of stock in a facility. Most effects were found within the vaccination programmes; very few were reported on the broader health systems. Effects were primarily reported to be temporary, around the time of introduction only.Conclusion
Although the new vaccine introductions were viewed as intrinsically positive, on the whole there was no evidence that they had any major impact, positive or negative, on the broader health systems. 相似文献60.