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51.
Lazar GA Dang W Karki S Vafa O Peng JS Hyun L Chan C Chung HS Eivazi A Yoder SC Vielmetter J Carmichael DF Hayes RJ Dahiyat BI 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(11):4005-4010
Antibody-dependent cell-mediated cytotoxicity, a key effector function for the clinical efficacy of monoclonal antibodies, is mediated primarily through a set of closely related Fcgamma receptors with both activating and inhibitory activities. By using computational design algorithms and high-throughput screening, we have engineered a series of Fc variants with optimized Fcgamma receptor affinity and specificity. The designed variants display >2 orders of magnitude enhancement of in vitro effector function, enable efficacy against cells expressing low levels of target antigen, and result in increased cytotoxicity in an in vivo preclinical model. Our engineered Fc regions offer a means for improving the next generation of therapeutic antibodies and have the potential to broaden the diversity of antigens that can be targeted for antibody-based tumor therapy. 相似文献
52.
Sergeeva LI Keurentjes JJ Bentsink L Vonk J van der Plas LH Koornneef M Vreugdenhil D 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(8):2994-2999
The possible role of the sucrose-splitting enzymes sucrose synthase and invertase in elongating roots and hypocotyls of Arabidopsis was tested by using a combination of histochemical methods and quantitative trait locus (QTL) analysis. Lengths of roots and hypocotyls correlated better with invertase activities than with sucrose synthase activities. The highest correlations were observed with activities in the elongating zones of roots. The genetic basis of these correlations was studied by using QTL analysis. Several loci, affecting invertase activity, colocated with loci that had an effect on root or hypocotyl length. Further fine mapping of a major locus for root length, but not for hypocotyl length (top chromosome 1), consistently showed colocation with the locus for invertase activity containing a gene coding for a vacuolar invertase. The analysis of a functional knockout line confirmed the role of this invertase in root elongation, whereas other invertase genes might play a role in hypocotyl elongation. Thus, we show the power of QTL analysis, combined for morphological and biochemical traits, followed by fine-mapping and mutant analysis, in unraveling the function of genes and their role in growth and development. 相似文献
53.
Sofia B. Gustafsson Anders Wallenius Hanna Zackrisson Dina Popova Linus Plym Forshell Stig O. P. Jacobsson 《Archives of toxicology》2013,87(11):1939-1951
Compounds acting on the cannabinoid (CB) receptors are involved in the control of cell fate, and there is an emerging consensus that CBs have anticancer effects. However, the CB-mediated effects are contradictory since some studies suggest stimulatory effects on cancer cell proliferation, and CBs have been shown to stimulate both proliferation and differentiation of other mitotic cells such as stem and progenitor cells. In this study, the concentration-dependent effects of synthetic and endogenous CBs on the viability of mouse P19 embryonal carcinoma (EC) cells have been examined by using fluorescence assays of cell membrane integrity, cell proliferation, oxidative stress, and detection of apoptosis and necrosis. All compounds examined produced a concentration-dependent decrease in cell viability in the micromolar range, with the potent CB receptor agonist HU 210 and the enantiomer HU 211 (with no CB receptor activity) being the most potent compounds examined with apparent IC50 values of 1 and 0.6 μM, respectively. The endogenous CB anandamide showed similar potency and efficacy as structurally related polyunsaturated fatty acids with no reported activity at the CB receptors. The rapid (within hours) decrease in cell viability induced by the examined CBs suggests cytocidal rather than antiproliferative effects and is dependent on the plating cell population density with the highest toxicity around 100 cells/mm2. The CB-induced cytotoxicity, which appears to involve CB receptors and the sphingomyelin–ceramide pathway, is a mixture of both apoptosis and necrosis that can be blocked by the antioxidants α-tocopherol and N-acetylcysteine. In conclusion, both synthetic and endogenous CBs produce seemingly unspecific cytotoxic effects in the P19 EC cells. 相似文献
54.
Lytsy B Sandegren L Tano E Torell E Andersson DI Melhus A 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2008,116(4):302-308
Between May and December 2005, 64 multidrug-resistant isolates of Klebsiella pneumoniae were detected from patients admitted to Uppsala University Hospital. This represented a dramatic increase in ESBL-producing K. pneumoniae compared to previous years. To investigate the epidemiology and to characterize the resistance mechanisms of the isolates, a study was initiated. Antibiotic susceptibility was determined by means of the Etest and the disc diffusion method. Extended-spectrum beta-lactamase (ESBL) production was identified by clavulanic acid synergy test and confirmed with PCR amplification followed by DNA sequencing. DNA profiles of the isolates were examined with pulsed-field gel electrophoresis (PFGE). All isolates were resistant or exhibited reduced susceptibility to cefadroxil, cefuroxime, cefotaxime, ceftazidime, aztreonam, piperacillin/tazobactam, ciprofloxacin, tobramycin, and trimethoprim-sulfamethoxazole. They produced ESBL of the CTX-M-15 type, and the involvement of a single K. pneumoniae clone was shown. This is the first major clonal outbreak of multiresistant ESBL-producing K. pneumoniae in Scandinavia. The outbreak demonstrates the epidemic potential of enterobacteria containing ESBLs of the CTX-M type, even in a country with a relatively low selective pressure and a low prevalence of multiresistant bacteria. 相似文献
55.
56.
Sara Järpestam Louise Martinell Christian Rylander Linus Lilja 《Acta anaesthesiologica Scandinavica》2023,67(9):1249-1255
Background
European guidelines recommend targeted temperature management (TTM) in post-cardiac arrest care. A large multicentre clinical trial, however, showed no difference in mortality and neurological outcome when comparing hypothermia to normothermia with early treatment of fever. The study results were valid given a strict protocol for the assessment of prognosis using defined neurological examinations. With the current range of recommended TTM temperatures, and applicable neurological examinations, procedures may differ between hospitals and the variation of clinical practice in Sweden is not known.Aim
The aim of this study was to investigate current practice in post-resuscitation care after cardiac arrest as to temperature targets and assessment of neurological prognosis in Swedish intensive care units (ICUs).Methods
A structured survey was conducted by telephone or e-mail in all Levels 2 and 3 (= 53) Swedish ICUs during the spring of 2022 with a secondary survey in April 2023.Results
Five units were not providing post-cardiac arrest care and were excluded. The response rate was 43/48 (90%) of the eligible units. Among the responding ICUs, normothermia (36–37.7°C) was applied in all centres (2023). There was a detailed routine for the assessment of neurological prognosis in 38/43 (88%) ICUs. Neurological assessment was applied 72–96 h after return of spontaneous circulation in 32/38 (84%) units. Electroencephalogram and computed tomography and/or magnetic resonance imaging were the most common technical methods available.Conclusion
Swedish ICUs use normothermia including early treatment of fever in post-resuscitation care after cardiac arrest and almost all apply a detailed routine for the assessment of neurological prognosis. However, available methods for prognostic evaluation varies between hospitals. 相似文献57.
58.
Singapore's regional health systems—a data‐driven perspective on frequent admitters and cross utilization of healthcare services in three systems
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59.
Chinwe O. Ewenighi Uchechukwu Dimkpa Joel C. Onyeanusi Adejumo Babtunde Linus U. M. Onoh Gladys O. Onoh 《Archives of environmental & occupational health》2017,72(5):258-263
To evaluate the level of total prostate-specific antigen (PSA) and effect of duration of exposure to pollutants in quarry workers, 5 mls of blood sample was collected from participants: 72 male quarry workers exposed to quarry pollutants and 72 unexposed controls. PSA estimations were done using the principle of ELISA. Mean total PSA, free PSA, and free-total PSA ratio levels of quarry workers did not differ from those of controls and was below the cutoff for the risk of prostate diseases. Higher mean total PSA and free PSA were observed in workers exposed for > 3 years compared to the unexposed control and workers exposed for ≤ 3 years. Age-adjusted linear regression indicated significant association (R = 0.515; p < .001) between the duration of exposure and total PSA level in quarry workers. This study suggests that longer duration of exposure to the quarry pollutants may elevate PSA level if precautions are not taken to minimize dose of exposure. 相似文献
60.
David M. Engelthaler Michael Valentine Jolene Bowers Jennifer Pistole Elizabeth M. Driebe Joel Terriquez Linus Nienstadt Mark Carroll Mare Schumacher Mary Ellen Ormsby Shane Brady Eugene Livar Del Yazzie Victor Waddell Marie Peoples Kenneth Komatsu Paul Keim 《Emerging infectious diseases》2016,22(4):734-738
The hyper-virulent emm59 genotype of invasive group A Streptococcus was identified in northern Arizona in 2015. Eighteen isolates belonging to a genomic cluster grouped most closely with recently identified isolates in New Mexico. The continued transmission of emm59 in the southwestern United States poses a public health concern. 相似文献