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81.
Retrovirus packaging cell lines that express the Moloney murine leukemia virus gag, pol, and env genes and a retroviral vector genome can produce virus particles that are capable of transducing cells. Normally if the packaging cell line does not produce a functional viral fusion glycoprotein, such as the retroviral envelope protein or a foreign viral glycoprotein, then the viruses will be incapable of transducing cells. We have found that incubating envelope protein-deficient virus particles bound to cells with chlorpromazine leads to transduction. Chlorpromazine (CPZ) is a membrane-active reagent that is commonly used to induce the hemifusion to fusion transition when membrane fusion is mediated by partially defective viral glycoproteins. The concentration and pH dependence of the promotion of transduction by CPZ is consistent with a role for CPZ micelle formation in viral entry. These data indicate that caution is warranted when experiments concerning membrane fusion completion promoted by CPZ are analyzed. 相似文献
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Scheduled (SDS) and unscheduled (UDS) DNA synthesis as well as nucleoid sedimentation was investigated in vitro under the influence of novobiocin (NB) and nalidixic acid (NA) using intact thymic (T-cells) and splenic (S-cells) rat cells and cells which were exposed to X-rays, UV irradiation, methyl methanesulfonate (MMS), and DNA polymerase inhibitors. At concentrations of 56.25 (S-cells) and 225 g/ml (T-cells), respectively, NB inhibited SDS in a dose-dependent manner. Within a concentration range of 225–900 g NB/ml, UDS of S-cells decreased to values far below the tracer ([3H-methyl]-thymidine) incorporation of control cells, whereas UDS of T-cells increased by at least 200%. Within a concentration range of 450–1800 g/ml, NA enhanced SDS and UDS by about 30% in S-cells and by 100% in T-cells. The stimulating activity of NB and/or NA could be eliminated specifically by the DNA polymerase inhibitor 2',3'-dideoxythymidine. Enhanced nucleoid sedimentation was observed at NB concentrations 750 g/ml; S-cells revealed a higher sedimentation rate than T-cells. It is suggested that NB (and NA) influence DNA topology in a rather cell specific manner, stimulating UDS of T-cells by a DNA polymerase — dependent repair-like mechanism. 相似文献
84.
Alfred K. Cheung Tara I. Chang William C. Cushman Susan L. Furth Fan Fan Hou Joachim H. Ix Gregory A. Knoll Paul Muntner Roberto Pecoits-Filho Mark J. Sarnak Sheldon W. Tobe Charles R.V. Tomson Lyubov Lytvyn Jonathan C. Craig David J. Tunnicliffe Martin Howell Marcello Tonelli Michael Cheung Johannes F.E. Mann 《Kidney international》2021,99(3):559-569
85.
Alex H.S. Harris Alfred C. Kuo Thomas R. Bowe Luisa Manfredi Narlina F. Lalani Nicholas J. Giori 《The Journal of arthroplasty》2021,36(1):112-117.e6
BackgroundApproximately 15%-20% of total knee arthroplasty (TKA) patients do not experience clinically meaningful improvements. We sought to compare the accuracy and parsimony of several machine learning strategies for developing predictive models of failing to experience minimal clinically important differences in patient-reported outcome measures (PROMs) 1 year after TKA.MethodsPatients (N = 587) in 3 large Veteran Health Administration facilities completed PROMs before and 1 year after TKA (92% follow-up). Preoperative PROMs and electronic health record data were used to develop and validate models to predict failing to experience at least a minimal clinically important difference in Knee Injury and Osteoarthritis Outcome Score (KOOS) Total, KOOS JR, and KOOS subscales (Pain, Symptoms, Activities of Daily Living, Quality of Life, and recreation). Several machine learning strategies were used for model development. Ten-fold cross-validation and bootstrapping were used to produce measures of overall accuracy (C-statistic, Brier Score). The sensitivity and specificity of various predicted probability cut-points were examined.ResultsThe most accurate models produced were for the Activities of Daily Living, Pain, Symptoms, and Quality of Life subscales of the KOOS (C-statistics 0.76, 0.72, 0.72, and 0.71, respectively). Strategies varied substantially in terms of the numbers of inputs required to achieve similar accuracy, with none being superior for all outcomes.ConclusionModels produced in this project provide estimates of patient-specific improvements in major outcomes 1 year after TKA. Integrating these models into clinical decision support, informed consent and shared decision making could improve patient selection, education, and satisfaction.Level of EvidenceLevel III, diagnostic study. 相似文献
86.
Julia M. Grottenthaler Annette Konzelmann Anette Stiegler Clemens Hinterleitner Sarah M. Bott Thomas Klag Christoph R. Werner Martina Hinterleitner Alfred Königsrainer Anil Batra Nisar P. Malek Silvio Nadalin Christoph P. Berg 《Transplant international》2021,34(11):2257-2265
Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) – a metabolite of ethanol – in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk. 相似文献
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W. K. Alfred Yung A. M. Castellanos P. Van Tassel R. P. Moser S. G. Marcus 《Journal of neuro-oncology》1990,9(1):29-34
Recombinant interferon beta (IFN-ser) has been administered by intravenous bolus injection three times weekly at a dose of 90 × 106 IU to 14, patients with recurrent malignant glioma in an ongoing study. The treatment period has ranged from 1 to 40 weeks. The most common adverse experiences were fever, chills, malaise, and headache. Fever, chills and headache were worse with the first two doses and were usually relieved with acetaminophen. All patients tolerated subsequent treatments without any difficulties. No neurologic or hematologic toxicities were observed. Of ten evaluable patients, five had progressive disease in 4 to 8 weeks; three had stable disease for 12 to 21 weeks; one has had a minor response for 13 weeks; and one has had a complete resolution of tumor for 150 + weeks. IFN-ser appears to have activity in human glioma and is well tolerated at this dosage and schedule. 相似文献