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21.
Retroviral display of antibody fragments; interdomain spacing strongly influences vector infectivity 总被引:1,自引:0,他引:1
S Ager BH Nilson FJ Morling KW Peng FL Cosset SJ Russell 《Canadian Metallurgical Quarterly》1996,7(17):2157-2164
Five different single-chain antibody fragments (scFv) against human cell-surface antigens were displayed on murine ecotropic retroviral vectors by fusing them to the Moloney SU envelope glycoprotein. The spacing between the scFv and the SU glycoprotein was varied by fusing the scFv to residue +7 or to residue +1 of Moloney SU and by inserting linker sequences of different lengths between the domains. All of the chimeric envelopes were efficiently incorporated into vector particles and could bind to human cells through their displayed antibody fragments, but did not infect them. The spacing between the scFvs and the SU glycoproteins had no significant effect on the efficiency of envelope expression or viral incorporation and did not affect the binding properties of the chimeric envelopes, nor did it influence the efficiency of targeted gene delivery to human cells by scFv-displaying vectors. However, on murine fibroblasts the infectivity of vectors incorporating the chimeric envelopes was strongly influenced by the length of the interdomain spacer. The titers were very low when the single-chain antibodies were fused through a tripeptide linker to SU residue +7 and were greatly enhanced (up to 10(5)-fold) when they were fused to SU residue +1 through a heptapeptide linker. These results point to the importance of steric interactions between the domains of chimeric envelope glycoproteins and may have implications for retroviral vector design for human gene therapy. 相似文献
22.
The effects of epithelial removal and cyclooxygenase inhibition on contractions induced by exogenous acetylcholine (ACh) and electrical field stimulation (EFS) were evaluated in horse tracheal strips and bronchial rings. Epithelial removal potentiated the response to ACh but had no influence on the response to EFS. The effect of epithelial removal was not altered by pretreating the tissues with meclofenamate, a cyclooxygenase inhibitor. In trachealis strips, meclofenamate augmented contractions induced by EFS but not by ACh. In bronchial rings, meclofenamate augmented EFS-induced contraction to a greater extent than ACh-induced contraction. These effects of meclofenamate were epithelium-independent. We conclude that horse airway epithelium produces a relaxant factor that is not a prostanoid. Endogenous prostanoids originating from non-epithelial sites inhibit only cholinergic nerves in the trachea but both parasympathetic nerves and smooth muscle in the bronchi. 相似文献
23.
The Morris water-escape task is an extensively used experimental paradigm to assess the spatial discrimination performance and effects of brain lesions and drugs on this performance. In the first experiment, we compared the acquisition of this task by different strains (CFW1, BALB, NMRI, and C57BL) of mice and their performance in a probe trial. In a second experiment, C57BL mice were tested in Morris mazes where black and white tanks were combined with white or black platforms to investigate if and how the contrast between the tank and the platform affects the performance of the mice. In addition, four brightness conditions were compared to investigate whether or not the degree of brightness of the tank itself affects the learning performance. The results of these experiments indicated that 1. mice could readily learn the Morris task, 2. one of the contrast conditions affected the swimming speed, 3. the maze brightness per se did not affect water escape performance at all, and that 4. the swimming speed can strongly bias the outcome of Morris water-escape experiments in mice. 相似文献
24.
DW Nigg FJ Wheeler DE Wessol J Capala M Chadha 《Canadian Metallurgical Quarterly》1997,33(1-2):93-104
The longitudinal, expert, all data (LEAD) procedure has been employed as a criterion for the assessment of the procedural validity of diagnostic instruments. This study evaluated the procedure's concurrent, discriminant and predictive validity. Interview and questionnaire data obtained from 100 individuals in a substance abuse treatment program were used to assess current and lifetime substance use disorders and common comorbid disorders. An experienced, doctoral-level clinician formulated LEAD diagnoses for each patient, based on an initial interview, ongoing clinical contact and the results of the research assessment and all available clinical records. LEAD-derived substance use diagnoses showed good concurrent, discriminant and predictive validity. The validity of comorbid diagnoses obtained using the LEAD procedure was generally fair to good. Comparison with diagnoses based only on the clinician's unstructured initial interview showed that the availability of additional data enhanced diagnostic validity. Diagnoses derived by a research technician using the Structured Clinical Interview for DSM-III-R showed validity comparable to that of LEAD diagnoses. To enhance its diagnostic validity, applications of the LEAD standard should include a structured interview. Other variations in the application of the LEAD standard, including a longer evaluation period, may also enhance its performance as a diagnostic criterion measure. 相似文献
25.
J Caballero Güeto R Arana G Calle FJ Caballero Güeto E García del Río M Sancho C Pi?ero 《Canadian Metallurgical Quarterly》1997,50(12):906-908
Propionibacterium acnes is often considered to be a contaminant but it has also been found to be the principal pathogen in serious infections. P. acnes is a rare cause of infective endocarditis. It has been suggested that aortic root abscesses are caused by bacteria that are particularly virulent. The strongest risk factor for serious infections by this bacteria is the presence of foreign bodies. A case is presented in which endocarditis of a native aortic valve caused by P. acnes was associated with an aortic root abscess. Transesophageal echocardiography is particularly helpful in the diagnosis of this severe complication of infective endocarditis. The literature for P. acnes endocarditis is reviewed. 相似文献
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YT van der Schouw WA van den Beld GA van der Sanden RA Binkhorst FJ Gabre?ls AL Verbeek 《Canadian Metallurgical Quarterly》1993,35(7):608-613
The authors conducted an assessment study of newly developed motor performance items for the diagnosis of myopathy. 17 children who had had muscle biopsy for this diagnosis in the recent past were administered 14 items based on the measurement of static, dynamic and explosive muscle strength and muscle endurance. Individual items did not have perfect discriminative power, but the results were encouraging enough to warrant detailed study with combinations of the items, so that in future fewer children will have to undergo unnecessary muscle biopsies. 相似文献
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30.
L Su-Hernández A Abascal-Macías FJ Méndez-Bueno R Paniagua D Amato 《Canadian Metallurgical Quarterly》1996,16(4):362-365
The rationale for anti-tumour necrosis factor-alpha (anti-TNFalpha) therapy in rheumatoid arthritis (RA) is based on experiments on cultures of human rheumatoidjoint tissue, supported by experiments in animal models, all of which demonstrated that anti-TNFalpha antibody had profound effects on the disease activity. Clinical trials have substantiated this concept, and we have used the serum samples from the clinical trials, as well as biopsies to study the changes occurring during anti-TNFalpha therapy as clues to the pathogenesis of RA. The major effects of anti-TNFalpha therapy are in downregulating cytokine activity, and in reducing leucocyte trafficking to the joints. 相似文献