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991.
Summary of complementation groups of UV-sensitive CHO cell mutants isolated by large-scale screening 总被引:7,自引:0,他引:7
Busch David; Greiner Carol; Lewis Kathy; Ford Ruth; Adair Gerald; Thompson Larry 《Mutagenesis》1989,4(5):349-354
A summary is given for the lineage and complementation groupassignments of 153 UV-sensitive mutants of the CHO AA8 cellline. The distribution of mutants among six complementationgroups was highly non-random, with the great majority of theisolates belonging to groups 1 and 2. This asymmetry is consistentwith the known hemizygosity of these two linked loci in CHOcells. The relative numbers of mutants induced in group 2 wasfound to depend greatly on the type of mutagen used. Mutagenesiswith UV radiation, ethyl methanesulfonate (EMS), N-methyl-N'-nitro-N-nitroso-guanidine and 7-bromomethylbenz[a]anthraceneproduced high frequencies of group 2 mutants. In contrast, ICR170and ICR191, which are thought to produce mostly frameshift mutations,yielded very few mutants in group 2. These results are of particularimportance in light of the recent finding that the human ERCC2gene, which corrects group 2 mutants, has very strong homologywith the yeast gene RAD3. RAD3 is an essential gene for viabilityin yeast, and the low recovery of group 2 mutants using theframeshift agents strongly suggests that frameshift mutationstend to be lethal in the hamster ERCC2 locus. Several mutagen-sensitivedouble mutants were isolated in two-step selections from EMS-,mitomycin C- or UV-sensitive parental cells, including the lineUVU1, the first mammalian line with two mutations that affectUV sensitivity. The first mutation inactivated excision repair,and the second mutation appears to have affected some otherrecovery process. UVU1 should be useful for studying recoveryprocesses that are separate from nucleotide excision repair.
1To whom correspondence should be addressed 相似文献
992.
William C. Stanley Ji Di Chen William R. Lee George A. Brooks 《European journal of applied physiology》1987,56(3):299-305
Summary Mechanisms involved in the control of pulmonary ventilation were studied in seven male subjects following 6 min of exercise on a cycle ergometer at 98w. Circulation to the legs was occluded by thigh cuffs (27 kPa) during the last 15 s of exercise and the subsequent 4 min of recovery. Respiratory gas exchange and the tidal partial pressures of O2 and CO2 were measured breathby-breath. The results were compared to control studies without occlusion. There was a significant increase in both systolic and diastolic blood pressures during occluded recovery. Following occlusion systolic pressure remained elevated while diastolic pressure returned to control values. Occlusion during recovery caused hyperventilation during the first 1.5 min after exercise as evidenced by significantly higher
, PETO2, and lower PETCO2. Following the release of the cuffs PETCO2,
, and heart rate all increased significantly above control values, while PETO2 decreased. PETCO2 rose abruptly 14.5±0.9 s after the release of the cuffs. Marked increases inV
E and heart rate were seen, and occurred 30.8±1.5 s and 12.8±1.3 s, respectively, after cuff release. The 16.3±1.4 s lag between the increase in PETCO2 and
after occlusion suggests that the ventilatory response to a sudden load of hypercapnic blood is not mediated by a pulmonary chemoreceptor. Other receptors, probably the peripheral chemoreceptors, appear to be responsible for hypercapnic hyperventilation. 相似文献
993.
Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection 总被引:8,自引:0,他引:8
Walther M Tongren JE Andrews L Korbel D King E Fletcher H Andersen RF Bejon P Thompson F Dunachie SJ Edele F de Souza JB Sinden RE Gilbert SC Riley EM Hill AV 《Immunity》2005,23(3):287-296
Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor. 相似文献
994.
995.
996.
Ludwig DL Witte L Hicklin DJ Prewett M Bassi R Burtrum D Pereira DS Jimenez X Fox F Saxena B Zhou Q Ma Y Kang X Patel D Barry M Kussie P Zhu Z Russell DA Petersen WL Jury TP Gaitan-Gaitan F Moran DL Delannay X Storrs BS Tou J Zupec ME Gustafson KS McIntyre J Tarnowski SJ Bohlen P 《Human antibodies》2004,13(3):81-90
Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed. Both corn antibodies were shown to be functionally indistinguishable from mammalian-derived C225 in demonstrating high-affinity binding to the EGF receptor, blocking of ligand-dependent signaling, and inhibiting cell proliferation. In addition, consistent with cetuximab, both corn antibodies possessed strong anti-tumor activity in vivo. Acute dose primate pharmacokinetic studies, however, revealed a marked increase in clearance for the glycosylated corn antibody, while the aglycosylated antibody possessed in vivo kinetics similar to cetuximab. This experimentation established that corn-derived receptor blocking monoclonal antibodies possess comparable efficacy to mammalian cell culture-derived antibody, and offer a cost effective alternative to large-scale mammalian cell culture production. 相似文献
997.
IL-10, an inflammatory/inhibitory cytokine,but not always 总被引:24,自引:0,他引:24
998.
Twells RC Mein CA Phillips MS Hess JF Veijola R Gilbey M Bright M Metzker M Lie BA Kingsnorth A Gregory E Nakagawa Y Snook H Wang WY Masters J Johnson G Eaves I Howson JM Clayton D Cordell HJ Nutland S Rance H Carr P Todd JA 《Genome research》2003,13(5):845-855
Patterns of linkage disequilibrium (LD) in the human genome are beginning to be characterized, with a paucity of haplotype diversity in "LD blocks," interspersed by apparent "hot spots" of recombination. Previously, we cloned and physically characterized the low-density lipoprotein-receptor-related protein 5 (LRP5) gene. Here, we have extensively analysed both LRP5 and its flanking three genes, spanning 269 kb, for single nucleotide polymorphisms (SNPs), and we present a comprehensive SNP map comprising 95 polymorphisms. Analysis revealed high levels of recombination across LRP5, including a hot-spot region from intron 1 to intron 7 of LRP5, where there are 109 recombinants/Mb (4882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. This region of high recombination could be delineated into three to four hot spots, one within a 601-bp interval. For LRP5, three haplotype blocks were identified, flanked by the hot spots. Each LD block comprised over 80% common haplotypes, concurring with a previous study of 14 genes that showed that common haplotypes account for at least 80% of all haplotypes. The identification of hot spots in between these LD blocks provides additional evidence that LD blocks are separated by areas of higher recombination. 相似文献
999.
1000.
The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor 总被引:13,自引:0,他引:13
Fox CJ Hammerman PS Cinalli RM Master SR Chodosh LA Thompson CB 《Genes & development》2003,17(15):1841-1854