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991.
Esposito G Texido G Betz UA Gu H Müller W Klein U Rajewsky K 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(3):1166-1171
The ubiquitously expressed, error-prone DNA polymerase beta (polbeta) plays a role in base excision repair, and the involvement of this molecule in the nonhomologous end joining (NHEJ) process of DNA repair has recently been demonstrated in yeast. Polbeta-deficient mice are not viable, and studies on conditional mutants revealed a competitive disadvantage of polbeta(-/-) vs. wild-type cells. We show here that polbeta-deficient mice survive up to day 18.5 postcoitum, but die perinatally; a circumstance that allowed the investigation of a potential role of polbeta in lymphocyte development by transfer of fetal liver cells (FLC) derived from polbeta(-/-) embryos into lethally irradiated hosts. FLC transfers using mutant cells lead to an almost normal reconstitution of the lymphocyte compartment, indicating that polbeta-deficiency does not prevent V(D)J recombination, which is known to employ factors of the NHEJ pathway. Mice reconstituted with polbeta(-/-) FLC mount a normal T cell-dependent immune response against the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP). Moreover, germinal center B cells from NP-immunized reconstituted mice show normal levels and patterns of somatic point mutations in their rearranged antibody genes, demonstrating that polbeta is not critically involved in somatic hypermutation. 相似文献
992.
993.
The (4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase.
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Y Gu G Cimino H Alder T Nakamura R Prasad O Canaani D T Moir C Jones P C Nowell C M Croce et al. 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(21):10464-10468
Chromosomal region 11q23 is frequently rearranged in acute lymphocytic leukemias (ALLs) and in acute myeloid leukemias (AMLs), mostly in reciprocal exchanges with various translocation partners. The most common of these translocations is t(4;11)(q21;q23). It is present in approximately 10% of ALL patients, most frequently in very young children. We have recently cloned a region of chromosome 11, the ALL-1 locus, found to be rearranged in malignant cells from patients with the t(4;11), t(9;11), t(11;19), t(1;11), t(6;11), t(10;11), and del(11q23) chromosomal abnormalities. Here we report the cloning and characterization of chromosomal breakpoints from leukemic cells with t(4;11) aberrations. The breakpoints cluster in regions of 7-8 kilobases on both chromosomes 4 and 11. The presence of heptamer- and nonamer-like sequences at the sites of breakage suggests that the VDJ recombinase utilized for immunoglobulin gene rearrangement is also directly involved in these translocations. We also show that leukemic cells with t(4;11) express altered RNAs transcribed from the derivative chromosomes 11 and 4. 相似文献
994.
内镜筛查及切除息肉病理检查在早期大肠癌诊断中的意义 总被引:5,自引:4,他引:5
为探讨临床内镜筛查及切除息肉病理检查在早期大肠癌诊断中的价值,总结分析了北医大三院1978年至1996年9月所有大肠镜检查的资料。18年间行大肠镜检查18123例、内镜下息肉切除2345例,共发现早期大肠癌80例、86个癌灶,占同期发现大肠癌总数的15.1%(86/569)。早期大肠癌的诊断率呈上升趋势,特别是1987年开展临床内镜筛查以来升高尤为显著。相关分析显示早期大肠癌的诊断率与内镜检查特别是内镜下息肉切除后的病理检查密切相关,提示该两项方法为诊断早期大肠癌的有效方法。 相似文献
995.
Hb A2 and its variant B2 (alpha 2 delta 2(16)(A13)Gly----Arg) were quantitated in the blood of subjects with three different types of beta-thalassemia and with the delta-B2 anomaly in cis or in trans to the beta-thalassemia determinant. In one family, the delta-B2 mutation was in cis to a newly discovered codon 47 (+A) frameshift. The levels of Hbs A2 and B2 were nearly the same and approximately 70% higher than those in simple Hb B2 heterozygotes. In two additional families, the delta-B2 variant was in trans to either a deletional beta-thalassemia (1,393 bp) involving part of the beta-globin gene and part of the beta-globin gene promoter, or to the -88 C----T promoter mutation. In both instances, the Hb B2 level was increased by approximately 80%, but the Hb A2 level was increased by approximately 270% and 200%, respectively. These data indicate two mechanisms that will cause an increase in delta chain production. One is consistent with a general mechanism concerning the relative excess of alpha chains in beta chain deficiencies which will combine with delta chains to form variable levels of Hb A2 dependent on the severity of the beta chain deficiency. The second concerns the loss of beta-globin gene promoter activity, perhaps by an absence of (or decreased) binding of specific protein(s) to this segment of DNA and a concomitant increase in delta-globin gene promoter activity in cis. 相似文献
996.
We have amplified and sequenced the 5' flanking and the second intervening sequence (IVS-II) regions of both the G gamma- and A gamma-globin genes of the beta S chromosomes from sickle cell anemia (SS) patients with homozygosities for five different haplotypes. The sequencing data, compared with previously published sequences for the normal chromosomes A and B, show many similarities to chromosome B for haplotypes 19, 20, and 17, while haplotypes 3 and 31 are remarkably similar to chromosome A and also similar to each other. Several unique mutations were found in the 5' flanking regions (G gamma and A gamma) of haplotypes 19 and 20 and in the IVS-II segments of the same genes of haplotypes 19, 20, and 17; the IVS-II of haplotypes 3 and 31 were identical to those of chromosome A. Dot-blot analyses of amplified DNA from additional SS patients with specific probes have confirmed that these mutations are unique for each haplotype. The two general patterns that have been observed among the five haplotypes have most probably arisen by gene conversion events between the A and B type chromosomes in the African population. These patterns correlate with high and low fetal hemoglobin expression, and it is speculated that these and other yet unknown gene conversions may contribute to the variations in hemoglobin F and G gamma levels observed among SS patients. In vitro expression experiments involving the approximately 1.3-kb 5' flanking regions of the G gamma- and A gamma-globin genes of the beta S chromosomes with the five different haplotypes failed to detect differences between the levels of expression, suggesting that the sequence variations observed between these segments of DNA are not the primary cause of the differences in hemoglobin F levels among the SS patients. 相似文献
997.
通过1987—1990年在无锡、如东、如皋3个市县的现场实验和河沟钉螺调查。发现低密度钉螺的消长与环境因子密切有关,只要环境适宜,即使留下1对钉螺,也能大量繁殖增长。实验沟放置有1、5和10对钉螺的螺笼经3年后,钉螺密度各增长了171.9倍、69.5倍和28.4倍。其螺口数分别增长了354倍、135倍和75倍,其中2条积水沟的1对钉螺组螺口数增长543和426.5倍。在现场1条水沟钉螺密度增长了34倍,1条河钉螺密度没有增长,但都没有自然消亡。提示当“基本消灭”或“消灭”以后,应重视低密度钉螺的清查,坚持长期监测,一旦发现钉螺,要及时杀灭。 相似文献
998.
A. D. Adekile M. N. Kitundu L. -H. Gu K. D. Lanclos O. O. Adeodu T. H. J. Huisman 《Annals of hematology》1992,65(1):41-45
Summary We have determined the haplotypes of 669 S and 109 A chromosomes from numerous members of 297 Nigerian families of various ethnic backgrounds. Among the S chromosomes, haplotype 19 was detected in 93.2%, haplotype 17 in 3.4%, and haplotype 20 in 0.1%, while 2.4% represented atypical haplotypes. As many as 60.6% of the A chromosomes exhibited haplotype 19 mutations, 8.2% had haplotype 3, and 1.8% had haplotype 20. Two siblings with elevated Hb F andG levels were heterozygous for a S chromosome with haplotype 19 and a second chromosome with a hybrid haplotype (termed 19B). In this hybrid chromosome, haplotype 3-like locus control region (LCR) [hypersensitive site-2 (HS-2)] sequences are in juxtaposition to those of the 5 flanking region of theG promoter of a S chromosome with haplotype 19. The presence of this hybrid chromosome is associated with highG values in individuals with both sickle cell anemia (SS) and sickle cell trait (AS); it closely resembles another hybrid S chromosome, termed 19 A, observed in a previously reported Turkish SS patient who was homozygous for this chromosome and had high Hb F and highG values. In both instances, it is hypothesized that the haplotype 3-like sequences of the LCR HS-2 contain genetic determinants that can combine with factors produced during hematopoietic stress, resulting in increased -globin gene expression.This study was supported in part, by a Fogarty International Research Fellowship Award No. 1FO5TW004414-01 (to A.D.A.) and by USPHS Research Grant HLB-41544 (to T.H.J.H.) 相似文献
999.
Genes for skeletal muscle myosin heavy chains are clustered and are not located on the same mouse chromosome as a cardiac myosin heavy chain gene. 总被引:18,自引:2,他引:18
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A Weydert P Daubas I Lazaridis P Barton I Garner D P Leader F Bonhomme J Catalan D Simon J L Guénet et al. 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(21):7183-7187
Myosin heavy chain (MHC) genes are expressed as several distinct isoforms in a tissue- and stage-specific manner; three skeletal muscle MHC isoforms appear sequentially during development. We have isolated cDNA clones, identified by RNA blot hybridization and by nucleotide sequence determination as coding for portions of the embryonic (pMHC2.2), perinatal (pMHC16.2A), and alpha(V1) cardiac (pMHC141 and pMHC101) MHC isoforms. These four probes and the adult skeletal MHC probe (pMHC32) have been used on Southern blots of genomic DNA to detect restriction fragment length polymorphisms defining the alleles for these genes in mouse species Mus musculus and Mus spretus. In this way, we followed the segregation of skeletal and cardiac MHC genes in 42 offspring resulting from an interspecies backcross. We found that the embryonic, perinatal, and adult skeletal MHC genes are clustered on chromosome 11 near the locus nude, the skeletal and cardiac MHC genes do not cosegregate, and the alpha(V1) cardiac MHC gene is located on chromosome 14 close to Np-1. This result is in contrast to that for other contractile protein genes such as the alkali myosin light chain and the actin multigene families, which are dispersed in the genome. 相似文献
1000.
Xiao-Ping Gu Yu-dong QIU Fu-Tao Xu Yong Jiang Yi-tao DING 《World journal of gastroenterology : WJG》2004,10(24)
AIM: To investigate the effect of pyrrolidine dithiocarbamate (PDTC), a novel nuclear factor-κB (NF-κB) inhibitor, on expression of multiple inflammatory mediators and neutrophilic inflammation of cold preserved grafts after rat liver transplantation and its significance.METHODS: Orthotopic liver transplantation (OLT) was performed after 24 h of cold storage using University of Wisconsin solution with varied concentrations of PDTC. We determined the time course of NF-κB activation and expression of multiple inflammatory signals, such as tumor necrosis factor-α (TNF-α), cytokine-inducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1(ICAM-1) by ElISA methods. Serum alanine aminotransferase (ALT), intrahepatic myeloperoxidase (MPO)/WBC (ameasure of neutrophil accumulation) and Mac-1 expression (a measure of circulating neutrophil activity) were also evaluated.RESULTS: PDTC decreased NF-κB activation induced by prolonged cold preservation in a dose dependent manner (from 20 mmol/L to 60 mmol/L), diminished TNF-α, CINC, ICAM-1 proteins in the grafts, and reduced the expression of increases in plasma TNF-α levels induced by prolonged cold preservation. Neutrophilic inflammation of the graft was significantly suppressed after preservation with PDTC (P<0.05). The total neutrophil accumulation in PDTC (40 mmol/L) group (7.04±0.97) was markedly reduced compared to control group (14.07±1.31) (P<0.05). Mac-1expression was significantly reduced in PDTC (40 mmol/L)group (181±11.3%) compared with the control group (281±13.2%) (P<0.05) at 6 h after reperfusion. Furthermore,PDTC inhibited the increased serum ALT levels after liver transplantation.CONCLUSION: PDTC can inhibit B NF-κB activation and expression of the inflammatory mediators, which are associated with improved graft viability via inhibiting intrahepatic neutrophilic inflammation. Our study suggests that a therapeutic strategy directed at inhibition of NF-κB activation in the transplanted liver might be effective in reducing intrahepatic neutrophilic inflammation, and would be beneficial to cold preserved grafts. 相似文献