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排序方式: 共有114条查询结果,搜索用时 15 毫秒
1.
Hardies SC; Martin SL; Voliva CF; Hutchison CA d; Edgell MH 《Molecular biology and evolution》1986,3(2):109-125
2.
Identification of a widely distributed 90-kDa glycoprotein that is homologous to the Hermes-1 human lymphocyte homing receptor 总被引:9,自引:0,他引:9
S T Pals F Hogervorst G D Keizer T Thepen E Horst C C Figdor 《Journal of immunology (Baltimore, Md. : 1950)》1989,143(3):851-857
Homing of recirculating lymphocytes from the blood into the lymphoid tissues is mediated by 90-kDa homing receptors on the lymphocyte cell surface, allowing selective binding to specialized endothelium lining high endothelial venules. This study describes two novel mAb, NKI-P1 and NKI-P2, directed against functional epitopes of a human lymphocyte homing receptor, gp90. Biochemical studies demonstrated that these antibodies recognize a 90-kDa glycoprotein which is similar to the Ag recognized by the mAb Hermes-1. This notion was confirmed by immunohistochemical studies showing identical reaction patterns. Furthermore, it was observed that NKI-P1 and NKI-P2 blocked adhesion of lymphocytes to high endothelial venules. Immunohistochemical, immunofluorescence, and immunoprecipitation studies revealed that gp90 is widely expressed on hemopoietic cells including lymphocytes, macrophages/dendritic cells, myeloid cells, and erythrocytes. The gp90 is also expressed on a number of nonhemopoietic cells such as endothelial cells, certain epithelial cells, and fibroblasts. In addition to its expression on normal cells, gp90 is present on a spectrum of tumor cell lines of lymphoid, monocytic, epithelial, glial, and melanocytic origin. In addition to the 90-kDa product, the antibodies immunoprecipitate several polypeptides in the range of 120 to 200 kDa. Interestingly, it was observed that certain mamma tumor cell-line cells lack the 90-kDa polypeptide indicating the heterogeneous expression of the molecules recognized by the antibodies. These results indicate that the 90-kDa glycoprotein homologues of the Hermes-1 human lymphocyte homing receptor are expressed on hemopoietic tissues as well as on a number of nonhemopoietic tissues and tumor cell lines. Although the function of these molecules in nonlymphoid cells is presently unknown, they might play a role in cell-cell or cell-matrix adhesion. 相似文献
3.
Arjan W. Griffioen Eveliene Horst Karl Heinz Heider Vera J. M. Wielenga GÜ Unther R. Adolf Peter Herrlich Steven T. Pals 《Cell communication & adhesion》1994,2(3):195-200
Recently, splice variants of CD44 have been described that confer metastatic potential to non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Using antibodies against variant CD44 (CD44v) sequences, we have examined the expression of variant CD44 glycoproteins on human lymphoid cells and tissues and in colorectal neoplasia. Lymphohematopoietic cells express low levels of CD44v glycoproteins. During the process of lymphocyte activation in vitro and in vivo, expression of CD44v glycoproteins is transiently upregulated. The reaction pattern of various antibodies indicates that these CD44 variants contain the domain encoded by exon v6, which is part of the variant that confers metastatic capability. In human colorectal neoplasia we observed overexpression of CD44 splice variants in all invasive carcinomas. Already at early stages of colorectal tumor progression exon v5 epitopes were overexpressed. Tumor progression was strongly related to expression of CD44 isoforms containing exon v6 encoded domains. The findings establish CD44 variants as tumor progression markers in colorectal cancer. 相似文献
4.
Summary Microsomal and soluble fractions of Pleurotus pulmonarius exhibited a reduced carbon monoxide difference spectrum with P450 maxima at 448nm and 450–452nm respectively. Substrate induced Type I spectra were observed on addition of benzo(a)pyrene to both fractions. Benzo(a)pyrene hydroxylation was measured using the aryl hydrocarbon hydroxylase assay and was observed to be P450 dependent as indicated by carbon monoxide inhibition together with the substrate binding characteristics. The activity of the fractions were observed to give Km of 200mM and 660mM and Vmax of 1.25 nmol/min/nmol P450 and 0.57 nmol/min/nmol P450 for the microsomal and cytosolic fractions respectively. 相似文献
5.
6.
Heparan sulfate-modified CD44 promotes hepatocyte growth factor/scatter factor-induced signal transduction through the receptor tyrosine kinase c-Met 总被引:14,自引:0,他引:14
van der Voort R Taher TE Wielenga VJ Spaargaren M Prevo R Smit L David G Hartmann G Gherardi E Pals ST 《The Journal of biological chemistry》1999,274(10):6499-6506
CD44 has been implicated in tumor progression and metastasis, but the mechanism(s) involved is as yet poorly understood. Recent studies have shown that CD44 isoforms containing the alternatively spliced exon v3 carry heparan sulfate side chains and are able to bind heparin-binding growth factors. In the present study, we have explored the possibility of a physical and functional interaction between CD44 and hepatocyte growth factor/scatter factor (HGF/SF), the ligand of the receptor tyrosine kinase c-Met. The HGF/SF-c-Met pathway mediates cell growth and motility and has been implicated in tumor invasion and metastasis. We demonstrate that a CD44v3 splice variant efficiently binds HGF/SF via its heparan sulfate side chain. To address the functional relevance of this interaction, Namalwa Burkitt's lymphoma cells were stably co-transfected with c-Met and either CD44v3 or the isoform CD44s, which lacks heparan sulfate. We show that, as compared with CD44s, CD44v3 promotes: (i) HGF/SF-induced phosphorylation of c-Met, (ii) phosphorylation of several downstream proteins, and (iii) activation of the MAP kinases ERK1 and -2. By heparitinase treatment and the use of a mutant HGF/SF with greatly decreased affinity for heparan sulfate, we show that the enhancement of c-Met signal transduction induced by CD44v3 was critically dependent on heparan sulfate moieties. Our results identify heparan sulfate-modified CD44 (CD44-HS) as a functional co-receptor for HGF/SF which promotes signaling through the receptor tyrosine kinase c-Met, presumably by concentrating and presenting HGF/SF. As both CD44-HS and c-Met are overexpressed on several types of tumors, we propose that the observed functional collaboration might be instrumental in promoting tumor growth and metastasis. 相似文献
7.
Out of Africa and back again: nested cladistic analysis of human Y chromosome variation 总被引:18,自引:3,他引:15
Hammer MF; Karafet T; Rasanayagam A; Wood ET; Altheide TK; Jenkins T; Griffiths RC; Templeton AR; Zegura SL 《Molecular biology and evolution》1998,15(4):427-441
We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544
individuals from Africa, Asia, Europe, Oceania, and the New World.
Phylogenetic analyses of these nine sites resulted in a tree for 10
distinct Y haplotypes with a coalescence time of approximately 150,000
years. The 10 haplotypes were unevenly distributed among human populations:
5 were restricted to a particular continent, 2 were shared between Africa
and Europe, 1 was present only in the Old World, and 2 were found in all
geographic regions surveyed. The ancestral haplotype was limited to African
populations. Random permutation procedures revealed statistically
significant patterns of geographical structuring of this paternal genetic
variation. The results of a nested cladistic analysis indicated that these
geographical associations arose through a combination of processes,
including restricted, recurrent gene flow (isolation by distance) and range
expansions. We inferred that one of the oldest events in the nested
cladistic analysis was a range expansion out of Africa which resulted in
the complete replacement of Y chromosomes throughout the Old World, a
finding consistent with many versions of the Out of Africa Replacement
Model. A second and more recent range expansion brought Asian Y chromosomes
back to Africa without replacing the indigenous African male gene pool.
Thus, the previously observed high levels of Y chromosomal genetic
diversity in Africa may be due in part to bidirectional population
movements. Finally, a comparison of our results with those from nested
cladistic analyses of human mtDNA and beta-globin data revealed different
patterns of inferences for males and females concerning the relative roles
of population history (range expansions) and population structure
(recurrent gene flow), thereby adding a new sex-specific component to
models of human evolution.
相似文献
8.
Hypomorphic mutations in the gene encoding a key Fanconi anemia protein, FANCD2, sustain a significant group of FA-D2 patients with severe phenotype 下载免费PDF全文
Kalb R Neveling K Hoehn H Schneider H Linka Y Batish SD Hunt C Berwick M Callen E Surralles J Casado JA Bueren J Dasi A Soulier J Gluckman E Zwaan CM van Spaendonk R Pals G de Winter JP Joenje H Grompe M Auerbach AD Hanenberg H Schindler D 《American journal of human genetics》2007,80(5):895-910
FANCD2 is an evolutionarily conserved Fanconi anemia (FA) gene that plays a key role in DNA double-strand-type damage responses. Using complementation assays and immunoblotting, a consortium of American and European groups assigned 29 patients with FA from 23 families and 4 additional unrelated patients to complementation group FA-D2. This amounts to 3%-6% of FA-affected patients registered in various data sets. Malformations are frequent in FA-D2 patients, and hematological manifestations appear earlier and progress more rapidly when compared with all other patients combined (FA-non-D2) in the International Fanconi Anemia Registry. FANCD2 is flanked by two pseudogenes. Mutation analysis revealed the expected total of 66 mutated alleles, 34 of which result in aberrant splicing patterns. Many mutations are recurrent and have ethnic associations and shared allelic haplotypes. There were no biallelic null mutations; residual FANCD2 protein of both isotypes was observed in all available patient cell lines. These analyses suggest that, unlike the knockout mouse model, total absence of FANCD2 does not exist in FA-D2 patients, because of constraints on viable combinations of FANCD2 mutations. Although hypomorphic mutations arie involved, clinically, these patients have a relatively severe form of FA. 相似文献
9.
JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献10.