排序方式: 共有8条查询结果,搜索用时 15 毫秒
1
1.
Adults of the human parasitic trematode Schistosoma mansoni, which causes
hepatosplenic/intestinal complications in humans, synthesize
glycoconjugates containing the Lewis x (Lex) Galbeta1-->4(Fucalpha1--
>3)GlcNAcbeta1-->R, but not sialyl Lewis x (sLex), antigen. We now
report on our analyses of Lexand sLexexpression in S.haematobium and
S.japonicum, which are two other major species of human schistosomes that
cause disease, and the possible autoimmunity to these antigens in infected
individuals. Antigen expression was evaluated by both ELISA and Western
blot analyses of detergent extracts of parasites using monoclonal
antibodies. Several high molecular weight glycoproteins in both S.
haematobium and S. japonicum contain the Lexantigen, but no sialyl
Lexantigen was detected. In addition, sera from humans and rodents infected
with S.haematobium and S.japonicum contain antibodies reactive with Lex.
These results led us to investigate whether Lexantigens are expressed in
other helminths, including the parasitic trematode Fasciola hepatica , the
parasitic nematode Dirofilaria immitis (dog heartworm), the ruminant
nematode Haemonchus contortus , and the free-living nematode Caenorhabditis
elegans . Neither Lexnor sialyl-Lexis detectable in these other helminths.
Furthermore, none of the helminths, including schistosomes, express Lea,
Leb, Ley, or the H- type 1 antigen. However, several glycoproteins from all
helminths analyzed are bound by Lotus tetragonolobus agglutinin , which
binds Fucalpha1-->3GlcNAc, and Wisteria floribunda agglutinin, which
binds GalNAcbeta1-->4GlcNAc (lacdiNAc or LDN). Thus, schistosomes may be
unique among helminths in expressing the Lexantigen, whereas many different
helminths may express alpha1,3-fucosylated glycans and the LDN motif.
相似文献
2.
Chumbalkar VC Subhashini C Dhople VM Sundaram CS Jagannadham MV Kumar KN Srinivas PN Mythili R Rao MK Kulkarni MJ Hegde S Hegde AS Samual C Santosh V Singh L Sirdeshmukh R 《Proteomics》2005,5(4):1167-1177
Gliomas are the most common of the primary intracranial tumors with astrocytomas constituting about 40%. Using clinically and histologically assessed astrocytomas, we have studied their protein profiles using a two-dimensional gel electrophoresis-mass spectrometry approach and identified differentially expressed proteins which may be useful molecular indicators to understand these tumors. Examination of the protein profiles of 27 astrocytoma samples of different grades revealed 72 distinct, differentially expressed proteins belonging to various functional groups such as cytoskeleton and intermediate filament proteins, heat shock proteins (HSPs), enzymes and regulatory proteins. Based on the consistency of their differential expression, 29 distinct proteins could be short-listed and may have a role in the pathology of astrocytomas. Some were found to be differentially expressed in both Grade III and IV astrocytomas while others were associated with a particular grade. A notable observation was underexpression of Prohibitin, a potential tumor suppressor protein, Rho-GDP dissociation inhibitor, Rho-GDI, a regulator of Rho GTPases and HSPs as well as destabilization of glial fibrillary acidic protein, GFAP, major protein of the glial filaments, in Grade III malignant tumors. We attempt to explain glioma malignancy and progression in terms of their combined role. 相似文献
3.
Maxim VC Greenberg Israel Ausin Simon WL Chan Shawn J Cokus Josh T Cuperus Suhua Feng Julie A Law Carolyn Chu Matteo Pellegrini James C Carrington Steven E Jacobsen 《Epigenetics》2011,6(3):344-354
De novo DNA methylation in Arabidopsis thaliana is catalyzed by the methyltransferase DRM2, a homolog of the mammalian de novo methyltransferase DNMT3. DRM2 is targeted to DNA by small interfering RNAs (siRNAs) in a process known as RNA-directed DNA Methylation (RdDM). While several components of the RdDM pathway are known, a functional understanding of the underlying mechanism is far from complete. We employed both forward and reverse genetic approaches to identify factors involved in de novo methylation. We utilized the FWA transgene, which is methylated and silenced when transformed into wild-type plants, but unmethylated and expressed when transformed into de novo methylation mutants. Expression of FWA is marked by a late-flowering phenotype, which is easily scored in mutant versus wild-type plants. By reverse genetics we discovered the requirement for known RdDM effectors AGO6 and NRPE5a for efficient de novo methylation. A forward genetic approach uncovered alleles of several components of the RdDM pathway, including alleles of clsy1, ktf1 and nrpd/e2, which have not been previously shown to be required for the initial establishment of DNA methylation. Mutations were mapped and genes cloned by both traditional and whole genome sequencing approaches. The methodologies and the mutant alleles discovered will be instrumental in further studies of de novo DNA methylation.Key words: DNA methylation, Arabidopsis, de novo, genetic screen, whole-genome sequencing 相似文献
4.
5.
Lotte Heimans Kirsten VC Wevers-de Boer KK Michel Koudijs Karen Visser Yvonne P Goekoop-Ruiterman Joop B Harbers Gerda M Steup-Beekman Leroy R Lard Bernard AM Grillet Tom WJ Huizinga Cornelia F Allaart 《Arthritis research & therapy》2013,15(5):R173
Introduction
The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment.Methods
In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models.Results
During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL.Conclusions
In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms.Trial registrations
ISRCTN11916566 and EudraCT2006-006186-16 相似文献6.
Núbia Boechat Alcione S Carvalho Kelly Salom?o Solange L de Castro Carlos F Araujo-Lima Francisco VC Mello Israel Felzenszwalb Claudia AF Aiub Taline Ramos Conde Helena PS Zamith Rolf Skupin Günter Haufe 《Memórias do Instituto Oswaldo Cruz》2015,110(4):492-499
Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and
cytotoxic properties have been attributed to the presence of the nitro group.
However, we synthesised nitroimidazoles with activity against the trypomastigotes of
Trypanosoma cruzi, but that were not genotoxic. Herein,
nitroimidazoles (11-19) bearing different substituent groups were investigated for
their potential induction of genotoxicity (comet assay) and mutagenicity
(Salmonella/Microsome assay) and the correlations of these
effects with their trypanocidal effect and with megazol were investigated. The
compounds were designed to analyse the role played by the position of the nitro group
in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable
groups at N-1 as an anion receptor group and the role of a methyl group at C-2.
Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to
those bearing NO2 at C-5. However, when there was a CH3
at C-2, the position of the NO2 group had no influence on the genotoxic activity.
Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3
at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl)
and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on
genotoxicity. This study contributes to the future search for new and safer
prototypes and provide. 相似文献
7.
Chumbalkar V Latha K Hwang Y Maywald R Hawley L Sawaya R Diao L Baggerly K Cavenee WK Furnari FB Bogler O 《Journal of proteome research》2011,10(3):1343-1352
An in-frame deletion mutation in Epidermal Growth Receptor (EGFR), ΔEGFR is a common and potent oncogene in glioblastoma (GBM), promoting growth and survival of cancer cells. This mutated receptor is ligand independent and constitutively active. Its activity is low in intensity and thought to be qualitatively different from acutely ligand stimulated wild-type receptor implying that the preferred downstream targets of ΔEGFR play a significant role in malignancy. To understand the ΔEGFR signal, we compared it to that of a kinase-inactivated mutant of ΔEGFR and wild-type EGFR with shotgun phosphoproteomics using an electron-transfer dissociation (ETD) enabled ion trap mass spectrometer. We identified and quantified 354 phosphopeptides corresponding to 249 proteins. Among the ΔEGFR-associated phosphorylations were the previously described Gab1, c-Met and Mig-6, and also novel phosphorylations including that of STAT5 on Y694/9. We have confirmed the most prominent phosphorylation events in cultured cells and in murine xenograft models of glioblastoma. Pathway analysis of these proteins suggests a preference for an alternative signal transduction pathway by ΔEGFR compared to wild-type EGFR. This understanding will potentially benefit the search for new therapeutic targets for ΔEGFR expressing tumors. 相似文献
8.
Delta epidermal growth factor receptor (ΔEGFR), an in-frame deletion mutant of the extracellular ligand-binding domain, which occurs in about 30% of glioblastoma, is a potent oncogene that promotes tumor growth and progression. The signaling of ΔEGFR is ligand-independent and low intensity, allowing it to evade the normal mechanisms of internalization and degradation by the endocytic machinery and hence is persistent. The basis of the oncogenic potential of ΔEGFR remains incompletely understood, including whether dimerization plays an important role in its signal and whether its oncogenic potential is dependent on its relatively low intensity, when compared with the acutely activated wild-type receptor. To examine these two important questions, we have generated a chimeric ΔEGFR that allows forced dimerization via domains derived from variants of the FKBP12 protein that are brought together by FK506 derivatives. Forced dimerization of chimeric ΔEGFR significantly increased the intensity of its signal, as measured by receptor phosphorylation levels, suggesting that the naturally occurring ΔEGFR does not form strong or stable dimers as part of its low level signal. Interestingly, the increased activity of dimerized, chimeric ΔEGFR did not promote receptor internalization, implying that reduced rate of endocytic downregulation of ΔEGFR is an inherent characteristic. Significantly, forced dimerization enhanced the oncogenic signal of the receptor, implying that the ΔEGFR is a potent oncogene despite, not because of its low intensity. 相似文献
1