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101.
Sunil Sheth Wissam Bleibel Chandrashekhar Thukral Yousif A-Rahim Guido Beldi Eva Csizmadia Simon C. Robson 《Purinergic signalling》2009,5(3):321-326
Radiation proctitis is an inflammatory process associated with persistent and refractory lower gastrointestinal bleeding.
Purinergic signaling regulates hemostasis, inflammation, and angiogenesis. For example, CD39, the vascular ectonucleotidase,
blocks platelet activation and is required for angiogenesis. Whether CD39 expression is affected by radiation injury is unknown.
The aim of this work was to study CD39 expression patterns after clinical radiation injury to the rectum. We prospectively
enrolled eight patients with radiation proctitis and five gender-matched controls. Biopsies were taken from normal-appearing
rectal mucosa of controls and from the normal sigmoid and abnormal rectum of patients. Expression patterns of CD39, P2Y2 receptor,
CD31, CD61 integrin, and vascular endothelial growth factor receptor 2 were examined by immunostaining; levels of CD39 were
further evaluated by Western blots. Chronic inflammatory lesions of radiation proctitis were associated with heightened levels
of angiogenesis. Immunohistochemical stains showed increased vascular expression of CD39, as confirmed by Western blots. CD39
was co-localized with vascular endothelial markers CD31 and CD61 integrin, as well as expressed by stromal tissues. Development
of neovasculature and associated CD39 expression in radiation proctitis may be associated with the chronic, refractory bleeding
observed in this condition. 相似文献
102.
Payal R. Sheth Lata Ramanathan Ashwin Ranchod Dianah Barrett Kimberly Gray Rumin Zhang 《Archives of biochemistry and biophysics》2010,503(2):191-201
Aurora B kinase plays a critical role in regulating mitotic progression, and its dysregulation has been linked to tumorigenesis. The structure of the kinase domain of human Aurora B and the complementary information of binding thermodynamics of known Aurora inhibitors is lacking. Towards that effort, we sought to identify a human Aurora B construct that would be amenable for large-scale protein production for biophysical and structural studies. Although the designed AurB69-333 construct expressed at high levels in Escherichia coli, the purified protein was largely unstable and prone to aggregation. We employed thermal-shift assay for high-throughput screening of 192 conditions to identify optimal pH and salt conditions that increased the stability and minimized aggregation of AurB69-333. Direct ligand binding analyses using temperature-dependent circular dichroism (TdCD) and TR-FRET-based Lanthascreen™ binding assay showed that the purified protein was folded and functional. The affinity rank-order obtained using TdCD and Lanthascreen™ binding assay correlated with enzymatic IC50 values measured using full-length Aurora B protein for all the inhibitors tested except for AZD1152. The direct binding results support the hypothesis that the purified human AurB69-333 fragment is a good surrogate for its full-length counterpart for biophysical and structural analyses. 相似文献
103.
Victor van der Meer Henk F van Stel Moira J Bakker Albert C Roldaan Willem JJ Assendelft Peter J Sterk Klaus F Rabe Jacob K Sont 《Respiratory research》2010,11(1):74
Background
Internet-based self-management has shown to improve asthma control and asthma related quality of life, but the improvements were only marginally clinically relevant for the group as a whole. We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma.Methods
In a 1-year randomised controlled trial involving 200 adults (18-50 years) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Questionnaire (ACQ). Participants were assigned either to the Internet group (n = 101) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group (UC) (n = 99). We analysed 3 subgroups: patients with well controlled (ACQ ≤ 0.75), partly controlled (0.75>ACQ ≤ 1.5) or uncontrolled (ACQ>1.5) asthma at baseline.Results
Overall monitoring adherence was 67% (95% CI, 60% to 74%). Improvements in ACQ score after 12 months were -0.14 (p = 0.23), -0.52 (p < 0.001) and -0.82 (p < 0.001) in the Internet group compared to usual care for patients with well, partly and uncontrolled asthma at baseline, respectively. Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma (+278 μg, p = 0.001), but not in patients with well or partly controlled asthma. After one year there were no differences in daily inhaled corticosteroid use or long-acting β2-agonists between the Internet group and usual care.Conclusions
Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients'' needs.Trial registration
Current Controlled Trials ISRCTN79864465 相似文献104.
Background
The assembly and spatial organization of enzymes in naturally occurring multi-protein complexes is of paramount importance for the efficient degradation of complex polymers and biosynthesis of valuable products. The degradation of cellulose into fermentable sugars by Clostridium thermocellum is achieved by means of a multi-protein "cellulosome" complex. Assembled via dockerin-cohesin interactions, the cellulosome is associated with the cell surface during cellulose hydrolysis, forming ternary cellulose-enzyme-microbe complexes for enhanced activity and synergy. The assembly of recombinant cell surface displayed cellulosome-inspired complexes in surrogate microbes is highly desirable. The model organism Lactococcus lactis is of particular interest as it has been metabolically engineered to produce a variety of commodity chemicals including lactic acid and bioactive compounds, and can efficiently secrete an array of recombinant proteins and enzymes of varying sizes. 相似文献105.
Balandya E Sheth S Sanders K Wieland-Alter W Lahey T 《Journal of immunology (Baltimore, Md. : 1950)》2010,185(12):7596-7604
Sexual intercourse is the major means of HIV transmission, yet the impact of semen on HIV infection of CD4(+) T cells remains unclear. To resolve this conundrum, we measured CD4(+) target cell infection with X4 tropic HIV IIIB and HC4 and R5 tropic HIV BaL and SF162 after incubation with centrifuged seminal plasma (SP) from HIV-negative donors and assessed the impact of SP on critical determinants of target cell susceptibility to HIV infection. We found that SP potently protects CD4(+) T cells from infection with X4 and R5 tropic HIV in a dose- and time-dependent manner. SP caused a diminution in CD4(+) T cell surface expression of the HIVR CD4 and enhanced surface expression of the HIV coreceptor CCR5. Consequently, SP protected CD4(+) T cells from infection with R5 tropic HIV less potently than it protected CD4(+) T cells from infection with X4 tropic HIV. SP also reduced CD4(+) T cell activation and proliferation, and the magnitude of SP-mediated suppression of target cell CD4 expression, activation, and proliferation correlated closely with the magnitude of the protection of CD4(+) T cells from infection with HIV. Taken together, these data show that semen protects CD4(+) T cells from HIV infection by restricting critical determinants of CD4(+) target cell susceptibility to HIV infection. Further, semen contributes to the selective transmission of R5 tropic HIV to CD4(+) target cells. 相似文献
106.
Caenorhabditis elegans UNC-96 is a new component of M-lines that interacts with UNC-98 and paramyosin and is required in adult muscle for assembly and/or maintenance of thick filaments 下载免费PDF全文
Mercer KB Miller RK Tinley TL Sheth S Qadota H Benian GM 《Molecular biology of the cell》2006,17(9):3832-3847
To gain further insight into the molecular architecture, assembly, and maintenance of the sarcomere, we have carried out a molecular analysis of the UNC-96 protein in the muscle of Caenorhabditis elegans. By polarized light microscopy of body wall muscle, unc-96 mutants display reduced myofibrillar organization and characteristic birefringent "needles." By immunofluorescent staining of known myofibril components, unc-96 mutants show major defects in the organization of M-lines and in the localization of a major thick filament component, paramyosin. In unc-96 mutants, the birefringent needles, which contain both UNC-98 and paramyosin, can be suppressed by starvation or by exposure to reduced temperature. UNC-96 is a novel approximately 47-kDa polypeptide that has no recognizable domains. Antibodies generated to UNC-96 localize the protein to the M-line, a region of the sarcomere in which thick filaments are cross-linked. By genetic and biochemical criteria, UNC-96 interacts with UNC-98, a previously described component of M-lines, and paramyosin. Additionally, UNC-96 copurifies with native thick filaments. A model is presented in which UNC-96 is required in adult muscle to promote thick filament assembly and/or maintenance. 相似文献
107.
During the past year studies with mouse models have significantly clarified our understanding of atherosclerosis. Noteworthy achievements include: the discovery of a number of novel genes and pathways; new evidence emphasizing the role of lymphocytes in atherogenesis; the development of mouse models exhibiting advanced lesions with evidence of thrombosis; and new results indicating an anti-atherogenic effect of testosterone. 相似文献
108.
Previously, treatment of Tamm-Horsfall glycoprotein (THp) from different
donors with endo-beta-galactosidase has been shown to liberate a tetra- and
a Sd(a)-active pentasaccharide, concluding the presence of N-linked
carbohydrate chains containing additional N - acetyllactosamine units.
These type of oligosaccharides were not found in a detailed structure
elucidation of the carbohydrate moiety of THp of one male donor, suggesting
a donor-specific feature for these type of structures. Therefore, THp was
isolated from four healthy male donors and each subjected to
endo-beta-galactosidase treatment in order to release these tetra- and
Sd(a)-active pentasaccharide. Differences were observed in the total amount
of released tetra- and Sda-active pentasaccharide of the used donors (42,
470, 478, 718 microg/100 mg THp), indicating that the presence of repeating
N-acetyllactosamine units incorporated into the N-glycan moiety of THp is
donor specific. Furthermore, a higher expression of the Sd(a) determinant
on antennae which display N-acetyllactosamine elongation was observed,
suggesting a better accessibility for the
beta-N-acetylgalactosaminyltransferase. In order to characterize the
N-glycans containing repeating N- acetyllactosamine units, carbohydrate
chains were enzymatically released from THp and isolated. The
tetraantennary fraction, which accounts for more than 33% of the total
carbohydrate moiety of THp, was used to isolate oligosaccharides containing
additional N - acetyllactosamine units. Five N-linked tetraantennary
oligosaccharides containing a repeating N-acetyllactosamine unit were
identified, varying from structures bearing four Sd(a) determinants to
structures containing no Sd(a) determinant (see below). One compound was
used in order to specify the branch location of the additional N-
acetyllactosamine unit, and it appeared that only the Gal-6' and Gal-8'
residues were occupied by a repeating N -acetyllactosamine unit.
相似文献
109.
H. B. Sheth K. K. Lee W. Y. Wong G. Srivastava O. Hindsgaul R. S. Hodges W. Paranchych R. T. Irvin 《Molecular microbiology》1994,11(4):715-723
Pseudomonas aeruginosa employs pili to mediate adherence to epithelial cell surfaces. The pilus adhesin of P. aeruginosa strains PAK and PAO has been shown to bind to the glycolipid asialo-GM1 (Lee et al., 1994 —accompanying article). PAK and PAO pili were examined for their abilities to bind to the synthetic βGalNAc(1–4)βGal (a minimal structural carbohydrate receptor sequence of asialo-GM1 and asialo-GM2 proposed by Krivan et al., 1988a) using solid-phase binding assays. Both pill specifically bound to βGalNAc(1–4)βGal. The binding of βGal-NAc(1–4)βGal-Biotin to the Immobilized PAK and PAO pili was inhibited by corresponding free pili. The receptor binding domain of the PAK pilus resides in the C-terminal disulphide-looped region (residues 128–144) of the pilin structural subunit (Irvin et al., 1989). Biotinylated synthetic peptides corresponding the C-terminal residues 128–144 of P. aeruginosa PAK and PAO pilin molecules were shown to bind to the βGalNAc(1–4)βGal-(bovine serum albumin (BSA)). The binding of biotinylated peptides to βGalNAc-(1–4)βGal-BSA was inhibited by PAK pili, Ac-KCTSDQDEOFIPKGCSK-OH (AcPAK(128–144)ox-OH) and Ac-ACKSTQDPMFTPKGCDN-OH (AcPAO(128–144)ox-OH) peptides. (In these peptides Ac denotes Nα -acetylation of the N-terminus, -OH means a peptide with a free a-carboxyl group at the C-terminus and the‘ox’denotes the oxidation of the sulphhydryl groups of Cys–129 and Cys–142.) Both acetylated peptides were also able to inhibit the binding of βGalNAc(1–4)βGal-biotin to the corresponding BSA-Peptide(128–144)ox-OH conjugates. The βGlcNAc(1–3)βGal(1–4)βGlc-biotin conjugate was unable to specifically bind to either Immobilized PAK and PAO pili or the respective C-termlnal peptides. The data above demonstrated that the P. aeruginosa pili recognize asialo-GM1 receptor analogue and that βGalNAc(1–4)βGal disaccharlde is sufficient for binding. Furthermore, the binding to βGalNAc(1–4)βGal was mediated by residues 128–144 of the pilin subunit. 相似文献
110.