排序方式: 共有34条查询结果,搜索用时 15 毫秒
1.
M Badasso C Frazao B L Sibanda V Dhanaraj C DeAlwis J B Cooper S P Wood T L Blundell K Murakami H Miyazaki 《Journal of molecular biology》1992,223(2):447-453
Inhibitor-complexed crystals of mouse and human renins suitable for X-ray analysis have been prepared. The mouse renin is complexed with a non-hydrolysable decapeptide analogue of rat angiotensinogen containing a hydroxyethylene isostere in place of the scissile bond. The crystals are monoclinic, space group P2(1) with cell dimensions a = 78.3 A, b = 117.8 A, c = 85.9 A, beta = 101.18 degrees containing four molecules per asymmetric unit. The human renin is fully glycosylated and complexed with a tetrapeptide containing norstatine. The complex crystallises in the cubic space group P2(1)3 with a = 143.1 A and has two molecules in the asymmetric unit. The rotation function of the mouse renin complex indicates pseudo 222 symmetry while that of human renin indicates a pseudo 2-fold axis. Full structural analyses of the two complexes are underway. 相似文献
2.
B A Naughton B Sibanda L Azar J San Roman 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1992,199(4):481-490
Hematotoxicity is associated with exposure to chemotherapeutic drugs and numerous other agents. Most measurements of the hematopoietic effects of prospective therapeutic drugs and environmental agents have been made in animal models. We tested the influence of various drugs on hematopoiesis in long-term cultures of Long-Evans rat bone marrow cells. These cultures were established on nylon screen-bone marrow stromal cell templates that were suspended in liquid medium. Previous phenotypic analyses of adherent zone cells of suspended nylon screen bone marrow cultures (NSBMC) using monoclonal antibodies and flow cytometry indicated that they maintain a multilineage character for extended periods in culture and display continuous proliferation of hematopoietic progenitors (colony-forming unit culture [CFU-C]). NSBMC of various ages were incubated for 21 hr with several concentrations of beta-D-cytosine arabinofuranoside, 5-fluorouracil, cyclophosphamide, or methotrexate. Adherent zone cells were dissociated enzymatically, phenotyped by flow cytometry, and assayed for colony-forming unit culture content. beta-D-cytosine arabinofuranoside, 5-fluorouracil, and methotrexate treatment of bone marrow cultures resulted in a dose-related diminution in colony-forming unit culture numbers in the adherent zones of NSBMC. Phenotypic analyses revealed similar trends but certain of these drugs manifested lineage specificities. Toxicity was also related to cyclophosphamide dose, but the presence of bone marrow stroma was necessary to demonstrate this effect in vitro. A subpopulation of these cells was found to metabolize ethoxyfluorescein ethyl ester to fluorescein after induction with 2,3,7,8-tetrachlorodibenzo-p-dioxin, an effect which was quantified by flow cytometry. NSBMC may be used to ascertain lineage-specific toxicities and evaluate the effects of drugs on the proliferation of hematopoietic progenitor cells. 相似文献
3.
Sibanda W Pillay V Danckwerts MP Viljoen AM van Vuuren S Khan RA 《AAPS PharmSciTech》2004,5(1):128-141
A Plackett-Burman design was employed to develop and optimize a novel crosslinked calcium-aluminum-alginatepectinate oilisphere
complex as a potential system for the in vitro site-specific release ofMentha piperita, an essential oil used for the treatment of irritable bowel syndrome. The physicochemical and textural properties (dependent
variables) of this complex were found to be highly sensitive to changes in the concentration of the polymers (0%–1.5% wt/vol),
crosslinkers (0%–4% wt/vol) and crosslinking reaction times (0.5–6 hours) (independent variables). Particle size analysis
indicated both unimodal and bimodal populations with the highest frequency of 2 mm oilispheres. Oil encapsulation ranged from
6 to 35 mg/100 mg oilispheres. Gravimetric changes of the crosslinked matrix indicated significant ion sequestration and loss
in an exponential manner, while matrix erosion followed Higuchi's cube root law. Among the various measured responses, the
total fracture energy was the most suitable optimization objective (R
2 =0.88, Durbin-Watson Index=1.21%, Coefficient of Variation (CV)=33.21%). The Lagrangian technique produced no significant
differences (P>.05) between the experimental and predicted total fracture energy values (0.0150 vs 0.0107 J). Artificial Neural Networks,
as an alternative predictive tool of the total fracture energy, was highly accurate (final mean square error of optimal network
epoch≈0.02). Fused-coated optimized oilispheres produced a 4-hour lag phase followed by zero-order kinetics (n>0.99), whereby
analysis of release data indicated that diffusion (Fickian constantk
1=0.74 vs relaxation constantk
2=0.02) was the predominant release mechanism. 相似文献
4.
Blundell TL Burke DF Chirgadze D Dhanaraj V Hyvönen M Innis CA Parisini E Pellegrini L Sayed M Sibanda BL 《Biological chemistry》2000,381(9-10):955-959
We review here signalling complexes that we have defined using X-ray analysis in our laboratory. They include growth factors and their receptors: nerve growth factor (NGF) and its hetero-hexameric 7S NGF storage complex, hepatocyte growth factor/scatter factor (HGF/SF) NK1 dimers and fibroblast growth factor (FGF1) in complex with its receptor (FGFR2) ectodomain and heparin. We also review our recent structural studies on intracellular signalling complexes, focusing on phosducin transducin GPry, CK2 protein kinase and its complexes, and the cyclin D-dependent kinase, Cdk6, bound to the cell cycle inhibitor p19INK4d. Comparing the structures of these complexes with others we show that the surface area buried in signalling interactions does not always give a good indication of the strength of the interactions. We show that conformational changes are often important in complexes with intermediate buried surface areas of 1500 to 2000 A2, such as Cdk6INK4 interactions. Some interactions involve recognition of continuous epitopes, where there is no necessity for a tertiary structure and very often the binding conformation is induced during the process of interaction, for example phosducin binding to the betagamma subunits (Gtbetagamma) of the heterotrimeric G protein transducin. 相似文献
5.
In this paper, the magnetohydrodynamic (MHD) axisymmetric stagnation-point flow of an unsteady and electrically conducting incompressible viscous fluid in with temperature dependent thermal conductivity, thermal radiation and Navier slip is investigated. The flow is due to a shrinking surface that is shrunk axisymmetrically in its own plane with a linear velocity. The magnetic field is imposed normally to the sheet. The model equations that describe this fluid flow are solved by using the spectral relaxation method. Here, heat transfer processes are discussed for two different types of wall heating; (a) a prescribed surface temperature and (b) a prescribed surface heat flux. We discuss and evaluate how the various parameters affect the fluid flow, heat transfer and the temperature field with the aid of different graphical presentations and tabulated results. 相似文献
6.
There are currently only a few theoretical studies on convective heat transfer in polymer nanocomposites. In this paper, the unsteady incompressible flow of a polymer nanocomposite represented by an Oldroyd-B nanofluid along a stretching sheet is investigated. Recent studies have assumed that the nanoparticle fraction can be actively controlled on the boundary, similar to the temperature. However, in practice, such control presents significant challenges and in this study the nanoparticle flux at the boundary surface is assumed to be zero. We have used a relatively novel numerical scheme; the spectral relaxation method to solve the momentum, heat and mass transport equations. The accuracy of the solutions has been determined by benchmarking the results against the quasilinearisation method. We have conducted a parametric study to determine the influence of the fluid parameters on the heat and mass transfer coefficients. 相似文献
7.
James N Armitage Nokuthaba Sibanda Paul J Cathcart Mark Emberton Jan H P van der Meulen 《BMJ (Clinical research ed.)》2007,335(7631):1199-1202
Objectives To investigate mortality in men admitted to hospital with acute urinary retention and to report on the effects of comorbidity on mortality.Design Analysis of the hospital episode statistics database linked to the mortality database of the Office for National Statistics.Setting NHS hospital trusts in England, 1998-2005.Participants All men aged over 45 who were admitted to NHS hospitals in England with a first episode of acute urinary retention.Main outcome measures Mortality in the first year after acute urinary retention and standardised mortality ratio against the general population.Results During the study period, 176 046 men aged over 45 were admitted to hospital with a first episode of acute urinary retention. In 100 067 men with spontaneous acute urinary retention, the one year mortality was 4.1% in men aged 45-54 and 32.8% in those aged 85 and over. In 75 979 men with precipitated acute urinary retention, mortality was 9.5% and 45.4%, respectively. In men with spontaneous acute urinary retention aged 75-84, the most prevalent age group, the one year mortality was 12.5% in men without comorbidity and 28.8% in men with comorbidity. The corresponding figures for men with precipitated acute urinary retention were 18.1% and 40.5%. Compared with the general population, the highest relative increase in mortality was in men aged 45-54 (standardised mortality ratio 10.0 for spontaneous and 23.6 for precipitated acute urinary retention) and the lowest for men 85 and over (1.7 and 2.4, respectively).Conclusions Mortality in men admitted to hospital with acute urinary retention is high and increases strongly with age and comorbidity. Patients might benefit from multi-disciplinary care to identify and treat comorbid conditions. 相似文献
8.
An attempt has been made to monitor by continuous fetal heart rate according all women admitted in labour. Altogether 85% of the 1070 patients delivered at one hospital were monitored in 1973 and 92% in 1974. Perinatal mortality fell significantly from levels in preceding years to 15-8 and 11-7 per 1000 births, respectively, in 1973 and 1974. The fall was primarily due to the elimination of intra-partum stillbirths and a significant reduction in neonatal mortality. The incidence of caesarean sections also fell from 9-7% in 1973 to 5-8% in 1974. All patients should be monitored because it is impossible to predict reliably intra-partum fetal distress from maternal "high-risk" factors present before the onset of labour. 相似文献
9.
Naughton BA Román JS Sibanda B Weintraub JP Kamali V 《Biotechnology and bioengineering》1994,43(8):810-825
Stromal cell-associated liver cell and bone marrow (BM) culture on three-dimensiional nylon screen or polyglycolic acid (PGA) felt templates conveys certain functional advantages to the parenchyma of these tissues. Hepatic parenchymal cells (PC) manifest long-term ( approximately 2 month) expression of liver-specific activities including cytochrome P450 enzyme activity and the synthesis of albumin, fibrinogen, transferrin, and other proteins. PC also undergo proliferation in association with stromal cells that were pre-established on these templates. PC mitoses are directly proportional to available space within the template for their expansion indication that geometric or sterotypic parameters influence the growth of these cells in vitro. BM cultured on a similar template exhibits long-term multilineage hematopoietic expression and limited expansion of progenitor cell numbers. Progenitor cell concentration within the cultures can be substantially enhanced if these cells are liberated from co-culture and reseeded onto a template containing fresh stromal cells. BM and liver cel cultures established on felt composed of bioresorbable PGA filaments was grafted into various sites in rats. Liver co-cultures generated sinusoids and other liver-like structures in situ; active hematopoietic blasts were observed at sites of BM co-culture grafts. Biodegradable polymer constructs may prove useful for certain clinical applications as vehicles for the delivery of tissues that were engineered in culture. 相似文献
10.
Novel developments in rapid mycotoxin detection 总被引:1,自引:0,他引:1
S. De Saeger L. Sibanda C. Paepens M. Lobeau B. Delmulle I. Barna-Vetro C. Van Peteghem 《Mycotoxin Research》2006,22(2):100-104
Rapid antibody-based mycotoxin screening techniques are designed to be used outside a laboratory environment, at the place
of sampling. Results are expected immediately, so that commodities can be further processed without delay. Because they are
used for mycotoxin analysis, very low levels (ppb and ppt range) should be detected. A further requirement is that the obtained
results are accurate with a false negative rate of <5% at the level of interest.
At first, plastic microtiter plates were used as solid phase materials for immobilizing antibodies (enzyme-linked immunosorbent
assays). However, to increase speed and user-friendliness, plastics were replaced by microporous membranes. As an example
a flow-through enzyme immunoassay for the detection of fumonisins in cornflakes with a cut-off value of 275 μg/kg is described.
No false negative results were observed and the false positive rate was 18%. However, enzyme labels, used to enable visual
evaluation of results, did not seem to be completely satisfactory in terms of stability and repeatability of the generated
signal. Therefore microparticle labels such as colloidal gold particles are used more and more,e.g. in a lateral flow dipstick immunoassay. When applied to the detection of aflatoxin B1 in pig feed a cut-off value of 5 μg/kg could be reached with no false negative results and a false positive rate of only
10%. Sample pretreatment for screening techniques should be rapid and simple. Preferably a simple solvent extraction is used,
followed by a filtration and dilution step. However, for strongly coloured or complex food matrices, this did not seem to
work. The combination of clean-up and detection in one single test device is a new approach. When using this clean-up tandem
assay column for the detection of ochratoxin A in roasted coffee, a cut-off value of 6 μg/kg was reached. No false positive
results were obtained, however, the false negative rate was 8%.
Presented at the EU-USA Bilateral Workshop on Toxigenic Fungi & Mycotoxins, New Orleans, USA, July 5–7, 2005
Financial support: Belgian Federal Science Policy Office (SPSDII-CPAA 15 project), IWT-Flanders (research project 020448/Toxi-Test)
and Bijzonder Onderzoeksfonds Ghent University (01 1D02803) 相似文献