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71.
Comparative study on glucocerebrosidase in spleens from patients with Gaucher disease. 总被引:1,自引:0,他引:1 下载免费PDF全文
J M Aerts W E Donker-Koopman S Brul S Van Weely M C Sa Miranda J A Barranger J M Tager A W Schram 《The Biochemical journal》1990,269(1):93-100
In Gaucher disease (glucosylceramide lipidosis), deficiency of glucocerebrosidase causes pathological storage of glucosylceramide, particularly in the spleen. A comparative biochemical and immunological analysis has therefore been made of glucocerebrosidase in spleens from normal subjects (n = 4) and from Gaucher disease patients with non-neuronopathic (n = 5) and neuronopathic (n = 5) phenotypes. The spleens from all Gaucher disease patients showed markedly decreased glucocerebrosidase activity. Discrimination of different phenotypes of Gaucher disease was not possible on the basis of the level of residual enzyme activity, or by measurements, using the immunopurified enzyme, of kinetic constants, pI or molecular mass forms. A severe decrease was found in the specific activity of glucocerebrosidase purified to homogeneity from the spleen of a patient with the non-neuronopathic phenotype of Gaucher disease, as compared with that of the enzyme purified from the spleen of a normal subject. This finding was confirmed by an immunological method developed for accurate assessment of the relative enzyme activity per molecule of glucocerebrosidase protein. The method revealed that the residual enzyme in the spleens of all investigated patients with a non-neuronopathic course of Gaucher disease had a more than 7-fold decreased activity of glucocerebrosidase (measured in the presence of taurocholate) per molecule of enzyme, and that the concentration of glucocerebrosidase molecules in the spleens of these patients was near normal. Observations made with immunoblotting experiments were consistent with these findings. In contrast, in the spleens of patients with neuronopathic phenotypes of Gaucher disease, the concentration of glucocerebrosidase molecules was severely decreased. 相似文献
72.
A W Schram M N Hamers M R Samson S Cordus A De Jonge I Brown D Robinson J M Tager 《Biochimica et biophysica acta》1979,568(1):59-70
1. The effect of detergents on the catalytic properties of alpha-galactosidase from human liver was studied using p-nitrophenyl-alpha-galactoside and galactosyl-alpha(1 leads to 4)-galactosyl-beta(1 leads to 4)-glucosylceramide (ceramide-3) as substrates. 2. The hydrolysis of p-nitrophenyl-alpha-galactoside by alpha-galactosidase was inhibited by commercial preparations of sodium taurocholate and by taurocholate purified from these preparations by thin-layer chromatography. The extent of inhibition was dependent on the concentration of the detergent and on the amount of protein present. The impurities present in the preparation also inhibited the hydrolysis. 3. The inhibition of taurocholate preparations of p-nitrophenyl-alpha-galactoside hydrolysis was pH-dependent. 4. The inhibition by taurocholate of p-nitrophenyl-alpha-galactoside hydrolysis can be partly overcome by adding glycosphingolipids. 5. No significant hydrolysis of ceramide-3 occurs in the absence of detergent. Upon adding increasing concentrations of taurocholate, the rate of hydrolysis increases to a maximum value. At still higher taurocholate concentrations the activity decreases. 6. The concentrations of taurocholate giving a maximal rate of hydrolysis of ceramide-3 is dependent on the amount of protein present and independent of the ceramide-3 concentration. 7. When the pH dependence of the rate of hydrolysis of ceramide-3 was measured in the presence of a commercially available preparation of pure taurocholate or of crude taurocholate, curves with different shapes were obtained. 相似文献
73.
Background
Development of efficient analytic methodologies for combining microarray results is a major challenge in gene expression analysis. The widely used effect size models are thought to provide an efficient modeling framework for this purpose, where the measures of association for each study and each gene are combined, weighted by the standard errors. A significant disadvantage of this strategy is that the quality of different data sets may be highly variable, but this information is usually neglected during the integration. Moreover, it is widely known that the estimated standard deviations are probably unstable in the commonly used effect size measures (such as standardized mean difference) when sample sizes in each group are small. 相似文献74.
75.
Gregory S. Vosganian Jill Waalen Kevin Kim Sejal Jhatakia Ethan Schram Tracey Lee Dan Riddell James R. Mason 《Cytotherapy》2012,14(10):1228-1234
Background aimsThe long-term stability of cryopreserved peripheral blood progenitor cells is an important issue for patients experiencing disease relapse. However, there is no consensus on how to evaluate the long-term effects of cryopreservation. We describe the effect of cryopreservation on viability and progenitor colony activity from 87 individual samples processed at the Scripps Green Hospital Stem Cell Processing Center (La Jolla, CA, USA).MethodsWe randomly selected 87 peripheral blood hematopoietic stem cell (PBHSC) samples from 60 patients and evaluated the effect of cryopreservation on sample viability and red and white cell colony activity after < 24 h and 7, 10 and 15 years of cryopreservation. Viability was assayed via trypan blue dye exclusion and activity was measured following 14 days of culture.ResultsAn age at collection older than 50 years may result in suboptimal activity and viability following long-term cryopreservation, while gender and disease status had no effect. Cryopreservation did not significantly affect white or red cell activity following 10 years of cryopreservation. However, for samples stored longer than 10 years, viability and activity significantly decreased. We noted a positive association between higher pre-cryopreservation %CD34 count and colony activity.ConclusionsCryopreservation of peripheral blood progenitor cells for up to 10 years results in no loss of clonogenic capacity, as determined by culture activity, although longer durations of storage may affect activity. Until validated methods are developed, cryopreserved grafts should be evaluated based on pre-freeze CD34+ cell counts as assayed by flow cytometry, and post-thaw sample evaluation should be reserved for patients identified as poor mobilizers. 相似文献
76.
Terry L. Margenau Steven P. AveLallemant David Giehtbrock Stephen T. Schram 《Hydrobiologia》2008,601(1):111-123
Northern pike (pike) Esox lucius Linnaeus are broadly distributed across Wisconsin and provide an important sport fishery for anglers. Historical management
has included use of angling regulations, stocking, and protection of critical habitat areas. Pike management is often a lower
priority in comparison to more intensively managed species such as muskellunge Esox masquinongy Mitchell and walleye Sander vitreous. Pike provide angling opportunities year around, with higher catch rates and live release during open water, and higher harvest
rates during winter. While length of pike caught during the two seasons is generally similar, there is some evidence that
larger fish are caught during winter months. Results from minimum length limit changes implemented in 1995 have been equivocal
and warrant further monitoring using standardized protocol to better determine effects on populations. If natural recruitment
is not limited, pike populations can reach high densities and stunting can result. Loss of nearshore habitat has continued
at an increased rate as more lake homes are built and shorelines graded, and altered with riprap, sand blankets, or sea walls.
If natural recruitment is lacking, fry or fingerling stocking sustains or rehabilitates populations. Most pike stocking occurs
in the southeastern portion of the state where habitat loss has been extensive. Stocking in other areas is largely to re-establish
populations following a chemical reclamation or from winterkill. Future management needs to establish sampling protocols to
ensure comparable data on both a temporal and a spatial scale. Long-term monitoring with these methods is essential to help
determine effects of various factors (e.g., regulations, habitat loss) on populations.
Guest editors: J. M. Farrell, C. Skov, M. Mingelbier, T. Margenau & J. E. Cooper
International Pike Symposium: Merging Knowledge of Ecology, Biology, and Management for a Circumpolar Species 相似文献
77.
Vincent Schram 《生物化学与生物物理学报:生物膜》2003,1616(2):165-173
Two small hydrophobic proteins, SP-B and SP-C, are responsible for rapid adsorption of pulmonary surfactant to the air/water interface. Despite their physiological importance, the number of protein molecules required to trigger an absorption event remains unknown. To investigate this issue, we varied the protein content of calf lung surfactant extract (CLSE) by dilution with protein-depleted surfactant lipids (neutral and phospholipids, N&PL). Vesicles of a constant size and of composition ranging between 100% N&PL and 100% CLSE were generated by probe sonication. Their adsorption kinetics to an air/water interface were monitored at different temperatures using a Wilhelmy plate to measure surface tension. When plotted versus protein concentration, the adsorption rates during the initial change in surface tension exhibit a diphasic behavior, first increasing rapidly and linearly between 0% and 25% CLSE, and then more slowly at higher concentrations. Direct linearity at low protein content (0-5% CLSE ratio) was confirmed at 37 °C. These observations argue against cooperative behavior, for which the adsorption rate would first rise slowly with the protein content, and then increase suddenly once the critical number of proteins on each vesicle is reached. The apparent activation energy Ea and the free energy of activation ΔG0*, calculated from the temperature dependence of adsorption, further support the view that at least the early stages of protein-induced surfactant adsorption proceeds through a sequence of events involving not several, but a single surfactant protein. 相似文献
78.
Development and characterization of highly polymorphic long TC repeat microsatellite markers for genetic analysis of peanut 总被引:4,自引:0,他引:4
Selma E Macedo Márcio C Moretzsohn Soraya C M Leal-Bertioli Dione MT Alves Ediene G Gouvea Vania CR Azevedo David J Bertioli 《BMC research notes》2012,5(1):1-10
Background
The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells.Methods
On immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity.Results
The expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both P < 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (P = 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both P < 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (P < 0.001), whereas in the metastases the expression was highest in tumor cell areas (P < 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (P < 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality.Conclusions
Stromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer. 相似文献79.
Vincent Schram Jean-François Tocanne André Lopez 《European biophysics journal : EBJ》1994,23(5):337-348
Fluorescence Recovery After Photobleaching experiments were simulated using a computer approach in which a membrane lipid leaflet was mimicked using a triangular lattice obstructed with randomly distributed immobile and non-overlapping circular obstacles. Influence of the radius r and area fraction c of these obstacles and of the radius R of the observation area on the relative diffusion coefficient D
* (Eq. (1)) and mobile fraction M was analyzed. A phenomenological equation relating D
* to r and c was established. Fitting this equation to the FRAP data we obtained with the probe NBD-PC embedded in bacteriorhodopsin/egg-PC multilayers suggests that this transmembrane protein rigidifies the surrounding lipid phase over a distance of about 18 Å (two lipid layers) from the protein surface. In contrast, analysis of published diffusion constants obtained for lipids in the presence of gramicidin suggests that in terms of lateral diffusion, this relatively small polypeptide does not significantly affect the surrounding lipid phase. With respect to the mobile fraction M, and for point obstacles above the percolation threshold, an increase in R led to a decrease in M which can be associated with the existence of closed domains whose average size and diffusion properties can be determined. Adaptation of this model to the re-interpretation of the FRAP data obtained by Yechiel and Edidin (J Cell Biol (1987) 115:755–760) for the plasma membrane of human fibroblasts consistently leads to the suggestion that the lateral organization of this membrane would be of the confined type, with closed lipid domains of 0.5 µm2 in area.Abbreviations and notations used BR
bacteriorhodopsin
- DMPC
dimyristoylphosphatidylcholine
- diOC18
dioctadecyloxatricarbocyanine
- egf-PC
egg-yolk phosphatidylcholine
- NBD-PC
1-acyl2-[t2-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl]-sn-glycero-3-phosphocholine
- MOPS
3-[N-morpholino]propane sulfonic acid
- FRAP
Fluoresence Recovery After photobleaching
- D
observed diffusion coefficient
-
D0
diffusion coefficient in the absence of obstacles
-
D
*
relative diffusion constant (Eq. 1)
-
M
mobile fraction
-
c
obstacle area fraction
-
r
obstacle radius
-
R
observation area radius
-
r
d
diffusion area radius
Correspondence to: A. Lopez 相似文献
80.
Jake K Nikota Fernando M Botelho Carla MT Bauer Manel Jordana Anthony J Coyle Alison A Humbles Martin R Stampfli 《Respiratory research》2011,12(1):39