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Various Biochemical (various + biochemical)
Terms modified by Various Biochemical Selected AbstractsCorrelation between severity of mucopolysaccharidoses and combination of the residual enzyme activity and efficiency of glycosaminoglycan synthesisACTA PAEDIATRICA, Issue 4 2009Ewa Piotrowska Abstract Aim: To develop a method for prediction of severity and clinical course of mucopolysaccharidoses (MPS), a group of inherited metabolic diseases. Methods: Various biochemical and clinical parameters (including estimation of the level of clinical severity, presence of specific mutations, residual enzyme activity, urinary glycosaminoglycan (GAG) excretion, storage of GAG in fibroblasts and efficiency of GAG synthesis) of patients suffering from MPS types II, IIIA and IIIB were determined. Correlations between genetic, biochemical and clinical parameters were tested. Results: We found that efficiency of GAG synthesis may contribute to the level of severity of MPS. It appears that (i) combination of low or average efficiency of GAG synthesis and the presence of residual activity of the enzyme is responsible for an attenuated phenotype, (ii) a lack of detectable residual enzyme activity causes a severe phenotype, irrespective of the efficiency of GAG synthesis and (iii) high efficiency of GAG synthesis leads to a severe phenotype, even if residual enzyme activity is detected. This correlation was found to be valid in 15 out of 17 patients tested. Conclusion: Analysis of efficiency of GAG synthesis and residual activity of the enzyme may be considered for prediction of severity of MPS patients' clinical phenotypes. [source] Female Premenopausal Fracture Risk Is Associated With Gc Phenotype,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2004Anna Lis Lauridsen Abstract The phenotype of the vitamin D binding and macrophage activating protein, Gc, is a predictor of premenopausal bone fracture risk, possibly mediated through activation of osteoclasts. This was concluded from a study on 595 Danish perimenopausal women 45-58 years of age (30,040 person years). Introduction: The multifunctional plasma protein Gc, also known as group-specific component, Gc globulin, or vitamin D binding protein (DBP), has two functions with relation to bone tissue: it is the major carrier protein of vitamin D in the circulation, and deglycosylation converts it into a very potent macrophage- and osteoclast-activating factor (Gc-MAF). There are several phenotypes of Gc, and in this study, we examined the relation between Gc phenotype and bone fragility. Materials and Methods: By isoelectric focusing we identified the Gc phenotype of 595 white recent postmenopausal women enrolled into the Danish Osteoporosis Prevention Study (DOPS) and identified three groups: Gc1-1 (n = 323), Gc1-2 (n = 230), and Gc2-2 (n = 42). Differences between the three groups were examined with respect to number of fractures before enrollment, BMC and BMD, and various biochemical and clinical parameters, including the concentration of Gc measured by immunonephelometry and the concentration of the macrophage marker soluble CD163 measured by ELISA. Results and Conclusions: The risk of having at least one premenopausal bone fracture (total number of women with fracture = 179) differed significantly (p = 0.017) in women with phenotype Gc1-1 (110/323 = 0.34), Gc1-2 (63/230 = 0.27), and Gc2-2 (6/42 = 0.14). The differences were even more striking (p = 0.005) for fractures caused by low-energy traumas. Using logistic regression, we found the relative risk of premenopausal fracture to be 0.32 (0.13-0.80) in Gc2-2 compared with Gc1-1. We propose that the Gc phenotypes cause differences in osteoclast activity, a theory supported by our finding of lower levels of Gc and of soluble CD163 in women with Gc2-2 compared with Gc1-1. [source] Ribosome's mode of function: myths, facts and recent results,JOURNAL OF PEPTIDE SCIENCE, Issue 3 2009Itai Wekselman Abstract Ribosomes translate the genetic code into proteins in all living cells with extremely high efficiency, owing to their inherent flexibility and to their spectacular architecture. During the last 6 decades, extensive effort has been made to elucidate the molecular mechanisms associated with their function, and a quantum jump has been made in recent years, once the three dimensional structures of ribosomes and their functional complexes have been determined. These illuminated key issues in ribosome function, confirmed various biochemical, genetic, and medical findings, and revealed mechanistic details beyond previous expectation, thus leading to conceptual revolutions, and turning old myths into actual facts. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] Hippocampal N -Methyl- d -Aspartate Receptor Subunit Expression Profiles in a Mouse Model of Prenatal Alcohol ExposureALCOHOLISM, Issue 2 2010Sabrina L. Samudio-Ruiz Background:, Although several reports have been published showing prenatal ethanol exposure is associated with alterations in N -methyl- d- aspartate (NMDA) receptor subunit levels and, in a few cases, subcellular distribution, results of these studies are conflicting. Methods:, We used semi-quantitative immunoblotting techniques to analyze NMDA receptor NR1, NR2A, and NR2B subunit levels in the adult mouse hippocampal formation isolated from offspring of dams who consumed moderate amounts of ethanol throughout pregnancy. We employed subcellular fractionation and immunoprecipitation techniques to isolate synaptosomal membrane- and postsynaptic density protein-95 (PSD-95)-associated pools of receptor subunits. Results:, We found that, compared to control animals, fetal alcohol-exposed (FAE) adult mice had: (i) increased synaptosomal membrane NR1 levels with no change in association of this subunit with PSD-95 and no difference in total NR1 expression in tissue homogenates; (ii) decreased NR2A subunit levels in hippocampal homogenates, but no alterations in synaptosomal membrane NR2A levels and no change in NR2A-PSD-95 association; and (iii) no change in tissue homogenate or synaptosomal membrane NR2B levels but a reduction in PSD-95-associated NR2B subunits. No alterations were found in mRNA levels of NMDA receptor subunits suggesting that prenatal alcohol-associated differences in subunit protein levels are the result of differences in post-transcriptional regulation of subunit localization. Conclusions:, Our results demonstrate that prenatal alcohol exposure induces selective changes in NMDA receptor subunit levels in specific subcellular locations in the adult mouse hippocampal formation. Of particular interest is the finding of decreased PSD-95-associated NR2B levels, suggesting that synaptic NR2B-containing NMDA receptor concentrations are reduced in FAE animals. This result is consistent with various biochemical, physiological, and behavioral findings that have been linked with prenatal alcohol exposure. [source] Arteriolar Involvement in the Microvascular Lesions of Diabetic Retinopathy: Implications for PathogenesisMICROCIRCULATION, Issue 1 2007TOM A. GARDINER ABSTRACT Diabetic retinopathy (DR) is the most widespread complication of diabetes mellitus and a major cause of blindness in the working population of developed countries. The clinicopathology of the diabetic retina has been extensively studied, although the relative contribution of the various biochemical and molecular sequelae of hyperglycemia remains ill defined. Many neural and microvascular abnormalities occur in the retina of short-term diabetic animals but it remains uncertain how closely these acute changes relate to chronic human disease. It is important to determine the relationship between alterations observed within the first weeks or months in short-term animal models, and human disease, where clinically manifest retinopathy occurs only after durations of diabetes measured in years. This review is focused on the retinal microvasculature, although it should be appreciated that pathological changes in this system often occur in parallel with abnormalities in the neural parenchyma that may be derivative or even causal. Nevertheless, it is useful to reevaluate the microvascular lesions that are manifest in the retina during diabetes in humans and long-term animal models, since in addition to providing useful clues to the pathogenic basis of DR as a disease entity, it is in the deterrence of such changes that the efficacy of any novel treatment regimes will be measured. In particular, an emphasis will be placed on the relatively unappreciated role of arteriolar dysfunction in the clinical manifestations and pathology of this disease. [source] Evaluation of the conformational propensities of peptide isosteres as a basis for selecting bioactive pseudopeptidesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 6 2001S. Gupta Abstract: Our aim was to compare the repertoires of conformers formed by the model zwitterionic peptides AA and AAA in aqueous solution with the conformational profiles of a range of their peptide isosteres, so as to facilitate selection of isosteres for synthesis and testing as biologically stable surrogates of bioactive di- and tripeptides. Comparisons were based upon the results of conformational analysis using a random search approach implemented within the SYBYL molecular modelling package, using zwitterionic molecules, simulated aqueous solvation using a dielectric constant of 80 and allowing all torsions to vary. For each compound, individual conformers were grouped on the basis of specific combinations of psi, phi and omega torsions and, using their energies, the aggregated percentage for each group was calculated using a Boltzmann distribution and displayed using a 3D pseudo Ramachandran plot relating percentage conformer to psi and phi torsions. Retroamide, N -methylamide and thioamide isosteres showed the best match to natural peptides and to the molecular recognition parameters defined for substrates of peptide transporters. The results should aid rational design of therapeutic agents in various areas, e.g. oral delivery of drugs by peptide transporters and of peptidase inhibitors. This approach may usefully be applied to various biochemical and pharmaceutical topics. [source] | ||||||||||