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Dose Dependence (dose + dependence)
Selected AbstractsPoster Session BP07: Neurodegenerative DiseasesJOURNAL OF NEUROCHEMISTRY, Issue 2002F. Jayman Presynaptic terminals contain an abundant 140-amino acid phosphoprotein, dubbed ,-synuclein, which is accumulated in Lewy bodies typically observed in neurons in neurodegenerative diseases, such as Parkinson's disease. In this study, the role of ,-synuclein in regulating cycle, differentiation, and survival of neuronal cells was studied using a rat dopaminergic cell line ZN27D. To delineate specific effects of ,-synuclein the same cell line was engineered to express human ,-synuclein and a vector-transfected cell line RK27 was used as a second control. All three cell lines showed significant proliferation even in serum-free medium, and complete inhibition of cell division and differentiation could be achieved in the ZN27D cells only when both dibutyryl cAMP (dbcAMP) and retinoic acid were present. In contrast, the ,-synuclein expressing cells could be differentiated in the presence of only dbcAMP. Dose dependence of MPP+(1-methyl-4-phenylpyridinium iodide)-mediated caspase3 activation was studied in undifferentiated ZN27D cells. At 200 ,m MPP+ a significant cleavage of the caspase3 substrate PARP was observed and it was reversed in the presence of ,-synuclein. MPP+ also inhibited aminophospholipid translocase (APTL), a P-type ATPase that is responsible for inner plasma membrane localization of phophotidylserine in healthy cells. The role of ,-synuclein in regulating cell cycle, differentiation, APTL activity and cell death is being investigated further in the dopaminergic ZN27D cell line. [source] Dose dependence of radiation damage for protein crystals studied at various X-ray energiesJOURNAL OF SYNCHROTRON RADIATION, Issue 1 2007Nobutaka Shimizu Radiation damage to protein crystals is the most serious problem in obtaining accurate structures from protein crystallography. In order to examine the photon energy dependence of radiation damage, 12 to 15 data sets from each of nine tetragonal lysozyme crystals were collected at nine different X-ray energies (6.5, 7.1, 8.3, 9.9, 12.4, 16.5, 20.0, 24.8 and 33.0,keV) using beamline BL41XU at SPring-8. All results were compared on the basis of absorbed dose, expressed in Gray (Gy). Crystallographic statistics, such as the values of lattice constants, Rmerge and I/,(I), for each data set degraded at all nine energies as the exposure time for each crystal increased. In all data sets, radiation damage was observed after the absorbed dose exceeded 106,Gy. However, from the point of view of crystallographic statistics normalized to the absorbed dose, no clear dependence on photon energy was observed in these results. Structural refinement showed that the average B -factor for the last data set was larger than that for the first data set at all energies tested. However, no energy dependence of radiation damage on B -factor was found. Furthermore, disruption of disulfide bonds due to radiation damage was observed in electron density maps even at the highest photon energy (33,keV) used in this study. Therefore, these results suggest that radiation damage in the energy range investigated could be evaluated based on absorbed dose without energy dependence, and that it is important to minimize the absorbed dose in a crystal sample for obtaining an accurate protein structure. [source] Lead accumulation in feathers of nestling black-crowned night herons (Nycticorax nycticorax) experimentally treated in the fieldENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2003Nancy H. Golden Abstract Although lead can attain high concentrations in feathers, interpretation of the biological significance of this phenomenon is difficult. As part of an effort to develop and validate noninvasive methods to monitor contaminant exposure in free-ranging birds, lead uptake by feathers of nestling black-crowned night herons (Nycticorax nycticorax) was evaluated in a controlled exposure study. Four- to 6-d-old heron nestlings (one/nest) at Chincoteague Bay, Virginia (USA), received a single intraperitoneal injection of dosing vehicle (control, n = 7) or a dose of lead nitrate in water (0.01, 0.05, or 0.25 mg Pb/g body wt of nestling; n = 6 or 7/dose) chosen to yield feather lead concentrations found at low- to moderately polluted sites. Nestlings were euthanized at 15 d of age. Lead accumulation in feathers was associated with concentrations in bone, kidney, and liver (r = 0.32,0.74, p < 0.02) but exhibited only modest dose dependence. Blood delta-aminolevulinic acid dehydratase activity was inhibited by lead, although effects on other biochemical endpoints were marginal. Tarsus growth rate was inversely related to feather lead concentration. Culmen growth rate was depressed in nestlings treated with the highest dose of lead but not correlated with feather lead concentration. These findings provide evidence that feathers of nestling herons are a sensitive indicator of lead exposure and have potential application for the extrapolation of lead concentrations in other tissues and the estimation of environmental lead exposure in birds. [source] Bifunctional Gd2O3/C Nanoshells for MR Imaging and NIR Therapeutic ApplicationsADVANCED FUNCTIONAL MATERIALS, Issue 2 2009Chih-Chia Huang Abstract This paper reports dual function Gd2O3/C nanoshells for application in MR contrast images and NIR-triggered killing cancer cells. The nanoshells are prepared using biological gelatin particles as core templates through a two-step thermal treatment. The surfaces of the nanoshells can be readily modified by poly(styrene-alt-maleic acid) (PSMA) polymer to improve their water-dispersible properties and increase their biocompatibility. The Gd2O3/C nanoshells show brightened images of kidney cortex and liver in mice, whereas the Gd2O3/C@PSMA nanoshells show a darkened liver signal. The biodistribution is measured as a function of time and shows that the nanoshells circulate in the vessels and are cleared out gradually from organs. The graphite carbon coated on the Gd2O3 nanoshells displays absorbance in the near-IR (NIR) region. A large extinction coefficient is obtained, indicating the potential of the nanoshells as photothermal agents. The Gd2O3/C@PSMA nanoshells conjugated with anti-epithermal growth factor receptor antibodies are used for targeting and destroying A549 lung cancer cells by means of NIR-triggered killing capability. Both laser power density and material dose dependence are investigated to evaluate photothermolysis in cancer cells. [source] Use of Oral Corticosteroids and Risk of FracturesJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2000T. P. Van Staa Abstract Treatment with oral corticosteroids is known to decrease bone density but there are few data on the attendant risk of fracture and on the reversibility of this risk after cessation of therapy. A retrospective cohort study was conducted in a general medical practice setting in the United Kingdom (using data from the General Practice Research Database [GPRD]). For each oral corticosteroid user aged 18 years or older, a control patient was selected randomly, who was matched by age, sex, and medical practice. The study comprised 244,235 oral corticosteroid users and 244,235 controls. The average age was 57.1 years in the oral corticosteroid cohort and 56.9 years in the control cohort. In both cohorts 58.6% were female. The most frequent indication for treatment was respiratory disease (40%). The relative rate of nonvertebral fracture during oral corticosteroid treatment was 1.33 (95% confidence interval [CI], 1.29,1.38), that of hip fracture 1.61 (1.47,1.76), that of forearm fracture 1.09 (1.01,1.17), and that of vertebral fracture 2.60 (2.31,2.92). A dose dependence of fracture risk was observed. With a standardized daily dose of less than 2.5 mg prednisolone, hip fracture risk was 0.99 (0.82,1.20) relative to control, rising to 1.77 (1.55,2.02) at daily doses of 2.5,7.5 mg, and 2.27 (1.94,2.66) at doses of 7.5 mg or greater. For vertebral fracture, the relative rates were 1.55 (1.20,2.01), 2.59 (2.16,3.10), and 5.18 (4.25,6.31), respectively. All fracture risks declined toward baseline rapidly after cessation of oral corticosteroid treatment. These results quantify the increased fracture risk during oral corticosteroid therapy, with greater effects on the hip and spine than forearm. They also suggest a rapid offset of this increased fracture risk on cessation of therapy, which has implications for the use of preventative agents against bone loss in patients at highest risk. [source] | ||||||||||