Electronic structure and optical properties of the impurity Cu+ in NaF.
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Biomedical subjects
Publications and source records attributed to J Meng.
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The authors describe new magnetic resonance (MR) spectroscopic and postprocessing methods for characterizing major proton peaks and their spectral T2 values in many small voxels throughout extensive regions of bone marrow within the adult lumbar spine. The techniques are based on spectroscopic interrogation of 128 voxels along columns oriented through the spine at eight TE values. Mean fat content measurements, based on quantification of the proton peaks of water and saturated fat (-CH2-)n, corrected for T2 decay, ranged from 40% to 60%. The mean T2 value of the lipid peak, 113 msec +/- 21, was significantly longer (P < .001) than that of water (71 msec +/- 14). The techniques combine features of MR spectroscopy and imaging most suited for spatially efficient coverage of bone marrow at spectral resolutions sufficient for intra-voxel fat or water content measurements. The methods introduced provide a practical, quantitative means for characterizing vertebral marrow in diseases affecting marrow cellularity.
A line scan Carr-Purcell-Meiboom-Gill (CPMG) spectroscopic imaging sequence has been implemented on a standard 1.5 T clinical scanner to map metabolite signals at multiple echo times from voxels along selected tissue columns through the brain. The CPMG multiecho spectroscopic image data sets are used to estimate brain metabolite T2 decay parameters in a group of healthy volunteers and in one tumor patient. Inherent trade-offs between T2 decay, spectral resolution, and echo spacing prove to be important limiting factors. In particular, separate quantitation of choline and creatine resonances at 1.5 T was not achieved in the present implementation. However, the ability to collect data sets suitable for T2 decay analyses of combined choline and creatine resonances and N-acetyl aspartate resonances in under 10 minutes may prove of clinical utility in the study of brain pathology.
OBJECTIVE: CYP3A is the major enzyme responsible for metabolism of the calcineurin inhibitors cyclosporine (CsA) and tacrolimus. Our objective was to determine the relationship between genetic polymorphisms of CYP3A5 with respect to interindividual variability in CsA and tacrolimus pharmacokinetics. METHODS: Kidney transplant recipients receiving CsA (n = 137) or tacrolimus (n = 30) were genotyped for CYP3A5*3 and *6 by a PCR/RFLP method. The patients were grouped according to the CYP3A5 genotype. Dose-adjusted trough levels were correlated with the corresponding genotype. RESULTS: At 3, 6, and 12 months, the tacrolimus dose-adjusted trough levels (dose-adjusted C0) showed a statistically significant difference between the group of CYP3A5*3/*3 (n = 19) and the group of CYP3A5*1 allele carriers. The former was higher than the latter. The CsA dose-adjusted C0 and the actual C0 did not display a significant relation (P < .05) between the group of CYP3A5*3/*3 and the group of CYP3A5*1 allele carriers. CONCLUSION: Patients with the CYP3A5*3/*3 genotype require less tacrolimus to reach target concentrations compared to those with the CYP3A5*1 allele.
A high level of 14C was found to bind irreversibly with the liver proteins of rainbow trout (Oncorhyncus mykiss) exposed to 135 mg/kg bodyweight of 14C-labelled furazolidone (14C-FZ) in fish feed daily for 10 days. After the cessation of 14C-FZ treatment, hepatic protein-bound 14C in trout stayed high for at least 30 days. The chemical identity of protein-bound 14C remained to be elucidated. However, a part of the protein-bound 14C in the liver and muscle could be released as 3-amino-2-oxazolidinone by acid hydrolysis. The formation of protein-bound 14C in the liver was investigated further with trout dosed intravenously with different 14C-FZ doses at 10 degrees C or with 5 mg/kg FZ at different water temperatures. 14C binding to the liver proteins was found to increase with increasing FZ dose or water temperature. Results of these studies indicate that protein-bound 14C in the muscle and liver of trout is related to the formation of reactive intermediates from FZ. However, additional studies on the identities of the protein-bound FZ residues are required before they can serve as useful biomarkers to monitor FZ exposure in farm fish.
OBJECTIVE: A line scan spectroscopic imaging method providing variable T2-weighted spectra from many small voxels along selected tissue columns was applied to study the chemical composition of hematopoietic and fatty marrow in the knees of adults and children. MATERIALS AND METHODS: Line scan Carr-Purcell-Meiboom-Gill (CPMG) spectroscopic imaging sequences were implemented on a 1.5 T clinical scanner. Variable T2-weighted proton spectra from 128 locations along 20 cm long, 5 mm2 columns oriented superiorly to inferiorly through knees were collected from eight healthy adults and eight children. RESULTS: In adult yellow marrow, olefinic protons, water, a composite lipid proton peak, and methyl/methylene protons contributed 6.4 +/- 0.4, 4.2 +/- 1.5, 7.2 +/- 0.5, and 82.2 +/- 1.9% (mean +/- SD) to the spectra, respectively. Marrow spectra were largely independent of position along the column. Marrow spectra of normal children showed distinct positional dependences. Epiphyseal marrow spectra of children (8-16 years old) resembled adult spectra but with more water (mean 15 vs. 4%). Metaphyseal marrow had higher, variable water content, reflecting the extent of marrow conversion and generally obscuring the olefinic proton peak. CONCLUSIONS: Spectroscopic imaging of columns is a time-efficient method for sampling extensive regions of bone marrow with high spatial resolution. It should prove useful for proton spectroscopic studies of hematologic pathologies and conditions requiring the monitoring of lipid composition.
MK886 (Merck Frosst) is a selective in vivo inhibitor of 5-lipoxygenase, active at nanomolar concentrations. At micromolar concentrations, it inhibited the proliferation of U937 monoblastoid cells and of cultured malignant cells from patients with chronic myelogenous leukemia. These cells became morphologically apoptotic, a form of physiologic cell death. U937 cell apoptosis was assessed by flow cytometry, ultrastructure, DNA laddering and immuno-histology for free 3'OH-DNA. MK886-induced apoptosis developed over time as cells were recruited in concert with reduction in their numbers. Some CML cells exhibited cytoplasmic changes of apoptosis without typical nuclear changes. Under conditions used for measuring Ca2+ with Fura 2, 10 micromolar MK886 increased U937 intracellular Ca2+ 4-fold or more over the 8 minute period of measurement. Since MK886 inhibits the association of arachidonic acid with the 5-lipoxygenase activating protein, altered arachidonic acid metabolism may have contributed to these results.
The 5-lipoxygenase inhibitors ETYA, SC41661A and MK886 reduced the proliferation and viability of Panc-1 human pancreatic cancer cells. The extent of inhibition depended upon drug concentration, and with continued culture, cells detached and stained with trypan blue. Although results from flow cytometry were those associated with programmed cell death, despite repeated attempts, no DNA laddering consistent with its later stages was detected, and studies with the TUNEL assay were negative. Light and electron microscopy of cells cultured with SC41661A provided morphologic evidence of a population of "dark" cells and of an incompletely expressed type 1 programmed cell death including margination of chromatin at the nuclear membrane and by consolidation and degeneration of cytoplasmic organelles, along with extensive vacuolization. Cells cultured with MK886 exhibited compact "dark" cells and an unusual cytoplasmic mode of cell death characterized by vacuolization and widely separated smooth internal membranes without diagnostic nuclear changes. This is in marked contrast to the extensive type 1 PCD induced by 5-lipoxygenase inhibitors cultured with human U937 monoblastoid cells. On balance, the response of Panc-1 cells to MK886 suggests expression of a variant type 2 (autophagic) cellular suicide, although some contribution from components of a "cytoplasmic" (type 3?) form of non-necrotic cell death may also be considered. In a European clinical trial, gamma linolenic acid, a polyunsaturated fatty acid that generates free radicals has been combined with 5-fluorouracil as chemotherapy for pancreatic cancer. Panc-1 cell proliferation was insensitive to inhibition by several chemotherapeutic agents employed clinically, including 5-fluorouracil, cisplatin or gemcitabine and only somewhat sensitive to GLA. When gamma linolenic acid was combined with MK886, the more effective of the two 5-lipoxygenase inhibitors, a synergistic reduction in Panc-1 cell number and viability occurred.