Biomedical subjects

P L Lee

Publications and source records attributed to P L Lee.

At least 19 recordsLinked to original sources

PubMed2006

Age-dependent increase of discoidin domain receptor 2 and matrix metalloproteinase 13 expression in temporomandibular joint cartilage of type IX and type XI collagen-deficient mice.

Our previous studies demonstrated that mutations in type IX and type XI collagens in mice caused osteoarthritis (OA)-like changes in knee and temporomandibular (TM) joints. We also found that the overexpression of matrix metalloproteinase 13 (Mmp-13) was probably due to the up-regulation of a collagen receptor, discoidin domain receptor 2 (Ddr2), which was responsible for knee cartilage degeneration in mutant mice. The objective of our study was to determine whether the expression of Mmp-3, Mmp-13 and Ddr2 was increased in OA-like TM joints in mutant mice using immunohistochemistry. We found that the staining for Ddr2, Mmp-13 and Mmp-derived type II collagen fragments in tissue sections from 6-month-old mice was increased in TM joints of the mutant mice. In contrast, we found no difference in the staining for Mmp-3 amongst the two mutant mice and their wild-type littermates. We conclude that, similar to previous observations in knee joints, the overexpression of Ddr2 and Mmp-13 may be responsible for the OA-like change in TM joints in mutant mice.

Aging↗

PubMed2006

MR spectroscopic changes in the rat hippocampus following proton radiosurgery.

PURPOSE: To identify MR spectroscopic changes in the rat hippocampus following proton radiosurgery. METHODS AND MATERIALS: A group of 12 rats were treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 30 CGE, 50 CGE, 70 CGE, 90 CGE were delivered to groups of 3 animals using single fraction technique. Animals were imaged using a standard 3 T GE Signa MRI at 4 months following treatment. An untreated animal was also studied. A 3'' surface coil was employed to obtain T1 weighted coronal pre- and post-gadolinium images (TR 600 and TE 30) and dual echo T2 weighted coronal images (TR 3000, TE 30/90). Volumetric analysis with custom software was done to evaluate areas of increased signal on T2 weighted images and the development of hydrocephalus was examined. Animals were sacrificed and specimens of the treated hippocampus were harvested for High Resolution Magic Angle Spinning MR Spectroscopy (HRMAS) followed by histopathology of the tissue samples. Peak values of choline, creatine, N-acetyl aspartate and lipids were evaluated and compared. RESULTS: Peak tissue injury occurred in the surviving 90 CGE animal by both T2 weighted and post-gadolinium imaging. Gadolinium enhancement was seen in decreasing volumes of tissue at dosage levels from 90 to 50 CGE. Hydrocephalus was seen on the untreated side in the 90 CGE animal likely because of mass effect, while it was seen in small degrees in the side of treatment in the 70 and 50 CGE animals. Histopathology showed changes at 90 and 70 CGE, but not at 50 or 30 CGE at this time point using H and E stains. HRMAS showed spectroscopic changes in the surviving 90 and 70 CGE animals but not in the 50 and 30 CGE animals. Statistical significance was not reached because of the small sample size. CONCLUSIONS: Following single dose proton radiosurgery of rat hippocampus, HRMAS is able to identify metabolic changes induced by radiation. Studies built on these principles may help develop non-invasive MR spectroscopic methods to distinguish radiation changes from tumor recurrence.

Animals↗

PubMed2006

Modeling a potential atmospheric release from a waste disposal facility at the savannah river site as an area source.

The Saltstone Facility was designed at the Savannah River Site (SRS) to treat and dispose of certain low-level liquid radioactive wastes. The final product of Saltstone is several large concrete vaults. As part of the performance assessment for Saltstone, reduction of dose to receptors downwind of the vaults have been estimated for treating the vaults as an area atmospheric source as opposed to a point source. The CAP88 model has the ability to handle area sources, but the methods are not appropriate for receptors close to the source such as those modeled at 100 m. Use of the area source as opposed to the point source can reduce the dose by as much as a factor of 5 depending on vault size. A method for quickly assessing the dose from an area source for near-in exposures is demonstrated here.

Air Movements↗

PubMed2005

On the structure of aragonite.

High-resolution synchrotron powder diffraction measurements were carried out at the 32-ID beamline of the Advanced Photon Source of Argonne National Laboratory in order to clarify the structure of geological aragonite, a widely abundant polymorph of CaCO(3). The investigated crystals were practically free of impurity atoms, as measured by wavelength-dispersive X-ray spectroscopy in scanning electron microscopy. A superior quality of diffraction data was achieved by using the 11-channel 111 Si multi-analyzer of the diffracted beam. Applying the Rietveld refinement procedure to the high-resolution diffraction spectra, we were able to extract the aragonite lattice parameters with an accuracy of about 20 p.p.m. The data obtained unambiguously confirm that pure aragonite crystals have orthorhombic symmetry.

Journal Article↗

PubMed2004

A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age.

OBJECTIVE: Differences in diagnostic criteria and methods have led to mixed results regarding the metabolite pattern of HIV-associated brain injury in relation to neurocognitive impairment. Therefore, a multicenter MRS consortium was formed to evaluate the neurometabolites in HIV patients with or without cognitive impairment. METHODS: Proton magnetic resonance spectroscopy (MRS) at short-echo time (30 ms) was assessed in the frontal white matter, basal ganglia, and parietal cortex of 100 HIV patients [61 with AIDS dementia complex (ADC) and 39 neuroasymptomatic (NAS)] and 37 seronegative (SN) controls. RESULTS: Compared to SN, NAS had higher glial marker myoinositol-to-creatine ratio (MI/Cr) in the white matter (multivariate analyses, adjusted P=0.001), while ADC showed further increased MI/Cr in the white matter and basal ganglia (both P<0.001), and increased choline compounds (Cho)/Cr in white matter (P=0.04) and basal ganglia (P<0.001). Compared to NAS, ADC showed a reduction in the neuronal marker N-acetyl compound (NA)/Cr in the frontal white matter (P=0.007). CSF, but not plasma, viral load correlated with MI/Cr and Cho/Cr in white matter and NAA/Cr in parietal cortex. HIV infection and aging had additive effects on Cho/Cr and MI/Cr in the basal ganglia and white matter. CONCLUSIONS: The results suggest that glial activation occurs during the NAS stages of HIV infection, whereas further inflammatory activity in the basal ganglia and neuronal injury in the white matter is associated with the development of cognitive impairment. Aging may further exacerbate brain metabolites associated with inflammation in HIV patient and thereby increase the risk for cognitive impairment.

AIDS Dementia Complex↗

PubMed2004

A previously undescribed frameshift deletion mutation of HFE (c.del277; G93fs) associated with hemochromatosis and iron overload in a C282Y heterozygote.

A 62-year-old white man with a hemochromatosis phenotype was found to be heterozygous for the C282Y mutation of the HFE gene. The H63D and S65C mutations of HFE were not present. As most C282Y heterozygotes do not develop a hemochromatosis phenotype, the coding region of the patient's HFE gene was sequenced and a previously undescribed frameshift mutation was identified in exon 2 (c.del277; G93fs) that resulted in a premature stop-codon. There were no coding region mutations of the ferroportin gene (FPN1). We performed human leukocyte antigen (HLA) typing of the patient and his brother who was heterozygous for the C282Y HFE mutation unassociated with a hemochromatosis phenotype. They shared only C282Y and the HLA haplotype A*03, B*14; hence, the c.del277 mutation was linked to the HLA haplotype A*02, B*44 and therefore not on the same chromosome as the C282Y mutation. Thus, the present patient's only intact HFE protein is C282Y, and this may explain his hemochromatosis phenotype.

Amino Acid Sequence↗

PubMed2003

Comparative study on conventional and low-flow nebulizers for arsenic speciation by means of microbore liquid chromatography with inductively coupled plasma mass spectrometry.

The performance of conventional and low-flow nebulizer systems with liquid chromatography in differentiating four arsenic species in urine was evaluated. Two low-flow (DIN and MCN) chamber assemblies and a conventional (CFN) nebulizer-spray chamber assembly were compared in the hyphenation of anion-exchange microbore liquid chromatography with inductively coupled plasma mass spectrometry. Under optimal analytical conditions, the detection limits of the four arsenic species were 0.2-0.6 ng ml(-1) for all the nebulizer systems tested. The chromatographic resolution was best in the case of DIN due to its minimal off-column dead volume and superior transport efficiency. Four arsenic species were determined in the certified reference materials NIST SRM 2670E and 2670N.

Arsenic↗

PubMed2003

High-energy diffuse scattering on the 1-ID beamline at the advanced photon source.

This paper reports on experiments in which high-energy (65.35 keV) X-rays were used to record the detailed diffuse diffraction patterns of a number of ceramic materials. The methodology has enabled a greater q-range to be explored (up to sintheta/lambda approximately 0.97) than is possible with laboratory-based experiments, with better q-space resolution and increased sensitivity, thus allowing previously unseen detail in diffraction patterns to be recorded. In all, 11 sections of data have been collected for Ca-CSZ, eight for Y-CSZ and six for wüstite.

Journal Article↗

PubMed2003

Patient mortality of active pulmonary tuberculosis requiring mechanical ventilation.

Mortality remains high among patients with pulmonary tuberculosis requiring mechanical ventilation (TBMV). This study was carried out to establish the mortality rates of TBMV and to identify factors that contribute to in-hospital mortality. From January 1996-April 2001, there were 825 patients with active pulmonary tuberculosis at the National Taiwan University Hospital, Taipei, Taiwan. Of these, 41 suffered acute respiratory failure and required mechanical ventilation in the intensive care unit (ICU). Of these 41 patients, 38 were followed up for 180 days. In-hospital deaths were documented in the medical records and all possible parameters contributing to mortality were collected. Of the 41 patients, 27 died in the hospital and 14 were discharged alive (in-hospital mortality rate 65.9%), with (mean +/- SD) 40.7 +/- 35.4 admission days before death. Of the 27 that died, 25 died during ICU admission and two died after being transferred to the ward. The mortality rate for the 180-day monitoring period was 79%. Factors contributing to in-hospital mortality included consolidations on chest radiographs and multiple organ failure. The mortality rate in the patients with pulmonary tuberculosis requiring mechanical ventilation is very high, with two factors affecting in-hospital mortality. These factors were multiple organ failure and consolidation on chest radiographs.

Aged↗

PubMed2002

Cryogenically cooled bent double-Laue monochromator for high-energy undulator X-rays (50-200 keV).

A liquid-nitrogen-cooled monochromator for high-energy X-rays consisting of two bent Si(111) Laue crystals adjusted to sequential Rowland conditions has been in operation for over two years at the SRI-CAT sector 1 undulator beamline of the Advanced Photon Source (APS). It delivers over ten times more flux than a flat-crystal monochromator does at high energies, without any increase in energy width (DeltaE/E approximately 10(-3)). Cryogenic cooling permits optimal flux, avoiding a sacrifice from the often employed alternative technique of filtration - a technique less effective at sources like the 7 GeV APS, where considerable heat loads can be deposited by high-energy photons, especially at closed undulator gaps. The fixed-offset geometry provides a fully tunable in-line monochromatic beam. In addition to presenting the optics performance, unique crystal design and stable bending mechanism for a cryogenically cooled crystal under high heat load, the bending radii adjustment procedures are described.

Journal Article↗

PubMed2002

Magnetic resonance spectroscopy: an in vivo tool for monitoring cerebral injury in SIV-infected macaques.

The purpose of our study was to demonstrate the feasibility of using in vivo proton Magnetic Resonance Spectroscopy (MRS) to monitor the brain manifestations of SIV infection in the macaque model of AIDS. Previous spectroscopy work on macaque brain tissue and in vivo work in humans is reviewed to provide the motivation and context for this study. We collected 34 MRS data sets on 14 uninfected rhesus macaques. From this data, we demonstrate that we are capable of detecting changes similar to those observed in human MRS studies for most metabolites using less than 10 animals. The juvenile macaques utilized in this study demonstrate age-related changes in the levels of N-acetyl aspartate (NAA), a neuronal marker. The quantity and distribution of neurochemicals in the macaque are found to be slightly, but significantly, different than in the human.

Aging↗

PubMed2001

Observation of the 22.5-keV resonance in (149)Sm by the nuclear lighthouse effect.

We have observed coherent nuclear resonant scattering of synchrotron radiation at the 22.5-keV resonance of (149)Sm. High-speed rotational sample motion led to an angular deflection of the resonantly scattered radiation off the nonresonant primary beam. This allowed us to determine the resonance energy of the first excited nuclear level of (149)Sm to be 22496(4) eV. Because of the angular deflection of the resonant photons, time spectra of coherent nuclear resonant scattering can be recorded as a function of a spatial coordinate. Time resolutions of a few 10 ps can be expected, which are beyond the limits of existing x-ray detection schemes.

Journal Article↗

PubMed2001

Improved common carotid elasticity and intima-media thickness measurements from computer analysis of sequential ultrasound frames.

B-mode ultrasound has gained popularity as a non-invasive method for direct visualization of superficial vessels. With B-mode ultrasound, arterial stiffness can be directly measured since image acquisition of the arterial wall thickness and vessel diameter can be obtained simultaneously in a dynamic fashion throughout the cardiac cycle. Recently, a method was developed to measure carotid arterial diameter and intima-media thickness (IMT) from B-mode images that utilizes computerized edge tracking-multiframe image processing that automatically measures arterial diameter and IMT in multiple sequential frames spanning several cardiac cycles. To evaluate this method, replicate B-mode common carotid artery ultrasound examinations and blood pressure measurements were obtained in 24 subjects 1-2 weeks apart. Approximately 80 sequential frames spanning two cardiac cycles were analyzed from each ultrasound examination to obtain maximum arterial diameter (D(max)), minimum arterial diameter (D(min)), and IMT using a computerized edge detection method. The intraclass correlations of D(max), D(min), and IMT were 0.97-0.99 and the mean absolute difference for these measurements were 0.03-0.11 mm. The coefficient of variation for D(max) and D(min) were 1.28 and 1.18%, respectively. The intraclass correlation for several standard arterial stiffness indices, Peterson's elastic modulus, Young's modulus, arterial distensibility, compliance, and the beta stiffness index ranged between 0.84 and 0.89. Additionally, it was determined that averaging IMT over five frames centered at D(min) reduced single frame IMT measurement variability by 27% (P=0.005) compared with IMT measured from a single frame corresponding to D(min). Comparison of the phasic relationship of D(max) and D(min) measured from the B-mode ultrasound image with the simultaneously recorded electrocardiogram (ECG) signal in the 24 subjects, provided a more accurate method of frame selection for arterial diameter extrema independent of the ECG signal. The method of computerized edge detection-sequential multiframe image processing presented in this paper represents a technological advance for image analysis of B-mode ultrasound images of common carotid arterial dimensions that is highly reproducible and directly applicable to noninvasive imaging of atherosclerosis.

Aged↗

PubMed2001

SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification.

Adaptive point mutation and amplification are induced responses to environmental stress, promoting genetic changes that can enhance survival. A specialized adaptive mutation mechanism has been documented in one Escherichia coli assay, but its enzymatic basis remained unclear. We report that the SOS-inducible, error-prone DNA polymerase (pol) IV, encoded by dinB, is required for adaptive point mutation in the E. coli lac operon. A nonpolar dinB mutation reduces adaptive mutation frequencies by 85% but does not affect adaptive amplification, growth-dependent mutation, or survival after oxidative or UV damage. We show that pol IV, together with the major replicase, pol III, can account for all adaptive point mutations at lac. The results identify a role for pol IV in inducible genetic change.

Adaptation, Physiological↗

PubMed2001

Human transferrin G277S mutation: a risk factor for iron deficiency anaemia.

Numerous polymorphisms of the transferrin gene result in a range of electrophoretic variants. We show that one of these mutations has a functional consequence. A G-->A mutation at cDNA nucleotide 829 (G277S) was associated with a reduction in total iron binding capacity (TIBC). In menstruating white women, the G277S genotype was a risk factor for iron deficiency anaemia: iron deficiency anaemia was present in 27% of homozygous G277S/G277S women, 10% of G277G/G277S heterozygous women and 5% of homozygous wild-type G277G/G277G women.

Adult↗

PubMed2001

Microsatellite variation in the yellowhammer Emberiza citrinella: population structure of a declining farmland bird.

In recent years, there has been much concern in the UK about population declines of widespread species in agricultural habitats. Conservation-orientated research on declining birds has focused on vital rates of survival and productivity. However, the environmental factors which may influence movements between populations of widespread species is poorly understood. Population genetic structure is an indirect description of dispersal between groups of individuals. To attempt to develop an understanding of genetic structuring in a widespread, but declining, farmland bird, we therefore investigated the yellowhammer, Emberiza citrinella, population in England and Wales using microsatellite data. Our first aim was to investigate whether there was genetic substructuring in the population. A second aim was to investigate if there was a relationship between genetic distances and various environmental variables. Finally, we analysed the microsatellite data for evidence of loss of genetic variation due to population decline. Our data showed a slight but significant structure within the yellowhammer population. This therefore cannot be considered a panmictic population. Our example from South Cumbria implies that high-altitude barriers may have a slight influence on population structure. However, on the whole, genetic distances between sample sites were not significantly correlated with geographical distances, degrees of population connectivity, high altitudes, or differences in precipitation between sites. Finally, we detected departures from mutation-drift equilibrium (excess heterozygosity), which is indicative of a loss of genetic variation through recent decline.

Alleles↗

PubMed2001

Hospital-based management of acute asthmatic exacerbation: an assessment of physicians' behavior in Taiwan.

This retrospective study was conducted to assess Taiwanese emergency physicians for their preference in management and adherence to guidelines in treating patients with acute exacerbation of asthma. One hundred twenty patients from hospitals of three different levels were evaluated by reviewing their medical records. Our study revealed that physicians from medical centers and regional hospitals assessed patients more often with arterial blood gas or pulse oximetry; prescribed more doses of beta2-agonist nebulizers; administered more doses of beta2-agonist nebulizers before administering parenteral aminophylline; and prescribed ipratropium nebulizers more often as adjunctive therapy. On the other hand, physicians from district hospitals more frequently prescribed parenteral aminophylline as the first-line medication and more often prescribed only a single dose of beta2-agonist nebulizer. Most emergency physicians in Taiwan did not adhere to guidelines. Specifically, these included omission of peak expiratory flow as the means to assess the severity of asthma exacerbation and response to treatment; suboptimal use of inhaled bronchodilators, such as beta2-agonists and ipratropium; and inappropriate use of parenteral aminophylline as the first-line medication.

Acute Disease↗

PubMed2000

Early brain injury in the SIV-macaque model of AIDS.

OBJECTIVE: To specify the type and severity of cellular damage in the central nervous system soon after infection and at later stages of disease in the SIV-macaque model of AIDS. DESIGN AND METHODS: Adjacent samples of frontal cortical gray matter were taken from three groups of macaques: uninfected controls (n = 4), acute (14 days post-infection; n = 4), and chronic (mean 2 years post-infection; n = 7). In vitro high resolution magnetic resonance spectroscopy of snap frozen intact tissue and quantitative neuropathology measurements of synaptophysin, calbindin, and glial fibrillary acidic protein (GFAP) in formalin-fixed tissue were performed. RESULTS: Losses in n-acetylaspartate and calbindin (indicating neuronal injury and/or death) and decreases in synaptophysin immunoreactivity (indicating synaptodendritic injury) were detected along with increases in GFAP (indicating reactive gliosis). Cellular injury worsened progressively with increased time after infection. CONCLUSIONS: These results are the first direct evidence that neuronal injury occurs soon after infection. The exacerbation of injury with time suggests a connection between the early response of the central nervous system and dementia, which occurs late in the course of infection. This connection may have broad implications for the study of and the development of therapies for damage of the central nervous system by HIV.

AIDS Dementia Complex↗