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Biomedical subjects

M Chen

Publications and source records attributed to M Chen.

At least 19 recordsLinked to original sources

HLA-A, -B, -C, -DRB1 allele and haplotype frequencies in an African American population.

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 564 consecutively recruited African American volunteers for an unrelated hematopoietic stem cell registry. The number of known alleles identified at each locus was 42 for HLA-A, HLA-B 67, HLA-C 33, and HLA-DRB1 44. Six novel alleles (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, and DRB1*130502) not observed in the initial sequence-specific oligonucleotide probe testing were characterized. The action of balancing selection, shaping more 'even' than expected allele frequency distributions, was inferred for all four loci and significantly so for the HLA-A and DRB1 loci. Two-, three-, and four-locus haplotypes were estimated using the expectation maximization algorithm. Comparisons with other populations from Africa and Europe suggest that the degree of European admixture in the African American population described here is lower than that in other African American populations previously reported, although HLA-A:B haplotype frequencies similar to those in previous studies of African American individuals were also noted.

Black or African American↗

Retrieving leaf area index for coniferous forest in Xingguo County, China with Landsat ETM+ images.

Spatial distributions of the leaf area index (LAI) needed for carbon cycle modeling in Xingguo County, China were estimated based on correlations between the field-measurements and vegetation indices (VIs). After making geometric and atmospheric corrections to two Landsat ETM+ images, one in January 2000 and the other in May 2003, three VIs (SR, NDVI, and RSR) were derived, and their separate correlations with ground LAI measurements were established. The correlation with RSR was the highest among the three VIs. The retrieved LAI values for January 2000 were lower than those for May 2003 because of a small seasonal variation in the coniferous forests (predominantly masson pine) and the decrease in the understorey vegetation during winter.

Atmosphere↗

Carbon sinks and sources in China's forests during 1901-2001.

This paper reports the annual carbon (C) balance of China's forests during 1901-2001 estimated using the Integrated Terrestrial Ecosystem C-budget model (InTEC). Annual carbon source and sink distributions are simulated for the same period using various spatial datasets including land cover and leaf area index (LAI) obtained from remote sensing, soil texture, climate, forest age, and nitrogen deposition. During 1901-1949, China's forests were a source of 21.0+/-7.8 Tg C yr(-1) due to disturbances (human activities). Its size increased to 122.3+/-25.3 Tg C yr(-1) during 1950-1987 due to intensified human activities in the late 1950s, early 1960s, 1970s and early 1980s. The forests became large sinks of 176.7+/-44.8 Tg C yr(-1) during 1988-2001, owing to large-scale plantation and forest regrowth in previously disturbed areas as well as growth stimulation by nondisturbance factors such as climatic warming, atmospheric CO(2) fertilization, and N deposition. From 1901 to 2001, China's forests were a small carbon source of 3.32 Pg C, about 32.9+/-22.3 Tg C yr(-1). The overall C balance in biomass from InTEC generally agrees with previous results derived from forest inventories of China's forests. InTEC results also include C stock variation in soils and are therefore more comprehensive than previous results. The uncertainty in InTEC results is still large, but it can be reduced if a detailed forest age map becomes available.

Agriculture↗

LAI inversion algorithm based on directional reflectance kernels.

Leaf area index (LAI) is an important ecological and environmental parameter. A new LAI algorithm is developed using the principles of ground LAI measurements based on canopy gap fraction. First, the relationship between LAI and gap fraction at various zenith angles is derived from the definition of LAI. Then, the directional gap fraction is acquired from a remote sensing bidirectional reflectance distribution function (BRDF) product. This acquisition is obtained by using a kernel driven model and a large-scale directional gap fraction algorithm. The algorithm has been applied to estimate a LAI distribution in China in mid-July 2002. The ground data acquired from two field experiments in Changbai Mountain and Qilian Mountain were used to validate the algorithm. To resolve the scale discrepancy between high resolution ground observations and low resolution remote sensing data, two TM images with a resolution approaching the size of ground plots were used to relate the coarse resolution LAI map to ground measurements. First, an empirical relationship between the measured LAI and a vegetation index was established. Next, a high resolution LAI map was generated using the relationship. The LAI value of a low resolution pixel was calculated from the area-weighted sum of high resolution LAIs composing the low resolution pixel. The results of this comparison showed that the inversion algorithm has an accuracy of 82%. Factors that may influence the accuracy are also discussed in this paper.

Algorithms↗

Spatial scaling between leaf area index maps of different resolutions.

We developed algorithms for spatial scaling of leaf area index (LAI) using sub-pixel information. The study area is located near Liping County, Guizhou Province, in China. Methods for LAI spatial scaling were investigated on LAI images with 960 m resolution derived in two ways. LAI from distributed calculation (LAID) was derived using Landsat ETM+ data (30 m), and LAI from lumped calculation (LAIL) was obtained from the coarse (960 m) resolution data derived through resampling the ETM+ data. We found that lumped calculations can be considerably biased compared to the distributed (ETM+) case, suggesting that global and regional LAI maps can be biased if surface heterogeneity within the mapping resolution is ignored. Based on these results, we developed algorithms for removing the biases in lumped LAI maps using sub-pixel land cover-type information, and applied these to correct one coarse resolution LAI product which greatly improved its accuracy.

China↗

Effects of rivastigmine on cognitive function in patients with traumatic brain injury.

OBJECTIVE: To compare the efficacy and safety of rivastigmine (3 to 6 mg/day) vs placebo over 12 weeks in patients with traumatic brain injury and persistent cognitive impairment. METHODS: This prospective, randomized, double-blind, placebo-controlled study was conducted in 157 patients at least 12 months after injury. The primary efficacy measures were the Cambridge Neuropsychological Test Automated Battery (CANTAB) Rapid Visual Information Processing (RVIP) A' subtest and the Hopkins Verbal Learning Test (HVLT). The primary efficacy outcome was the proportion of patients who demonstrated 1.0 SD or greater improvement from baseline at week 12 on CANTAB RVIP A' or HVLT. RESULTS: The percentage of responders at week 12 on either the CANTAB RVIP A' or HVLT was 48.7% for rivastigmine and 49.3% for placebo (p = 0.940). Furthermore, for the overall study population, there were no significant differences for any of the secondary efficacy variables. In a subgroup of patients with moderate to severe memory impairment (n = 81), defined as 25% impairment or greater on HVLT at baseline, rivastigmine was significantly better than placebo for a number of measures, including the proportion of HVLT responders and CANTAB RVIP mean latency. CONCLUSIONS: Rivastigmine was safe and well tolerated in patients with traumatic brain injury with cognitive deficits. Rivastigmine shows promising results in the subgroup of patients with traumatic brain injury with moderate to severe memory deficits.

Adolescent↗

4f delocalization in Gd: inelastic x-ray scattering at ultrahigh pressure.

We present resonant inelastic x-ray scattering and x-ray emission spectroscopy results on Gd metal to 113 GPa which suggest Kondo-like aspects in the delocalization of 4f electrons. Analysis of the resonant inelastic x-ray scattering data reveals a prolonged and continuous delocalization with volume throughout the entire pressure range, so that the volume-collapse transition at 59 GPa is only part of the phenomenon. Moreover, the Lgamma1 x-ray emission spectroscopy spectra indicate no apparent change in the bare 4f moment across the collapse, suggesting that Kondo screening is responsible for the expected Pauli-like behavior in magnetic susceptibility.

Journal Article↗

Observation of a fast electron beam emitted along the surface of a target irradiated by intense femtosecond laser pulses.

A novel fast electron beam emitting along the surface of a target irradiated by intense laser pulses is observed. The beam is found to appear only when the plasma density scale length is small. Numerical simulations reveal that the electron beam is formed due to the confinement of the surface quasistatic electromagnetic fields. The results are of interest for potential applications of fast electron beams and deep understanding of the cone-target physics in the fast ignition related experiments.

Journal Article↗

Gene expression profiling of human placentas from preeclamptic and normotensive pregnancies.

The aim of this study was to investigate patterns of gene expression in placental samples from patients with preeclampsia (PE), persistent bilateral uterine artery notching (without PE), and normal controls. This study included placental tissue from nine women with PE, seven with uncomplicated pregnancies and five with bilateral uterine artery notching in Doppler velocimetry tracings. Human cDNA microarrays with 6500 transcripts/genes were used and the results verified with real-time PCR and in-situ hybridization. Multidimensional scaling method and random permutation technique demonstrated significant differences among the three groups examined. Within the 6.5K arrays, 6198 elements were unique cDNA clones representing 5952 unique UniGenes and 5695 unique LocusLinks. Multidimensional scaling plots showed 5000 genes that met our quality criteria; among these, 366 genes were significantly different in at least one comparison. Differences in three genes of interest were confirmed with real-time PCR and in-situ hybridization; acid phosphatase 5 was shown to be overexpressed in PE samples and calmodulin 2 and v-rel reticuloendotheliosis viral oncogene homolog A (RELA) were downregulated in PE and uterine artery notch placentas. In conclusion downregulation of RELA and calmodulin 2 might represent an attempt by the placenta to compensate for elevations in intracellular calcium, possibly caused by hypoxia and/or apoptosis, in both pregnancies with uterine artery notching and preeclampsia.

Adult↗

Placental volume measured by three-dimensional ultrasound in the prediction of fetal alpha(0)-thalassemia: a preliminary report.

OBJECTIVE: To evaluate the use of placental volume measured by three-dimensional (3D) ultrasound in predicting fetal homozygous alpha(0)-thalassemia (Hb-Bart's disease). METHODS: From June 2002 to May 2004 singleton pregnancies at risk of alpha(0)-thalassemia and normal controls were studied prospectively at 9-12 weeks of gestation. Affected fetuses were suspected to have alpha(0)-thalassemia by two-dimensional (2D) ultrasound and confirmed by DNA analysis. Placental volume was measured on 3D ultrasound by a multiplanar technique. Intra- and interobserver agreement of measurements was assessed. The placental volume/crown-rump length quotient of the affected fetuses was compared with that of normal fetuses. RESULTS: The final study group comprised 105 pregnancies; 43 were at risk of alpha(0)-thalassemia and 62 were normal controls. Eleven (10.5%) fetuses were affected by alpha(0)-thalassemia, all from the at-risk group, and the others were normal. Intra- and interobserver agreement of volume measurement by 3D ultrasound was relatively poor; this was reflected in the wide limits of agreement, which ranged from -10.82 to 40.86 mL. The mean +/- SD placental volume/crown-rump length quotient in affected pregnancies was larger than that in unaffected pregnancies (1.37 +/- 0.65 vs. 1.13 +/- 0.39), but this difference was not significant (P > 0.05). CONCLUSIONS: Assessment of placental volume by 3D ultrasound does not seem to be superior to 2D ultrasound in the first-trimester prediction of alpha(0)-thalassemia.

Adult↗

Subtelomeric rearrangements and 22q11.2 deletion syndrome in anomalous growth-restricted fetuses with normal or balanced G-banded karyotype.

OBJECTIVE: To determine the frequencies of cryptic subtelomeric rearrangements and 22q11.2 deletion in anomalous growth-restricted fetuses with normal or balanced G-banded karyotypes. METHODS: This was a study of 27 consecutive fetuses at a median gestational age of 26 (range, 19-33) weeks, that had intrauterine growth restriction (IUGR) as well as at least one major structural anomaly, and a normal or balanced G-banded karyotype. The median maternal age was 29 (range, 17-39) years. Fluorescence z in-situ hybridization (FISH) diagnosis of the cultured amniocytes with the probe TUPLE 1, and then the Chromoprobe Multiprobe-T system were used, respectively, to screen for the frequency of 22q11.2 deletion syndrome and subtelomeric rearrangements involving the 41 unique chromosome ends (i.e. excluding the five short arms of acrocentric autosomes (no. 13, 14, 15, 21 and 22)). Those that had suspected deleted subtelomeres were reanalyzed with a specific subtelomeric probe, TelVysion. RESULTS: Of the 27 fetuses, three (11%) were affected with 22q11.2 deletion syndrome and two (7.4%) had subtelomeric deletions (one monosomy 21q22.3, one monosomy 1p36.3). Of the 11 fetuses with congenital heart defects, three (27.3%) had 22q11.2 deletion syndrome and one (9.1%) had monosomy 1p36.3. In the remaining 16 fetuses without congenital heart defects, none had 22q11.2 deletion syndrome. However, one (6.3%) had cryptic rearrangement involving subtelomeres. CONCLUSION: Prenatal subtelomeric FISH screening is technically feasible using cultured amniocytes. We propose that 22q11.2 deletion syndrome and cryptic subtelomere rearrangements may be important etiologies of fetuses with IUGR and at least one structural anomaly, along with a normal karyotype or one that is balanced by traditional G-banding. Fetuses with congenital heart defects and IUGR should undergo FISH to exclude 22q11.2 deletion syndrome. In fetuses with IUGR and at least one major structural anomaly but without congenital heart defects, screening of subtelomeric rearrangements may contribute to further elucidation of the underlying etiology.

Adolescent↗

Suppressive effect of elongation factor 2 on apoptosis induced by HIV-1 viral protein R.

Rapid CD4+ lymphocyte depletion due to cell death caused by HIV infection is one of the hallmarks of acquired immunodeficiency syndrome. HIV-1 viral protein R (Vpr) induces apoptosis and is believed to contribute to CD4+ lymphocyte depletion. Thus, identification of cellular factors that potentially counteract this detrimental viral effect will not only help us to understand the molecular action of Vpr but also to design future antiviral therapies. In this report, we describe identification of elongation factor 2 (EF2) as such a cellular factor. Specifically, EF2 protein level is responsive to vpr gene expression; it is able to suppress Vpr-induced apoptosis when it is overproduced beyond its physiological level. EF2 was initially identified through a genome-wide multicopy suppressor search for Vpr-induced apoptosis in a fission yeast model system. Overproduction of fission yeast Ef2 completely abolishes Vpr-induced cell killing in fission yeast. Similarly, overexpression of the human homologue of yeast Ef2 in a neuroblastoma SKN-SH cell line and two CD4+ H9 and CEM-SS T-cell lines also blocked Vpr-induced apoptosis. The anti-apoptotic property of EF2 is demonstrated by its ability to suppress caspase 9 and caspase 3-mediated apoptosis induced by Vpr. In addition, it also reduces cytochrome c release induced by Vpr, staurosporine and TNFalpha. The fact that overproduction of EF2 blocks Vpr-induced cell death both in fission yeast and human cells, suggested that EF2 posses a highly conserved anti-apoptotic activity. Moreover, the responsive elevation of EF2 to Vpr suggests a possible host innate antiviral response.

Apoptosis↗

Adenovirus-delivered DKK3/WNT4 and steroidogenesis in primary cultures of adrenocortical cells.

The Wnt family molecules Dickkopf-3 (DKK3) and WNT4 are present at higher concentrations in the zona glomerulosa than in the rest of the adrenal cortex. In order to study direct effects of these proteins on adrenocortical cell function, we created adenoviruses encoding human DKK3 and WNT4. When added to cultured human adrenocortical cells, DKK3 inhibited aldosterone and cortisol biosynthesis, either alone or together with cyclic AMP. WNT4 increased steroidogenesis when added alone but decreased it in the presence of cyclic AMP. A control adenovirus encoding GFP had no effect. RNA was prepared from cultured cells and was assayed by real-time PCR. CYP11A1 (cholesterol side-chain cleavage enzyme), HSD3B2 (3beta-hydroxysteroid dehydrogenase type II), CYP17 (17 alpha-hydroxylase), CYP21 (21-hydroxylase) and CYP11B1 (11 beta-hydroxylase) mRNAs were all increased by cyclic AMP, whereas CYP11B2 (aldosterone synthase) was unaffected. DKK3 decreased cyclic AMP-stimulated CYP17. WNT4 increased both CYP17 and CYP21 in the absence of cyclic AMP. Both DKK3 and WNT4 increased the level of CYP11B2. These data show that these Wnt signaling molecules have multiple actions on steroidogenesis in adrenocortical cells, including effects on overall steroidogenesis (aldosterone and cortisol biosynthesis) and distinct effects on steroidogenic enzyme mRNA levels. The co-localization of DKK3 and WNT4 in the glomerulosa and their stimulation of CYP11B2 imply an action on glomerulosa-specific function.

Adaptor Proteins, Signal Transducing↗

Cell transplantation with a catheter-based approach: an efficient method for the treatment of heart failure with multiple lesions.

Cell transplantation is emerging as a potential therapeutic approach for the treatment of heart failure. At present, popular methods of cell delivery may not be efficient in perfusing cells through the whole myocardium. We have developed a novel catheter-based method for global transplantation of cells. Heart failure was induced in rabbit by intravenous administration of doxorubicin. Autologous bone marrow mononuclear cells were transplanted into failing hearts via the root of the aorta. Bilateral sinus aortae and coronary arteries were visualized by angiography during the cell transplantation procedure; there was no intraprocedural death. Four weeks after cell transplantation, there was an improvement in the mean left ventricular ejection fraction from baseline 72.13% to 81.54% (P = 0.034). Transplanted cells were observed throughout the cardiac layers of left and right ventricles. In conclusion, cell transplantation through the root of the aorta is a useful approach to globally supply cells into the heart.

Animals↗

Statistical methods for expression quantitative trait loci (eQTL) mapping.

Traditional genetic mapping has largely focused on the identification of loci affecting one, or at most a few, complex traits. Microarrays allow for measurement of thousands of gene expression abundances, themselves complex traits, and a number of recent investigations have considered these measurements as phenotypes in mapping studies. Combining traditional quantitative trait loci (QTL) mapping methods with microarray data is a powerful approach with demonstrated utility in a number of recent biological investigations. These expression quantitative trait loci (eQTL) studies are similar to traditional QTL studies, as a main goal is to identify the genomic locations to which the expression traits are linked. However, eQTL studies probe thousands of expression transcripts; and as a result, standard multi-trait QTL mapping methods, designed to handle at most tens of traits, do not directly apply. One possible approach is to use single-trait QTL mapping methods to analyze each transcript separately. This leads to an increased number of false discoveries, as corrections for multiple tests across transcripts are not made. Similarly, the repeated application, at each marker, of methods for identifying differentially expressed transcripts suffers from multiple tests across markers. Here, we demonstrate the deficiencies of these approaches and propose a mixture over markers (MOM) model that shares information across both markers and transcripts. The utility of all methods is evaluated using simulated data as well as data from an F(2) mouse cross in a study of diabetes. Results from simulation studies indicate that the MOM model is best at controlling false discoveries, without sacrificing power. The MOM model is also the only one capable of finding two genome regions previously shown to be involved in diabetes.

Animals↗

Comparative pharmacokinetics and pharmacodynamic target attainment of ertapenem in normal-weight, obese, and extremely obese adults.

Little is known of the effects of obesity on ertapenem drug disposition and pharmacodynamics. Thirty healthy volunteers in three body mass index (BMI) groups (10 per group), normal weight (BMI, 18.5 to 24.9 kg/m2), class I-II obesity (BMI, 30 to 39.9 kg/m2), and class III obesity (BMI, >or=40 kg/m2), were administered a 1-g dose of ertapenem. Serum concentrations were obtained over 24 h. Population pharmacokinetic data were obtained using a nonparametric adaptive grid followed by Monte Carlo simulation to determine the probability of obtaining the free drug exposure targets of the time that the free drug concentration remains above the MIC (fT>MIC) of 20% and 40% for bacteriostatic and maximal bactericidal activity, respectively. Compared to the subjects in the obese groups, area under the concentration-time curve from 0 h to infinity was significantly higher in the normal-weight subjects, whereas the total central compartment volume was higher in the class III obese subjects (P MIC of 20% with a 90% probability was attained at MICs of MIC, 40%), no group attained the target at the 90% probability level at any tested MIC. The results suggest that the standard 1-g ertapenem dose may not provide adequate drug exposure for any body mass index classification for MICs in excess of 0.25 to 0.5 microg/ml.

Adult↗

Leisure activity and risk of cognitive impairment: the Chongqing aging study.

The authors followed 5,437 people aged 55 years and older with normal baseline Mini-Mental State Examination score annually for 5 years. The mean incidence of cognitive impairment was 2.3% per year. Cognitive activities in both the individual item (playing board games and reading) and the composite measure were associated with the reduced risk of cognitive impairment, while watching television was associated with an increased risk of cognitive impairment.

Aged↗