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Biomedical subjects

W Chen

Publications and source records attributed to W Chen.

At least 91 records · Page 5Linked to original sources

Modified Szabo's wave equation models for lossy media obeying frequency power law.

Szabo's models of acoustic attenuation [Szabo, J. Acoust. Soc. Am. 96(1), 491-500 (1994)] comply well with the empirical frequency power law involving noninteger and odd-integer exponent coefficients while guaranteeing causality, but nevertheless encounter the troublesome issues of hypersingular improper integral and obscurity in implementing initial conditions. The purpose of this paper is to ease or remove these drawbacks of the Szabo's models via the Caputo fractional derivative concept. The positive time-fractional derivative is also introduced to include the positivity of the attenuation processes.

Journal Article↗

SV40 early region oncoproteins and human cell transformation.

We now understand neoplastic transformation to be the consequence of multiple acquired genetic alterations. The combination of these acquired changes confer the various phenotypes that constitute the clinical features of cancer. Although only rare human cancers derive from a viral etiology, the study of DNA tumor viruses that transform rodent and human cells has led to a greater understanding of the molecular events that program the malignant state. In particular, investigation of the viral oncoproteins specified by the Simian Virus 40 Early Region (SV40 ER) has revealed critical host cell pathways, whose perturbation play an essential role in the experimental transformation of mammalian cells. Recent work has re-investigated the roles of two SV40 ER oncoproteins, the large T antigen (LT) and the small t antigen (ST), in human cell transformation. Co-expression of these two oncoproteins, together with the telomerase catalytic subunit, hTERT, and an oncogenic version of the H-Ras oncoprotein, suffices to transform human cells. LT inactivates two key tumor suppressor pathways by binding to the retinoblastoma protein (pRB) and p53. The ability of ST to transform human cells requires interactions with PP2A, an abundant family of serine-threonine phosphatases. Here we review recent developments in our understanding of how these two viral oncoproteins facilitate human cell transformation.

Animals↗

Is obesity a high-risk factor for laparoscopic colorectal surgery?

BACKGROUND: The aim of this study was to assess the outcome of laparoscopic colorectal surgery in obese patients and compare it to that of a nonobese group of patients who underwent similar procedures. METHODS: All 162 consecutive patients who underwent an elective laparoscopic or laparoscopic-assisted segmental colorectal resection between August 1991 and December 1997 were evaluated. Body mass index (BMI; kg/m2) was used as an objective index to indicate massive obesity. The parameters analyzed included BMI, age, gender, comorbid conditions, diagnosis, procedure, American Society of Anesthesiologists classification score, operative time, estimated blood loss, transfusion requirements, intraoperative complications, conversion to laparotomy, postoperative complications, length of hospitalization, and mortality. RESULTS: Thirty-one patients (19.1%) were obese (23 males and 8 females). Conversion rates were significantly increased in the obese group (39 vs 13.5%, p = 0.01), with an overall conversion rate of 18%. The postoperative complication rate in the obese group was 78% versus 24% in the nonobese group (p <0.01). Specifically, rates of ileus and wound infections were significantly higher in the obese group [32.3 vs. 7.6% (p <0.01) and 12.9 vs 3.1%. (p = 0.03), respectively]. Furthermore, hospital stay in the obese group was longer (9.5 days) than in the nonobese group (6.9 days, p = 0.02). CONCLUSION: Laparoscopic colorectal segmental resections are feasible in obese patients. However, increased rates of conversion to laparotomy should be anticipated and the risk of postoperative complications is significantly increased, prolonging the length of hospitalization when compared to that of nonobese patients.

Adolescent↗

Different excitation and reception distributions with a single-loop transmit-receive surface coil near a head-sized spherical phantom at 300 MHz.

Calculations and experiments were used to examine the B(1) field behavior and signal intensity distribution in a 16-cm diameter spherical phantom excited by a 10-cm diameter surface coil at 300 MHz. In this simple system at this high frequency very complex RF field behavior exists, resulting in different excitation and reception distributions. Included in this work is a straightforward demonstration that coil receptivity is proportional to the magnitude of the circularly polarized component of the B(1) field that rotates in the direction opposite to that of nuclear precession. It is clearly apparent that even in very simple systems in head-sized samples at this frequency it is important to consider the separate excitation and reception distributions in order to understand the signal intensity distribution.

Head↗

Applications of Kalman filtering to real-time trace gas concentration measurements.

A Kalman filtering technique is applied to the simultaneous detection of NH3 and CO2 with a diode-laser-based sensor operating at 1.53 micrometers. This technique is developed for improving the sensitivity and precision of trace gas concentration levels based on direct overtone laser absorption spectroscopy in the presence of various sensor noise sources. Filter performance is demonstrated to be adaptive to real-time noise and data statistics. Additionally, filter operation is successfully performed with dynamic ranges differing by three orders of magnitude. Details of Kalman filter theory applied to the acquired spectroscopic data are discussed. The effectiveness of this technique is evaluated by performing NH3 and CO2 concentration measurements and utilizing it to monitor varying ammonia and carbon dioxide levels in a bioreactor for water reprocessing, located at the NASA-Johnson Space Center. Results indicate a sensitivity enhancement of six times, in terms of improved minimum detectable absorption by the gas sensor.

Algorithms↗

Otosclerosis: a genetically heterogeneous disease involving at least three different genes.

Otosclerosis is caused by abnormal bone homeostasis of the otic capsule, resulting in hearing impairment in 0.3%-0.4% of the white population. The etiology of the disease remains unclear and environmental as well as genetic factors have been implicated. We localized the first autosomal-dominant locus to chromosome 15 in 1998 (OTSC1) in an Indian family and, recently, we reported the localization of a second gene for otosclerosis to a 16 cM interval on chromosome 7q (OTSC2). In this study, we recruited and analyzed nine additional families (seven Belgian and two Dutch families with 53 affected and 20 unaffected subjects) to investigate the importance of these loci in autosomal-dominant otosclerosis. We completed linkage analysis with three microsatellite markers of chromosome 15 (D15S652, D15S1004, D15S657) and five microsatellite markers of chromosome 7 (D7S495, D7S2560, D7S684, D7S2513, D7S2426). In two families, results compatible with linkage to OTSC2 were found, but in the seven remaining families OTSC1 and OTSC2 were excluded. Heterogeneity testing provided significant evidence for genetic heterogeneity, with an estimated 25% of families linked to OTSC2. These results indicate that, besides OTSC1 and OTSC2, there must be at least one additional otosclerosis locus.

Chromosomes, Human, Pair 15↗

HLA-DPB1 allelic frequency of the Pumi ethnic group in south-west China and evolutionary relationship of Pumi with other populations.

A sequencing-based typing of the HLA-DPB1 gene was carried out in 51 unrelated healthy individuals from the Yunnan Pumi ethnic minority. A total of 18 DPB1 alleles, in which DPB1*0501 (52.0%) and DPB1*0402 (15.7%) greatly predominated, were found, of which alleles DPB1*20011, 2201, 3601, 3701, 3801, 4901, 5001 and 8001 were recorded for the first time in the Chinese population. This may be because the typing methods used in previous genotyping of Chinese populations were of lower sensitivity than that used in our study. A dendrogram constructed by the maximum likelihood method showed that the Pumi ethnic minority belongs to the Asian/Australasian cluster and has the closest relationship to Trobriander, implying an unusual relationship between Australasian and South China populations. However, the Yi ethnic minority, which also comes from the ancient Qiang, did not show a very close relationship with the Pumi. This is probably because the Pumi were historically assimilated by local south-west China populations.

Asian People↗

A novel DRB1*09 allelic sequence in the Jing ethnic minority of China.

A new DRB1 allele, DRB1*0902, has been identified in an individual of the Jing ethnic minority. Its sequence was confirmed by sequencing of PCR products and clones. This allele differed by three nucleotides from DRB1*09012 at positions 157, 161 and 166, and resulted in amino acid motif substitution from VAES to DAEY.

Amino Acid Motifs↗

Approaching healthy body mass index norms for children and adolescents from health-related physical fitness.

Current body mass index (BMI) norms for children and adolescents are developed from a reference population that includes obese and slim subjects. The validity of these norms is influenced by the observed secular increase in body weight and BMI. We hypothesized that the performance of children in health-related physical fitness tests would be negatively related to increased BMIs, and therefore fitness tests might be used as criteria for developing a more appropriate set of BMI norms. We evaluated the existing data from a nation-wide fitness survey for students in Taiwan (444 652 boys and 433 555 girls) to examine the relationship between BMI and fitness tests. The fitness tests used included: an 800/1600-m run/walk; a standing long jump; bent-leg curl-ups; and a sit-and-reach test. The BMI percentiles developed from the subgroup whose test scores were better than the 'poor' quartile in all four tests were compared with those of the whole population and linked to the adult criteria for overweight and obesity. The BMIs were significantly related to the results of fitness testing. A total of 43% of students had scores better than the poorest quartile in all of their tests. The upper BMI percentile curves of this fitter subgroup were lower than those of the total population. The 85th and 95th BMI percentile values of the fitter 18-year-old-students (23.7 and 25.5 kg m(-2) for boys; 22.6 and 24.6 kg m(-2) for girls) linked well with the adult cut-off points of 23 and 25 kg m(-2), which have been recommended as the Asian criteria for adult overweight and obesity. Hence, the BMI norms for children and adolescents could be created from selected subgroups that have better physical fitness. We expect that the new norms based on this approach will be used not only to assess the current status of obesity or overweight, but also to encourage activity and exercise.

Adolescent↗

Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3.

Clinical otosclerosis (OMIM 166800/605727) has a prevalence of 0.2-1% among white adults, making it the single most common cause of hearing impairment in this group. It is caused by abnormal bone homeostasis of the otic capsule with the consequent development of sclerotic foci that invade the stapedio-vestibular joint (oval window) interfering with free motion of the stapes. Impaired ossicular chain mobility results in a conductive hearing loss. We identified the first locus for otosclerosis (OTSC1) on chromosome 15 in 1998 and reported a second locus (OTSC2) on chromosome 7 last year. Here we present results of a genome wide linkage study on a large Cypriot family segregating otosclerosis. Results of this study exclude linkage to OTSC1 and OTSC2 and identify a third locus, OTSC3, on chromosome 6p. The defined OTSC3 interval covers the HLA region, consistent with reported associations between HLA-A/HLA-B antigens and otosclerosis.

Chromosome Mapping↗

Nested case-control study of lung cancer in four Chinese tin mines.

OBJECTIVES: To evaluate the relation between occupational dust exposure and lung cancer in tin mines. This is an update of a previous study of miners with high exposure to dust at four tin mines in southern China. METHODS: A nested case-control study of 130 male lung cancer cases and 627 controls was initiated from a cohort study of 7855 subjects employed at least 1 year between 1972 and 1974 in four tin mines in China. Three of the tin mines were in Dachang and one was in Limu. Cumulative total exposure to dust and cumulative exposure to arsenic were calculated for each person based on industrial hygiene records. Measurements of arsenic, polycyclic aromatic hydrocarbons (PAHs), and radon in the work sites were also evaluated. Odds ratios (ORs), standard statistic analysis and logistic regression were used for analyses. RESULTS: Increased risk of lung cancer was related to cumulative exposure to dust, duration of exposure, cumulative exposure to arsenic, and tobacco smoking. The risk ratios for low, medium, and high cumulative exposure to dust were 2.1 (95% confidence interval (95% CI) 1.1 to 3.8), 1.7 (95% CI 0.9 to 3.1), and 2.8 (95% CI 1.6 to 5.0) respectively after adjustment for smoking. The risk for lung cancer among workers with short, medium, and long exposure to dust were 1.9 (95% CI 1.0 to 3.5), 2.3 (95% CI 1.3 to 4.1), and 2.3 (95% CI 1.2 to 4.2) respectively after adjusting for smoking. Several sets of risk factors for lung cancer were compared, and the best predictive model included tobacco smoking (OR=1.6, 95% CI 1.1 to 2.4) and cumulative exposure to arsenic (ORs for different groups from low to high exposure were 2.1 (95% CI 1.1 to 3.9); 2.1 (95% CI 1.1 to 3.9); 1.8 (95% CI 1.0 to 3.6); and 3.6 (95% CI 1.8 5 to 7.3)). No excess of lung cancer was found among silicotic subjects in the Limu tin mine although there was a high prevalence of silicosis. Exposures to radon were low in the four tin mines and no carcinogenic PAHs were detected. CONCLUSIONS: These findings provide little support for the hypothesis that respirable crystalline silica induces lung cancer. Ore dust in work sites acts as a carrier, the exposure to arsenic and tobacco smoking play a more important part in carcinogenesis of lung cancer in tin miners. Silicosis seems not to be related to the increased risk of lung cancer.

Adult↗

The human melanocortin-1 receptor locus: analysis of transcription unit, locus polymorphism and haplotype evolution.

The complete sequence of the MC1R locus has been assembled, the coding region of the gene is intronless and placed within a 12 kb region flanked by the NULP1 and TUBB4 genes. The immediate promoter region has an E-box site with homology to the M-box consensus known to bind the microphthalmia transcription factor (MITF); however, promoter deletion analysis and transactivation studies have failed to show activation through this element by MITF. Polymorphism within the coding region, immediate 5' promoter region and a variable number tandem repeat (VNTR) minisatellite within the locus have been examined in a collection of Caucasian families and African individuals. Haplotype analysis shows linkage disequilibrium between the VNTR and MC1R coding region red hair variant alleles which can be used to estimate the age of these missense changes. Assuming a mean VNTR mutation rate of 1% and a star phylogeny, we estimate the Arg151Cys variant arose 7500 years before the present day, suggesting these variants may have arisen in the Caucasian population more recently than previously thought.

Amino Acid Sequence↗

beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins.

One aspect of the function of the beta-arrestins is to serve as scaffold or adapter molecules coupling G-protein coupled receptors (GPCRs) to signal transduction pathways distinct from traditional second messenger pathways. Here we report the identification of Dishevelled 1 and Dishevelled 2 (Dvl1 and Dvl2) as beta-arrestin1 (betaarr1) interacting proteins. Dvl proteins participate as key intermediates in signal transmission from the seven membrane-spanning Frizzled receptors leading to inhibition of glycogen synthase kinase-3beta (GSK-3beta), stabilization of beta-catenin, and activation of the lymphoid enhancer factor (LEF) transcription factor. We find that phosphorylation of Dvl strongly enhances its interaction with betaarr1, suggesting that regulation of Dvl phosphorylation and subsequent interaction with betaarr1 may play a key role in the activation of the LEF transcription pathway. Because coexpression of the Dvl kinases, CK1epsilon and PAR-1, with Dvl synergistically activates LEF reporter gene activity, we reasoned that coexpression of betaarr1 with Dvl might also affect LEF-dependent gene activation. Interestingly, whereas betaarr1 or Dvl alone leads to low-level stimulation of LEF (2- to 5-fold), coexpression of betaarr1 with either Dvl1 or Dvl2 leads to a synergistic activation of LEF (up to 16-fold). Additional experiments with LiCl as an inhibitor of GSK-3beta kinase activity indicate that the step affected by betaarr1 is upstream of GSK-3beta and most likely at the level of Dvl. These results identify betaarr1 as a regulator of Dvl-dependent LEF transcription and suggest that betaarr1 might serve as an adapter molecule that can couple Frizzled receptors and perhaps other GPCRs to these important transcription pathways.

Adaptor Proteins, Signal Transducing↗

Crystal structure of Sar1-GDP at 1.7 A resolution and the role of the NH2 terminus in ER export.

The Sar1 GTPase is an essential component of COPII vesicle coats involved in export of cargo from the ER. We report the 1.7-A structure of Sar1 and find that consistent with the sequence divergence of Sar1 from Arf family GTPases, Sar1 is structurally distinct. In particular, we show that the Sar1 NH2 terminus contains two regions: an NH2-terminal extension containing an evolutionary conserved hydrophobic motif that facilitates membrane recruitment and activation by the mammalian Sec12 guanine nucleotide exchange factor, and an alpha1' amphipathic helix that contributes to interaction with the Sec23/24 complex that is responsible for cargo selection during ER export. We propose that the hydrophobic Sar1 NH2-terminal activation/recruitment motif, in conjunction with the alpha1' helix, mediates the initial steps in COPII coat assembly for export from the ER.

Animals↗

Granular flows through vertical pipes controlled by an electric field.

The flow of granular nickel particles moving down vertical pipes from a hopper in the presence of a local, horizontal ac electric field is studied experimentally. The flow is initiated by opening the bottom outlet of the pipe after the pipe is fully filled with particles from the hopper. The mass of particles flowing out of the pipe is measured as a function of time by an electronic balance. The time dependence of the steady-state flow rate Q, under each fixed voltage V, is obtained. Depending on the magnitude of V, two types of flow behaviors are observed. For low V ( or =V(c)), no interface exists and the whole region between the hopper and the electrodes are densely filled; only one constant flow rate Q(A2) is observed. (The precise meaning of Q(A2) and Q(B) are defined in the text.) The steady-state flow rates Q(A2) and Q(B) measured for each V, are plotted as a function of V. The flow rate Q(A2) is a monotonically decreasing function of V, which can be approximately fitted by a power law, with an exponent of -0.8, while Q(B) is found to be voltage independent. These features result from a competition between the blocking effect of the electric-field region and the gravity-driven pushing effect from the hopper outlet. The local electric field is able to retard the downward movement of a dense column existing above it, but is ineffective in doing so when the column above is dilute in density.

Journal Article↗

Deregulation of FCGR2B expression by 1q21 rearrangements in follicular lymphomas.

We report here the molecular cloning and characterization of a t(1;14)(q21;q32) in a follicular lymphoma (FL) with an unusual BCL2 aberration. Fluorescence in situ hybridization (FISH) and Southern blot analysis of tumor cells identified the translocation breakpoint within the 5' switch region of IGHG (Sgamma). We cloned the chimeric breakpoint region approximately 1.5 kbp downstream from the HindIII site of 5'Sgamma2 on chromosome 14q32 and identified a 360-bp novel segment with homology to the CpG island clone 11h8. Two BAC clones containing this sequence were isolated and mapped to 1q21 by FISH. BAC 342/P13 contained sequences homologous to Fcgamma receptors 2A, 3A, 2B, 3B, and a heat shock protein gene HSP70B. The translocation brought the Sgamma2 region of a productive IGH allele 20 approximately 30 kbp upstream of FCGR2B. As a result of the translocation, the b2 isoform of FCGR2B was overexpressed in the tumor. Screening of a panel of 76 B-cell lymphomas with 1q21-23 cytogenetic aberrations by Southern blot analysis using breakpoint probes identified an additional FL with a t(14;18)(q32;q21) and a breakpoint in the FCGR2B region. These results suggest that FCGR2B may be deregulated by 1q21 aberration in BCL2 rearranged FLs and possibly play a role in their progression.

Adult↗