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Biomedical subjects

Y M Wang

Publications and source records attributed to Y M Wang.

At least 19 recordsLinked to original sources

Single molecule measurements of repressor protein 1D diffusion on DNA.

We used single-molecule imaging techniques and measured the one-dimensional diffusion of LacI repressor proteins along elongated DNA to address the long-standing puzzle of why some proteins find their targets faster than allowed by 3D diffusion. Our analysis of the LacI transcription factor's diffusion yielded four main results: (1) LacI diffuses along nonspecific sequences of DNA in the form of 1D Brownian motion; (2) the observed 1D diffusion coefficients D1vary over an unexpectedly large range, from 2.3x10(-12) cm2/s to 1.3x10(-9) cm2/s; (3) the lengths of DNA covered by these 1D diffusions vary from 120 nm to 2920 nm; and (4) the mean values of D1 and the diffusional lengths indeed predict a LacI target binding rate 90 times faster than the 3D diffusion limit.

Bacterial Proteins↗

Extent and pattern of DNA methylation alteration in rice lines derived from introgressive hybridization of rice and Zizania latifolia Griseb.

We have reported previously that introgression by Zizania latifolia resulted in extensive DNA methylation changes in the recipient rice genome, as detected by a set of pre-selected DNA segments. In this study, using the methylation-sensitive amplified polymorphism (MSAP) method, we globally assessed the extent and pattern of cytosine methylation alterations in three typical introgression lines relative to their rice parent at approximately 2,700 unbiased genomic loci each representing a recognition site cleaved by one or both of the isoschizomers, HpaII/MspI. Based on differential digestion by the isoschizomers, it is estimated that 15.9% of CCGG sites are either fully methylated at the internal Cs and/or hemi-methylated at the external Cs in the rice parental cultivar Matsumae. In comparison, a statistically significant increase in the overall level of both methylation types was detected in all three studied introgression lines (19.2, 18.6, 19.6%, respectively). Based on comparisons of MSAP profiles between the isoschizomers within the rice parent and between parent and the introgression lines, four major groups of MSAP banding patterns are recognized, which can be further divided into various subgroups as a result of inheritance of, or variation in, parental methylation patterns. The altered methylation patterns include hyper- and hypomethylation changes, as well as inter-conversion of hemi- to full-methylation, or vice versa, at the relevant CCGG site(s). Most alterations revealed by MSAP in low-copy loci can be validated by DNA gel blot analysis. The changed methylation patterns are uniform among randomly selected individuals for a given introgression line within or among selfed generations. Sequencing on 31 isolated fragments that showed different changing patterns in the introgression line(s) allowed their mapping onto variable regions on one or more of the 12 rice chromosomes. These segments include protein-coding genes, transposon/retrotransposons and sequences with no homology. Possible causes for the introgression-induced methylation changes and their implications for genome evolution and crop breeding are discussed.

Cytosine↗

Superplastic carbon nanotubes.

The theoretical maximum tensile strain--that is, elongation--of a single-walled carbon nanotube is almost 20%, but in practice only 6% is achieved. Here we show that, at high temperatures, individual single-walled carbon nanotubes can undergo superplastic deformation, becoming nearly 280% longer and 15 times narrower before breaking. This superplastic deformation is the result of the nucleation and motion of kinks in the structure, and could prove useful in helping to strengthen and toughen ceramics and other nanocomposites at high temperatures.

Journal Article↗

Measurement of crystal thickness and orientation from selected-area Fourier transformation of a high-resolution electron hologram.

Precise knowledge of crystal thickness and orientation is critical for reliable interpretation of high-resolution transmission electron micrographs. In this paper, we propose a criterion of S(2)(T, u, v), which measures the crystal thickness by intensity matching of the selected-area Fourier transform of experimental holograms with the calculated electron diffraction pattern at a series of trial thicknesses (T) and crystal tilts (u, v). This criterion has been demonstrated successfully for local thickness determination from a simulated high-resolution image of a wedge-shaped YBa(2)Cu(3)O(7-delta) and from an experimental hologram of a Si crystal.

Crystallization↗

Single-molecule studies of repressor-DNA interactions show long-range interactions.

We have performed single-molecule studies of GFP-LacI repressor proteins bound to bacteriophage lambda DNA containing a 256 tandem lac operator insertion confined in nanochannels. An integrated photon molecular counting method was developed to determine the number of proteins bound to DNA. By using this method, we determined the saturated mean occupancy of the 256 tandem lac operators to be 13, which constitutes only 2.5% of the available sites. This low occupancy level suggests that the repressors influence each other even when they are widely separated, at distances on the order of 200 nm, or several DNA persistence lengths.

Bacteriophage lambda↗

Maximum entropy image deconvolution applied to structure determination for crystal Nd1.85Ce0.15CuO4-delta.

Eight [100] images from a through-focus series of tetragonal crystal Nd1.85Ce0.15CuO4-delta were transformed separately into the structure images by means of maximum entropy image deconvolution. The constructed projected structure model based on the deconvoluted image is confirmed by image simulation. It is demonstrated that the image deconvolution is still successful even when some reflections fall in the vicinity of zero cross of contrast transfer function. The effectiveness and advantages of the technique are discussed.

Journal Article↗

A further discussion on the peculiarity of maximum entropy image deconvolution in HREM.

Some important features observed in the maximum entropy image deconvolution in HREM were studied and demonstrated as a supplement to previous publications in Ultramicroscopy 35 (1991) 339 and 62 (1996) 141. It has been shown that in the process of image deconvolution how the errors of assigned electron-optical parameters can be compensated and the effect of crystal thickness can be corrected. The 'negative-potential problem' has been solved more perfectly than before via the normalization of sum total entropy.

Journal Article↗

Assessment of the combined effect of plasma exchange and plasma perfusion on patients with severe hepatitis awaiting orthotopic liver transplantation.

To determine if plasma exchange combined with plasma perfusion is a reliable and effective temporary liver support treatment for patients on the waiting list for OLT, we tested this method in 5 patients with end-stage and 3 patients with middle-stage severe hepatitis. Four patients were successfully controlled until a donor liver was available 4 to 13 days later. In contrast, the remaining 4 patients were not adequately controlled by this treatment and experienced aggravated disease progression, dying 3 to 8 days after treatment while still awaiting OLT. Of those 4 patients who received OLT, 2 patients died from multi-organ failure caused by hepatic failure, while the other 2 survived. These findings show that plasma exchange combined with plasma perfusion provides temporary support for some patients on the waiting list for OLT. The ability of patients to successfully bridge to OLT is closely associated with the degree of liver failure, complications, multi-organ failure, and the length of the waiting period for a donor liver.

Adult↗

Adverse effect of drug-induced emotional problems on work and daily activities. A principal component as an independent predictor of ADRs in Shanghai patients with osteo-arthropathy taking nabumetone.

OBJECTIVE: To discover principal components among assessed items from the WHO-SF36 survey by principal component analysis (PCA) and then to establish the relationship between the candidate principal component and the incidence of ADRs induced by nabumetone in Shanghai osteoarthropathy patients. METHOD: A total of 145 patients were interviewed using the WHO-SF36 questionnaire for quality of life (QOL) assessment before the administration of nabumetone. The sub-items of the questionnaire were analyzed using PCA and several comprehensive variables were established. Relationships between these newly formed variables and the overall incidence of adverse drug reactions (ADRs) caused by nabumetone were evaluated using univariate and multivariate analyses. RESULTS: Several principal components were identified and their linear parameters were estimated using PCA. Through univariate analysis, only 1 principal component--"adverse effect on work and daily activities as a result of emotional problems"--was found related to the incidence of ADRs. The odds ratio (OR) was 1.28 with 95% confidence intervals (CI) of 1.11 and 1.48, p = 0.0384. This result was validated using a multivariate logistic analysis performed on all the alternative candidate covariates, including family income, a history of ADRs on NSAIDs, the course of the disease, level of education, control of stress, coffee consumption and consumption of salty food. The covariate information was taken from other parts of the clinical report form (CRF) used in this research. The analysis proved that the principal component, adverse effect on work and daily activities as a result of emotional problems, was an independent factor related to the overall incidence of ADRs. The odds ratio (OR) from the logistic analysis was 1.34, with 95% confidence intervals (CI) of 1.16 and 1.55, p = 0.0309. CONCLUSIONS: The principal component identified can be applied to overcome some limitations in the WHO-SF36 questionnaire such as high correlation between variables, information overlaps and weak representation of variables and the statistical data analysis of QOL can therefore be made more effective. The study shows that the principal component "adverse effect on work and daily activities as a result of emotional problems" is an independent predictor of the overall incidence of ADRs induced by nabumetone.

Activities of Daily Living↗

Risk factors of adverse drug reaction caused by nimesulide in Shanghai patients with osteoarthropathy.

The aim of this study was to investigate the risk factors for adverse drug reactions (ADRs) to nimesulide in patients from Shanghai with osteoarthropathy. A retrospective epidemiological study was performed to obtain information (observational variables) on demographics, primary disease, family history of disease, quality of life, dietary habits, lifestyle, use of nonsteroidal anti-inflammatory drugs (NSAIDs) and ADR history of NSAIDs. Univariate and multivariate analyses were performed to establish the relationship between these observational variables and the occurrence of ADRs caused by nimesulide. Among the 726 variables, five risk factors for ADRs to nimesulide were identified. The study showed an increased risk for ADR occurrence with increased scoring of the following four factors: (i) "Concomitant drug therapy" (odds ratio [OR]: 4.66, 95% confidence intervals [CI]: 1.26-17.26, p < 0.05); (ii) "Compared with six months ago, how would you rate your health in general now?" (OR: 1.38, 95% CI: 1.03-1.84, p < 0.05); (iii) "General feeling of health status" (OR: 1.27, 95% CI: 1.03-1.56, p < 0.05) and (iv) "1 expect my health to get worse" (OR: 2.05, 95% CI: 1.22-3.44, p < 0.01). There was a decreased risk for ADR occurrence with increased scoring of the factor "Have you ever suffered from depression that impacted on your life?" (OR: 0.15, 95% CI: 0.03-0.66, p < 0.05). The predictive model for the overall incidence rate of ADRs caused by nimesulide was then established. In conclusion, the predictive model helps to indicate the risk of ADRs to nimesulide and provides clinicians with an alternative method for decision making when prescribing this drug.

Anti-Inflammatory Agents, Non-Steroidal↗

[Pulse oximetry screening for sleep-disordered breathing in stroke].

BACKGROUND: The prevalence of sleep-disordered breathing, particularly obstructive sleep apnea, among stroke patients is high. Routine screening with the current diagnostic gold standard of polysomnography is not feasible. Pulse oximetry could be a simple screening test. METHODS: The signal of pulse oximetry, recorded during full polysomnography in 184 stroke patients during neurological rehabilitation, was analyzed automatically by software for desaturations >/= 4 %. The polysomnographic apnoea-hypopnoea-index (AHI) was used as the diagnostic gold standard and compared with the oxygen desaturation index (ODI). RESULTS: Correlation between AHI of PSG and ODI of oximetry was r = 0.84 (p < 0.001). Dependent on the definition of SDB (AHI 10, 15, 20 or 30/h) and the cut-off-point for the ODI (e. g. 15/h) sensitivity was 32 - 83 % and specificity 99 - 96 %. The diagnostic accuracy as determined by the area under the ROC-curve was 96 %. CONCLUSION: Automated analysis of pulse oximetry gives reasonable results for screening for SDB in stroke patients and could be used in populations with high pre-test probability.

Female↗

Role of reactive oxygen intermediates in Japanese encephalitis virus infection in murine neuroblastoma cells.

Infection with Japanese encephalitis virus (JEV), a mosquito-borne, neurotropic flavivirus, may cause acute encephalitis in humans and induce severe cytopathic effects in various types of cultured cells. This study attempted to determine whether JEV infection induces free radical generation and whether oxidative stress contributes to virus-induced cell death in neuroblastoma cells. A rise in the intracellular level of free radicals indicated by the 2',7'-dichlorofluorescein fluorescence was observed in N18 cells following JEV infection. Cellular flavon-containing enzymes were involved in JEV-induced fluorescent change. Cells were moderately protected from JEV-induced death by diphenyleneiodonium, a flavon-containing enzyme inhibitor, whereas common antioxidants such as N-acetylcysteine, pyrrolidine dithiocarbamate, Tiron, and Trolox turned out to be ineffective. These results suggest that the direct antioxidant action is not helpful in prevention of JEV-induced neuronal cell death.

Animals↗

Stabilization of an elevated heavy metal contaminated site.

Heavy metal contamination is a common problem that is encountered at many uncontrolled sites. Immobilization is seen as a promising technology for heavy metal remediation. Here, we report a remediation case study of an elevated and multi-metal contaminated site containing Cd, Cu, Ni, Pb, and Zn. In a laboratory test, when the soil was stabilized with reagent grade stabilizers (CaHPO(4) and CaCO(3)), the toxicity characteristic leaching procedure (TCLP) extractable concentrations of Cd, Cu, Pb, and Zn were reduced by more than 87%. The greatest reduction was shown with Pb (99.8%). In the field, Ca(H(2)PO(4))(2) due to lower cost and higher solubility replaced CaHPO(4). The TCLP results of the field treatment showed that the extractable concentrations of Cd, Cu, Pb, and Zn were significantly reduced after 30 days of stabilization. The reduction ratios were 98% (Cd), 97% (Cu), 99% (Pb), and 96% (Zn). Although, the reduction ratio of Ni was only 65%, the average extractable concentration was still less than 4.0mg/l. The percent reduction can, therefore, be considered reasonable. The significant reduction of extractable metal concentrations showed that the stabilizers, a combination of Ca(H(2)PO(4))(2) and CaCO(3), successfully immobilized heavy metals on the site.

Carbonates↗

Purification, sequencing, and phylogenetic analyses of novel Lys-49 phospholipases A(2) from the venoms of rattlesnakes and other pit vipers.

Basic phospholipase A(2) homologs with Lys49 substitution at the essential Ca(2+)-binding site are present in the venom of pit vipers under many genera. However, they have not been found in rattlesnake venoms before. We have now screened for this protein in the venom of rattlesnakes and other less studied pit vipers. By gel filtration chromatography and RP-HPLC, Lys49-phospholipase-like proteins were purified from the venoms of two rattlers, Crotalus atrox and Crotalus m. molossus, and five nonrattlers, Porthidium nummifer, Porthidium godmani, Bothriechis schlegelii, Trimeresurus puniceus, and Trimeresurus albolabris. Their N-terminal amino acid sequences were shown to be characteristic for this phospholipase subfamily. The purified basic proteins from rattlesnakes caused myonecrosis and edema in experimental animals. We have also cloned the cDNAs and solved the complete sequences of four novel Lys49-phospholipases from the venom glands of C. atrox, P. godmani, B. schlegelii, and Deinagkistrodon acutus (hundred-pace). Phylogenetic analyses based on the amino acid sequences of 28 Lys49-phospholipases separate the pitviper of the New World from those of the Old World, and the arboreal Asiatic species from the terrestrial Asiatic species. The implications of the phylogeny tree to the systematics of pit vipers, and structure-function relationship of the Lys49-phospholipases are discussed.

Amino Acid Substitution↗

Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes respiration in heart failure.

Adaptive servo-ventilation (ASV) is a novel method of ventilatory support designed for Cheyne-Stokes respiration (CSR) in heart failure. The aim of our study was to compare the effect of one night of ASV on sleep and breathing with the effect of other treatments. Fourteen subjects with stable cardiac failure and receiving optimal medical treatment were tested untreated and on four treatment nights in random order: nasal oxygen (2 L/min), continuous positive airway pressure (CPAP) (mean 9.25 cm H(2)O), bilevel (mean 13.5/5.2 cm H(2)O), or ASV largely at the default settings (mean pressure 7 to 9 cm H(2)O) during polysomnography. Thermistor apnea + hypopnea index (AHI) declined from 44.5 +/- 3.4/h (SEM) untreated to 28.2 +/- 3.4/h oxygen and 26.8 +/- 4.6/h CPAP (both p < 0.001 versus control), 14.8 +/- 2.3/h bilevel, and 6.3 +/- 0.9/h ASV (p < 0.001 versus bilevel). Effort band AHI behaved similarly. Arousal index decreased from 65.1 +/- 3.9/h untreated to 29.8 +/- 2.8/h oxygen and 29.9 +/- 3.2/h CPAP, to 16.0 +/- 1.3/h bilevel and 14.7 +/- 1.8/h ASV (p < 0.01 versus all except bilevel). There were large increases in slow-wave and rapid eye movement (REM) sleep with ASV but not with oxygen or CPAP. All subjects preferred ASV to CPAP. One night ASV suppresses central sleep apnea and/or CSR (CSA/CSR) in heart failure and improves sleep quality better than CPAP or 2 L/min oxygen.

Aged↗

Phase I and pharmacokinetic study of the novel MDR1 and MRP1 inhibitor biricodar administered alone and in combination with doxorubicin.

PURPOSE: To evaluate the safety, tolerability, and pharmacokinetics of biricodar (VX-710), an inhibitor of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP1), alone and with doxorubicin in patients with advanced malignancies. The effect of VX-710 on the tissue distribution of (99m)Tc-sestamibi, a P-gp and MRP1 substrate, was also evaluated. PATIENTS AND METHODS: Patients with solid malignancies refractory to standard therapy first received a 96-hour infusion of VX-710 alone at 20 to 160 mg/m(2)/h. After a 3-day washout, a second infusion of VX-710 was begun, on the second day of which doxorubicin 45 mg/m(2) was administered. Cycles were repeated every 21 to 28 days. (99m)Tc-sestamibi scans were performed before and during administration of VX-710 alone. RESULTS: Of the 28 patients who enrolled, 25 patients were eligible for analysis. No dose-limiting toxicity (DLT) was observed in the nine assessable patients who received 120 mg/m(2)/h or less. Among seven patients receiving VX-710 160 mg/m(2)/h, two DLTs were seen: reversible CNS toxicity and febrile neutropenia. All other adverse events were mild to moderate and reversible. Plasma concentrations of VX-710 in patients who received at 120 and 160 mg/m(2)/h were two- to fourfold higher than concentrations required to fully reverse drug resistance in vitro. VX-710 exhibited linear pharmacokinetics with a harmonic mean half-life of 1.1 hours. VX-710 enhanced hepatic uptake and retention of (99m)Tc-sestamibi in all patients. CONCLUSION: A 96-hour infusion of VX-710 at 120 mg/m(2)/h plus doxorubicin 45 mg/m(2) has acceptable toxicity in patients with refractory malignancies. The safety and pharmacokinetics of VX-710 plus doxorubicin warrant efficacy trials in malignancies expressing P-gp and/or MRP1.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

New vortex-matter size effect observed in Bi(2)Sr(2)CaCu(2)O(8 + delta).

The vortex-matter 3D to 2D phase transition is studied in micron-sized Bi(2)Sr(2)CaCu(2)O(8 + delta) single crystals using local Hall magnetization measurements. At a given temperature, the second magnetization peak, the signature of a possible 3D--2D vortex phase transition, disappears for samples smaller than a critical length. We suggest that this critical length should be equated with the 2D vortex lattice ab-plane correlation length R(2D)(c). The magnitude and temperature dependence of R(2D)(c) agree well with Larkin-Ovchinnikov collective pinning theory.

Journal Article↗