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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

[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↗

Differential expression and geographic variation of the venom phospholipases A2 of Calloselasma rhodostoma and Trimeresurus mucrosquamatus.

To investigate the geographic variations in venoms of two medically important pitvipers, we have purified and characterized the phospholipases A2 (PLA2s) from the pooled venoms of Calloselasma rhodostoma from Malaysia, Thailand, Indonesia, and Vietnam, as well as the individual venom of Trimeresurus mucrosquamatus collected from both North and South Taiwan. Enzymatic and pharmacological activities of the purified PLA2s were also investigated. The complete amino acid sequences of the purified PLA2s were determined by sequencing the corresponding cDNAs from the venom gland and shown to be consistent with their molecular weight data and the N-terminal sequences. All the geographic venom samples of C. rhodostoma contain a major noncatalytic basic PLA2-homolog and two or three acidic PLA2s in different proportions. These acidic PLA2s contain Glu6-substitutions and show distinct inhibiting specificities toward the platelets from human and rabbit. We also found that the T. mucrosquamatus venoms from North Taiwan but not those from South Taiwan contain an Arg6-PLA2 designated as TmPL-III. Its amino acid sequence is reported for the first time. This enzyme is structurally almost identical to the low- or nonexpressed Arg6-PLA2 from C. rhodostoma venom gland, and thus appears to be a regressing venom component in both of the Asian pitvipers.

Amino Acid Sequence↗

Serine protease isoforms of Deinagkistrodon acutus venom: cloning, sequencing and phylogenetic analysis.

The major coagulating fibrinogenase of Deinagkistrdon acutus venom, designated acutobin, was purified by anion-exchange chromatography, gel filtration and reverse-phase HPLC. Approximately 80% of its protein sequence was determined by sequencing the various fragments derived from CNBr cleavage and digestion with endoprotease. Extensive screening of the venom gland cDNA species after amplification by PCR resulted in the isolation of four distinct cDNA clones encoding acutobin and three other serine proteases, designated Dav-PA, Dav-KN and Dav-X. The complete amino acid sequences of these enzymes were deduced from the cDNA sequences. The amino-acid sequence of acutobin contains a single chain of 236 residues including four potential N-glycosylation sites. The purified acutobin (40 kDa) contains approx. 30% carbohydrate by weight, which could be partly removed by N-glycanase. The phylogenetic tree of the complete amino acid sequences of 40 serine proteases from 18 species of Crotalinae shows functional clusters reflecting parallel evolution of the three major venom enzyme subtypes: coagulating enzymes, kininogenases and plasminogen activators. The possible structural elements responsible for the functional specificity of each subtype are discussed.

Agkistrodon↗

Isolation of a choline monooxygenase cDNA clone from Amaranthus tricolor and its expressions under stress conditions.

Plants synthesize the osmoprotectant glycine betaine (GB) via choline-->betaine aldehyde-->glycine betaine[1]. Two enzymes are involved in the pathway, choline monooxygenase (CMO) and betaine aldehyde dehydrogenase (BADH). A full length CMO cDNA (1,643bp) was cloned from Amaranthus tricolor. The open reading frame encoded a 442-amino acid polypeptide, which showed 69% identity with CMOs in Spinacia oleracea L. and Beta vulgaris L. DNA gel blot analysis indicated the presence of one copy of CMO gene in the A. tricolor genome. The expressions of CMO and BADH proteins in A.tricolor leaves significantly increased under salinization, drought and heat stress (42 degrees C), as determined by immunoblot analysis, but did not respond to cold stress (4 degrees C), or exogenous ABA application. The increase of GB content in leaves was parallel to CMO and BADH contents.

Aldehyde Oxidoreductases↗

Regeneration of plants from callus tissues of hairy roots induced by Agrobacterium rhizogenes on Alhagi pseudoalhagi.

The legume forage Alhagi pseudoalhagi was transformed by the Agrobacterium rhizogenes strain A4 using cotyledon and hypocotyl segments as infection materials. Regenerated plants were achieved from sterile calli derived from hairy roots, which occurred at or near the infection sites. The regenerated plants from hairy root were characterized by normal leaf morphology and stem growth but a shallow and more extensive root system than normal plants. Opine synthesis, PCR and Southern blot confirmed that T-DNA had been integrated into the A. pseudoalhagi genome. Acetosyringone (AS) was found to be vital for successful transformation of A. pseudoalhagi.

Fabaceae↗

Recombinant adenovirus expressing adeno-associated virus cap and rep proteins supports production of high-titer recombinant adeno-associated virus.

It has been difficult to produce a chimeric vector containing both Ad and AAV rep and cap, and to grow such chimeric vectors in 293 cells. By recombination in vitro in a bacterial host, we were able to produce recombinant plasmid AdAAV (pAdAAVrep-cap), which could be used to generate recombinant AdAAV (rAdAAVrep-cap) after transfection into 293 cells. A recombinant adenovirus, rAdAAVGFP, in which the green fluorescent protein (GFP) gene is flanked by the AAV terminal repeats cloned into the E1-deleted site of Ad was also generated. Co-infection of rAdAAVrep-cap together with rAdAAVGFP into 293 cells resulted in production of high titers of rAAV expressing GFP. It was noted that the titer of rAdAAVrep-cap was lower than the titer of control AdCMVLacZ. The lower titer of rAdAAvrep-cap was associated with expression of Rep protein. Non-homologous recombination occurs after high passage and results in deletions within the AAV rep genes. These results indicate that (1) rAdAAVrep-cap can be produced; (2) rAdAAVrep-cap + rAdAAVGFP is a convenient and efficient way to transfect 293 cells to grow high titer rAAV; and (3) frozen stock is required to avoid propagation of rep-deleted pAdAAVrep-cap.

Adenoviridae↗

Actinopolymorpha singaporensis gen. nov., sp. nov., a novel actinomycete from the tropical rainforest of Singapore.

A novel actinomycete was isolated from soil in the tropical rainforest of Singapore. The cells of this actinomycete are highly pleomorphic. In the early stages of growth, most cells are of irregular squarish shape and varied sizes. Cells remain attached after cell division, often forming chains or aggregates of a few cells. Cells at the end of a chain tend to elongate. With prolonged cultivation, cells show different degrees of elongation and enlargement, producing branched hyphae of uneven thickness. At the periphery of the colony, long hyphae form, which are divided into alternating segments of elongated cells and chains of squarish cells. This actinomycete is considerably salt-tolerant, able to grow in the presence of 15% NaCl. Chemotaxonomically, it contains LL-diaminopimelic acid (DAP) in the cell wall, type PI phospholipids and MK-9(H6) as the predominant menaquinone. 16S rDNA sequence analysis assigned this actinomycete to the family Nocardioidaceae, but its 16S rDNA shared no more than 91.2% sequence similarity with other members of the family. Based on phenotypic, chemotaxonomic and phylogenetic evidence, it is proposed that this actinomycete be classified as a new species in a new genus, Actinopolymorpha singaporensis gen. nov., sp. nov.

Actinomycetales↗

Treatment of obstructive sleep apnoea with nasal continuous positive airway pressure in stroke.

The prevalence of obstructive sleep apnoea (OSA) following stroke is high and OSA is associated with increased morbidity, mortality and poor functional outcome. Nasal continuous positive airway pressure (nCPAP) is the treatment of choice for OSA, but its effects in stroke patients are unknown. The effectiveness and acceptance of treatment with nCPAP in 105 stroke patients with OSA, admitted to rehabilitation was prospectively investigated. Subjective wellbeing was measured with a visual analogue scale in 41 patients and 24-h blood pressure was determined in 16 patients before and after 10 days of treatment. Differences were compared between patients who did and did not accept treatment. There was an 80% reduction of respiratory events with concomitant increase in oxygen saturation and improvement in sleep architecture. No serious side-effects were noticed. Seventy-four patients (70.5%) continued treatment at home. Nonacceptance was associated with a lower functional status, as measured by the Barthel Index, and the presence of aphasia. Ten days after initiation of nCPAP, compliant users showed a clear improvement in wellbeing (differences in visual analogue scale (deltaVAS) mean+/-SD 26+/-26 mm) versus noncompliant patients (deltaVAS 2+/-25 mm, p=0.021). Only the compliant group had a reduction in mean nocturnal blood pressure (deltaBP; -8+/-7.3 mmHg versus 0.8+/-8.4 mmHg, p=0.037). Stroke patients with obstructive sleep apnoea can be treated effectively with nasal continuous positive airway pressure and show a similar improvement and primary acceptance to obstructive sleep apnoea patients without stroke. Continuous positive airway pressure acceptance is associated with improved wellbeing and decreased nocturnal blood pressure.

Activities of Daily Living↗

Signaling pathway mediated by kappa-opioid receptor is impaired in cardiac hypertrophy.

AIM: The responses of the intracellular calcium ([Ca2+]i) and the intracellular pH (pHi) to kappa-opioid receptor stimulation were determined in the single right ventricular myocytes isolated from the hearts of chronically hypoxic rats which exhibited right ventricular hypertrophy (RVH). METHODS: With the spectrofluorometric method, the electrically-induced [Ca2+]i transient and pHi were measured in myocytes loaded with fura-2 and BCECF [2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorscein], respectively. RESULTS: U50,488H, a selective kappa-opioid agonist decreased the electrically-induced [Ca2+]i transient and increased the pHi. The effect of U50,488H was mediated by protein kinase C (PKC). In the RVH, the effect of U50,488H on the [Ca2+]i transient and the pHi were significantly attenuated. In parallel, 4-phorbol 12-myristate 13-acetate (PMA), an activator of PKC, also decreased the [Ca2+]i transient and increased the pHi. In the RVH, the effects of PMA were blunted. The recovery of pHi, which was blocked by ethylisopropyl-amiloride (EIPA), following an acid loading induced by washout of 10 mmol/L NH4)Cl exposing to the cells for 10 min was the same in the RVH and control myocytes. CONCLUSION: kappa-Opioid receptor signaling was impaired in the cardiac hypertrophy due to a defect in the coupling of PKC signaling with its effector.

Animals↗