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Biomedical subjects

J Wu

Publications and source records attributed to J Wu.

At least 91 records · Page 5Linked to original sources
PubMed2003

Diluted II-VI oxide semiconductors with multiple band gaps.

We report the realization of a new mult-band-gap semiconductor. Zn(1-y)Mn(y)OxTe1-x alloys have been synthesized using the combination of oxygen ion implantation and pulsed laser melting. Incorporation of small quantities of isovalent oxygen leads to the formation of a narrow, oxygen-derived band of extended states located within the band gap of the Zn(1-y)Mn(y)Te host. When only 1.3% of Te atoms are replaced with oxygen in a Zn0.88Mn0.12Te crystal the resulting band structure consists of two direct band gaps with interband transitions at approximately 1.77 and 2.7 eV. This remarkable modification of the band structure is well described by the band anticrossing model. With multiple band gaps that fall within the solar energy spectrum, Zn(1-y)Mn(y)OxTe1-x is a material perfectly satisfying the conditions for single-junction photovoltaics with the potential for power conversion efficiencies surpassing 50%.

Journal Article↗
PubMed2003

Differential expression of Kir6.1 and SUR2B mRNAs in the vasculature of various tissues in rats.

ATP-sensitive K(+) channels (K(ATP)) couple the intermediary metabolism to cellular excitability and play an important role in the cardio-protective effect of ischemic preconditioning and the activity-dependent autoregulation of cerebral circulation. Although previous studies using PCR and Northern blot suggest that the vascular isoform may consist of Kir6.1 and SUR2B, their expression and precise distribution in various vasculatures remain unknown. To illustrate their vascular expression, we performed this study using in situ hybridization histochemistry. Antisense riboprobes were synthesized by in vitro transcription and labeled with digoxigenin. Distributions of these mRNAs in the various blood vessels were revealed under a bright-field microscope. The expression of Kir6.1 and SUR2B mRNAs was observed in small and intermediate arteries as well as arterioles in several tissues, including basilar, vertebral, mesenteric, coronary and renal arteries. The transcripts were found in arterial smooth muscles. Also, we observed Kir6.1/SUR2B expression in capillary beds. The Kir6.1 and SUR2B expression pattern showed clear overlap, suggesting that they may form heteromeric K(ATP) channels in these tissues. The Kir6.1 and SUR2B stains were detected in aorta and renal tubular cells although their expression level was extremely low. In contrast, the Kir6.1 and SUR2B mRNAs were not seen in vena cava, other small veins, myocardium and skeletal muscles. With their strong expression in small arteries and capillaries, it is very likely that the Kir6.1 and SUR2B form the vascular isoform of K(ATP) channels in these vasculatures.

ATP-Binding Cassette Transporters↗
PubMed2003

Magnetic phase separation in La1-xSrxCoO3 by 59Co nuclear magnetic resonance.

59Co NMR measurements on La1-xSrxCoO3 reported here establish unequivocally, for the first time, the coexistence of ferromagnetic regions, spin-glass regions, and hole-poor low spin regions at all x values from 0.1 to 0.5. A zero external field NMR spectrum, which is assigned to the ferromagnetic regions, has a spectral shape that is nearly x independent at 1.9 K, as are the relaxation times, T1 and T2. The integrated spectral area increases rapidly with x up to x = 0.2 and then decreases slightly for larger x. In a field of 9.97 T, a narrow NMR line is observed at 102 MHz, identical to that found in x = 0 samples in previous work. The integrated intensity of this spectrum decreases rapidly with increasing x, and is ascribed to hole-poor low spin regions. Beneath this spectrum, a third broad line, with a peak at 100 MHz, is assigned to a spin- or cluster-glass-like phase.

Journal Article↗
PubMed2003

Monte Carlo simulations on marker grouping and ordering.

Four global algorithms, maximum likelihood (ML), sum of adjacent LOD score (SALOD), sum of adjacent recombinant fractions (SARF) and product of adjacent recombinant fraction (PARF), and one approximation algorithm, seriation (SER), were used to compare the marker ordering efficiencies for correctly given linkage groups based on doubled haploid (DH) populations. The Monte Carlo simulation results indicated the marker ordering powers for the five methods were almost identical. High correlation coefficients were greater than 0.99 between grouping power and ordering power, indicating that all these methods for marker ordering were reliable. Therefore, the main problem for linkage analysis was how to improve the grouping power. Since the SER approach provided the advantage of speed without losing ordering power, this approach was used for detailed simulations. For more generality, multiple linkage groups were employed, and population size, linkage cutoff criterion, marker spacing pattern (even or uneven), and marker spacing distance (close or loose) were considered for obtaining acceptable grouping powers. Simulation results indicated that the grouping power was related to population size, marker spacing distance, and cutoff criterion. Generally, a large population size provided higher grouping power than small population size, and closely linked markers provided higher grouping power than loosely linked markers. The cutoff criterion range for achieving acceptable grouping power and ordering power differed for varying cases; however, combining all situations in this study, a cutoff criterion ranging from 50 cM to 60 cM was recommended for achieving acceptable grouping power and ordering power for different cases.

Algorithms↗
PubMed2003

A threonine residue (Thr71) at the intracellular end of the M1 helix plays a critical role in the gating of Kir6.2 channels by intracellular ATP and protons.

ATP-sensitive K+ (K(ATP)) channels are known to be gated by several intracellular molecules, but the gating mechanisms remain unclear. To understand the relationship of channel gating to ligand binding, we studied Kir6.2 channel gating by ATP and protons, which inhibit and activate the channel, respectively. We have previously shown that a threonine residue (Thr71) is critical for the pH sensitivity of Kir6.2 channel. If this site is involved in channel gating rather than ligand binding, it should affect channel gating by both ATP and proton. To test this hypothesis we performed a mutation analysis. Site-specific mutations of Thr71 to a bulky residue reduced the ATP sensitivity by >100-fold and eliminated the pH sensitivity. Single-channel activity of these mutants was stabilized at the open state with no detectable rundown. Mutations to a small amino acid had little effect on the ATP and pH sensitivities. Mutations to intermediate amino acids reduced but did not abolish the ATP and pH sensitivities. Hydrophobicity is not critical, as both polar and nonpolar amino acids are found in each group. Mutation to a positively charged lysine markedly exacerbated the pH- but not ATP-sensitivity, whereas mutation to glutamate moderately reduced ATP and pH sensitivities. These results indicate that the residue mass is critical for Kir6.2 channel gating, a mass that should be below 120 daltons with no charge. The existence of such a site as Thr71 involved in channel gating by both ATP and proton suggests that channel gating in the K(ATP) channel likely is separate from ligand binding.

Adenosine Triphosphate↗
PubMed2003

Enhancement of taxol production and release in Taxus chinensis cell cultures by ultrasound, methyl jasmonate and in situ solvent extraction.

This study evaluates the use of a novel mechanical stimulus, ultrasound (US), and a putative chemical elicitor, methyl jasmonate (MJ), combined with in situ solvent extraction (two-phase culture), to enhance taxol production by Taxus chinensis cells in suspension culture. The volumetric taxol yield was increased 1.5- to 1.8-fold with 2 min US treatment once or twice during a 4-week culture period, about 5-fold with 60-120 microM MJ, and 7- to 9-fold by in situ solvent extraction of taxol with dibutyl phthalate (DBP) (11% v/v). The percent of extracellular taxol or taxol release was also significantly increased. The combined use of US (day 5 or 9) and MJ treatment (day 7) resulted in taxol yields 20-50% higher than each of the treatments used alone. The most favorable strategy for taxol production was the application of US or MJ treatment, followed by in situ solvent extraction, giving rise to a taxol yield of 33-35 mg/l, about 17-fold higher than the control, at 1.9 mg/l. It was found that the organic solvent DBP, as well as US and MJ, stimulated the enzyme activity of secondary metabolic pathways, which was partially responsible for the enhanced taxol production.

Acetates↗
PubMed2003

Effect of simulated microgravity on aged pea seed vigour and related physiological properties.

We used simulated microgravity to treat aged pea seeds, in order to observe its effect on seed vigour and related physiological properties. The result shows that microgravity obviously promotes the germination rate, vitality index, germination index, and keeps the activity of protective enzyme, with conductivity and the content of MDA decreased. These effects gradually disappeared for a certain period after the microgravity administration.

Fabaceae↗
PubMed2003

Mutational analysis of roles for extracellular cysteine residues in the assembly and function of human alpha 7-nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptors (nAChR) containing alpha7 subunits self-assemble into simple, homopentameric complexes. However, successful heterologous expression of functional alpha7-nAChR has only been achieved in a few host cell types, such as the SH-EP1 human epithelial cell line. All ionotropic glycine receptor, GABA(A) receptor, 5-HT(3) receptor, and nAChR subunits contain a pair of highly conserved cysteine residues (C150 and C164 for alpha7 subunits) in their N-terminal extracellular domain. These residues are thought to be involved in the formation of a conserved cystine loop that is critical to the proper folding and assembly of subunits. However, nAChR alpha7 (and alpha8) subunits also contain a third cysteine residue, C138, N-terminal to the conserved cysteine pair. Using SH-EP1 cells as a host for heterologous expression, we evaluated the roles of C138, C150, and C164 in subunit folding, assembly, and cell surface expression and function of alpha7-nAChR. Results indicate that mutation of C138, but not of C150 or C164, yields an nAChR that can assemble to form (125)I-labeled alpha-bungarotoxin binding sites expressed on the cell surface. Further, whole-cell patch clamp recordings demonstrate that mutation of C138 to alanine does not alter the function of the fully assembled alpha7-nAChR. These results indicate that C150 and C164 are required for surface expression, but that C138 is neither necessary for nor inhibitory toward the surface expression and function of human alpha7-nAChR. These results suggest that disulfide bond formation between C138 and either C150 or C164, if it occurs, has no significant effect on alpha7-nAChR assembly or function.

Alanine↗
PubMed2003

Thrombin exacerbates brain edema in focal cerebral ischemia.

Thrombin contributes to edema formation after intracerebral hemorrhage. Recent studies suggest that thrombin may also play a role in ischemic brain damage. In the present study, adult male Sprague-Dawley rats were anesthetized with pentobarbital. Middle cerebral artery (MCA) was occluded using the suture method. We found that brain thrombin activity was elevated after permanent MCA occlusion as was prothrombin messenger RNA expression. Intracerebral injection of a thrombin inhibitor, hirudin, reduced neurological deficits following cerebral ischemia. In contrast, intracerebral administration of exogenous thrombin (at a dose that is non-toxic to normal brain), markedly exacerbated brain edema after transient focal cerebral ischemia. These results indicate that extravascular thrombin inhibition may be a new therapeutic target for cerebral ischemia.

Animals↗
PubMed2003

Thrombin preconditioning upregulates transferrin and transferrin receptor and reduces brain edema induced by lysed red blood cells.

Pretreatment with a low dose of thrombin reduces brain edema after both hemorrhagic and ischemic stroke. We call this phenomenon thrombin preconditioning (TPC) or thrombin-induced brain tolerance. The present study examines whether TPC can attenuate the brain edema induced by lysed red blood cells (RBCs) to determine whether thrombin production early in an intracerebral hemorrhage (ICH) might alter potentially injurious events associated with clot resolution. It also examines whether TPC might be protective by altering iron handling within the brain, particularly through modulating transferrin (Tf) and transferrin receptor (TfR) levels. Brain edema was measured by wet/dry weight. Western blot analysis and immunohistochemistry were used for Tf and TfR measurements. We found that TPC reduces lysed RBC-induced brain edema and upregulates both Tf and TfR levels in the brain. Thrombin formation after an ICH may be part of a signaling cascade that acts to limit potentially injurious events associated with clot resolution through altering iron-handling proteins.

Animals↗
PubMed2003

Toxicity of chlorpyrifos adsorbed on humic colloids to larval walleye (Stizostedion vitreum).

After application, organophosphorus insecticides (OPs) are often strongly adsorbed to soil constituents. Because of their relatively low water solubility, OPs may be transferred from field to stream adsorbed on suspended solids. However, we are not aware of research done to evaluate the bioavailability (i.e., toxicity) of OPs transported on suspended solids to fish. We conducted 48-h static toxicity tests to determine the toxicity of chlorpyrifos in aqueous solution and adsorbed on calcium-saturated humic acid (HA) to three larval stages of walleye (Stizostedion vitreum). Three concentrations of chlorpyrifos adsorbed on HA, a HA control, and a chlorpyrifos-only treatment were tested. Fish that survived the 48-h static toxicity tests were analyzed to determine total cholinesterase (ChE) activity. In general, survival of all larval stages of walleye exposed to chlorpyrifos-HA complexes was less than that of walleye exposed to HA controls and the chlorpyrifos-only treatment, which were not toxic to walleye. Cholinesterase inhibition of larval walleye exposed to chlorpyrifos-HA complexes was similar to the ChE inhibition observed in larval walleye exposed to chlorpyrifos in the aqueous phase. These laboratory experiments indicate potential toxicity of chlorpyrifos-soil complexes to larval fish.

Animals↗
PubMed2003

Complete nucleotide sequence and genome organization of a Chinese isolate of tobacco bushy top virus.

The complete nucleotide sequence of a Chinese isolate of tobacco bushy top virus (TBTV), designated TBTV-Ch, was determined from cDNA generated from double-stranded RNA extracted from diseased tobacco. The genome is 4152 nucleotides (nt) in size, contains four putative open reading frames (ORFs) and untranslated regions of 10 nt and 645 nt at the 5' and 3' ends, respectively. In genome organization and in the amino acid sequence of its potential products, the RNA of TBTV-Ch is similar to other umbraviruses sequenced to date. The results suggested that TBTV should be regarded as a definitive species of the genus Umbravirus.

Base Sequence↗
PubMed2003

A consensus development approach to define national research priorities in bone metastases: proceedings from NCIC CTG workshop.

AIMS: A 1-day workshop was conducted to gather interested Canadian radiation oncologists to identify priority research questions that could be answered through clinical trials under the auspices of the National Cancer Institute of Canada--Clinical Trials Group (NCIC-CTG) Symptom Control committee. MATERIALS AND METHODS: In preparation for the workshop, a survey of Canadian radiation oncologists resulted in four research areas in symptom control, including radiation-induced mucosal reactions, fatigue, radiotherapy for brain metastases and radiotherapy for bone metastases. The first half of the workshop consisted of plenary sessions where the research setting and perspective was defined for each area. This was followed by deliberations by a subgroup of researchers with special interest in the topic area. The bone-metastases subgroup deliberated the clinical context, the scientific merits and the required methodology of research questions related to the role of radiotherapy in early treatment of bone metastases, the role of re-irradiation, the role of systemic radiotherapy and patient selection for different fractionation schedules. A list of prioritised clinical studies was proposed. RESULTS: The question of single vs multi-fraction re-irradiation for symptomatic bone metastases was identified as most pertinent to the Canadian radiation oncologists present. A multi-centre, international intergroup study is undergoing protocol development. Other study concepts, such as an alternative dose-schedule of 17 Gy/2 fractions/1 week for intermediate-prognosis patients, and early referral for radiation oncologist assessment of early or mildly symptomatic bone metastases for good-prognosis patients, require further methodological development before a clinical trial can be proposed. CONCLUSION: An NCIC-CTG workshop provided an update on current evidence-based knowledge in palliative radiotherapy for bone metastases. New trial concepts were discussed among practitioners and clinical investigators to promote dialogue and collaboration. The proposal of an international intergroup randomised trial of single vs multiple fraction re-irradiation for painful bone metastases received the most support among participants.

Bone Neoplasms↗
PubMed2003

Increased phosphorylation of the GluR1 subunit of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor in rats following intradermal injection of capsaicin.

Ionotropic glutamate receptors are ligand-gated ion channels that help mediate rapid excitatory neurotransmission in the CNS. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are critical for synaptic plasticity in central nociceptive transmission. The current study was designed to investigate the role of the AMPA receptor subunit, GluR1, and its phosphorylated forms (at Ser-831 and Ser-845) in central sensitization in rat spinal cord. Western blots and immunohistochemistry were performed to examine the expression and localization of GluR1 and the phosphorylated forms of GluR1 (phospho-GluR1) at Ser-831 and Ser-845 with specific antibodies. Results showed that immunolabeling of GluR1 protein in rat spinal cord can be detected at 110 kD, and two phospho-GluR1 proteins were found at 106 kD. A significant upregulation of phospho-GluR1 both at Ser-831 and Ser-845 was found by 5 min after capsaicin treatment, and this increase lasted at least 60 min. Immunostaining showed that GluR1 and its phosphorylated forms were localized in the superficial laminae of dorsal horn and quantitative image analysis supported the immunoblotting results. Our findings are consistent with the suggestions that AMPA receptors show increased responsiveness because of their phosphorylation and that this may contribute to central sensitization following intradermal injection of capsaicin.

Animals↗
PubMed2003

Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone.

Prostate adenocarcinoma is associated with the formation of osteoblastic metastases in bone. It is hypothesized that osteoclastogenesis is a critical component in the development of skeletal metastases. These findings, however, were generally noted in predominantly osteolytic lesions. The pathophysiology of osteoblastic lesions remains unknown but the type of bone lesion formed may be influenced by the cytokines produced by prostate tumors. To test this theory, we implanted PC-3 and LAPC-9 cells into the tibias of SCID mice. These mice were sacrificed at 1, 2, 4, 6, and 8 weeks after implantation and histologic analysis was performed on these tibias. PCR analysis was also performed on bulk tumors. The results showed that the PC-3 implanted tibias developed pure osteolytic lesions while the LAPC-9 implanted tibias developed pure osteoblastic lesions on radiographs. Analysis of tibias after injection with PC-3 cells revealed progressive osteolytic lesions with abundant osteoclast activity at 2 weeks and destruction of the proximal tibia at 6 weeks after cell implantation. In contrast, the LAPC-9 cells formed osteoblastic lesions six weeks after cell injection. There were rare osteoclasts prior to the establishment of the osteoblastic lesions but greater osteoclast activity was noted with remodeling of the osteoblastic lesion 8 weeks after implantation of the tumor cells. PCR analysis revealed that PC-3 cells produced RANKL, IL-1, and TNF-alpha, which are associated with osteoclastogenesis. In contrast, LAPC-9 cells produced osteoprotegerin, which blocks osteoclast production and no detectable levels of RANKL or IL-1 and only minimal amounts of TNF-alpha were noted. These cells secreted BMP-2, -4, -6, and IL-6, which are associated with bone formation. These results suggest that the role of the osteoclast in the development of a metastatic lesion is variable depending on the phenotype of the prostate cancer cells, and that tumor-induced osteolysis may not be required for osteoblastic metastases.

Animals↗
PubMed2003

[Volume-effect in radiation therapy part one: volume-effect and tumour].

Volume is an important parameter of radiation therapy. Local control is inversely related to tumor size and the complication rate increases with the importance of the irradiated volume. Although the effect of irradiated volume has been widely reported since the beginning of radiotherapy, it has been less studied than other radiation parameters such as dose, fractionation, or treatment duration. One of the first organ system in which the adverse effect of increased volume was well defined is the skin. Over the last twenty years, numerous mathematical models have been developed for different organs. In this report we will discuss the relation between irradiated volume and tumor control. In a second article we will study the impact of irradiated volume on radiation adverse effects.

Humans↗
PubMed2003

Poly(cationic lipid)-mediated in vivo gene delivery to mouse liver.

We have previously demonstrated that liposomes generated from poly(cationic lipid) (PCL) and cholesterol (Chol) have low cytotoxicity, are serum resistant, and display a transfection efficiency in vitro similar to commercially available cationic liposomes. Our in vivo experiments demonstrated that PCL-Chol liposomes bound much less avidly to serum proteins than did liposomes composed of 1,2-bis(dioleoyloxy)-3-(trimethylamonio)propane (DOTAP)-Chol or DOTAP-L-alpha dioleoyl phosphatidylethanolamine (DOPE). Injection of the lipoplexes (PCL-Chol+DNA) through the portal vein after partial hepatectomy (PH) led to much higher reporter gene expression (luciferase) in the liver than did naked DNA injection. Marked green fluorescent protein expression was visualized in almost all hepatocytes in the liver of mice receiving lipoplex injection, even in the absence of PH. Subcutaneous injection of thyroid hormone triiodothyromine (T(3)) significantly promoted hepatocyte regeneration and markedly enhanced PCL-Chol-mediated gene transfer in mouse liver when the lipoplex was administrated through either portal or tail vein. With T(3) pretreatment, PCL-Chol exerted a better gene transfer efficacy in mouse liver than DOTAP-Chol or DOTAP-DOPE. Two injections of lipoplexes through an indwelling catheter in the portal vein extended the transgene expression at a high level when T(3) injection was repeated. In conclusion, our findings demonstrate that the polymerized cationic liposomes are very stable in the blood and are effective agents for in vivo gene delivery, and that thyroid hormone administration offers a non-invasive approach to enhance liposome-mediated liver gene delivery.

Animals↗