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Biomedical subjects

K Wu

Publications and source records attributed to K Wu.

At least 19 recordsLinked to original sources
PubMed2006

Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellullar carcinoma.

Hepatitis B virus (HBV)-encoded X antigen (HBxAg) contributes to the development of hepatocellular carcinoma (HCC). A frequent characteristic of HCC is reduced or absent expression of the cell adhesion protein, E-cadherin, although it is not known whether HBxAg plays a role. To address this, the levels of E-cadherin were determined in HBxAg-positive and -negative HepG2 cells in culture, and in tumor and surrounding nontumor liver from a panel of HBV carriers. The results showed an inverse relationship between HBxAg and E-cadherin expression both in tissue culture and in vivo. In HBxAg-positive cells, E-cadherin was suppressed at both the mRNA and protein levels. This was associated with hypermethylation of the E-cadherin promoter. Depressed E-cadherin correlated with HBxAg trans-activation function, as did the migration of HepG2 cells in vitro. Decreased expression of E-cadherin was also associated with the accumulation of beta-catenin in the cytoplasm and/or nuclei in tissues and cell lines, which is characteristic of activated beta-catenin. Additional work showed that HBxAg-activated beta-catenin. Together, these results suggest that the HBxAg is associated with decreased expression of E-cadherin, accumulation of beta-catenin in the cytoplasm and nucleus, and increased cell migration, which may contribute importantly to hepatocarcinogenesis.

Cadherins↗
PubMed2005

Surface hydration and its effect on fluorinated SAM formation on SiO2 surfaces.

Substrate hydration is demonstrated to be crucial to film quality during self-assembled (SA) film deposition of tridecafluoro-1,1,2,2,-tetrahydrooctyltrichlorosilane (FOTS) from the vapor phase. The surface hydration was studied by thermogravimetric analysis, and a model was developed to predict the conditions necessary to desorb all of the water adsorbed on a fused silica surface without significantly altering the concentration of the surface hydroxyl groups. The nature of the SA film was investigated as a function of the degree of rehydration of the dehydrated silica surface. The wettability and microstructure of the SA films were examined by water contact angle, ellipsometry, X-ray photoelectron spectroscopy, and atomic force microscopy. There is an optimum degree of substrate hydration, on the order of 1-1.2 monolayers of adsorbed water, required to produce a dense, durable and uniform FOTS film with high water repellency and a smooth surface.

Journal Article↗
PubMed2005

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗
PubMed2005

Penetrating injury to the soft palate causing retropharyngeal air collection.

Pharyngeal injuries caused by trauma are common and have been reported previously in the medical literature. In some cases of a penetrating injury there is a collection of air in the retropharyngeal space that can be shown on lateral soft tissue radiography of the neck. If this condition is not diagnosed or adequately treated the patient may develop severe complications such as mediastinitis. A case is reported of a patient with penetrating injury caused by a curtain rail and the subsequent treatment is described.

Adult↗
PubMed2005

Basement membrane peptides: functional considerations and biomedical applications in autoimmunity.

Basement membranes are specialized extracellular matrices that surround certain cell types (muscle cells, adipose cells, etc) and are present under the basal surface of cells exhibiting polarity (epithelial, endothelial and mesothelial cells). They have a unique macromolecular composition, consisting mainly of type IV collagen isoforms, laminin isoforms, entactin/nidogen, and perlecan. These components self associate and interact with each other to form networks. Other macromolecules may be found in specialized basement membranes. In this short review, the role of selected basement membrane proteins in autoimmune diseases will be highlighted. As an example, Goodpasture's syndrome will be presented and the relatively long quest for identification of the antigenic epitope on specific domains of the alpha3(IV)NC1 will be summarized. Chagas disease will be discussed as an example of laminin-mediated autoimmunity, with emphasis on the role of sugar-based antigenic epitope(s) will be presented. Immune-mediated tubulointerstitial nephritis will be introduced and the role of a synthetic peptide in detecting proximal tubule damage in acute renal failure will be discussed. Auto-immune diseases where other basement membrane macromolecules are involved will be mentioned. Finally, the importance of understanding the functions served by domains at close proximity to the antigenic epitope(s) will be highlighted.

Autoantigens↗
PubMed2005

Inhibition of hepatitis B virus replication by recombinant small interfering RNAs.

RNA interference (RNAi) is a biological phenomenon in which introduction of a small, double-stranded interfering RNAs (siRNAs) into a cell causes a specific degradation of homologous single-stranded RNA. siRNA can be delivered into the cell by different approaches including synthetic RNA, in vitro transcribed RNA and RNA transcribed from polymerase III-based recombinant vectors. As hepatitis B (HB) represents a worldwide health problem, we attempted to develop a fast and easy approach to generation and screening of specific siRNA-targeted HB virus (HBV) genes. Using PCR amplification, specific siRNA expression cassettes (SECs) were developed and used to generate effective siRNAs against HB virus (HBV) replication and gene expression in mammalian cells. After screening, we identified two SECs that expressed siRNAs which efficiently decreased the level of HBV pre-c/c gene expression in transfected Bel-7402 cells by 81.9% and 87.3%, respectively. In addition, the level of HBV DNA was decreased by 83.5% and 85.2% in HepG2 2.2.15 cells, respectively. This study provides (i) a new effective application of RNA interference to study viral gene function and viral replication and (ii) a new tool for the prevention and treatment of human HBV infection.

DNA, Viral↗
PubMed2004

Identification and characterisation of a novel KCNQ1 mutation in a family with Romano-Ward syndrome.

Romano-Ward syndrome (RWS), the autosomal dominant form of the congenital long QT syndrome, is characterised by prolongation of the cardiac repolarisation process associated with ventricular tachyarrhythmias of the torsades de pointes type. Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be responsible for this disorder. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequence analysis have identified a KCNQ1 mutation in a family that were clinically conspicuous due to several syncopes and prolonged QTc intervals in the ECG. The mutant subunit was expressed and functionally characterised in the Xenopus oocyte expression system. A novel heterozygous missense mutation with a C to T transition at the first position of codon 343 (CCA) of the KCNQ1 gene was identified in three concerned family members (QTc intervals: 500, 510 and 530 ms, respectively). As a result, proline 343 localised within the highly conserved transmembrane segment S6 of the KCNQ1 channel is replaced by a serine. Co-expression of mutant (KCNQ1-P343S) and wild-type (KCNQ1) cRNA in Xenopus oocytes produced potassium currents reduced by approximately 92%, while IKs reconstitution experiments with a combination of KCNQ1 mutant, wild-type and KCNE1 subunits yielded currents reduced by approximately 60%. A novel mutation (P343S) identified in the KCNQ1 subunit gene of three members of a RWS family showed a dominant-negative effect on native IKs currents leading to prolongation of the heart repolarisation and possibly increases the risk of malign arrhythmias with sudden cardiac death.

Amino Acid Sequence↗
PubMed2004

Blocked nose and snoring in a 6-year-old boy.

Nasal obstruction, mouth-breathing, snoring and deafness are common symptoms seen in children presenting to the otorhinolaryngology clinic. The aetiopathologies are frequently due to adenotonsillar hypertrophy and otitis media with effusion. Rarely however, nasal obstruction and snoring may be associated with more sinister pathology. We report a case of a child with nasopharyngeal B-cell Non-Hodgkin's lymphoma whose initial symptoms were of nasal obstruction and snoring.

Burkitt Lymphoma↗
PubMed2004

Treatment of home oxygen induced rhinitis: an unusual use for a nasal obturator.

Patients requiring home oxygen can experience drying and crusting of nasal mucosa. On occasion it can be severe causing significant discomfort. In this report we present such a case. To prevent nasal airflow and hence reduce symptoms the patient was fitted with a nasal obturator. The use of the nasal obturator resulted in a rapid resolution of her symptoms. In this case the use of the nasal obturator was reversible and a simple solution for the treatment of a difficult condition.

Dimethylpolysiloxanes↗
PubMed2003

Increased dendritic excitability in hippocampal ca1 in vivo in the kainic acid model of temporal lobe epilepsy: a study using current source density analysis.

We used kainic acid in rats as an animal model of temporal lobe epilepsy, and studied the synaptic transmission in hippocampal subfield CA1 of urethane-anesthetized rats in vivo. Dendritic currents were revealed by field potential mapping, using a single micropipette or a 16-channel silicon probe, followed by current source density analysis. We found that the population excitatory postsynaptic potentials in the basal dendrites and distal apical dendrites of CA1 were increased in kainate-treated as compared with control rats following paired-pulse, but not single-pulse, stimulation of CA3b or medial perforant path. In contrast, the trisynaptic midapical dendritic response in CA1 following medial perforant path stimulation was decreased in kainate-treated as compared with control rats. Increased coupling between excitatory postsynaptic potential and the population spike in CA1 was found after kainate seizures. Short-latency, presumably monosynaptic CA1 population spikes following medial perforant path stimulation was found in kainate-treated but not control rats. An enhancement of dendritic excitability was evidenced by population spikes that invaded into or originated from the distal apical dendrites of CA1 in kainate-treated but not control rats. Reverberation of hippocampo-entorhinal activity was evidenced by recurrent excitation of CA1 following CA3b stimulation in kainate-treated but not control rats. Blockade of inhibition by intraventricularly administered bicuculline induced excitatory potentials in CA1 that were stronger and more prolonged in kainate-treated than control rats. The bicuculline-induced excitation was mainly blocked by non-N-methyl-D-aspartate receptor antagonists. We conclude that kainate seizures induced disinhibition in CA1 that unveiled excitation at the basal and distal apical dendrites, resulting in enhancement of the direct entorhinal cortex to CA1 input and reverberations via the hippocampo-entorhinal loop. These changes in the output of the hippocampus from CA1 are likely detrimental to the behavioral functions of the hippocampus and they may contribute to increased seizure susceptibility after kainate seizures.

Action Potentials↗
PubMed2002

In situ spatial patterns of soil bacterial populations, mapped at multiple scales, in an arable soil.

Very little is known about the spatial organization of soil microbes across scales that are relevant both to microbial function and to field-based processes. The spatial distributions of microbes and microbially mediated activity have a high intrinsic variability. This can present problems when trying to quantify the effects of disturbance, management practices, or climate change on soil microbial systems and attendant function. A spatial sampling regime was implemented in an arable field. Cores of undisturbed soil were sampled from a 3 x 3 x 0.9 m volume of soil (topsoil and subsoil) and a biological thin section, in which the in situ distribution of bacteria could be quantified, prepared from each core. Geostatistical analysis was used to quantify the nature of spatial structure from micrometers to meters and spatial point pattern analysis to test for deviations from complete spatial randomness of mapped bacteria. Spatial structure in the topsoil was only found at the microscale (micrometers), whereas evidence for nested scales of spatial structure was found in the subsoil (at the microscale, and at the centimeter to meter scale). Geostatistical ranges of spatial structure at the micro scale were greater in the topsoil and tended to decrease with depth in the subsoil. Evidence for spatial aggregation in bacteria was stronger in the topsoil and also decreased with depth in the subsoil, though extremely high degrees of aggregation were found at very short distances in the deep subsoil. The data suggest that factors that regulate the distribution of bacteria in the subsoil operate at two scales, in contrast to one scale in the topsoil, and that bacterial patches are larger and more prevalent in the topsoil.

Agriculture↗
PubMed2002

Introgression of a quantitative trait locus for yield from Glycine soja into commercial soybean cultivars.

The value of exotic germplasm in broadening the genetic base of most crops has been demonstrated many times. However, the difficulties involved in working with exotic germplasm have limited their utility in plant breeding. Unwanted linkages often thwart the successful incorporation of beneficial exotic genes into commercial lines. Thus, the use of exotics in traditional breeding makes the process of crop improvement a tedious, time-consuming and expensive endeavor. The availability of molecular markers makes it possible to isolate specific genomic regions and transfer them into commercial varieties with minimal linkage drag. We found a yield-enhancing quantitative trait locus (QTL) from Glycine soja (Siebold and Zucc.) by evaluating a population of 265 BC(2) individuals from a cross between HS-1 and PI 407305. The yield QTL was located on linkage group B2(U26) of the soybean [Glycine max (L.) Merrill] genetic linkage map. In a 2-year, multi-location study, individuals carrying the PI 407305 haplotype at the QTL locus demonstrated a 9.4% yield advantage over individuals that did not contain the exotic haplotype. When tested in a more uniform "HS-1-like" background in two locations, we observed an 8% yield advantage for lines that carry the PI 407305 haplotype. We further assessed the QTL effect in various elite soybean genetic backgrounds. The yield effect was consistently observed in only two of six genetic backgrounds. Individuals carrying the PI 407305 haplotype at the QTL locus had a 9% yield advantage in yield trials across locations. Despite the limited adaptability of this yield-QTL across genetic backgrounds, this study demonstrates the potential of exotic germplasm for yield enhancement in soybean.

Alleles↗
PubMed2002

Multidrug-resistance-associated protein MGr1-Ag is identical to the human 37-kDa laminin receptor precursor.

We report the isolation and functional characterization of the gene encoding MGr1-Ag, a multidrug-resistance-associated protein. A lambdagt11 cDNA library derived from colorectal carcinoma SW480 cells was screened with monoclonal antibody MGr1. DNA homology analysis of 22 positive clones (designated R1-R22) suggested human 37-kDa laminin receptor precursor (37LRP, R7/R9/R15/R16/R19/R20) and a novel gene (R22) as candidate genes encoding MGr1-Ag. Western blot analysis showed that anti-R20 serum reacted with a unique protein band that was consistent with MGr1-Ag, while anti-R22 serum could not react with MGr1-Ag. The coding gene for MGr1-Ag was amplified using reverse transcription-PCR. Sequence analysis revealed that the MGr1-Ag and 37LRP genes shared the same coding sequence. An in vitro drug sensitivity assay indicated that down-regulation of 37LRP by an antisense technique could significantly enhance the cytotoxicity of anticancer drugs to gastric cancer cells. Thus we draw the conclusion that MGr1-Ag is identical to 37LRP.

Carcinoma↗
PubMed2002

The immunogenetics and pathogenesis of gastric cancer. Highlights of the First Sino-European Workshop on the Immunogenetics and Pathogenesis of Gastric Cancer.

Clinical scientists from eight European countries and China gathered in the ancient Chinese capital of Xi'an on April 26-28, 2001 to discuss collaboration on a modern approach to gastric cancer prevention. Participants at the First Sino-European Workshop on Immunogenetics and Pathogenesis of Gastric Cancer presented their most up-to-date research results on topics ranging from epidemiology and immune mechanisms to Helicobacter pylori and vaccine development. Researchers then formed groups with their Chinese or European counterparts to plan future research endeavors which will benefit Chinese and European populations alike. After 3 years of organization between the Institute of Digestive Diseases of the Fourth Medical University in Xi'an, China and the Laboratory of Immunogenetics, VU University Medical Center in Amsterdam, the first workshop came into being under the joint sponsorship of the Commission of the European Union, National Natural Science Foundation of China and the Institute of Digestive Diseases, Xi'an, China. As gastric cancer is the most prevalent malignant tumor in China, the workshop was of special significance to the Chinese researchers and to the Chinese population in general. During the workshop, presentations on the epidemiology of gastric cancer showed that this disease is in fact common the world over: it is the second most common cancer next to lung cancer and about 1 million new cases were diagnosed in 2000. Three-quarters of the cases of gastric cancer occur in Asia, and approximately 80% of these cases are in China and Japan. Genetic factors and environmental factors such as diet and H. pylori infection play a role in gastric carcinogenesis. As a recognized cause of gastric cancer, H. pylori was the subject of various presentations ranging from immunological studies, molecular analysis of strains and pathogenesis to vaccine development. Specific areas of discussion included bacterial-epithelial interactions in H. pylori infection, epidemiology in China, global distribution of vacA and cagA genotypes, new evidence for host factors, nonsteroidal antiinflammatory drugs and H. pylori as independent risk factor for gastric cancer, new diagnostic techniques for H. pylori using serum levels of pepsinogen I, and autoimmune processes in corpus atrophy. Vaccine development using a variety of strategies against H. pylori was the subject of an entire session of talks. Oral immunization with urease with Escherichia coli heat labile enterotoxin was shown to be safe and immunogenic in humans as a mucosal adjuvant. Results of a study using attenuated Salmonella typhimurium as a vehicle for DNA-mediated immunization in mice were also presented. A final presentation discussed an ongoing trial comparing strain variability in the vacA and cagA gene sequences and disease expression between H. pylori infection in Europe and China. Researchers also discussed the role of IL1 gene family and TNF gene polymorphisms in gastric pathology and various immune mechanisms involved in gastric cancer, such as down-regulation of NF kappa B, IL-1 and IL-1RA, cyclooxygenase signalling, and identification of MGAg antibodies. An interactive discussion followed each presentation and ideas and suggestions were provided. According to specialty, the presenters were then assigned to groups of four or five to make plans for joint research projects. A number of international and Chinese observers were present, including representatives from the European Commission, the World Health Organization and the Chinese National Center for Biotechnology Development, and offered input on the financial feasibility of such projects.

China↗
PubMed2001

Tumor therapy with targeted atomic nanogenerators.

A single, high linear energy transfer alpha particle can kill a target cell. We have developed methods to target molecular-sized generators of alpha-emitting isotope cascades to the inside of cancer cells using actinium-225 coupled to internalizing monoclonal antibodies. In vitro, these constructs specifically killed leukemia, lymphoma, breast, ovarian, neuroblastoma, and prostate cancer cells at becquerel (picocurie) levels. Injection of single doses of the constructs at kilobecquerel (nanocurie) levels into mice bearing solid prostate carcinoma or disseminated human lymphoma induced tumor regression and prolonged survival, without toxicity, in a substantial fraction of animals. Nanogenerators targeting a wide variety of cancers may be possible.

Actinium↗
PubMed2001

1H and (17)O NMR detection of a lanthanide-bound water molecule at ambient temperatures in pure water as solvent.

Lanthanide complexes of a tetra-amide derivative of DOTA (structure 4 in text) with four extended carboxymethyl esters have been characterized by X-ray crystallography and multinuclear NMR spectroscopy. [Eu(4)(H(2)O)](triflate)(3) crystallized from water in the monoclinic, P(21/)(c) space group (a = 10.366 A, b = 22.504 A, c = 23.975 A, and beta = 97.05 degrees ). The Eu(3+) cation is bound to four macrocyclic nitrogen atoms (mean Eu-N = 2.627 A) and four amide oxygen atoms (mean Eu-O(amide) = 2.335 A) in a square antiprismatic geometry with a twist angle of 38.5 degrees between the N4 and O4 planes. A single bound water molecule (Eu-O(W) = 2.414 A) occupies a typical monocapped position on the O4 surface. In pure water, resonances corresponding to a single Eu(3+)-bound water molecule were observed in the (1)H (53 ppm) and (17)O (-897 ppm) NMR spectra of [Eu(4)(H(2)O)](triflate)(3) at 25 degrees C. A fit of the temperature-dependent Eu(3+)-bound (1)H and (17)O water resonance line widths in acetonitrile-d(3) (containing 4% v/v (17)O enriched water) gave identical lifetimes (tau(m)(298)) of 789 +/- 50 micros (in water as solvent; a line shape analysis of the Eu(3+)-bound water resonance gave a tau(m)(298) = 382 +/- 5 micros). Slow water exchange was also evidenced by the water proton relaxivity of Gd(4) (R(1) = 2.2 mM(-1) s(-1), a value characteristic of pure outer-sphere relaxation at 25 degrees C). With increasing temperature, the inner-sphere contribution gradually increased due to accelerated chemical exchange between bound water and bulk water protons. A fitting of the relaxation data (T(1)) to standard SBM theory gave a water proton lifetime (tau(m)(298)) of 159 micros, somewhat shorter than the value determined by high-resolution (1)H and (17)O NMR of Eu(4). Exchange of the bound water protons in Gd(4) with bulk water protons was catalyzed by addition of exogenous phosphate at 25 degrees C (R(1) increased to 10.0 mM(-1) s(-1) in the presence of 1500-fold excess HPO(4)(2-)).

Magnetic Resonance Spectroscopy↗