Biomedical subjects

Q Chen

Publications and source records attributed to Q Chen.

At least 73 records · Page 4Linked to original sources

PubMed2003

Construction of two BAC libraries from the wild Mexican diploid potato, Solanum pinnatisectum, and the identification of clones near the late blight and Colorado potato beetle resistance loci.

To facilitate isolation and characterization of disease and insect resistance genes important to potato, two bacterial artificial chromosome (BAC) libraries were constructed from genomic DNA of the Mexican wild diploid species, Solanum pinnatisectum, which carries high levels of resistance to the most important potato pathogen and pest, the late blight and the Colorado potato beetle (CPB). One of the libraries was constructed from the DNA, partially digested with BamHI, and it consists of 40328 clones with an average insert size of 125 kb. The other library was constructed from the DNA partially digested with EcoRI, and it consists of 17280 clones with an average insert size of 135 kb. The two libraries, together, represent approximately six equivalents of the wild potato haploid genome. Both libraries were evaluated for contamination with organellar DNA sequences and were shown to have a very low percentage (0.65-0.91%) of clones derived from the chloroplast genome. High-density filters, prepared from the two libraries, were screened with ten restriction fragment length polymorphism (RFLP) markers linked to the resistance genes for late blight, CPB, Verticillium wilt and potato cyst nematodes, and the gene Sr1 for the self-incompatibility S-locus. Thirty nine positive clones were identified and at least two positive BAC clones were detected for each RFLP marker. Four markers that are linked to the late blight resistance gene Rpi1 hybridized to 14 BAC clones. Fifteen BAC clones were shown to harbor the PPO (polyphenol oxidase) locus for the CPB resistance by three RFLP probes. Two RFLP markers detected five BAC clones that were linked to the Sr1 gene for self-incompatibility. These results agree with the library's predicted extent of coverage of the potato genome, and indicated that the libraries are useful resources for the molecular isolation of disease and insect resistance genes, as well as other economically important genes in the wild potato species. The development of the two potato BAC libraries provides a starting point, and landmarks for BAC contig construction and chromosome walking towards the map-based cloning of agronomically important target genes in the species.

Animals↗

PubMed2003

Unambiguous identification of JC polyomavirus strains transmitted from parents to children.

JC polyomavirus (JCV), the etiological agent of progressive multifocal leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically, then persisting in renal tissue. It has been proposed that JCV is transmitted mainly from parents to children through long-term cohabitation. The objective of this study was to further elucidate the mode of JCV transmission. In 5 families, we selected parent/child pairs between whom JCV was probably transmitted (judged on the basis of the identity of a 610-bp JCV DNA sequence between the parent and child). We established 5 to 9 complete JCV DNA clones from the urine of each parent or child. The complete sequences of these clones were determined and compared in each family. Nucleotide substitutions were detected in 4 parents and 1 child, and sequence rearrangements (deletions or duplications) were found in 2 parents and 2 children. Phylogenetic comparison of the detected sequences indicated that the diversity of JCV DNA sequences was generated in each family (i.e. not caused by multiple infection). We found that in 4 of the 5 families, a sequence detected in the parent was completely identical to one in the child. These findings provided further support for the proposed mode of JCV transmission, i.e. parent-to-child transmission during cohabitation.

Adult↗

PubMed2003

Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza virus vaccine candidate.

H9N2 subtype influenza A viruses have been identified in avian species worldwide and were isolated from humans in 1999, raising concerns about their pandemic potential and prompting the development of candidate vaccines to protect humans against this subtype of influenza A virus. Reassortant H1N1 and H3N2 human influenza A viruses with the internal genes of the influenza A/Ann Arbor/6/60 (H2N2) (AA) cold-adapted (ca) virus have proven to be attenuated and safe as live virus vaccines in humans. Using classical genetic reassortment, we generated a reassortant virus (G9/AA ca) that contains the hemagglutinin and neuraminidase genes from influenza A/chicken/Hong Kong/G9/97 (H9N2) (G9) and six internal gene segments from the AA ca virus. When administered intranasally, the reassortant virus was immunogenic and protected mice from subsequent challenge with wild-type H9N2 viruses, although it was restricted in replication in the respiratory tract of mice. The G9/AA ca virus bears properties that are desirable in a vaccine for humans and is available for clinical evaluation and use, should the need arise.

Adaptation, Physiological↗

PubMed2003

Congenital lack of COX-2 affects mechanical and geometric properties of bone in mice.

We compared the mechanical properties of bones from mice lacking either a functional cycloxygenase-1 (C57BL6/DBA COX-1-/-; n = 9) or COX-2 (C57BL6/DBA COX-2-/-; n = 9) gene and wild type mice (C57BL6/DBA; n = 10). Twenty-eight right femora from 3-month-old male mice were used to determine bulk structural and material properties of bone by three-point bending. Bone matrix properties were also measured by nanoindentation to access the changes in bulk mechanical properties due to changes in bone matrix or bone geometry. The bulk material properties (elastic modulus, P < 0.05; ultimate stress, P < 0.01) of COX-2-/- bones were lower than those of wild-type mice whereas the bulk structural properties (stiffness, P > 0.2; breaking force, P > 0.1) were similar to those of the wild-type mice. COX-2-/- mice had a longer moment of inertia but their cortical bones were thinner and contained many more intra-cortical pores compared with the bones of the other two groups. Finally, the bone matrix properties of COX-1-/- mice, COX-2-/- mice and their heterozygous littermates were similar to those of C57BL6/DBA wild-type mice.

Animals↗

PubMed2003

Enkephalinergic striatal projection neurons become less affected by quinolinic acid than substance P-containing striatal projection neurons as rats age.

While the excitotoxic vulnerability of striatal neurons is known to be greater in juvenile than adult animals, it is uncertain if striatal neuron types decline differentially in their vulnerability with age. To examine this issue, we unilaterally injected quinolinic acid (QA), an N-methyl-d-aspartate (NMDA) receptor agonist, into the striatum of juvenile and adult rats, and used in situ hybridization histochemistry with oligonucleotide probes for preproenkephalin and preprotachykinin mRNA to label surviving enkephalinergic (ENK) and substance P-containing (SP) neurons in adjacent sections through the injection center. The results confirmed that the region of severe damage is greater in young than adult animals, but revealed that at the very center of the QA injection, labeled neuron abundance was lower in adult than juvenile striatum. In juvenile rats, the vulnerability of the ENK neurons at all distances from the injection center was the same as that of the SP neurons. By contrast, in adult rats, the ENK neuron survival was greater than the SP neuron survival at all distances beyond the lesion center. The SP neuron survival outside the injection center in the adult rats was similar to that in juvenile rats, while the ENK neuron survival beyond the injection center was better in adult than juvenile rats. These data indicate that there is an age-dependent decrease in the vulnerability of ENK but not SP striatal projection neurons to QA-mediated injury in rats. The results also raise the possibility that, if an excitotoxic process is involved in HD pathogenesis, a differential age-related decline in the sensitivity of striatal projection neuron types to this process may contribute to the more uniform striatal neuron loss in juvenile-onset Huntington's disease (HD) and the more differential loss in adult-onset HD.

Aging↗

PubMed2003

Simultaneous magnetic resonance gadolinium-enhanced 2D perfusion and 3D angiographic imaging.

A method was implemented and tested that allows the simultaneous acquisition of magnetic resonance 2D slice selective perfusion and 3D angiographic data during a single bolus injection of a contrast agent. High quality contrast-enhanced perfusion images and angiograms of the lung, kidney and heart were obtained in healthy volunteers. Combined perfusion and angiography provided additional information with an acceptable increase in acquisition time. No image artifacts were attributed to the technique. The combined information may be useful in detecting, as well as characterizing, vascular abnormalities.

Adult↗

PubMed2003

1H magnetic resonance spectroscopy of nanomelic chicken cartilage: effect of aggrecan depletion on cartilage T2.

OBJECTIVE: To determine the effect of proteoglycan depletion on cartilage proton magnetic resonance (MR) spectroscopy T2 using nanomelic chicken cartilage, a genetic mutant that completely lacks aggrecan. DESIGN: Proton MR spectroscopic T2 measurements of normal embryonic and nanomelic femoral epiphyseal cartilage were obtained using a 96-echo pulse sequence with inter-echo delay times increased logarithmically over the TE period of 60 micros to 1.7 s. The relative intensity and distribution of cartilage T2 components were determined by fitting signal decay curves to a multi-exponential function. The number of T2 components in the signal decay curves was determined by the degree of freedom limited r2 of the fit. RESULTS: For normal fetal chicken cartilage, 97.6 +/- 0.2% (mean +/- 95% confidence interval) of the total signal comprises a long T2 component (179.1 +/- 1.3 ms) with a relatively small short T2 component (0.5 +/- 0.4 ms). The T2 distribution for nanomelic cartilage is more heterogeneous with four components identified: two short T2 components (0.5 +/- 0.02 and 7.3 +/- 0.6 ms), a large intermediate component (56.4 +/- 5.6 ms), and a broadly distributed long component (137.5 +/- 16.6 ms). In nanomelic cartilage there is greater heterogeneity of cartilage T2 indicating greater variation in water proton mobility and exchange of water with the extracellular matrix. CONCLUSION: Absence of aggrecan in the extracellular cartilage matrix produces greater heterogeneity in cartilage T2, but will not increase T2 as has been previously reported with degenerative change of the collagen matrix.

Aggrecans↗

PubMed2003

Cadmium effects on Ichthyophthirius: evidence for metal-sequestration in fish tissues following administration of recombinant vaccines.

We are developing Tetrahymena thermophila as a delivery system for recombinant vaccines against parasitic protozoa, including the common fish parasite, Ichthyophthirius multifiliis. T. thermophila cell lines expressing I. multifiliis genes under the control of a cadmium-inducible metallothionein gene promoter conferred strong protection against a lethal parasite challenge when administered parenterally to naive fish. Nevertheless, given that heavy metals can be toxic to parasites, a question arose as to whether protection resulted from Cd residues carried over with the vaccine, rather than acquired immunity per se. To address this issue, we examined the sensitivity of I. multifiliis to Cd in vitro and determined Cd concentrations in different host tissues following i.p. injection of juvenile channel catfish with the recombinant vaccine. We found that CdCl2 at concentrations > or = 50 ppb were lethal to I. multifiliis theronts in vitro. Furthermore, Cd concentrations were clearly elevated in fish tissues and reached levels equivalent to 74 ng/g wet weight (74 ppb) in the skin within 14 days of injection with recombinant T. thermophila. Nevertheless, fish injected with non-transformed Tetrahymena grown in the presence or absence of CdCl2 showed no significant difference in either relative survival or parasite load following direct challenge with I. multifiliis.

Animals↗

PubMed2003

Air flow and particle control with different ventilation systems in a classroom.

Most ventilation and air conditioning systems are designed without much concern about how settling particles behave in ventilation air flows. For displacement ventilation systems, designers normally assume that all pollutants follow the buoyant air flow into an upper zone, where they are evacuated. This is, however, not always true. Previous studies show that high concentrations of settling respirable particles can be found in the breathing zone, and that the exposure rates can be a health hazard to occupants. The emphasis here is on how ventilation systems should be designed to minimize respirable airborne particles in the breathing zone. The supply and exhaust conditions of the ventilation air flow are shown to play an important role in the control of air quality. Computer simulation programs of computational fluid dynamics (CFD) type are used. Particle concentrations, thermal conditions and modified ventilation system solutions are reported.

Air Movements↗

PubMed2003

Enantiomeric interactions between nucleic acid bases and amino acids on solid surfaces.

Molecular interaction between nucleic acid bases and amino acids is a fundamental process in biology. The adsorption of the molecules on surfaces provides the opportunity to study such interactions in great detail by exploiting the high-resolution imaging capabilities of scanning tunnelling microscopy (STM). The chemisorption of prochiral molecules, such as adenine, on a metal surface causes the adsorbed species to become chiral. Subsequent interactions with inherently chiral molecules may then lead to the formation of diastereoisomers, if the enantiomeric interaction process is sufficiently strong. In the case of adenine adsorption on Cu[110], the chiral adsorbates form homochiral chains. Here, we show that the adenine chain direction is fully correlated with the chirality, and that the alpha-amino acid, phenylglycine, shows a strong chiral preference in its interaction with these chains. STM images clearly demonstrate that S-phenylglycine (R-phenylglycine) binds only to chains rotated 19.5 degrees (anti-) clockwise from the [001] direction. Closer examination reveals that the enantiomeric interaction involves double rows of phenylglycine molecules and the adenine chains. This is the first observation at the molecular level of diastereoisomeric interaction, and demonstrates that STM is a powerful method for studying the details of these interactions.

Adenine↗

PubMed2003

The late increase in intracellular free radical oxygen species during apoptosis is associated with cytochrome c release, caspase activation, and mitochondrial dysfunction.

Mitochondria play central roles in cellular metabolism and apoptosis and are a major source of reactive oxygen species (ROS). We investigated the role of ROS and mitochondria in radiation-induced apoptosis in multiple myeloma cells. Two distinct levels of ROS were generated following irradiation: a small increase observed early, and a pronounced late increase, associated with depletion of reduced glutathione (GSH) and collapse of mitochondrial membrane potential (deltapsi(m)). Exogenous ROS and caspase-3 induced deltapsi(m) drop and cytochrome c release from mitochondria, which could be prevented by molecular (dominant-negative caspase-9) and pharmacologic (zVAD-fmk) caspase inhibitors and overexpression of Bcl-2. Exogenous ROS also induced mitochondrial permeability transition (PT) pore opening and cytochrome c release in isolated mitochondria, which could be blocked by inhibition of PT with cyclosporin A. These results indicate that the late ROS production is associated with increased PT pore opening and decreased deltapsi(m), and GSH, events associated with caspase activation and cytochrome c release.

Amino Acid Chloromethyl Ketones↗

PubMed2003

Scanning probe microscopy with landmark referenced control for direct biological investigations.

We report the successful use of continuous wavelet transforms applied to atomic force microscope data sets for landmark recognition of biological features. The data sets were images of mixed red and white blood cells. Contrast enhancement followed by continuous wavelet transform of the data was used to successfully distinguish erythrocytes from neutrophil and monocyte leukocytes within the mixed cell images. All of the above are spherical objects between 6 and 8 microns in diameter, which demonstrates the ability to sort similar biological objects into distinct classes. The implications for development of on-line scanning probe recognition microscopy are discussed.

Algorithms↗

PubMed2003

Correction for simultaneous catheter eccentricity and tilt in intravascular elastography.

Intravascular elastography can provide significant new information about the elastic properties of vascular tissue and plaque, useful for the diagnosis of disease and appropriate selection of interventional methods. Knowledge of the plaque composition, vulnerability and its elastic properties can assist the clinician in selecting appropriate interventional techniques. However, several noise sources have to be addressed to obtain quality intravascular elastograms. Misalignment of the vessel lumen and the ultrasound beam can produce erroneous strain estimates in elastography. Errors in the strain estimate are introduced due to the eccentricity and tilt of the intravascular transducer within the vessel lumen. Previous work in this area has provided theoretical expressions for the correction of eccentricity and tilt errors when they occur independent of each other. However, under most imaging conditions, both eccentricity and tilt errors are simultaneously present. In this paper, we extend the theoretical correction factor by accounting for the influence of both of these errors occurring simultaneously in the positioning of the catheter within the vessel lumen.

Blood Vessels↗

PubMed2003

Generation and characterization of an H9N2 cold-adapted reassortant as a vaccine candidate.

H9N2 subtype avian influenza viruses have been identified in avian species worldwide, and infections in pigs were confirmed in Hong Kong in 1998. Subsequently, H9N2 viruses were isolated from two children in Hong Kong in 1999, and five human infections were reported from China, raising the possibility that H9N2 viruses pose a potential pandemic threat for humans. These events prompted us to develop a vaccine candidate to protect humans against this subtype of influenza A viruses. Reassortant H1N1 and H3N2 human influenza A viruses with the six internal gene segments of A/Ann Arbor/6/60 (H2N2)(AA) cold-adapted (ca) virus have been tested extensively in humans and have proved to be attenuated and safe as live virus vaccines. Using classical genetic reassortment, we generated a reassortant that contains the hemagglutinin and neuraminidase genes from A/chicken/Hong Kong/G9/97 (H9N2) and six internal gene segments from the AAca virus. The G9/AAca reassortant virus exhibits the ca phenotype and the temperature-sensitive phenotypes of the AAca virus and was attenuated in mice. The reassortant virus was immunogenic and protected mice from wild-type H9N2 virus challenge. The G9/AAca virus bears the in vitro and in vivo phenotypes specified by the AAca virus and will be evaluated as a potential vaccine candidate in humans.

Acclimatization↗

PubMed2002

The incremental direct costs associated with behavioral symptoms in AD.

OBJECTIVE: To determine the incremental costs associated with behavioral symptoms in patients with AD. METHODS: A total of 128 patients with probable AD were enrolled into this study. Cognitive function and extrapyramidal features were assessed in patients with AD. Caregivers were interviewed to determine use of health care services, receipt of unpaid care, severity of behavioral symptoms (Neuropsychiatric Inventory [NPI]), and comorbid medical conditions in patients with AD. Healthcare utilization data were multiplied by unit costs to estimate direct formal costs. Unpaid caregiving hours were multiplied by an hourly wage to estimate direct informal costs. The annual incremental direct costs of additional behavioral symptoms were estimated with multiple regression equations. RESULTS: Annual, direct costs were significantly higher in patients with AD at or above the median score on the NPI (high NPI group), after adjusting for group differences in severity of cognitive impairment and comorbid conditions. Patients in the high NPI group had formal costs between US$3,162 and US$5,919 higher than the low NPI group and total direct costs between US$10,670 and US$16,141 higher, depending on the severity of cognitive impairments. Models for the entire sample estimated that a one-point increase in the NPI score would result in an annual increase of between US$247 and US$409 in total direct costs, depending on the value of unpaid caregiving. CONCLUSIONS: Behavioral symptoms in patients with AD significantly increase direct costs of care.

Aged↗

PubMed2002

The structure of trititanate nanotubes.

A comprehensive chemical and structural analysis is made of a new type of trititanate nanotube, which is synthesized via the reaction of TiO(2) particles with NaOH aqueous solution. It is found that the trititanate nanotubes are multi-walled scroll nanotubes with an inter-shell spacing of about 0.78 nm and an average diameter of about 9 nm. An atomic model of the nanotube is derived based on information from powder X-ray diffraction, selective-area electron diffraction, high-resolution electron microscopy and structure simulations. A model nanotube may be constructed by wrapping a (100) sheet of H(2)Ti(3)O(7) along [001] with the tube axis parallel to [010].

Journal Article↗

PubMed2002

Genomic-scale analysis of gene expression profiles in TNF-alpha treated human umbilical vein endothelial cells.

OBJECTIVE AND DESIGN: TNF-alpha is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, and in the control of cell proliferation, differentiation and programmed cell death. However, it is known that TNF-alpha is also the founding member of a still growing family of cytokines with diverse bioregulative functions. Its detailed molecular mechanisms on endothelial activation and injury remain to be elucidated. This study was aimed at determining genomic-scale gene expression profiles in TNF-alpha treated human endothelial cells. MATERIALS AND METHODS: In this study cultured human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-alpha (10 ng/ml) for 2 and 16 h, respectively, and the gene expression pattern was profiled using a cDNA array representing 14,000 gene/cDNA clusters. RESULTS: In total, 72 known human genes were identified the expression levels of which altered over 2-fold in response to TNF-a stimulation. Such alteration was confirmed for IL-8 and MCP-1, with an independent quantitative mRNA assay. It was observed that genes with related biological functions were often temporally co-regulated. CONCLUSIONS: These results indicate the transcriptional pathways mediated by TNF-alpha inside the HUVECs. Expression profiling in HUVECs responding to TNF-alpha stimulation should give an understanding of the molecular mechanisms involved in vascular inflammation.

Cells, Cultured↗

PubMed2002

Ultrasound monitoring of temperature change during radiofrequency ablation: preliminary in-vivo results.

Radiofrequency (RF) ablation is an interstitial focal ablative therapy that can be used in a percutaneous fashion and permits in situ destruction of hepatic tumors. However, local tumor recurrence rates after RF ablative therapy are as high as 34% to 55%, which may be due in part to the inability to monitor accurately temperature profiles in the tissue being ablated, and to visualize the subsequent zone of necrosis (thermal lesion) formed. The goal of the work described in this paper was to investigate methods for the real-time and in vivo monitoring of the spatial distribution of heating and temperature elevation to achieve better control of the degree of tissue damage during RF ablation therapy. Temperature estimates are obtained using a cross-correlation algorithm applied to RF ultrasound (US) echo signal data acquired at discrete intervals during heating. These temperature maps were used to display the initial temperature rise and to continuously update a thermal map of the treated region. Temperature monitoring is currently performed using thermosensors on the prongs (tines) of the RF ablation probe. However, monitoring the spatial distribution of heating is necessary to control the degree of tissue damage produced.

Animals↗