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Biomedical subjects

Q Yu

Publications and source records attributed to Q Yu.

At least 73 records · Page 4Linked to original sources
PubMed2000

Microfluidic tectonics: a comprehensive construction platform for microfluidic systems.

A microfluidic platform for the construction of microscale components and autonomous systems is presented. The platform combines liquid-phase photopolymerization, lithography, and laminar flow to allow the creation of complex and autonomous microfluidic systems. The fabrication of channels, actuators, valves, sensors, and systems is demonstrated. Construction times can be as short as 10 min, providing ultrarapid prototyping of microfluidic systems.

Journal Article↗
PubMed2000

Essential regions of the tRNA primer required for HIV-1 infectivity.

Human immunodeficiency virus (HIV), like all retroviruses, requires a cellular tRNA as a primer for initiation of reverse transcription. In a previous study, we demonstrated that an HIV-1 with a primer binding site complementary to yeast tRNA(Phe) (psHIV-Phe) was not infectious unless yeast tRNA(Phe) was supplied in trans. This unique in vivo complementation system has now been used to define the elements of the tRNA required for HIV-1 replication. Mutant tRNA(Phe) with deletions in TPsiC stem-loop, anticodon stem-loop or D stem-loop of the tRNA were generated and assessed for the capacity to rescue psHIV-Phe. Mutant tRNA(Phe) with disrupted TPsiC stem-loop did not rescue psHIV-Phe. In contrast, a mutant tRNA(Phe) without the D stem-loop was fully functional for the rescue. The tRNA anticodon stem-loop region was found to be important for efficient complementation. The results of our studies demonstrate for the first time the importance of specific structural and sequence elements of the tRNA primer for HIV-1 reverse transcription and define new targets for interruption of HIV-1 replication.

Base Sequence↗
PubMed2000

Stabilization of neoclassical tearing modes by an externally applied static helical field.

The effect of a static helical magnetic field on the nonlinear growth of the neoclassical tearing mode (NTM) is investigated. The NTM is found to be stabilized by an externally applied helical field of a different helicity if the field magnitude is sufficiently large, suggesting a very simple method for stabilizing the NTM. The mechanism responsible for this stabilization is the decreased fundamental harmonic pressure perturbation of the NTM in the presence of the helical field.

Journal Article↗
PubMed2000

Hypoxia augments conversion of big-endothelin-1 and endothelin ET(B) receptor-mediated actions in rat lungs.

We have examined the effect of endothelin-1, sarafotoxin-6C, big-endothelin-1 and other agents on perfused lungs from chronically hypoxic rats. Increases in pulmonary perfusion pressure induced by big-endothelin-1, endothelin-1, phenylephrine and potassium chloride were enhanced in hypoxic lungs, while the constrictor action of sarafotoxin-6C was not increased. When basal pulmonary perfusion pressure was raised, low doses of endothelin-1 and sarafotoxin-6C produced decreases in pulmonary perfusion pressure which were significantly greater in chronically hypoxic lungs, whereas responses to sodium nitroprusside were unchanged. Endothelin ET(B) receptor-mediated bronchoconstrictor responses were also potentiated in hypoxic lungs, whereas responses to carbachol were not. In hypoxic lungs, conversion of big-endothelin-1 to endothelin-1 was significantly increased. These data provide evidence for a generalised increase in vasomotor activity in chronically hypoxic lungs, and a more selective increase in endothelin ET(B) receptor-mediated vasodilator and bronchoconstrictor responses. Hypoxia also augments the conversion of big-endothelin-1 to endothelin-1.

Animals↗
PubMed2000

Complete suppression of neoclassical tearing modes with current drive at the electron-cyclotron-resonance frequency in ASDEX upgrade tokamak

Noninductive current drive has been performed in the tokamak ASDEX upgrade by injection of radiofrequency waves at the second harmonic of the electron-cyclotron frequency in order to suppress unwanted disturbances of the magnetic-field configuration. The current has been driven parallel [co-electron cyclotron current drive (ECCD)] and antiparallel (counter-ECCD) to the plasma current to compare the effect of heating with direct current drive in the magnetic island. For the first time it has been shown experimentally that total stabilization of neoclassical tearing modes is possible with co-ECCD. The experiments verify the role of direct current drive as opposed to local heating.

Journal Article↗
PubMed2000

Specific inhibition of FGF-induced MAPK activation by the receptor-like protein tyrosine phosphatase LAR.

LAR is a widely expressed receptor-like protein tyrosine phosphatase that is implicated in regulation of intracellular signaling triggered by both cell adhesion and peptide growth factors. Genetic studies revealed that LAR regulates neuron axon path finding in Drosophila and mammary gland epithelial cell differentiation in mice. The molecular mechanism underlying the tissue specific function of LAR has not been clearly understood. We investigated the role and mechanism of LAR in peptide growth factors EGF and FGF signaling in human tissue culture cells in which the expression of LAR is under the control of an inducible promoter. We found that although both EGF and FGF induce activation of mitogen-activated protein kinase (MAPK), LAR only inhibits FGF-induced MAPK activation. LAR does not interact directly with the peptide growth factor receptors, since the ligand-induced autophosphorylation of growth factor receptors was not affected by induction of LAR. The specific effect of LAR on FGF-induced MAPK activation appeared to be mediated by specific inhibition of the phosphorylation of two signal transducers that act downstream of the FGF receptor, FRS2 and a 180 kDa protein, and by prevention of their interaction with the adaptor protein GRB2. In contrast, LAR selectively inhibited the epidermal growth factor (EGF)-induced phosphorylation of p130CAS and the formation of the complex between p130CAS and GRB2 but this effect did not influence the activation of MAPK by EGF. These data suggest that LAR and similar receptor-like protein tyrosine phosphatases may contribute to the regulation of transmembrane signaling by selectively inhibiting the tyrosine phosphorylation of specific signal transducers that act downstream of the plasma membrane-associated tyrosine kinases. The consequent inhibition of the formation of signaling complexes by these proteins may contribute to the specificity of the signals generated by specific peptide growth factors as well as extracellular matrix proteins.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Functional hydrogel structures for autonomous flow control inside microfluidic channels

Hydrogels have been developed to respond to a wide variety of stimuli, but their use in macroscopic systems has been hindered by slow response times (diffusion being the rate-limiting factor governing the swelling process). However, there are many natural examples of chemically driven actuation that rely on short diffusion paths to produce a rapid response. It is therefore expected that scaling down hydrogel objects to the micrometre scale should greatly improve response times. At these scales, stimuli-responsive hydrogels could enhance the capabilities of microfluidic systems by allowing self-regulated flow control. Here we report the fabrication of active hydrogel components inside microchannels via direct photopatterning of a liquid phase. Our approach greatly simplifies system construction and assembly as the functional components are fabricated in situ, and the stimuli-responsive hydrogel components perform both sensing and actuation functions. We demonstrate significantly improved response times (less than 10 seconds) in hydrogel valves capable of autonomous control of local flow.

Journal Article↗
PubMed2000

Fast (3 Hz and 10 Hz) and slow (respiratory) rhythms in cervical sympathetic nerve and unit discharges of the cat.

1. In seven decerebrate cats, recordings were taken from the preganglionic cervical sympathetic (CSy) nerves and from 74 individual CSy fibres. Correlation and spectral analyses showed that nerve and fibre discharges had several types of rhythm that were coherent (correlated) between population and unit activity: respiratory, '3 Hz' (2-6 Hz, usually cardiac related), and '10 Hz' (7-13 Hz). 2. Almost all units (73/74) had respiratory modulation of their discharge, either phasic (firing during only one phase) or tonic (firing during both the inspiratory (I) and expiratory (E) phases). The most common pattern consisted of tonic I-modulated firing. When the vagi were intact, lung afferent input during I greatly reduced CSy unit and nerve discharge, as evaluated by the no-inflation test. 3. The incidence of unit-nerve coherent fast rhythms (3 Hz or 10 Hz ranges) depended on unit discharge pattern: they were present in an appreciable fraction (30/58 or 52 %) of tonic units, but in only a small fraction (2/15 or 13 %) of phasic units. 4. When baroreceptor innervation (aortic depressor amd carotid sinus nerves) was intact, rhythms correlated to the cardiac cycle frequency were found in 20/34 (59 %) of units. The cardiac origin of these rhythms was confirmed by residual autospectral and partial coherence analysis and by their absence after baroreceptor denervation. 4. The 10 Hz coherent rhythm was found in 7/34 units when baroreceptor innervation was intact, where it co-existed with the cardiac-locked rhythm; after barodenervation it was found in 9/50 neurones. Where both rhythms were present, the 10 Hz component was sometimes synchronized in a 3:1 ratio to the 3 Hz (cardiac-related) frequency component. 5. The tonic and phasic CSy units seem to form distinct populations, as indicated by the differential responses to cardiac-related afferent inputs when baroreceptor innervation is intact. The high incidence of cardiac-related correlation found among tonic units suggests that they are involved in vasomotor regulation. The high incidence of respiratory modulation of discharge suggests that the CSy units may be involved in regulation of the nasal vasculature and consequent ventilation-related control of nasal airway resistance.

Action Potentials↗
PubMed2000

A truncated cytoplasmic topoisomerase IIalpha in a drug-resistant lung cancer cell line is encoded by a TOP2A allele with a partial deletion of exon 34.

To study the problem of acquired resistance to widely used anti-cancer drugs that target the 170 kDa topoisomerase IIalpha (topo IIalpha), a drug-resistant human small-cell lung cancer cell line, H209/VP, was selected in VP-16. H209/VP cells express reduced levels of the 170 kDa topo IIalpha that is localized normally in the nucleus and also express lower levels of a 160 kDa topo IIalpha-related protein that is located predominantly in the cytoplasm. Band depletion immunoblotting experiments suggest that the H209/VP nuclear 170 kDa topo IIalpha is able to form ternary complexes with DNA and VP-16 in intact cells, but the ability of the cytoplasmic 160 kDa protein to do so is greatly diminished. Sequence analysis of the 3; end of the H209/VP mutant topo IIalpha mRNA and the TOP2A gene indicates that the mRNA is missing 200 nt that corresponds to exon 34 because the partial loss of the minimal 3; splice-acceptor sequence at the beginning of exon 34 results in splicing of exon 33 to exon 35. The protein predicted to be encoded by this mutant mRNA does not contain the COOH-terminal 109 amino acids of the wild-type enzyme that we have demonstrated contain a strongly functional nuclear localization signal sequence. Consequently, our data explain both the size and the cytoplasmic localization of the H209/VP mutant topo IIalpha. The mutant TOP2A allele in H209/VP cells differs from those in previously characterized cell lines with cytoplasmic topo IIalpha and extends the number of types of resistance-associated deletions in this region to 4. These findings indicate that this region of the TOP2A gene may be a hot spot for mutations.

3' Untranslated Regions↗
PubMed2000

Engineered salt-insensitive alpha-defensins with end-to-end circularized structures.

We designed a retro-isomer and seven circularized "beta-tile" peptide analogs of a typical rabbit alpha-defensin, NP-1. The analogs retained defensin-like architecture after the characteristic end-to-end, Cys(3,31) (C I:C VI), alpha-defensin disulfide bond was replaced by a backbone peptide bond. The retro-isomer of NP-1 was as active as the parent compound, suggesting that overall topology and amphipathicity governed its antimicrobial activity. A beta-tile design with or without a single cross-bracing disulfide bond sufficed for antimicrobial activity, and some of the analogs retained activity against Escherichia coli and Salmonella typhimurium in NaCl concentrations that rendered NP-1 inactive. The new molecules had clustered positive charges resembling those in protegrins and tachyplesins, but were less cytotoxic. Such simplified alpha-defensin analogs minimize problems encountered during the oxidative folding of three-disulfide defensins. In addition, they are readily accessible to a novel thia zip cyclization procedure applicable to large unprotected peptide precursors of 31 amino acids in aqueous solutions. Collectively, these findings provide new and improved methodology to create salt-insensitive defensin-like peptides for application against bacterial diseases.

Amino Acid Sequence↗
PubMed2000

Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis.

We have uncovered a novel functional relationship between the hyaluronan receptor CD44, the matrix metalloproteinase-9 (MMP-9) and the multifunctional cytokine TGF-beta in the control of tumor-associated tissue remodeling. CD44 provides a cell surface docking receptor for proteolytically active MMP-9 and we show here that localization of MMP-9 to cell surface is required for its ability to promote tumor invasion and angiogenesis. Our observations also indicate that MMP-9, as well as MMP-2, proteolytically cleaves latent TGF-beta, providing a novel and potentially important mechanism for TGF-beta activation. In addition, we show that MMP-9 localization to the surface of normal keratinocytes is CD44 dependent and can activate latent TGF-beta. These observations suggest that coordinated CD44, MMP-9, and TGF-beta function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote tumor growth and invasion.

Animals↗
PubMed2000

Ethnic differences in essential tremor.

BACKGROUND: Ethnic differences in the clinical characteristics (severity and distribution) of essential tumor (ET) have not been studied. The presence of these differences suggests that ET is not a homogeneous disease and that there is variability in disease expression under different circumstances. As part of a community-based study, we evaluated a multiethnic group of cases. OBJECTIVE: To assess whether there are ethnic differences in the clinical characteristics of ET. METHODS: Elderly residents of Washington Heights-Inwood, New York, were enrolled in a community-based health study (N = 2117). Participants underwent a medical interview and a neurological examination conducted by a neurologist, and subjects with ET were identified. These subjects with ET were then enrolled in a community-based study of ET and underwent a tremor interview, a videotaped tremor examination, and in some cases, a performance-based test of function and quantitative computerized tremor analysis. A total tremor score (range, 0-36, with 0 indicating no tremor and 36 indicating maximum tremor) was assigned to each subject based on 2 neurologists' ratings of the tremor examination. RESULTS: Among 62 subjects with ET (white [n = 16], African American [n = 18], and Hispanic [n = 28]), there were ethnic differences in the total tremor score (F = 3.68, P = .03). In a multiple regression model adjusting for age, white subjects had a mean total tremor score that was 5.3 points lower than that of nonwhite subjects (P = .008). We divided the nonwhite group into African American and Hispanic subgroups. In a regression model adjusting for age and duration, the white group had a mean total tremor score that was 6.1 points lower than that of the Hispanic group (P = .07) and 7.2 points lower than that of the African American group (P = .05). The mean performance-based test score was 1.7 times higher in the African American group and 2.1 times higher in the Hispanic group compared with the white group (P = .38). No subjects in the African American group had head tremor, while 4 subjects in the white group (25%) and 8 subjects in the Hispanic group (29%) did have head tremor (chi2 = 6.17, P = .05). CONCLUSIONS: There are ethnic differences in the expression of ET, suggesting that ET is not a homogeneous disorder. These differences may reflect phenotypic variability caused by genotypic differences or differences in exposure to environmental factors that influence tremor.

Black or African American↗
PubMed2000

High-level, stable expression of blood group antigens in a heterologous system.

The detection and identification of blood group antibodies in patients is crucial for successful allogeneic blood transfusions. Current methods are highly subjective and rely on red blood cells (RBCs), which simultaneously express many blood group antigens, have a short shelf-life, and carry potential biohazard risks. To overcome these problems, we have used the approach of expressing individual blood group antigen-bearing proteins in a heterologous system. We report here the high-level surface expression of type I (Knops), type II (Kell), and type III/multi-pass (Duffy) membrane proteins that carry blood group antigens in mouse erythroleukaemic (MEL) cells using a vector containing the beta-globin locus control region. Importantly, the antigens expressed were detected specifically by a panel of patients' sera containing alloantibodies at sensitivities that are comparable to antigen-positive RBCs. Furthermore, in contrast to other mammalian expression systems, antigen expression was stable following freezing and thawing of the cell lines. Thus, this system has the potential both to replace the current use of RBCs by providing a one step method to detect and identify blood group antibodies and to allow the automation of antibody identification for the clinical laboratory.

Animals↗
PubMed2000

Base-catalyzed epimerization of the butenolide in annonaceous acetogenins.

The elusive epimerization process in the chiral butenolide moiety of Annonaceous acetogenins was examined under several sets of conditions commonly used for elimination leading to the alpha, beta-unsaturated lactone and the results provide practical guidance in choosing elimination conditions.

4-Butyrolactone↗
PubMed2000

Validation of a portable instrument for assessing tremor severity in epidemiologic field studies.

BACKGROUND: An important part of epidemiologic and genetic studies of essential tremor (ET) is an assessment of tremor severity. Clinical rating scales are semiquantitative and computerized tremor analysis, available at tertiary medical centers, is not transportable into the field. As part of an epidemiologic study, we modified the Klove-Matthews Motor Steadiness Battery, collecting objective quantitative data on tremor severity in patients with ET and control subjects. OBJECTIVE: To describe the modified Klove-Matthews Motor Steadiness Battery, validate this test battery against several other measures of tremor severity, demonstrate test-retest reliability, and provide standard reference values for normal control subjects and patients with ET who undergo this test battery. METHODS: Patients with ET and control subjects, ascertained from both a clinic and a community, underwent a standardized evaluation including a demographic and medical questionnaire, tremor disability questionnaire, videotaped tremor examination, performance-based test, modified Klove-Matthews Motor Steadiness Battery (Groove-Type Steadiness Tester [GTST] and Nine-Hole Steadiness Tester [NHST]), and quantitative computerized tremor analysis. RESULTS: There were 19 patients with ET and 28 control subjects. NHST and GTST total scores were correlated significantly with the tremor disability questionnaire score (r = 0.63, p = 0.001 and r = 0.49, p = 0.016), total tremor score (tremor examination, r = 0.68, p<0.001 and r = 0.41, p = 0.005), performance-based test score (r = 0.81, p<0.001 and r = 0.65, p = 0.001), and quantitative computerized tremor analysis results (for example, spiral drawing, r = 0.62, p = 0.01 and r = 0.58, p = 0.019). Test-retest reliability was generally high (r = 0.79-0.94, p<0.001). CONCLUSION: The modified Klove-Matthews Motor Steadiness Battery provides a reliable and valid means to collect objective quantitative data on tremor severity. Rapidity of administration and ease of transport make it a potentially useful tool in epidemiologic and genetic field studies.

Adult↗
PubMed2000

Validity and test-retest reliability of a disability questionnaire for essential tremor.

BACKGROUND: One important outcome in clinical trials is patients' own opinions about whether the medication alleviates their symptoms and improves their ability to function. A valid and reliable method with which to assess this subjective information is important. OBJECTIVE: To determine the validity and test-retest reliability of the Columbia University Disability Questionnaire for Essential Tremor (ET). METHODS: Patients with ET underwent a 2.5-hour evaluation, including a 36-item tremor disability questionnaire, to assess the functional impact of tremor, a 26-item videotaped tremor examination rated by a neurologist, a 15-item performance-based test, and quantitative computerized tremor analysis. We determined the validity and test-retest reliability of the tremor disability questionnaire. Correlations between variables were assessed using Pearson's correlation coefficients and test-retest reliability with the weighted kappa statistic. RESULTS: Ninety-five patients with ET participated. The score on tremor disability questionnaire correlated with the neurologist's clinical ratings (r = 0.57, p <0.001) and the total score on the performance-based test (r = 0.69, p < 0.001). Correlations with quantitative computerized tremor analysis results were less robust, but each remained significant, including mean amplitude of dominant arm tremor while arms were extended (r = 0.56, p <0.001), while drawing a spiral (r = 0.42, p = 0.01), and while pouring (r = 0.34, p = 0.04). The questionnaire was readministered to 32 subjects, and the test-retest reliability was substantial (weighted kappa = 0.67). CONCLUSIONS: This Tremor Disability Questionnaire demonstrated substantial reliability, and it correlated with multiple measures of tremor severity, including a neurologist's clinical ratings, a performance-based test of function, and quantitative computerized tremor analysis results. The questionnaire would be useful in clinical trials in which it could be used as a reliable and valid tool to assess disability in ET.

Activities of Daily Living↗
PubMed2000

Amplification and analysis of DNA flanking known sequences of a novel herpesvirus from green turtles with fibropapilloma Brief report.

A 1,632-bp fragment, flanking the original 483-bp region of the DNA polymerase gene of a novel herpesvirus found in tissues of green turtles (Chelonia mydas) with fibropapilloma, was amplified from the circularized EcoRI-cut DNA extracted from tumor tissues by inverse PCR. The resultant 2,019-bp partial sequence of the DNA polymerase gene of the newfound herpesvirus, including the original 483-bp region, showed a high degree of homology at both the nucleotide and amino acid levels with that of other human and animal herpesviruses. Phylogenetic analysis confirmed that this novel herpesvirus belonged to the Alphaherpesvirinae subfamily.

Alphaherpesvirinae↗