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Biomedical subjects

Q Yao

Publications and source records attributed to Q Yao.

At least 19 recordsLinked to original sources
PubMed2003

Intra-articular adenoviral-mediated gene transfer of trail induces apoptosis of arthritic rabbit synovium.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that primarily affects joints. In rheumatoid joints there is extensive synovial proliferation with diseased synovium becoming highly aggressive, attaching to the articular cartilage and bone to form what is termed a pannus. The formation of active pannus is central to erosive disease and resulting joint destruction. In this study, we examined the ability to eliminate the hyperplastic synovium by adenoviral-mediated gene transfer of human TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF family that is able to induce apoptosis through interaction with receptors containing death domains, DR4 and DR5. Infection of synovial cells derived from RA patients with Ad.TRAIL resulted in significant apoptosis in three out of five lines. Moreover, primary rabbit synovial fibroblasts were also sensitive to Ad.TRAIL-mediated gene transfer. In a rabbit model of arthritis, intra-articular gene transfer of TRAIL induced apoptosis in cells within the synovial lining, reduced leukocytic infiltration and stimulated new matrix synthesis by cartilage. These results demonstrate that TRAIL can affect the viability of the cells populating the activated synovium in arthritic joints and suggest that the delivery of TRAIL to arthritic joints may represent a non-invasive mechanism for inducing pannus regression.

Adenoviridae↗
PubMed2002

Identification of metastasis-associated genes in early stage non-small cell lung cancer by subtractive hybridization.

Non-small cell lung cancer (NSCLC) is a leading cause of death and a substantial fraction of patients with surgically resected disease ultimately dies due to distant metastasis. To identify gene expression differences in early stage adenocarcinoma that either did or did not metastasize within a 5-year period, we employed a subtractive hybridization strategy of pooled RNA from primary adenocarcinomas (stage I) of the lung. Individual clones (n=225) of the subtracted cDNA library were sequenced. Further analyses of mRNA expression levels in a cohort of 70 NSCLC patients (stage I to IIIA) showed that the metastasis association of the identified genes was stage and histology specific. Cox regression analyses identified two genes (EIF4A1, MALA1) to be independent prognostic parameters for patients' survival in stage I and II disease. These findings could help to identify early-stage NSCLC patients at high risk for the development of distant metastasis.

Biomarkers, Tumor↗
PubMed2001

Rapid assembly of structurally defined and highly functionalized conjugated dienes via tethered enyne metathesis.

[reaction: see text] Conjugated dienes are versatile building blocks in organic synthesis, and the development of new methods for their synthesis remains an important topic in modern synthetic organic chemistry. We describe here an expedient synthesis of highly functionalized conjugated dienes through sequential silicon-tethered ring-closing enyne metathesis mediated by Grubbs' Ru carbene catalysts and Tamao oxidation. Notable attributes of this methodology include short synthetic manipulations and the structural complexity it confers on the resulting diene moiety.

Journal Article↗
PubMed2001

HIV envelope proteins differentially utilize CXCR4 and CCR5 coreceptors for induction of apoptosis.

The involvement of CXCR4 and CCR5 coreceptors in apoptosis induced by the HIV envelope (Env) proteins has not been well defined. We found that simian human immunodeficiency virus (SHIV) virus-like particles (VLPs) containing HIV Env proteins preferentially induce apoptosis of cells corresponding to their coreceptor usage in a CD4+ T cell line. We also demonstrated that induction of apoptosis by SHIV VLPs is correlated with coreceptor usage in a non-T cell line. We examined the effects of SHIV VLPs containing Env proteins derived from either a T-cell-tropic HIV (BH10) strain or a dual-tropic HIV (89.6) strain on induction of apoptosis in recombinant CD4+ human osteosarcoma (HOS) cells expressing either CXCR4 (HOS-CD4.CXCR4) or CCR5 coreceptors (HOS-CD4.CCR5). HOS-CD4.CXCR4 or HOS-CD4.CCR5 cells were activated with concanavalin A and cocultured with VLPs. By TUNEL (TdT-mediated dUTP-X nick end labeling) fluorescence staining and flow cytometry assays, SHIV BH10 VLPs were found to preferentially induce apoptosis in HOS-CD4.CXCR4 cells but not in HOS-CD4 or HOS-CD4.CCR5 cells. On the other hand, SHIV 89.6 VLPs induced an elevated level of apoptosis in both HOS-CD4.CXCR4 and HOS-CD4.CCR5 cells in a dose-dependent fashion. These data demonstrate that T-cell-tropic BH10 Env preferentially utilizes CXCR4, but not CCR5, for induction of apoptosis, whereas dual-tropic 89.6 Env induces apoptosis in both CXCR4- and CCR5-containing cell lines.

Apoptosis↗
PubMed2001

Oligomeric interactions between phospholamban molecules regulate Ca-ATPase activity in functionally reconstituted membranes.

Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, and functions as an endogenous inhibitor of Ca-ATPase transport activity. To identify whether oligomeric interactions between PLB molecules are involved in regulating Ca-ATPase transport activity, we have investigated functional interactions between PLB and the Ca-ATPase in proteoliposomes of purified PLB functionally co-reconstituted with the SERCA2a isoform of the Ca-ATPase isolated from cardiac sarcoplasmic reticulum (SR). The calcium sensitivity of this reconstituted preparation and functional stimulation by cAMP-dependent protein kinase (PKA) are virtually identical to those of the Ca-ATPase in cardiac SR microsomes, ensuring the functional relevance of this reconstituted preparation. Interactions between PLB molecules were measured following covalent modification of the single lysine (i.e., Lys(3)) in PLB isolated from cardiac SR membranes with fluorescein isothiocyanate (FITC) prior to co-reconstitution with the Ca-ATPase. FITC modification of PLB does not interfere with the ability of PLB to inhibit the Ca-ATPase, since FITC-PLB co-reconstituted with the Ca-ATPase exhibits a similar calcium dependence of Ca-ATPase activation to that observed in native SR membranes. Thus, the functional arrangement of PLB with the Ca-ATPase is not modified by FITC modification. Using changes in the anisotropy of FITC-PLB resulting from fluorescence resonance energy transfer (FRET) between proximal PLB molecules to measure the average size and spatial arrangement of FITC chromophores, we find that PLB self-associates to form oligomers whose spatial arrangement with respect to one another is in agreement with earlier suggestions that PLB exists predominantly as a homopentamer. The inability of PKA to activate PLB following covalent modification with FITC permits functional interactions between PLB molecules associated with the Ca-ATPase activation to be identified. A second-order loss of Ca-ATPase activation by PKA is observed as a function of the fractional contribution of FITC-PLB, indicating that PKA-dependent activation of two PLB molecules within a quaternary complex containing the Ca-ATPase is necessary for activation of the Ca-ATPase. We suggest that the requirement for activation of two PLB molecules by PKA represents a physiological mechanism to ensure that activation of the Ca-ATPase following beta-adrenergic stimulation in the heart only occurs above a threshold level of PKA activation.

Animals↗
PubMed2001

Three membrane-proximal amino acids in the human parainfluenza type 2 (HPIV 2) F protein are critical for fusogenic activity.

In this study, we investigated the role of the membrane-proximal region of the human parainfluenza virus type 2 (HPIV2) F protein by mutational analysis, including deletion, insertion, and substitution. Deletion or replacement of the entire 12 amino acid region (aa 474-485) of the HPIV2 F protein completely abolished its fusion activity when coexpressed with the HPIV2 HN protein. Deletion of groups of four of aa 478-485, single alanine, or other amino acid substitutions among aa 478-485 had minimal or limited effects on HPIV2 F/HN-induced cell fusion. However, a significant reduction in, or complete inhibition of, fusion activity was observed when aa 474-477 were deleted, or the N475, F476, or F477 residues were singly substituted with alanine. In addition, insertions of four amino acids at this region or deletion of eight or more amino acids significantly reduced F protein fusion activity. The oligomerization patterns and levels of cell surface expression of the mutant F proteins were compared to those of the wild-type HPIV2 F protein. The mutant HPIV2 F proteins defective in fusion were also found to be unable to initiate hemifusion, indicating that there is a specific requirement for three specific amino acids as well as the spacing in this region for initiating lipid mixing.

Amino Acids↗
PubMed2001

Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation.

Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects joints. During the pathogenesis of rheumatoid arthritis, the synovial lining becomes dramatically thickened and hyperplastic. This highly aggressive tissue invades and destroys articular cartilage and bone. Several lines of evidence suggest that the proliferation of the synovial tissue may be due to disruption in the control of the cell cycle or apoptotic pathways. In particular, mutations in the tumor suppressor protein p53 have been found in synovial tissue from RA joints. We have examined the effects of overexpression of p53 by adenoviral infection in synovial cells in culture and in synovial tissue in vivo in a rabbit model of arthritis. Here we demonstrate that p53 overexpression resulted in significant apoptosis in human and rabbit synovial cells in culture. Furthermore, intraarticular injection of Ad-p53 resulted in extensive and rapid induction of synovial apoptosis in the rabbit knee without affecting cartilage metabolism. Interestingly, a significant reduction in the leukocytic infiltrate was observed within 24 h postinfection of Ad.p53. These results suggest that intraarticular gene transfer of p53 is able to induce synovial apoptosis as well as reduce inflammation and thus may be useful clinically for the treatment of RA.

Adenoviridae↗
PubMed2001

Atrial fibrillation: a risk factor for increased mortality--an AVID registry analysis.

Emerging evidence suggests that atrial fibrillation is not a benign arrhythmia. It is associated with increased risk of death. The magnitude of association is controversial and potential causes remain unknown. Patients in the registry of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial form the basis for this report. Baseline variables, in particular the presence or absence of a history of atrial fibrillation/flutter, were examined in relation to survival. Multivariate Cox regression was used to adjust for differences in important baseline co-variables using 27 pre-selected variables. There were 3762 subjects who were followed for an average of 773+/-420 days; 1459 (39 %) qualified with ventricular fibrillation and 2303 (61 %) with ventricular tachycardia. A history of atrial fibrillation/flutter was present in 24.4 percent. There were many differences in baseline variables between those with and those without a history of atrial fibrillation/flutter. After adjustment for baseline differences, a history of atrial fibrillation/flutter remained a significant independent predictor of mortality, (relative risk=1.20; 95 % confidence intervals=1.03-1.40; p=0.020). Antiarrhythmic drug use, other than amiodarone or sotalol, was also a significant independent predictor of mortality (relative risk 1.34; 95 % confidence intervals 1.07-1.69, p=0.011. Atrial fibrillation/flutter is a significant independent risk factor for increased mortality in patients presenting with ventricular tachyarrhythmias. This risk may have been overestimated in previous studies that could not adjust for the proarrhythmic effects of antiarrhythmic drugs other than amiodarone or sotalol.

Aged↗
PubMed2001

Lead- and device-related complications in the antiarrhythmics versus implantable defibrillators trial.

BACKGROUND: Implantation of transvenous implantable cardioverter defibrillators (ICDs) by use of a nonthoracotomy approach has become routine therapy for survivors of life-threatening tachyarrhythmias. The purpose of this study was to identify and prospectively characterize the frequency of lead- and ICD-related complications from the Antiarrhythmics versus Implantable Defibrillators (AVID) Trial. METHODS AND RESULTS: Between June 1, 1993, and April 7, 1997, 539 patients received nonthoracotomy ICDs either as initial treatment assignment (477) or as crossover from medical management (62). A total of 62 first complications occurred. The subclavian route of insertion resulted in more complications than the cephalic vein route, 46 of 339 (14%) versus 6 of 135 (4%), P = .005, as did the abdominal versus pectoral generator site, 31 of 238 (13%) versus 17 of 291 (6%), P<.02. Most dislodgements and system infections tended to occur in the 3 months after implantation, whereas lead fractures continued to occur throughout follow-up. Failure to use perioperative antibiotics was a predictor of system infection (P = .001). CONCLUSIONS: These data suggest that cephalic vein access and pectoral generator site may result in fewer complications. The continued occurrence of lead fractures and the need for premature system revision supports the practice of close routine ICD system surveillance.

Anti-Arrhythmia Agents↗
PubMed2001

[Cerebral watershed infarcts].

OBJECTIVE: To investigate the clinical types and characteristics of cerebral watershed infarcts (CWI). METHODS: Analysis of the clinical data and imaging characteristics of 192 cases with CWI confirmed by CT scan or MRI. RESULTS: In 69 cases (35.9%), CWI appeared as wedge-shaped areas on CT scan or MRI, the infarcts located at marginal zones between the anterior and middle cerebral arteries and were usually associated clinically with hemiparesis, transcortical motor aphasia and dementia. In 74 cases (38.5%) the infarcts also appeared as wedge-shaped areas on CT scan and MRI, but located at marginal zones between the middle and posterior cerebral arteries, the patients mainly showed mild hemiparesis and apathy. In 49 cases (25.5%), the long-line or triangle-shaped infarct areas usually located at marginal zones between the superficial and deep territory of the middle cerebral arteries in the basal ganglia and posterolateral angulus frontalis. CONCLUSION: The presentation of CWI is complicated, and the diagnosis of that mainly depends on imaging studies such as CT scan and MRI.

Adult↗
PubMed2001

[Morphological observation of Mahaim's fibers in 7 cases].

OBJECTIVE: To investigate the Mahaim's fibers of the cardiac conduction system (CCS) of human hearts and study their morphological features. METHODS: The CCS from 165 cases of sudden death without extracardiac causes and those from 760 cases of non-cardiac death were sampled using a method established by the authors. Serial sections were prepared for histological observation. RESULTS: Mahaim's fibers were discovered in 7 cases, 5 cases were in the sudden death group, accounting for 3% in that group, 2 cases were in the non-cardiac death group, accounting for 0.26% in that group. All cases belonged to the bundle-ventricular branch type. The characteristics of Mahaim's fibers were found to be as follows. Their transverse diameter was 10 - 35 microns. The bodies of the Mahaim's fibers that originated from A-V bundle were slender with nucleus in the middle of the cell. While the shape of cells from the left bundle branch varied according to the origin of the Mahaim's fiber with size enlarging from up downward. Both types of cells showed abundant lightly stained cytoplasm, similar to A-V bundle and left bundle branch cells. The cells were not bifurcated and some of them were surrounded by a thin layer of fibrous tissue. CONCLUSION: Mahaim's fibers are not a rarity and it is an abnormal development of an A-V by-path.

Adolescent↗
PubMed2001

[Study on gas chromatographic method for the evaluation of residual solvents by using wide bore open tubular columns].

A GC method using wide bore open tubular columns was developed to evaluate residual organic solvents. Sixteen organic solvents commonly used for pharmaceutical synthesis were analysed. The effects of different polarity columns and extraction solvents on the assay of residual solvents were studied in this work. It showed that most solvents can be well separated from each other on non-polar or less polar wide-bore columns. Extraction solvents differed in their extraction recovery and peak shape. Satisfactory results can be obtained when the proposed method was employed and a suitable extraction solvent was selected. The procedures summarized in this paper can be used as a guidance for the evaluation of residual organic solvents in bulk pharmaceuticals.

Chromatography, Gas↗
PubMed2001

[Audiological findings of the aging across the urban and rural of Suzhou].

OBJECTIVE: To determine the epidemiological characteristics of old people's hearing. METHOD: Questionnaires, physical examination, audiometry and bio-chemical tests were performed on the elders above 60 years old in part of the urban and rural area of Suzhou with random sample survey. RESULT: A total of 1,040 individuals was investigated, among which 505 were from urban, and 535 were from rural. 33 of 505 senior citizen (6.53%) were nososacusis, 282 (55.84%) were presbycusis and 21 (4.16%) were noise-induced deafness; In the rural area, 35 of 535 (6.54%) were nososacusis, 232 (43.36%) were presbycusis, and 4 (0.75%) were noise deafness. There was significant difference of the incidence of presbycusis between urban and rural. The audiometric thresholds chart manifested that the threshold elevated with age increasing especially in high-frequency. CONCLUSION: The etiology of hearing loss of elders was mainly due to presbycusis. The higher incidence of psychotic disorder in urban probably caused a correspondingly higher incidence of presbycusis. So the prevention and cure of some age-induced diseased (e.g. hypertension, arteriosclerosis and diabetes) may be helpful to release and improve presbycusis.

Aged↗
PubMed2000

Direct interaction between endothelial nitric-oxide synthase and dynamin-2. Implications for nitric-oxide synthase function.

Endothelial nitric-oxide synthase (eNOS) is regulated in part through specific protein interactions. Dynamin-2 is a large GTPase residing within similar membrane compartments as eNOS. Here we show that dynamin-2 binds directly with eNOS thereby augmenting eNOS activity. Double label confocal immunofluorescence demonstrates colocalization of eNOS and dynamin in both Clone 9 cells cotransfected with green fluorescent protein-dynamin and eNOS, as well as in bovine aortic endothelial cells (BAEC) expressing both proteins endogenously, predominantly in a Golgi membrane distribution. Immunoprecipitation of eNOS from BAEC lysate coprecipitates dynamin and, conversely, immunoprecipitation of dynamin coprecipitates eNOS. Additionally, the calcium ionophore, a reagent that promotes nitric oxide release, enhances coprecipitation of dynamin with eNOS in BAEC, suggesting the interaction between the proteins can be regulated by intracellular signals. In vitro studies demonstrate that glutathione S-transferase (GST)-dynamin-2 quantitatively precipitates both purified recombinant eNOS protein as well as in vitro transcribed (35)S-labeled eNOS from solution indicating a direct interaction between the proteins in vitro. Scatchard analysis of binding studies demonstrates an equilibrium dissociation constant (K(d)) of 27.6 nm. Incubation of purified recombinant eNOS protein with GST-dynamin-2 significantly increases eNOS activity as does overexpression of dynamin-2 in ECV 304 cells stably transfected with eNOS-green fluorescent protein. These studies demonstrate a direct protein-protein interaction between eNOS and dynamin-2, thereby identifying a new NOS-associated protein and providing a novel function for dynamin. These events may have relevance for eNOS regulation and trafficking within vascular endothelium.

Animals↗
PubMed2000

Common structure in panels of short ecological time-series.

Typically, in many studies in ecology, epidemiology, biomedicine and others, we are confronted with panels of short time-series of which we are interested in obtaining a biologically meaningful grouping. Here, we propose a bootstrap approach to test whether the regression functions or the variances of the error terms in a family of stochastic regression models are the same. Our general setting includes panels of time-series models as a special case. We rigorously justify the use of the test by investigating its asymptotic properties, both theoretically and through simulations. The latter confirm that for finite sample size, bootstrap provides a better approximation than classical asymptotic theory. We then apply the proposed tests to the mink-muskrat data across 81 trapping regions in Canada. Ecologically interpretable groupings are obtained, which serve as a necessary first step before a fuller biological and statistical analysis of the food chain interaction.

Animals↗
PubMed2000

Induction of long-term protective effects against heterologous challenge in SIVhu-infected macaques.

A group of three rhesus macaques were inoculated with SIV isolated from a human (SIVhu) accidentally exposed and infected with SIVsm. Extensive sequence analyses of SIVhu obtained from the human and macaques following infection indicated the presence of truncated nef. Not only did nef fail to repair itself in vivo postinfection (p.i.), but instead, further mutations added additional stop codons with increasing time p.i. Infection of these animals was associated with minimal acute viral replication, followed by undetectable plasma viral loads and only intermittent PCR detection up to 5 years p.i. The three SIVhu infected and three control monkeys were then challenged with the heterologous highly pathogenic SHIV89.6p. All three controls became infected and showed rapid declines in peripheral CD4(+) lymphocytes, disease, and death at 10 and 32 weeks p.i., respectively. In contrast, all three animals previously infected with SIVhu are healthy and exhibit stable CD4(+) lymphocyte levels and undetectable plasma viral loads at >20 months post-SHIV89. 6p challenge. Only transient, low levels of SHIV replication were noted in these animals. Whereas responses to SIVgag/pol were noted, no evidence for SIV/SHIV envelope cross-reactivity was detected by antibody or CTL analyses, suggesting that the protective immune mechanisms to the heterologous challenge isolate were most likely not directed to envelope but rather to other viral determinants.

Animals↗
PubMed2000

Phospholamban remains associated with the Ca2+- and Mg2+-dependent ATPase following phosphorylation by cAMP-dependent protein kinase.

We have used fluorescence and spin-label EPR spectroscopy to investigate how the phosphorylation of phospholamban (PLB) by cAMP-dependent protein kinase (PKA) modifies structural interactions between PLB and the Ca(2+)- and Mg(2+)-dependent ATPase (Ca-ATPase) that result in enzyme activation. Following covalent modification of N-terminal residues of PLB with dansyl chloride or the spin label 4-isothiocyanato-2,2,6,6-tetramethylpiperidine-N-oxyl ('ITC-TEMPO'), we have co-reconstituted PLB with affinity-purified Ca-ATPase isolated from skeletal sarcoplasmic reticulum (SR) with full retention of catalytic function. The Ca(2+)-dependence of the ATPase activity of this reconstituted preparation is virtually identical with that observed using native cardiac SR before and after PLB phosphorylation, indicating that co-reconstituted sarcoplasmic/endoplasmic-reticulum Ca(2+)-ATPase 1 (SERCA1) and PLB provide an equivalent experimental model for SERCA2a-PLB interactions. Phosphorylation of PLB in the absence of the Ca-ATPase results in a greater amplitude of rotational mobility, suggesting that the structural linkage between the transmembrane region and the N-terminus is destabilized. However, whereas co-reconstitution with the Ca-ATPase restricts the amplitude of rotational motion of PLB, subsequent phosphorylation of PLB does not significantly alter its rotational dynamics. Thus structural interactions between PLB and the Ca-ATPase that restrict the rotational mobility of the N-terminus of PLB are retained following the phosphorylation of PLB by PKA. On the other hand, the fluorescence intensity decay of bound dansyl is sensitive to the phosphorylation state of PLB, indicating that there are changes in the tertiary structure of PLB coincident with enzyme activation. These results suggest that PLB phosphorylation alters its structural interactions with the Ca-ATPase by inducing structural rearrangements between PLB and the Ca-ATPase within a defined complex that modulates Ca(2+)-transport function.

Animals↗