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Biomedical subjects

X Ye

Publications and source records attributed to X Ye.

At least 91 records · Page 5Linked to original sources
PubMed2000

Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers.

This study was conducted to evaluate the potential pharmacokinetic interaction between fenofibrate and pravastatin. A total of 23 healthy adult volunteers received single-dose 201 mg fenofibrate alone, 201 mg fenofibrate + 40 mg pravastatin, and 40 mg pravastatin alone in a three-period crossover experiment. Plasma samples were collected at predetermined times and were analyzed with validated methods for the quantitation of fenofibric acid, pravastatin, and 3 alpha-hydroxy-isopravastatin (3 alpha-iso-PV). Pharmacokinetic parameters of these three compounds were calculated using noncompartmental methods and compared by analyses of variance and bioavailability assessments. Concomitant administration of fenofibrate and pravastatin did not affect the pharmacokinetics of either fenofibric acid or pravastatin. However, the AUC0-infinity and Cmax of 3 alpha-iso-PV were increased by 26% and 29%, respectively. The moderate increase in the formation of this pravastatin metabolite should not raise any clinical concerns due to its much lower pharmacological potency compared to pravastatin and lack of toxicity.

Adult↗
PubMed2000

Evidence for autosomal recessive inheritance of infantile dilated cardiomyopathy: studies from the Eastern Province of Saudi Arabia.

Familial dilated cardiomyopathy is being increasingly recognized, but affected individuals <10 y are rarely identified. We describe the natural history of dilated cardiomyopathy and evaluate the mode of inheritance among infants of Arab descent from the Eastern Province of Saudi Arabia. We evaluated 55 consecutive cases of dilated cardiomyopathy in patients <10 y of age seen during a 5-y interval. Echocardiography was the primary diagnostic modality. The 55 cases represented 20% of the offspring of 41 families of Arab descent. In 19 families (46%), parents were first cousins; there was no obvious consanguinity in 22 families (54%). Age at presentation was <30 mo (95%) (range, 1 to 100 mo); males (38%) and females (62%) were affected. Patients died (25 patients, 46%), improved (15 patients, 27%), or recovered (15 patients, 27%). The left ventricular shortening fraction at diagnosis ranged from 5 to 28% and did not differ in those who died, improved, or recovered. Complex segregation analysis of the family data using the mixed model of inheritance showed that a model of recessive inheritance best fits the data. Recessively inherited dilated cardiomyopathy has been infrequently reported, perhaps because it may be difficult to recognize in other patient groups in which consanguineous marriage is uncommon and the number of children per family is small. In the setting of consanguineous marriage, homozygosity mapping should lead to identification of the gene(s) causing dilated cardiomyopathy in the families we studied.

Age of Onset↗
PubMed2000

Botulinum toxin C3 inhibits hyperalgesia in mice with partial sciatic nerve injury.

Mice with partial ligation of the sciatic nerve exhibited marked increase in the second phase nociceptive biting and licking behavior following intraplantar injection of formalin. The intrathecal pretreatment with botulinum toxin C3 dose-dependently attenuated the hyperalgesia in the second phase. These results suggest that a small G protein, Rho, and its downstream mechanisms are involved in the hyperalgesia following partial nerve injury.

Animals↗
PubMed2000

Neurotrophin dependence domain: a domain required for the mediation of apoptosis by the p75 neurotrophin receptor.

The mechanisms underlying neurotrophin dependence, and cellular dependent states in general, are unknown. We show that a 29 amino acid region in the intracellular domain of the common neurotrophin receptor, p75NTR, is required for the mediation of apoptosis by p75NTR. Furthermore, contrary to results obtained with Fas, monomeric p75NTR is required for apoptosis induction, whereas multimerization inhibits the pro-apoptotic effect. Within the 29-residue domain required for apoptosis induction by p75NTR, a 14-residue region is sufficient as a peptide inducer of apoptosis. This 14-residue peptide requires the positively charged carboxyterminal residues for its effect on cell death, and these same residues are required by the full-length p75NTR. These studies define a novel type of domain that mediates neurotrophin dependence, and suggest that other cellular dependent states may be mediated by proteins displaying similar domains.

Amino Acid Sequence↗
PubMed2000

Adenovirus-mediated transfer of regulable gene expression.

The past several years have seen significant progress in the development of adenoviral vectors with markedly decreased pathological potential and greatly increased capacity for incorporation of foreign DNA. Paralleling these developments in gene transfer technology have been remarkable advances in both the design and optimization of gene regulatory systems. Ultimately, the goal of these gene regulatory systems is control of transgene expression in vivo by the administration of an exogenous compound. With the prospect of clinical human gene therapy on the horizon, the co-evolution of safe and efficient gene transfer strategies, with effective regulation of transgene expression, represents an essential step towards therapeutically viable gene transfer protocols. This review introduces recent advances in both adenoviral-based vectors and gene regulatory systems, and examines those studies in which adenoviral vectors and gene-regulatory systems have been combined in vivo.

Adenoviridae↗
PubMed2000

[Anterior corpectomy combined with cervical spine locking plate for treatment of multilevel cervical spondylotic myelopathy].

OBJECTIVE: To study the value of cervical spine locking plate (CSLP) combined with anterior corpectomy in treating multilevel cervical spondylotic myelopathy (CSM). METHODS: In 55 CSM patients, 36 were male and 19 female, aged on average 51.5 years. The duration of illness was 13 months on average. Pathological segments in 47 patients included two functional segments and in 8 three functional segments. All patients were treated with anterior corpectomy and self-iliac bone graft and CSLP fixation. RESULTS: 51 patients were followed up for 26 months on average. All grafting bones got solid fusion in 12 to 16 weeks postoperatively. Intervertebral spaces were restored after operation. The physiological curve of the cervical spine was good. The effective rate of operation was 94.1% (48/51) and the excellent rate 78.4% (40/51). The JOA score rose from 8.3 points before operation to 14.1 points after operation. CONCLUSIONS: Anterior corpectomy and osteosynthesis of multilevel cervical spondylotic myelopathy are indicated for CSLP fixation. CSLP in the treatment of cervical spine instability is prospective.

Aged↗
PubMed2000

[Photoluminescence study of star-like C60(CH3)x(PAN)x copolymer].

Thin film of new synthesized C60(CH3)x(PAN)x copolymer was fabricated by physical jet deposition (PJD) technique. C60 molecule lies in the center of the star-like copolymers. PAN main chain is modified around the C60 molecules. Absorption and photoluminescence spectra show that there are strong interaction between C60 molecule and PAN, which depends on the length of PAN chain. Partly excitation transfer process between C60 molecule and PAN was observed, which leads to the fluorescence quenching of the PAN.

English Abstract↗
PubMed1999

TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction.

The common neurotrophin receptor, p75(NTR), has been shown to signal in the absence of Trk tyrosine kinase receptors, including induction of neural apoptosis and activation of NF-kappaB. However, the mechanisms by which p75(NTR) initiates these intracellular signal transduction pathways are unknown. Here we report interactions between p75(NTR) and the six members of TRAF (tumor necrosis factor receptor-associated factors) family proteins. The binding of different TRAF proteins to p75(NTR) was mapped to distinct regions in p75(NTR). Furthermore, TRAF4 interacted with dimeric p75(NTR), whereas TRAF2 interacted preferentially with monomeric p75(NTR). TRAF2-p75(NTR), TRAF4-p75(NTR), and TRAF6-p75(NTR) interactions modulated p75(NTR)-induced cell death and NF-kappaB activation with contrasting effects. Coexpression of TRAF2 with p75(NTR) enhanced cell death, whereas coexpression of TRAF6 was cytoprotective. Furthermore, overexpression of TRAF4 abrogated the ability of dimerization to prevent the induction of apoptosis normally mediated by monomeric p75(NTR). TRAF4 also inhibited the NF-kappaB response, whereas TRAF2 and TRAF6 enhanced p75(NTR)-induced NF-kappaB activation. These results demonstrate that TRAF family proteins interact with p75(NTR) and differentially modulate its NF-kappaB activation and cell death induction.

Apoptosis↗
PubMed1999

Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate prevents In vivo expression of proinflammatory genes.

Background-The inability to inhibit multiple mediators of septic shock represents a major hurdle in the treatment of septic shock. In vivo inhibition of nuclear factor (NF)-kappaB activation, a transcription factor regulating expression of many proinflammatory genes, could provide a useful strategy for the treatment of septic shock. Methods and Results-In rats challenged with lipopolysaccharide (LPS) 8 mg/kg IV, we determined the time course of NF-kappaB activation and expression of multiple inflammatory signals: tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), cytokine-inducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM)-1. We studied the effects of in vivo inhibition of NF-kappaB activation using pyrrolidine dithiocarbamate (PDTC) on the expression of these mediators. NF-kappaB activation preceded the induction of TNF-alpha, COX-2, CINC, and ICAM-1 mRNAs. PDTC prevented the LPS-induced NF-kappaB activation but did not inhibit activation of the transcription factors AP-1, Sp-1, and CREB. PDTC inhibited the LPS-induced expression of TNF-alpha, COX-2, CINC, and ICAM-1 mRNA and proteins and reduced the LPS-induced increases in plasma TNF-alpha, 6-keto-prostaglandin F(1alpha), and CINC concentrations. Inhibition of expression of these mediators prevented the increases in myeloperoxidase activity (a measure of neutrophil sequestration) in the heart, lungs, and liver. Conclusions-NF-kappaB activation correlates with LPS-induced expression of TNF-alpha, COX-2, CINC, and ICAM-1 genes in vivo. PDTC inhibits NF-kappaB activation and expression of these proinflammatory genes and their products. Thus, blocking NF-kappaB activation may be an effective strategy in the treatment of septic shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Long-term regulated expression of growth hormone in mice after intramuscular gene transfer.

Effective delivery of secreted proteins by gene therapy will require a vector that directs stable delivery of a transgene and a regulatory system that permits pharmacologic control over the level and kinetics of therapeutic protein expression. We previously described a regulatory system that enables transcription of a target gene to be controlled by rapamycin, an orally bioavailable drug. Here we demonstrate in vivo regulation of gene expression after intramuscular injection of two separate adenovirus or adeno-associated virus (AAV) vectors, one encoding an inducible human growth hormone (hGH) target gene, and the other a bipartite rapamycin-regulated transcription factor. Upon delivery of either vector system into immunodeficient mice, basal plasma hGH expression was undetectable and was induced to high levels after administration of rapamycin. The precise level and duration of hGH expression could be controlled by the rapamycin dosing regimen. Equivalent profiles of induction were observed after repeated administration of single doses of rapamycin over many months. AAV conferred stable expression of regulated hGH in both immunocompetent and immunodeficient mice, whereas adenovirus-directed hGH expression quickly extinguished in immunocompetent animals. These studies demonstrate that the rapamycin-based regulatory system, delivered intramuscularly by AAV, fulfills many of the conditions necessary for the safe and effective delivery of therapeutic proteins by gene therapy.

Adenoviridae↗
PubMed1999

The endothelial cell protein C receptor (EPCR) functions as a primary receptor for protein C activation on endothelial cells in arteries, veins, and capillaries.

Plasma protein C functions as an anticoagulant when it is converted to the active form of serine protease. Protein C activation has been found to be mediated by the endothelial cell surface thrombin/thrombomodulin (TM) complex. In addition, we recently identified the endothelial cell protein C/activated protein C receptor (EPCR) which is capable of high-affinity binding for protein C. In this study, we established monoclonal antibodies (mAbs) against EPCR including several function blocking antibodies. Immunohistochemical analysis using these mAbs demonstrated that EPCR is widely expressed in the endothelial cells of arteries, veins, and capillaries in the lung, heart, and skin. Function blocking anti-EPCR mAbs strongly inhibited protein C activation mediated by primary cultured arterial endothelial cells which express abundant EPCR. Anti-EPCR mAbs also prevent protein C activation mediated by microvascular endothelial cells. These results indicate that EPCR functions as an important regulator for the protein C pathway in various types of vessels.

Antibodies, Monoclonal↗
PubMed1999

Integrated mapping package--a physical mapping software tool kit.

We have developed an integrated physical mapping computer software package (IMP), originally designed to support the physical mapping of human chromosome 13 and expanded to support several gene-identification projects based on the positional candidate approach. IMP displays map data in a form that provides useful guidelines to the end users. An integrated map with high resolution and confidence is constructed from different types of mapping data, including hybridization experiments, STS-based PCR assays, genetic linkage mapping, cDNA localization, and FISH data. The map is also designed to provide suggestions for specific experiments that are required to obtain maps with even higher resolution and confidence. To this end, the optimization employs multiple constraints that take into account already established STS "scaffold" maps. This software thus serves as an important general tool kit for physical mapping, sequencing, and gene-hunting projects.

Algorithms↗
PubMed1999

Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer.

Stable delivery of a therapeutic protein under pharmacologic control was achieved through in vivo somatic gene transfer. This system was based on the expression of two chimeric, human-derived proteins that were reconstituted by rapamycin into a transcription factor complex. A mixture of two adeno-associated virus vectors, one expressing the transcription factor chimeras and one containing erythropoietin (Epo) under the control of a promoter responsive to the transcription factor, was injected into skeletal muscle of immune-competent mice. Administration of rapamycin resulted in 200-fold induction of plasma Epo. Stable engraftment of this humanized system in immune-competent mice was achieved for 6 months with similar results for at least 3 months in a rhesus monkey.

Animals↗
PubMed1999

Dynamics of placodal lineage development revealed by targeted transgene expression.

Examination of the expression pattern of the winged-helix transcription factor BF-1 outside of the neural tube in mouse embryos suggests that BF-1 is restricted to a population of cells that gives rise to the ectodermal placodes and their derivatives. Within the sensory cranial nerve ganglia, the expression of BF-1 distinguishes cells that arise from the placodes from those derived from the neural crest. Expression of a lacZ transgene targeted to the BF-1 locus was used to follow the placodal lineage during mouse development. Analysis of placodal development in mice with a targeted deletion of BF-1 reveals that, although BF-1 is required for proliferation of the cells arising from the nasal placode, it is not required for the proliferation, survival, or both, of placode-derived cells in the sensory cranial nerve ganglia. Dev Dyn 1999;215:332-343.

Animals↗
PubMed1999

A color-selectable and site-specific integrative transformation system for gene expression studies in the dematiaceous fungus Wangiella (Exophiala) dermatitidis.

To explore potential virulence factors in the dematiaceous (melanized) fungus Wangiella dermatitidis, we established a gene expression system with properties of homologous transformation and color identification. Using a polyketide synthase gene (WdPKS1) fragment for targeting, we found that 52% of transformants became albinos easily distinguishable from nonspecific transformants. Southern analysis confirmed that the integrations were at the WdPKS1 locus, which however did not affect transformant growth. With a heterologous promoter, P-glaA, enhanced expression of lacZ was found at 37 degrees C. Our results indicated that this system allows the efficient production of isogenic strains for gene function analysis in W. dermatitidis.

Amino Acid Sequence↗
PubMed1999

Inducible lethal ventricular arrhythmias in swine with pacing-induced heart failure.

INTRODUCTION: Rapid pacing-induced heart failure provides an excellent animal model for the study of heart failure. We studied the development of ventricular tachyarrhythmias using programmed stimulation in a pacing-induced heart failure model. We also studied action potential characteristics and the relationship between action potential and heart rate. METHODS AND RESULTS: Ten pigs were instrumented and were studied before the onset and every week after rapid pacing was instituted. Weekly echocardiograms and programmed stimulation were done in a sedated state. In vitro electrophysiologic studies were done on left ventricular myocardium in 4 heart-failure animals and 4 controls. All animals developed progressive heart failure with left ventricular dilatation and reduced percentage fractional shortening. No arrhythmias were induced at baseline or the first and second weeks. Ventricular fibrillation was induced in one animal on the third week and 4 animals on week 4, while there was no appreciable worsening in echocardiographic indices of ventricular dysfunction between weeks 3 and 4. Ventricular effective refractory period was unchanged during the 4 weeks. In vitro studies showed action potential prolongation in heart failure myocardium. However, action potential duration at pacing rates >100 bpm were similar to controls. No early or delayed afterdepolarizations were observed. CONCLUSION: This study demonstrated an increased susceptibility to ventricular fibrillation with the development of heart failure which was not related to the degree of ventricular dysfunction. Also, the normalization of action potential duration at higher heart rates suggests that the increased incidence of inducible ventricular fibrillation in this model may not be solely due to prolonged action potential duration.

Animals↗
PubMed1999

RNA architecture dictates the conformations of a bound peptide.

BACKGROUND: The biological function of several viral and bacteriophage proteins, and their arginine-rich subdomains, involves RNA-mediated interactions. It has been shown recently that bound peptides adopt either beta-hairpin or alpha-helical conformations in viral and phage peptide-RNA complexes. We have compared the structures of the arginine-rich peptide domain of HIV-1 Rev bound to two RNA aptamers to determine whether RNA architecture can dictate the conformations of a bound peptide. RESULTS: The core-binding segment of the HIV-1 Rev peptide class II RNA aptamer complex spans the two-base bulge and hairpin loop of the bound RNA and the carboxy-terminal segment of the bound peptide. The bound peptide is anchored in place by backbone and sidechain intermolecular hydrogen bonding and van der Waals stacking interactions. One of the bulge bases participates in U*(A*U) base triple formation, whereas the other is looped out and flaps over the bound peptide in the complex. The seven-residue hairpin loop is closed by a sheared G*A mismatch pair with several pyrimidines looped out of the hairpin fold. CONCLUSIONS: Our structural studies establish that RNA architecture dictates whether the same HIV-1 Rev peptide folds into an extended or alpha-helical conformation on complex formation. Arginine-rich peptides can therefore adapt distinct secondary folds to complement the tertiary folds of their RNA targets. This contrasts with protein-RNA complexes in which elements of RNA secondary structure adapt to fit within the tertiary folds of their protein targets.

Arginine↗