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Publications (8)26.31 Total impact

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    ABSTRACT: The authors developed an anonymous, Web-based survey instrument available globally, and collected data from 171 pemphigus vulgaris (PV) patients to assemble epidemiologic data pertaining to an extensive set of clinical parameters in demographically diverse populations. The results showed female predominance, prevalent onset of disease in the fifth decade of life, and a strong correlation of PV with thyroid disease and type 1 diabetes in patients and family members. Most patients have a history of either mucosal-only or mucocutaneous lesions, but numerous patients self-report cutaneous lesions only, without previous or concurrent mucosal lesions, especially in the non-North American PV population.
    Dermatologic clinics 07/2011; 29(3):393-404, vii-iii. · 1.29 Impact Factor
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    ABSTRACT: Proton pump inhibitors (PPIs) are widely prescribed to treat gastrointestinal diseases. However, concerns have been raised regarding their long-term use. Gastric acid suppression may decrease iron absorption, and it remains uncertain whether iron-deficiency anemia may result from chronic PPI therapy. We aimed to explore the association between chronic PPI use and iron-deficiency anemia. We conducted a retrospective cohort study of adult patients in an academic outpatient setting who received PPI therapy for at least 1 year between January 1, 2004 and January 1, 2006. We compared the change in hematologic indices among patients receiving PPI therapy for at least 1 year with matched controls. Of the 98 patients on chronic PPI therapy who met inclusion criteria, 35% had no documented indication for such therapy. At baseline, demographics and hematologic indices were similar between PPI-users and controls. Among patients on PPI therapy, all hematologic indices decreased from baseline, including hemoglobin (-0.19 g/dL, P=0.03), hematocrit (-0.63%, P=0.02), and mean corpuscular volume (-0.49 fL, P=0.05). PPI users had significant decreases in mean hemoglobin and hematocrit (P<0.01 for both) compared with matched controls. After adjustment for confounders, including rates of esophagogastroduodenoscopy, colonoscopy and remote cancer status, the odds ratio of decreasing hemoglobin by 1.0 g/dL while on chronic PPI therapy was 5.03 (95% CI, 1.71-14.78, P<0.01), while the odds ratio of decreasing hematocrit by 3% was 5.46 (95% CI, 1.67-17.85, P<0.01). Among adult patients receiving chronic PPI therapy, there is a significant decrease in hematologic indices from baseline.
    Digestive Diseases and Sciences 02/2011; 56(8):2349-53. · 2.26 Impact Factor
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    ABSTRACT: Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) is the best-studied baculovirus and most commonly used virus vector for baculovirus expression vector systems. The effect of AcMNPV infection on host cells is incompletely understood. A microarray based on Spodoptera frugiperda ESTs was used to investigate the impact of AcMNPV on host gene expression in cultured S. frugiperda, Sf21 cells. Most host genes were down-regulated over the time course of infection, although a small number were up-regulated. The most highly up-regulated genes encoded heat shock protein 70s and several poorly characterized proteins. Regulated genes with the highest score identified by functional annotation clustering included primarily products required for protein expression and trafficking in the ER and golgi. All were significantly down-regulated by approximately 12h post-infection. Microarray data were validated by qRT-PCR. This study provides the first comprehensive host transcriptome overview of Sf21 cells during AcMNPV infection.
    Virology 01/2011; 412(1):167-78. · 3.35 Impact Factor
  • Clinical Gastroenterology and Hepatology - CLIN GASTROENTEROL HEPATOL. 01/2011; 9(2):185-186.
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    ABSTRACT: Genetic strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases. The endosymbiotic bacterium Wolbachia has long been promoted as a potential vehicle for introducing disease-resistance genes into mosquitoes, thereby making them refractory to the human pathogens they transmit. Given the large overlap in tissue distribution and intracellular localization between Wolbachia and dengue virus in mosquitoes, we conducted experiments to characterize their interactions. Our results show that Wolbachia inhibits viral replication and dissemination in the main dengue vector, Aedes aegypti. Moreover, the virus transmission potential of Wolbachia-infected Ae. aegypti was significantly diminished when compared to wild-type mosquitoes that did not harbor Wolbachia. At 14 days post-infection, Wolbachia completely blocked dengue transmission in at least 37.5% of Ae. aegypti mosquitoes. We also observed that this Wolbachia-mediated viral interference was associated with an elevated basal immunity and increased longevity in the mosquitoes. These results underscore the potential usefulness of Wolbachia-based control strategies for population replacement.
    PLoS Pathogens 01/2010; 6(4):e1000833. · 8.14 Impact Factor
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    ABSTRACT: Two fifths of the world's population is at risk from dengue. The absence of effective drugs and vaccines leaves vector control as the primary intervention tool. Understanding dengue virus (DENV) host interactions is essential for the development of novel control strategies. The availability of genome sequences for both human and mosquito host greatly facilitates genome-wide studies of DENV-host interactions. We developed the first draft of the mosquito protein interaction network using a computational approach. The weighted network includes 4,214 Aedes aegypti proteins with 10,209 interactions, among which 3,500 proteins are connected into an interconnected scale-free network. We demonstrated the application of this network for the further annotation of mosquito proteins and dissection of pathway crosstalk. Using three datasets based on physical interaction assays, genome-wide RNA interference (RNAi) screens and microarray assays, we identified 714 putative DENV-associated mosquito proteins. An integrated analysis of these proteins in the network highlighted four regions consisting of highly interconnected proteins with closely related functions in each of replication/transcription/translation (RTT), immunity, transport and metabolism. Putative DENV-associated proteins were further selected for validation by RNAi-mediated gene silencing, and dengue viral titer in mosquito midguts was significantly reduced for five out of ten (50.0%) randomly selected genes. Our results indicate the presence of common host requirements for DENV in mosquitoes and humans. We discuss the significance of our findings for pharmacological intervention and genetic modification of mosquitoes for blocking dengue transmission.
    BMC Genomics 01/2010; 11:380. · 4.40 Impact Factor
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    ABSTRACT: To study the incidence and extent of the occasionally noted hypotension after intravenous (IV) infusions of fosphenytoin (FOS) and levetiracetam (LEV) in patients presenting with acute cerebral symptoms. Retrospective data collection of consecutive patients with acute cerebral symptoms who received IV infusions of a single dose of 750 mg or more of either fosphenytoin or levetiracetam and had documented blood pressure values in the 2h prior and the 2h after their IV infusion. More than 10 mmHg drop in the systolic, diastolic and MBP was observed in the FOS group following the IV infusion (-16.82 mmHg, -11.60 mmHg, and 13.34 mmHg, respectively). However, there was not a significant change in the MBP after LEV infusion (1.54 mmHg, 1.84 mmHg, and 1.74 mmHg for systolic, diastolic and MBP change, respectively). The difference in the systolic, diastolic and MBP changes between the two groups was statistical significant (all p values are <0.0001) after adjusting for age, clinical presentations of the patients and if they were on any antihypertensive medication in the hospital. Sixty two percent of patients who received FOS had >10 mmHg decrease in their MBP. In the LEV group, only 2 of the 50 patients (4%) had >10 mmHg decrease in their MBP. The difference in proportion of the patients with >10 mmHg drop in MBP between the two study groups is also statistically significant (p<0.001) for age, clinical presentations of the patients and if they were on any antihypertensive medication in the hospital. IV infusion of FOS in subjects presenting with acute cerebral symptoms may cause significant decreases in their blood pressure. This was not seen in patients receiving IV LEV infusions. Since maintaining adequate cerebral perfusion pressure is a key point in the management of patients with acute cerebral symptoms, the results of this study may carry a clinical impact on the management of this subgroup of patients.
    Epilepsy research 10/2009; 87(2-3):268-71. · 2.48 Impact Factor
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    ABSTRACT: Intracellular Wolbachia bacteria are obligate, maternally-inherited, endosymbionts found frequently in insects and other invertebrates. The success of Wolbachia can be attributed in part to an ability to alter host reproduction via mechanisms including cytoplasmic incompatibility (CI), parthenogenesis, feminization and male killing. Despite substantial scientific effort, the molecular mechanisms underlying the Wolbachia/host interaction are unknown. Here, an in vitro Wolbachia infection was generated in the Drosophila S2 cell line, and transcription profiles of infected and uninfected cells were compared by microarray. Differentially-expressed patterns related to reproduction, immune response and heat stress response are observed, including multiple genes that have been previously reported to be involved in the Wolbachia/host interaction. Subsequent in vivo characterization of differentially-expressed products in gonads demonstrates that Angiotensin Converting Enzyme (Ance) varies between Wolbachia infected and uninfected flies and that the variation occurs in a sex-specific manner. Consistent with expectations for the conserved CI mechanism, the observed Ance expression pattern is repeatable in different Drosophila species and with different Wolbachia types. To examine Ance involvement in the CI phenotype, compatible and incompatible crosses of Ance mutant flies were conducted. Significant differences are observed in the egg hatch rate resulting from incompatible crosses, providing support for additional experiments examining for an interaction of Ance with the CI mechanism. Wolbachia infection is shown to affect the expression of multiple host genes, including Ance. Evidence for potential Ance involvement in the CI mechanism is described, including the prior report of Ance in spermatid differentiation, Wolbachia-induced sex-specific effects on Ance expression and an Ance mutation effect on CI levels. The results support the use of Wolbachia infected cell cultures as an appropriate model for predicting in vivo host/Wolbachia interactions.
    BMC Genomics 02/2008; 9:1. · 4.40 Impact Factor