Exploring the Parameters of China's Economic Influence.

To what extent do China's linkages to the global economy translate into political influence in other countries? This topic is the focus of copious amounts of policy and scholarly attention in the USA and around the world. Yet without thoughtful conceptualization of key assumptions and creation of research designs that allow identification of mechanisms of potential influence, we cannot gain an accurate understanding of Chinese influence. How can we assess Beijing's intentions? Through what mechanisms-both intended and unintended-might influence arise, and under what conditions is influence most likely to occur? To what degree are Chinese companies agents of the state and therefore tools of economic statecraft? What factors condition how host countries react to economic ties with China? In this article, we explore existing scholarship on these questions, and assess promising directions for future research.

Identification of genes differentially expressed in association with reduced azole susceptibility in Saccharomyces cerevisiae.

OBJECTIVE: An isolate of S. cerevisiae with reduced susceptibility to fluconazole and itraconazole was developed in the laboratory and used to identify genes that are differentially expressed in association with this phenotype. METHODS: S. cerevisiae strain ATCC 9763 was passaged in increasing concentrations of itraconazole. Itraconazole and fluconazole MICs for the initial isolate (9763S) were 2 and 16 mg/L and for the final isolate (9763I) were 16 and > or =64 mg/L, respectively. Duplicate sets of total RNA from 9763S and 9763I were isolated and hybridized to Affymetrix S98 yeast arrays. To validate results, six differentially expressed genes were further examined by RT-PCR. RESULTS: Of the nearly 6400 open reading frames represented on the array, a total of 116 genes (1.8%) were found to be differentially expressed. Cell wall maintenance genes TIR4 and CCW12, sterol metabolism gene UPC2, small molecule transport genes AUS1 and YHK8, and stress response gene CUP1-1 were expressed at a level at least 2.5-fold higher than the expression level found in 9763S. Eleven energy generation genes, ionic homeostasis genes FRE1, FRE2 and FRE4, and sterol metabolism genes ERG8 and ERG13 were expressed at least 2.5-fold lower than the expression level found in 9763S. CONCLUSIONS: Several genes found to be differentially expressed in this study have been shown previously to be differentially expressed in the fungal response to azole treatment. In addition, the potential role of AUS1 and/or YHK8 as mediators of drug efflux is intriguing and warrants further study.

Voriconazole: a new triazole antifungal agent.

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

Differential expression of genes encoding immunomodulatory proteins in response to amphotericin B in human mononuclear cells identified by cDNA microarray analysis.

Amphotericin B (AMB) is an antifungal agent that possesses immunomodulatory properties that may contribute to its infusion-related toxicity and activity. It has previously been shown to induce the expression of genes encoding the cytokines interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha and the chemokines IL-8 and macrophage inflammatory protein (MIP)-1 beta in the human monocytic cell line THP-1. In an effort to identify additional AMB-responsive genes, the gene expression profiles of both THP-1 cells and human peripheral blood mononuclear cells (hPBMCs) on exposure to AMB were assessed using cDNA microarray analysis. In addition to genes known to be AMB responsive, we found the genes encoding IL-1 alpha and MIP-1 alpha to be AMB responsive in both THP-1 cells and hPBMCs. Increases in MIP-1 alpha and MIP-1 beta were also observed in the supernatants of hPBMCs exposed to AMB. The expression of several genes in response to AMB was unique to either cell type. Furthermore, variability in gene expression in hPBMCs was observed between donors. These genes and respective gene products may have significance in the infusion-related toxicity and activity of AMB.