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Pratt School of Engineering
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Publications of Aimee K Zaas    :chronological  alphabetical  combined listing:

%% Papers Published   
   Author = {M Chen and D Carlson and A Zaas and CW Woods and GS Ginsburg and A Hero
             3rd and J Lucas and L Carin},
   Title = {Detection of viruses via statistical gene expression
   Journal = {IEEE transactions on bio-medical engineering},
   Volume = {58},
   Number = {3},
   Pages = {468-79},
   Year = {2011},
   Month = {March},
   ISSN = {1558-2531},
   url = {},
   Abstract = {We develop a new bayesian construction of the elastic net
             (ENet), with variational bayesian analysis. This modeling
             framework is motivated by analysis of gene expression data
             for viruses, with a focus on H3N2 and H1N1 influenza, as
             well as Rhino virus and RSV (respiratory syncytial virus).
             Our objective is to understand the biological pathways
             responsible for the host response to such viruses, with the
             ultimate objective of developing a clinical test to
             distinguish subjects infected by such viruses from subjects
             with other symptom causes (e.g., bacteria). In addition to
             analyzing these new datasets, we provide a detailed analysis
             of the bayesian ENet and compare it to related
   Language = {eng},
   Doi = {10.1109/TBME.2010.2059702},
   Key = {fds191235}

   Author = {CD Pfeiffer and G Garcia-Effron and AK Zaas, JR Perfect and DS
             Perlin, BD Alexander},
   Title = {Breakthrough invasive candidiasis in patients on
   Journal = {Journal of clinical microbiology},
   Volume = {48},
   Number = {7},
   Pages = {2373-80},
   Year = {2010},
   Month = {July},
   ISSN = {1098-660X},
   url = {},
   Keywords = {Adolescent • Adult • Aged • Antifungal Agents
             • Candida • Candidiasis • Drug Resistance,
             Fungal • Echinocandins • Female • Fungal
             Proteins • Glucosyltransferases • Humans •
             Lipopeptides • Male • Microbial Sensitivity Tests
             • Middle Aged • administration & dosage •
             complications • drug effects* • genetics •
             genetics* • isolation & purification •
             microbiology* • pharmacology • therapeutic
   Abstract = {For Candida species, a bimodal wild-type MIC distribution
             for echinocandins exists, but resistance to echinocandins is
             rare. We characterized isolates from patients with invasive
             candidiasis (IC) breaking through >or=3 doses of micafungin
             therapy during the first 28 months of its use at our center:
             MICs were determined and hot-spot regions within FKS genes
             were sequenced. Eleven of 12 breakthrough IC cases
             identified were in transplant recipients. The median
             duration of micafungin exposure prior to breakthrough was 33
             days (range, 5 to 165). Seventeen breakthrough isolates were
             recovered: FKS hot-spot mutations were found in 5 C.
             glabrata and 2 C. tropicalis isolates; of these, 5
             (including all C. glabrata isolates) had micafungin MICs of
             >2 microg/ml, but all demonstrated caspofungin MICs of >2
             microg/ml. Five C. parapsilosis isolates had wild-type FKS
             sequences and caspofungin MICs of 0.5 to 1 microg/ml, but
             4/5 had micafungin MICs of >2 microg/ml. The remaining
             isolates retained echinocandin MICs of <or=2 microg/ml and
             wild-type FKS gene sequences. Breakthrough IC on micafungin
             treatment occurred predominantly in severely
             immunosuppressed patients with heavy prior micafungin
             exposure. The majority of cases were due to C. glabrata with
             an FKS mutation or wild-type C. parapsilosis with elevated
             micafungin MICs. MIC testing with caspofungin identified all
             mutant strains. Whether the naturally occurring polymorphism
             within the C. parapsilosis FKS1 gene responsible for the
             bimodal wild-type MIC distribution is also responsible for
             micafungin MICs of >2 microg/ml and clinical breakthrough or
             an alternative mechanism contributes to the nonsusceptible
             echinocandin MICs in C. parapsilosis requires further
   Language = {eng},
   Doi = {10.1128/JCM.02390-09},
   Key = {fds191208}

   Author = {AK Zaas and H Aziz and J Lucas, JR Perfect and GS
   Title = {Blood gene expression signatures predict invasive
   Journal = {Science translational medicine},
   Volume = {2},
   Number = {21},
   Pages = {21ra17},
   Year = {2010},
   Month = {March},
   ISSN = {1946-6242},
   url = {},
   Keywords = {Algorithms • Animals • Bacteremia • Candida
             albicans • Candidiasis • Disease Progression
             • Gene Expression Profiling* • Male • Mice
             • Mice, Inbred BALB C • Species Specificity •
             Time Factors • blood* • diagnosis • genetics
             • genetics* • isolation & purification* •
             microbiology • pathogenicity*},
   Abstract = {Candidemia is the fourth most common bloodstream infection,
             with Candida albicans being the most common causative
             species. Success in reducing the associated morbidity and
             mortality has been limited by the inadequacy and time delay
             of currently available diagnostic modalities. Focusing on
             host response to infection, we used a murine model to
             develop a blood gene expression signature that accurately
             classified mice with candidemia and distinguished candidemia
             from Staphylococcus aureus bacteremia. Validation of the
             signature was achieved in an independent cohort of mice.
             Genes represented in the signature have known associations
             with host defense against Candida and other microorganisms.
             Our results demonstrate a temporal pattern of host molecular
             responses that distinguish candidemia from S. aureus-induced
             bacteremia and establish a novel paradigm for infectious
             disease diagnosis.},
   Language = {eng},
   Doi = {10.1126/scitranslmed.3000715},
   Key = {fds191210}

   Author = {SL LaFayette and C Collins and AK Zaas and WA Schell and M
             Betancourt-Quiroz, AA Gunatilaka, JR Perfect and LE
   Title = {PKC signaling regulates drug resistance of the fungal
             pathogen Candida albicans via circuitry comprised of Mkc1,
             calcineurin, and Hsp90.},
   Journal = {PLoS pathogens},
   Volume = {6},
   Number = {8},
   Year = {2010},
   ISSN = {1553-7374},
   url = {},
   Keywords = {Animals • Antifungal Agents • Calcineurin •
             Candida albicans • Drug Resistance, Fungal •
             Fungal Proteins • HSP90 Heat-Shock Proteins •
             Immunoblotting • Mice • Microbial Sensitivity
             Tests • Mitogen-Activated Protein Kinases •
             Protein Kinase C • Reverse Transcriptase Polymerase
             Chain Reaction • Saccharomyces cerevisiae • Signal
             Transduction • genetics • genetics* •
             metabolism • metabolism* • pharmacology •
   Abstract = {Fungal pathogens exploit diverse mechanisms to survive
             exposure to antifungal drugs. This poses concern given the
             limited number of clinically useful antifungals and the
             growing population of immunocompromised individuals
             vulnerable to life-threatening fungal infection. To identify
             molecules that abrogate resistance to the most widely
             deployed class of antifungals, the azoles, we conducted a
             screen of 1,280 pharmacologically active compounds. Three
             out of seven hits that abolished azole resistance of a
             resistant mutant of the model yeast Saccharomyces cerevisiae
             and a clinical isolate of the leading human fungal pathogen
             Candida albicans were inhibitors of protein kinase C (PKC),
             which regulates cell wall integrity during growth,
             morphogenesis, and response to cell wall stress.
             Pharmacological or genetic impairment of Pkc1 conferred
             hypersensitivity to multiple drugs that target synthesis of
             the key cell membrane sterol ergosterol, including azoles,
             allylamines, and morpholines. Pkc1 enabled survival of cell
             membrane stress at least in part via the mitogen activated
             protein kinase (MAPK) cascade in both species, though
             through distinct downstream effectors. Strikingly,
             inhibition of Pkc1 phenocopied inhibition of the molecular
             chaperone Hsp90 or its client protein calcineurin. PKC
             signaling was required for calcineurin activation in
             response to drug exposure in S. cerevisiae. In contrast,
             Pkc1 and calcineurin independently regulate drug resistance
             via a common target in C. albicans. We identified an
             additional level of regulatory control in the C. albicans
             circuitry linking PKC signaling, Hsp90, and calcineurin as
             genetic reduction of Hsp90 led to depletion of the terminal
             MAPK, Mkc1. Deletion of C. albicans PKC1 rendered
             fungistatic ergosterol biosynthesis inhibitors fungicidal
             and attenuated virulence in a murine model of systemic
             candidiasis. This work establishes a new role for PKC
             signaling in drug resistance, novel circuitry through which
             Hsp90 regulates drug resistance, and that targeting stress
             response signaling provides a promising strategy for
             treating life-threatening fungal infections.},
   Language = {eng},
   Doi = {10.1371/journal.ppat.1001069},
   Key = {fds191202}

   Author = {SH Ahn and H Deshmukh and N Johnson and LG Cowell and TH Rude and WK Scott and CL Nelson and AK Zaas and DA Marchuk and S Keum and S Lamlertthon and BK
             Sharma-Kuinkel, GD Sempowski and VG Fowler Jr},
   Title = {Two genes on A/J chromosome 18 are associated with
             susceptibility to Staphylococcus aureus infection by
             combined microarray and QTL analyses.},
   Journal = {PLoS pathogens},
   Volume = {6},
   Number = {9},
   Pages = {e1001088},
   Year = {2010},
   ISSN = {1553-7374},
   url = {},
   Keywords = {Animals • Apoptosis Regulatory Proteins •
             Biological Markers • Blotting, Western •
             Chemokines • Chromosome Mapping • Chromosomes,
             Mammalian • Cytokines • Enzyme-Linked
             Immunosorbent Assay • Flow Cytometry • Gene
             Expression Profiling • Genetic Predisposition to
             Disease* • Humans • Macrophages, Peritoneal •
             Male • Mice • Mice, Inbred A • Mice, Inbred
             C57BL • Neutrophils • Oligonucleotide Array
             Sequence Analysis • Phenotype • Polymorphism,
             Single Nucleotide • Quantitative Trait Loci • RNA,
             Messenger • RNA, Small Interfering • Reverse
             Transcriptase Polymerase Chain Reaction • Sepsis •
             Staphylococcal Infections • Staphylococcus aureus
             • antagonists & inhibitors • cytology •
             genetics • genetics* • metabolism •
             microbiology • pathogenicity • pathology •
   Abstract = {Although it has recently been shown that A/J mice are highly
             susceptible to Staphylococcus aureus sepsis as compared to
             C57BL/6J, the specific genes responsible for this
             differential phenotype are unknown. Using chromosome
             substitution strains (CSS), we found that loci on
             chromosomes 8, 11, and 18 influence susceptibility to S.
             aureus sepsis in A/J mice. We then used two candidate gene
             selection strategies to identify genes on these three
             chromosomes associated with S. aureus susceptibility, and
             targeted genes identified by both gene selection strategies.
             First, we used whole genome transcription profiling to
             identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr.
             18) genes on our three chromosomes of interest that are
             differentially expressed between S. aureus-infected A/J and
             C57BL/6J. Second, we identified two significant quantitative
             trait loci (QTL) for survival post-infection on chr. 18
             using N(2) backcross mice (F(1) [C18A]xC57BL/6J). Ten genes
             on chr. 18 (March3, Cep120, Chmp1b, Dcp2, Dtwd2, Isoc1,
             Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two
             significant QTL regions and were also identified by the
             expression array selection strategy. Using real-time PCR, 6
             of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8, and
             Seh1l) showed significantly different expression levels
             between S. aureus-infected A/J and C57BL/6J. For two
             (Tnfaip8 and Seh1l) of these 6 genes, siRNA-mediated
             knockdown of gene expression in S. aureus-challenged
             RAW264.7 macrophages induced significant changes in the
             cytokine response (IL-1 beta and GM-CSF) compared to
             negative controls. These cytokine response changes were
             consistent with those seen in S. aureus-challenged
             peritoneal macrophages from CSS 18 mice (which contain A/J
             chromosome 18 but are otherwise C57BL/6J), but not C57BL/6J
             mice. These findings suggest that two genes, Tnfaip8 and
             Seh1l, may contribute to susceptibility to S. aureus in A/J
             mice, and represent promising candidates for human genetic
             susceptibility studies.},
   Language = {eng},
   Doi = {10.1371/journal.ppat.1001088},
   Key = {fds191223}

   Author = {B Chen and M Chen and J Paisley and A Zaas and C Woods and GS Ginsburg and A
             Hero 3rd, J Lucas and D Dunson and L Carin},
   Title = {Bayesian inference of the number of factors in
             gene-expression analysis: application to human virus
             challenge studies.},
   Journal = {BMC bioinformatics},
   Volume = {11},
   Pages = {552},
   Year = {2010},
   ISSN = {1471-2105},
   url = {},
   Keywords = {Bayes Theorem • Gene Expression Profiling • Gene
             Expression* • Humans • Oligonucleotide Array
             Sequence Analysis • Orthomyxoviridae • Respiratory
             Syncytial Viruses • Rhinovirus • Virus
             Physiological Processes* • genetics • metabolism
             • methods • methods*},
   Abstract = {BACKGROUND: Nonparametric Bayesian techniques have been
             developed recently to extend the sophistication of factor
             models, allowing one to infer the number of appropriate
             factors from the observed data. We consider such techniques
             for sparse factor analysis, with application to
             gene-expression data from three virus challenge studies.
             Particular attention is placed on employing the Beta Process
             (BP), the Indian Buffet Process (IBP), and related
             sparseness-promoting techniques to infer a proper number of
             factors. The posterior density function on the model
             parameters is computed using Gibbs sampling and variational
             Bayesian (VB) analysis. RESULTS: Time-evolving
             gene-expression data are considered for respiratory
             syncytial virus (RSV), Rhino virus, and influenza, using
             blood samples from healthy human subjects. These data were
             acquired in three challenge studies, each executed after
             receiving institutional review board (IRB) approval from
             Duke University. Comparisons are made between several
             alternative means of per-forming nonparametric factor
             analysis on these data, with comparisons as well to
             sparse-PCA and Penalized Matrix Decomposition (PMD), closely
             related non-Bayesian approaches. CONCLUSIONS: Applying the
             Beta Process to the factor scores, or to the singular values
             of a pseudo-SVD construction, the proposed algorithms infer
             the number of factors in gene-expression data. For real data
             the "true" number of factors is unknown; in our simulations
             we consider a range of noise variances, and the proposed
             Bayesian models inferred the number of factors accurately
             relative to other methods in the literature, such as
             sparse-PCA and PMD. We have also identified a "pan-viral"
             factor of importance for each of the three viruses
             considered in this study. We have identified a set of genes
             associated with this pan-viral factor, of interest for early
             detection of such viruses based upon the host response, as
             quantified via gene-expression data.},
   Language = {eng},
   Doi = {10.1186/1471-2105-11-552},
   Key = {fds191227}

   Author = {AK Zaas and M Chen and J Varkey and T Veldman and AO Hero 3rd and J Lucas and Y Huang and R Turner and A Gilbert and R Lambkin-Williams and NC Øien, B Nicholson and S Kingsmore and L Carin and CW Woods and GS
   Title = {Gene expression signatures diagnose influenza and other
             symptomatic respiratory viral infections in
   Journal = {Cell host & microbe},
   Volume = {6},
   Number = {3},
   Pages = {207-17},
   Year = {2009},
   Month = {September},
   ISSN = {1934-6069},
   url = {},
   Keywords = {Blood Cells • Cells, Cultured • Cohort Studies
             • Gene Expression Profiling • Humans •
             Influenza A virus • Influenza, Human • Respiratory
             Tract Infections • Virus Diseases • Virus
             Physiological Phenomena • diagnosis • diagnosis*
             • genetics • genetics* • metabolism •
             methods* • physiology • virology},
   Abstract = {Acute respiratory infections (ARIs) are a common reason for
             seeking medical attention, and the threat of pandemic
             influenza will likely add to these numbers. Using human
             viral challenge studies with live rhinovirus, respiratory
             syncytial virus, and influenza A, we developed peripheral
             blood gene expression signatures that distinguish
             individuals with symptomatic ARIs from uninfected
             individuals with >95% accuracy. We validated this "acute
             respiratory viral" signature-encompassing genes with a known
             role in host defense against viral infections-across each
             viral challenge. We also validated the signature in an
             independently acquired data set for influenza A and
             classified infected individuals from healthy controls with
             100% accuracy. In the same data set, we could also
             distinguish viral from bacterial ARIs (93% accuracy). These
             results demonstrate that ARIs induce changes in human
             peripheral blood gene expression that can be used to
             diagnose a viral etiology of respiratory infection and
             triage symptomatic individuals.},
   Language = {eng},
   Doi = {10.1016/j.chom.2009.07.006},
   Key = {fds191232}

   Author = {SD Singh and N Robbins and AK Zaas and WA Schell, JR Perfect and LE
   Title = {Hsp90 governs echinocandin resistance in the pathogenic
             yeast Candida albicans via calcineurin.},
   Journal = {PLoS pathogens},
   Volume = {5},
   Number = {7},
   Pages = {e1000532},
   Year = {2009},
   Month = {July},
   ISSN = {1553-7374},
   url = {},
   Keywords = {Analysis of Variance • Animals • Antifungal Agents
             • Azoles • Calcineurin • Candida albicans
             • Candidiasis • DNA-Binding Proteins •
             Disease Models, Animal • Drug Resistance, Fungal •
             Echinocandins • Fungal Proteins • HSP90 Heat-Shock
             Proteins • Lipopeptides • Male • Mice •
             Stress, Physiological • Transcription Factors •
             antagonists & inhibitors • drug effects • drug
             therapy • genetics • metabolism • metabolism*
             • microbiology • pharmacology •
   Abstract = {Candida albicans is the leading fungal pathogen of humans,
             causing life-threatening disease in immunocompromised
             individuals. Treatment of candidiasis is hampered by the
             limited number of antifungal drugs whose efficacy is
             compromised by host toxicity, fungistatic activity, and the
             emergence of drug resistance. We previously established that
             the molecular chaperone Hsp90, which regulates the form and
             function of diverse client proteins, potentiates resistance
             to the azoles in C. albicans and in the model yeast
             Saccharomyces cerevisiae. Genetic studies in S. cerevisiae
             revealed that Hsp90's role in azole resistance is to enable
             crucial cellular responses to the membrane stress exerted by
             azoles via the client protein calcineurin. Here, we
             demonstrate that Hsp90 governs cellular circuitry required
             for resistance to the only new class of antifungals to reach
             the clinic in decades, the echinocandins, which inhibit
             biosynthesis of a critical component of the fungal cell
             wall. Pharmacological or genetic impairment of Hsp90
             function reduced tolerance of C. albicans laboratory strains
             and resistance of clinical isolates to the echinocandins and
             created a fungicidal combination. Compromising calcineurin
             function phenocopied compromising Hsp90 function. We
             established that calcineurin is an Hsp90 client protein in
             C. albicans: reciprocal co-immunoprecipitation validated
             physical interaction; Hsp90 inhibition blocked calcineurin
             activation; and calcineurin levels were depleted upon
             genetic reduction of Hsp90. The downstream effector of
             calcineurin, Crz1, played a partial role in mediating
             calcineurin-dependent stress responses activated by
             echinocandins. Hsp90's role in echinocandin resistance has
             therapeutic potential given that genetic compromise of C.
             albicans HSP90 expression enhanced the efficacy of an
             echinocandin in a murine model of disseminated candidiasis.
             Our results identify the first Hsp90 client protein in C.
             albicans, establish an entirely new role for Hsp90 in
             mediating resistance to echinocandins, and demonstrate that
             targeting Hsp90 provides a promising therapeutic strategy
             for the treatment of life-threatening fungal
   Language = {eng},
   Doi = {10.1371/journal.ppat.1000532},
   Key = {fds191230}

   Author = {RS Shapiro and P Uppuluri and AK Zaas and C Collins and H Senn, JR
             Perfect and J Heitman and LE Cowen},
   Title = {Hsp90 orchestrates temperature-dependent Candida albicans
             morphogenesis via Ras1-PKA signaling.},
   Journal = {Current biology : CB},
   Volume = {19},
   Number = {8},
   Pages = {621-9},
   Year = {2009},
   Month = {April},
   ISSN = {1879-0445},
   url = {},
   Keywords = {Animals • Candida albicans • Candidiasis •
             Cyclic AMP-Dependent Protein Kinases • Cyclic
             Nucleotide Phosphodiesterases, Type 1 • Cyclic
             Nucleotide Phosphodiesterases, Type 2 • Fungal Proteins
             • GTPase-Activating Proteins • HSP90 Heat-Shock
             Proteins • Humans • Hyphae • Isoenzymes
             • Mice • Morphogenesis • Quorum Sensing
             • Signal Transduction • cytology • genetics
             • growth & development* • metabolism •
             metabolism* • physiology • physiology* • ras
   Abstract = {BACKGROUND: Hsp90 is an environmentally contingent molecular
             chaperone that influences the form and function of diverse
             regulators of cellular signaling. Hsp90 potentiates the
             evolution of fungal drug resistance by enabling crucial
             cellular stress responses. Here we demonstrate that in the
             leading fungal pathogen of humans, Candida albicans, Hsp90
             governs cellular circuitry required not only for drug
             resistance but also for the key morphogenetic transition
             from yeast to filamentous growth that is crucial for
             virulence. This transition is normally regulated by
             environmental cues, such as exposure to serum, that are
             contingent upon elevated temperature to induce
             morphogenesis. The basis for this temperature dependence has
             remained enigmatic. RESULTS: We show that compromising Hsp90
             function pharmacologically or genetically induces a
             transition from yeast to filamentous growth in the absence
             of external cues. Elevated temperature relieves
             Hsp90-mediated repression of the morphogenetic program.
             Hsp90 regulates morphogenetic circuitry by repressing
             Ras1-PKA signaling. Modest Hsp90 compromise enhances the
             phenotypic effects of activated Ras1 signaling whereas
             deletion of positive regulators of the Ras1-PKA cascade
             blocks the morphogenetic response to Hsp90 inhibition.
             Consistent with the requirement for morphogenetic
             flexibility for virulence, depletion of C. albicans Hsp90
             attenuates virulence in a murine model of systemic disease.
             CONCLUSIONS: Hsp90 governs the integration of environmental
             cues with cellular signaling to orchestrate fungal
             morphogenesis and virulence, suggesting new therapeutic
             strategies for life-threatening infectious disease. Hsp90's
             capacity to govern a key developmental program in response
             to temperature change provides a new mechanism that
             complements the elegant repertoire that organisms utilize to
             sense temperature.},
   Language = {eng},
   Doi = {10.1016/j.cub.2009.03.017},
   Key = {fds191234}

   Author = {LE Cowen and SD Singh, JR Köhler and C Collins and AK Zaas and WA
             Schell, H Aziz and E Mylonakis, JR Perfect and L Whitesell and S
   Title = {Harnessing Hsp90 function as a powerful, broadly effective
             therapeutic strategy for fungal infectious
   Journal = {Proceedings of the National Academy of Sciences of the
             United States of America},
   Volume = {106},
   Number = {8},
   Pages = {2818-23},
   Year = {2009},
   Month = {February},
   ISSN = {1091-6490},
   url = {},
   Keywords = {Animals • Antifungal Agents • Fluconazole •
             Fungi • HSP90 Heat-Shock Proteins • Humans •
             Male • Mice • Microbial Sensitivity Tests •
             Mycoses • drug effects • drug therapy •
             genetics • microbiology • pharmacology •
             physiology* • physiopathology • therapeutic use
             • therapy*},
   Abstract = {Invasive fungal infections are a leading cause of mortality
             among immunocompromised individuals. Treatment is
             notoriously difficult with the limited armamentarium of
             antifungal drugs, whose efficacy is compromised by host
             toxicity, a limited activity spectrum, or the emergence of
             drug resistance. We previously established that the
             molecular chaperone Hsp90 enables the emergence and
             maintenance of fungal drug resistance. For the most
             prevalent fungal pathogen of humans, Candida albicans, Hsp90
             mediates resistance to azoles, which inhibit ergosterol
             biosynthesis and are the most widely deployed antifungals in
             the clinic. For the emerging opportunistic pathogen
             Aspergillus terreus, Hsp90 is required for basal resistance
             to echinocandins, which inhibit beta(1, 3)-glucan synthesis
             and are the only new class of antifungals to reach the
             clinic in decades. Here, we explore the therapeutic
             potential of Hsp90 inhibitors in fungal disease using a
             tractable host-model system, larvae of the greater wax moth
             Galleria mellonella, and a murine model of disseminated
             disease. Combination therapy with Hsp90 inhibitors that are
             well tolerated in humans and an azole rescued larvae from
             lethal C. albicans infections. Combination therapy with an
             Hsp90 inhibitor and an echinocandin rescued larvae from
             infections with the most lethal mold, Aspergillus fumigatus.
             In a murine model of disseminated candidiasis, genetic
             compromise of C. albicans HSP90 expression enhanced the
             therapeutic efficacy of an azole. Thus, harnessing Hsp90
             provides a much-needed strategy for improving the treatment
             of fungal disease because it enhances the efficacy of
             existing antifungals, blocks the emergence of drug
             resistance, and exerts broad-spectrum activity against
             diverse fungal pathogens.},
   Language = {eng},
   Doi = {10.1073/pnas.0813394106},
   Key = {fds191218}

   Author = {JW Baddley, JR Perfect and RA Oster and RA Larsen and GA Pankey and H
             Henderson, DW Haas and CA Kauffman and R Patel and AK Zaas and PG
   Title = {Pulmonary cryptococcosis in patients without HIV infection:
             factors associated with disseminated disease.},
   Journal = {European journal of clinical microbiology & infectious
             diseases : official publication of the European Society of
             Clinical Microbiology},
   Volume = {27},
   Number = {10},
   Pages = {937-43},
   Year = {2008},
   Month = {October},
   ISSN = {1435-4373},
   url = {},
   Keywords = {Adult • Aged • Antigens, Fungal •
             Cryptococcosis • Cryptococcus neoformans • Female
             • Humans • Male • Meningitis, Cryptococcal
             • Middle Aged • Pneumonia • Retrospective
             Studies • Risk Factors • blood • diagnosis*
             • isolation & purification* • microbiology*},
   Abstract = {Cryptococcus neoformans is an uncommonly recognized cause of
             pneumonia in HIV-negative patients. Because of its
             propensity to disseminate to the meninges and other sites, a
             lumbar puncture is recommended for patients with pulmonary
             cryptococcosis, regardless of other risk factors. This study
             explored clinical and laboratory features to help predict
             which patients had pulmonary disease alone versus those who
             had pulmonary plus extrapulmonary disease. A retrospective
             chart review at 15 medical centers was performed from 1990
             to 2000 of all HIV-negative patients who had pulmonary
             cryptococcosis. Demographic, clinical, radiographic, and
             laboratory features were evaluated to determine factors that
             differentiated those patients who had extrapulmonary
             disease. Among 166 patients who had pulmonary
             cryptococcosis, 122 had pulmonary infection only and 44 had
             pulmonary plus extrapulmonary (disseminated) disease. A
             negative serum cryptococcal antigen titer was more common in
             patients with pulmonary disease alone (p < 0.01).
             Multivariate analysis demonstrated that patients who had
             disseminated disease were more likely than those who only
             had pulmonary disease to have cirrhosis (p = 0.049),
             headache (p < 0.001), weight loss (p = 0.003), fever (p =
             0.035), altered mental status (p < 0.001), and to be
             receiving high-dose corticosteroids (p = 0.008). In this
             large cohort of HIV-negative patients with pulmonary
             cryptococcosis, there were easily distinguished clinical and
             laboratory features among patients with pulmonary disease
             alone versus those with pulmonary plus extrapulmonary
             disease. These findings may be helpful in the evaluation of
             HIV-negative patients with pulmonary cryptococcosis with
             regard to the need for lumbar puncture or to search for
             disseminated disease.},
   Language = {eng},
   Doi = {10.1007/s10096-008-0529-z},
   Key = {fds191209}

   Author = {AK Zaas},
   Title = {Echinocandins: a wealth of choice--how clinically different
             are they?},
   Journal = {Current opinion in infectious diseases},
   Volume = {21},
   Number = {4},
   Pages = {426-32},
   Year = {2008},
   Month = {August},
   ISSN = {1535-3877},
   url = {},
   Keywords = {Antifungal Agents • Aspergillosis • Candidiasis
             • Chemoprevention • Drug Therapy, Combination
             • Echinocandins • Fungi • Humans •
             Triazoles • drug effects • drug therapy •
             drug therapy* • pharmacology • prevention &
             control • therapeutic use • therapeutic
   Abstract = {OBJECTIVE: The recent decade has been a 'golden age' for
             antifungal therapy. The introduction of a novel class of
             antifungals, the echinocandins, has revolutionized the
             therapy for invasive candidiasis, provided increasing
             options for antifungal prophylaxis in high-risk patients and
             energized the debate regarding combination antifungal
             therapy for invasive mycoses. RESULTS: Randomized,
             controlled data exist for each echinocandin in the treatment
             of invasive candidiasis, and experts largely believe the
             agents to be equivalent in this setting. Future trials of
             combined echinocandin-triazole therapy for invasive
             aspergillosis are desired. Additionally, maximal dosing
             limitations are being pursued. CONCLUSIONS: The
             echinocandins as a class offer an advance in the treatment
             of invasive candidiasis, an additional option for
             prophylaxis and an attractive choice for the study of
             combination antifungal therapy. Particularly for the major
             indication (treatment of invasive candidiasis), major
             clinical differences between agents have not been
   Language = {eng},
   Doi = {10.1097/QCO.0b013e328307c79c},
   Key = {fds191236}

   Author = {AK Zaas and G Liao and JW Chien and C Weinberg and D Shore and SS Giles and KA
             Marr, J Usuka and LH Burch and L Perera, JR Perfect and G Peltz and DA
   Title = {Plasminogen alleles influence susceptibility to invasive
   Journal = {PLoS genetics},
   Volume = {4},
   Number = {6},
   Pages = {e1000101},
   Year = {2008},
   Month = {June},
   ISSN = {1553-7404},
   url = {},
   Keywords = {Alleles* • Animals • Aspergillosis •
             Aspergillus fumigatus • Female • Genetic
             Predisposition to Disease* • Humans • Lung
             Diseases, Fungal • Mice • Mice, Inbred A •
             Mice, Inbred AKR • Mice, Inbred BALB C • Mice,
             Inbred C3H • Mice, Inbred C57BL • Mice, Inbred DBA
             • Mice, Inbred MRL lpr • Mice, Inbred NZB •
             Mice, Knockout • Plasminogen • Signal Transduction
             • genetics* • immunology • microbiology*
             • mortality • pathogenicity • pathology
             • physiology},
   Abstract = {Invasive aspergillosis (IA) is a common and life-threatening
             infection in immunocompromised individuals. A number of
             environmental and epidemiologic risk factors for developing
             IA have been identified. However, genetic factors that
             affect risk for developing IA have not been clearly
             identified. We report that host genetic differences
             influence outcome following establishment of pulmonary
             aspergillosis in an exogenously immune suppressed mouse
             model. Computational haplotype-based genetic analysis
             indicated that genetic variation within the biologically
             plausible positional candidate gene plasminogen (Plg; Gene
             ID 18855) correlated with murine outcome. There was a single
             nonsynonymous coding change (Gly110Ser) where the minor
             allele was found in all of the susceptible strains, but not
             in the resistant strains. A nonsynonymous single nucleotide
             polymorphism (Asp472Asn) was also identified in the human
             homolog (PLG; Gene ID 5340). An association study within a
             cohort of 236 allogeneic hematopoietic stem cell transplant
             (HSCT) recipients revealed that alleles at this SNP
             significantly affected the risk of developing IA after HSCT.
             Furthermore, we demonstrated that plasminogen directly binds
             to Aspergillus fumigatus. We propose that genetic variation
             within the plasminogen pathway influences the pathogenesis
             of this invasive fungal infection.},
   Language = {eng},
   Doi = {10.1371/journal.pgen.1000101},
   Key = {fds191233}

   Author = {S Garantziotis and JW Hollingsworth and AK Zaas and DA
   Title = {The effect of toll-like receptors and toll-like receptor
             genetics in human disease.},
   Journal = {Annual review of medicine},
   Volume = {59},
   Pages = {343-59},
   Year = {2008},
   ISSN = {0066-4219},
   url = {},
   Keywords = {Disease Susceptibility • Humans • Polymorphism,
             Genetic • Signal Transduction • Toll-Like
             Receptors • etiology* • physiology •
   Abstract = {Toll-like receptors (TLRs) enable innate immune recognition
             of endogenous and exogenous prototypic ligands. They also
             orchestrate innate and adaptive immune response to
             infection, inflammation, and tissue injury. Given their
             significance in the immune response, it is not surprising
             that genetic variations of TLRs can affect their function
             and by extension affect the response of the organism to
             environmental stimuli. The genetics of TLRs provides
             important insights in gene-environment interactions in
             health and disease, and it may enable scientists to assess
             patients' susceptibility to diseases or predict their
             response to treatments.},
   Language = {eng},
   Doi = {10.1146/},
   Key = {fds191220}

   Author = {AJ Reddy and AK Zaas and KE Hanson and SM Palmer},
   Title = {A single-center experience with ganciclovir-resistant
             cytomegalovirus in lung transplant recipients: treatment and
   Journal = {The Journal of heart and lung transplantation : the official
             publication of the International Society for Heart
   Volume = {26},
   Number = {12},
   Pages = {1286-92},
   Year = {2007},
   Month = {December},
   ISSN = {1557-3117},
   url = {},
   Keywords = {Adult • Antiviral Agents • Cytomegalovirus •
             Cytomegalovirus Infections • Drug Resistance, Viral
             • Drug Therapy, Combination • Female •
             Foscarnet • Ganciclovir • Genetic Predisposition
             to Disease • Humans • Lung Transplantation* •
             Male • Middle Aged • Mutation • Opportunistic
             Infections • Phosphotransferases (Alcohol Group
             Acceptor) • Postoperative Complications* •
             Retrospective Studies • Treatment Outcome • drug
             therapy* • etiology • genetics • therapeutic
   Abstract = {BACKGROUND: Cytomegalovirus (CMV) disease is a major cause
             of morbidity and mortality after lung transplantation
             despite ganciclovir prophylaxis. The emergence of
             ganciclovir-resistant CMV in lung transplant patients has
             been reported, although the optimal strategy for the
             management of these infections remains uncertain. A review
             of the results of glanciclovir susceptibility testing in
             lung transplant recipients was performed. METHODS: We found
             54% (113 of 210) of lung transplant patients developed CMV
             infection over a 4-year study period with
             ganciclovir-resistant CMV infection occurring in >5% of
             patients (6 of 113). The demographic and clinical
             characteristics of patients who developed
             ganciclovir-resistant vs -sensitive CMV infection were
             similar, although 50% (3 of 6) patients who developed
             resistance were CMV mismatched (D(+)/R(-) serology). All
             patients' CMV isolates had mutations in the UL97 gene. In
             addition, the 3 mismatch patients also had CMV with
             mutations in the UL54 gene. RESULTS: Treatment with a
             combination of foscarnet and ganciclovir or foscarnet alone
             for ganciclovir-resistant infection led to a significant
             reduction in virologic load in all patients (p = 0.03),
             although transient increases in viremia were observed in
             some patients early after treatment. Renal function worsened
             after treatment, but overall it was not significantly
             different from pre-treatment values (p = 0.07). CONCLUSIONS:
             Single or combination therapy with foscarnet is effective
             for treatment of ganciclovir-resistant isolates and
             excessive concern regarding toxicity should not preclude
             consideration of these treatments when clinically
   Language = {eng},
   Doi = {10.1016/j.healun.2007.09.012},
   Key = {fds191228}

   Author = {JW Hollingsworth and S Shofer and A Zaas},
   Title = {Successful treatment of Ochroconis gallopavum infection in
             an immunocompetent host.},
   Journal = {Infection},
   Volume = {35},
   Number = {5},
   Pages = {367-9},
   Year = {2007},
   Month = {October},
   ISSN = {0300-8126},
   url = {},
   Keywords = {Aged • Antifungal Agents • Ascomycota •
             Female • Humans • Mycoses • Pneumonia •
             Radiography, Thoracic • drug therapy* • isolation
             & purification* • microbiology* • therapeutic
   Abstract = {Ochroconis gallopavum, a dematiaceous fungus, is a rare
             cause disease in immunocompromised patients and epidemic
             encephalitis in poultry. We report the first case of active
             O. gallopavum pulmonary infection in an immunocompetent host
             with rapid and complete response to oral antifungal
   Language = {eng},
   Doi = {10.1007/s15010-007-6054-7},
   Key = {fds191231}

   Author = {ES Dodds Ashley and AK Zaas and AF Fang and B Damle, JR
   Title = {Comparative pharmacokinetics of voriconazole administered
             orally as either crushed or whole tablets.},
   Journal = {Antimicrobial agents and chemotherapy},
   Volume = {51},
   Number = {3},
   Pages = {877-80},
   Year = {2007},
   Month = {March},
   ISSN = {0066-4804},
   url = {},
   Keywords = {Adolescent • Adult • Antifungal Agents • Area
             Under Curve • Cross-Over Studies • Female •
             Humans • Male • Middle Aged • Pyrimidines
             • Tablets • Triazoles • administration &
             dosage • adverse effects • pharmacokinetics*},
   Abstract = {Voriconazole is a triazole antifungal agent used to treat
             serious, invasive fungal infections including aspergillosis
             and candidemia. Limitations with existing formulations of
             voriconazole including restricted utility in patients with
             renal dysfunction (intravenous preparation) and the
             unavailability of an oral suspension in some countries make
             the administration of crushed tablets desirable in many
             clinical scenarios. However, concerns that this approach may
             alter the systemic absorption of voriconazole exist.
             Therefore, an open-label, randomized, two-way crossover
             comparative pharmacokinetic (PK) study using healthy
             volunteers was performed to compare these methods of tablet
             administration. In a random sequence, subjects received
             voriconazole tablets either crushed or whole. The
             voriconazole dose was 400 mg every 12 h for 1 day orally
             followed by 200 mg every 12 h orally for 5.5 days. Study
             periods were separated by 7 days. PK parameters were
             determined by the noncompartmental method. An equivalence
             approach with no-effect boundaries of 80 to 125% was used to
             assess bioequivalence. Twenty healthy subjects (10 males;
             aged 20 to 43 years) were enrolled in and completed the
             study. The adjusted mean areas under the plasma
             concentration-time curve from 0 to tau, where tau equals 12
             h, for the crushed and whole tablet groups were 9,793 and
             11,164 ng . h/ml, respectively (ratio, 87.72; 90% confidence
             interval [CI], 80.97, 95.04). The ratio of the maximum
             concentration of drug in serum for the crushed tablet versus
             whole tablet arms was 94.94 (90% CI, 86.51, 104.22). The
             only difference noted between groups was a slightly faster
             time to maximum concentration of drug in serum when subjects
             received crushed tablets, 0.5 h versus 1.5 h (90% CI, -0.75,
             -0.25). Treatment-related adverse events occurred in 12
             subjects receiving whole tablets and 9 subjects receiving
             crushed tablets; all were mild. The administration of
             crushed voriconazole tablets is bioequivalent to
             whole-tablet administration.},
   Language = {eng},
   Doi = {10.1128/AAC.01263-06},
   Key = {fds191205}

   Author = {SS Giles and AK Zaas and MF Reidy, JR Perfect, JR
   Title = {Cryptococcus neoformans is resistant to surfactant protein A
             mediated host defense mechanisms.},
   Journal = {PloS one},
   Volume = {2},
   Number = {12},
   Pages = {e1370},
   Year = {2007},
   ISSN = {1932-6203},
   url = {},
   Keywords = {Animals • Bronchoalveolar Lavage Fluid •
             Cryptococcus neoformans • Macrophages, Alveolar •
             Mice • Mice, Knockout • Phagocytosis •
             Pulmonary Surfactant-Associated Protein A • Rats •
             Rats, Sprague-Dawley • genetics • immunology
             • microbiology • physiology*},
   Abstract = {Initiation of a protective immune response to infection by
             the pathogenic fungus Cryptococcus neoformans is mediated in
             part by host factors that promote interactions between
             immune cells and C. neoformans yeast. Surfactant protein A
             (SP-A) contributes positively to pulmonary host defenses
             against a variety of bacteria, viruses, and fungi in part by
             promoting the recognition and phagocytosis of these
             pathogens by alveolar macrophages. In the present study we
             investigated the role of SP-A as a mediator of host defense
             against the pulmonary pathogen, C. neoformans. Previous
             studies have shown that SP-A binds to acapsular and
             minimally encapsulated strains of C. neoformans. Using in
             vitro binding assays we confirmed that SP-A does not
             directly bind to a fully encapsulated strain of C.
             neoformans (H99). However, we observed that when C.
             neoformans was incubated in bronchoalveolar fluid, SP-A
             binding was detected, suggesting that another alveolar host
             factor may enable SP-A binding. Indeed, we discovered that
             SP-A binds encapsulated C. neoformans via a previously
             unknown IgG dependent mechanism. The consequence of this
             interaction was the inhibition of IgG-mediated phagocytosis
             of C. neoformans by alveolar macrophages. Therefore, to
             assess the contribution of SP-A to the pulmonary host
             defenses we compared in vivo infections using SP-A null mice
             (SP-A-/-) and wild-type mice in an intranasal infection
             model. We found that the immune response assessed by
             cellular counts, TNFalpha cytokine production, and fungal
             burden in lungs and bronchoalveolar lavage fluids during
             early stages of infection were equivalent. Furthermore, the
             survival outcome of C. neoformans infection was equivalent
             in SP-A-/- and wild-type mice. Our results suggest that
             unlike a variety of bacteria, viruses, and other fungi,
             progression of disease with an inhalational challenge of C.
             neoformans does not appear to be negatively or positively
             affected by SP-A mediated mechanisms of pulmonary host
   Language = {eng},
   Doi = {10.1371/journal.pone.0001370},
   Key = {fds191203}

   Author = {H Aziz and A Zaas and GS Ginsburg},
   Title = {Peripheral blood gene expression profiling for
             cardiovascular disease assessment.},
   Journal = {Genomic medicine},
   Volume = {1},
   Number = {3-4},
   Pages = {105-12},
   Year = {2007},
   ISSN = {1871-7934},
   url = {},
   Abstract = {Whole blood gene expression profiling has the potential to
             be informative about dynamic changes in disease states and
             to provide information on underlying disease mechanisms.
             Having demonstrated proof of concept in animal models, a
             number of studies have now tried to tackle the complexity of
             cardiovascular disease in human hosts to develop better
             diagnostic and prognostic indicators. These studies show
             that genomic signatures are capable of classifying patients
             with cardiovascular diseases into finer categories based on
             the molecular architecture of a patient's disease and more
             accurately predict the likelihood of a cardiovascular event
             than current techniques. To highlight the spectrum of
             potential applications of whole blood gene expression
             profiling approach in cardiovascular science, we have chosen
             to review the findings in a number of complex cardiovascular
             diseases such as atherosclerosis, hypertension and
             myocardial infarction as well as thromboembolism, aortic
             aneurysm, and heart transplant.},
   Language = {eng},
   Doi = {10.1007/s11568-008-9017-x},
   Key = {fds191206}

   Author = {AK Zaas and ES Dodds Ashley and BD Alexander, MD Johnson, JR
   Title = {Caspofungin for invasive candidiasis at a tertiary care
             medical center.},
   Journal = {The American journal of medicine},
   Volume = {119},
   Number = {11},
   Pages = {993.e1-6},
   Year = {2006},
   Month = {November},
   ISSN = {1555-7162},
   url = {},
   Keywords = {Antifungal Agents • Candida albicans • Candida
             glabrata • Candida tropicalis • Candidiasis •
             Drug Administration Schedule • Echinocandins •
             Female • Humans • Male • Medical Records
             • North Carolina • Peptides, Cyclic •
             Retrospective Studies • Severity of Illness Index
             • Treatment Outcome • administration & dosage
             • diagnosis • drug effects • drug therapy*
             • epidemiology • therapeutic use*},
   Abstract = {BACKGROUND: Caspofungin is emerging as first-line therapy
             for invasive candidiasis. Data on the use of caspofungin for
             treatment for invasive candidiasis are limited to clinical
             trials and case reports. We report a single-center
             experience with 104 consecutive courses of caspofungin for
             the treatment of invasive candidiasis to evaluate a
             real-world performance of this drug. METHODS: A
             retrospective chart review of patients receiving caspofungin
             at a tertiary care medical center was performed. Patient
             information and microbiologic data were abstracted from
             patient charts and electronic medical records. RESULTS: Of
             241 patients receiving caspofungin for all indications, 122
             (51%) had proven invasive candidiasis. There were 104
             treatment courses for candidiasis in 99 patients available
             for review. Bloodstream (66%) and abdominal infections (25%)
             were the most common sites of infection. Most infections
             were non-albicans (80/104, 77%; including patients infected
             with more than one species). Clinical cure rates at the end
             of therapy were 83% (57/69) for bloodstream infections and
             84% (22/26) for abdominal infections. Caspofungin did not
             clear candidiasis in 14 episodes (microbiologic cure rate
             75%, 42/56). CONCLUSIONS: The clinical use of caspofungin
             has been successful in the treatment of invasive
             candidiasis, even in patients with prior antifungal
             exposure. In this unselected review, caspofungin performed
             similarly as in clinical trials, and clinicians should
             consider caspofungin as first-line therapy for invasive
             candidiasis, particularly non-albicans species.},
   Language = {eng},
   Doi = {10.1016/j.amjmed.2006.02.029},
   Key = {fds191216}

   Author = {WJ Steinbach, JR Perfect and CH Cabell and VG Fowler and GR Corey and JS
             Li, AK Zaas and DK Benjamin Jr},
   Title = {A meta-analysis of medical versus surgical therapy for
             Candida endocarditis.},
   Journal = {The Journal of infection},
   Volume = {51},
   Number = {3},
   Pages = {230-47},
   Year = {2005},
   Month = {October},
   ISSN = {1532-2742},
   url = {},
   Keywords = {Adolescent • Adult • Antifungal Agents •
             Candida • Candidiasis • Child • Child,
             Preschool • Endocarditis • Humans • Infant
             • Infant, Newborn • Treatment Outcome •
             classification • drug effects • drug therapy
             • drug therapy* • microbiology • mortality
             • surgery • surgery* • therapeutic
   Abstract = {OBJECTIVE: The optimal management of Candida infective
             endocarditis (IE) is unknown. METHODS: We reviewed all 879
             cases of Candida IE reported from 1966-2002 in the
             peer-reviewed literature to better understand the role of
             medical and surgical therapies. This review included 163
             patients from 105 reports that met our inclusion criteria:
             31 cases treated with antifungal monotherapy, 25 cases
             treated with medical antifungal combination therapy, and 107
             cases treated with adjunctive surgical plus medical
             antifungal therapy. We also used meta-analytic techniques to
             evaluate 22 observational case-series (72 patients) of the
             105 reports with two or more patients with definite Candida
             IE. RESULTS: We found that in patients who underwent
             adjunctive surgery there was a lower reported proportion of
             deaths [prevalence odds ratio (POR)=0.56; 95% confidence
             interval (CI)=0.16, 1.99)]. Higher mortality was noted in
             patients treated prior to 1980 (POR=2.03; 95% CI=0.55,
             7.61), treated with antifungal monotherapy (POR=1.49; 95%
             CI=0.39, 5.81), infected with Candida parapsilosis
             (POR=1.51; 95% CI=0.41, 5.52), or with left-sided
             endocarditis (POR=2.36; 95% CI=0.55, 10.07). CONCLUSIONS:
             Medical antifungal therapy of Candida IE is poorly
             characterized, and recent antifungal developments lend
             promise for those patients who cannot undergo
   Language = {eng},
   Doi = {10.1016/j.jinf.2004.10.016},
   Key = {fds191213}

   Author = {AK Zaas and DA Schwartz},
   Title = {Innate immunity and the lung: defense at the interface
             between host and environment.},
   Journal = {Trends in cardiovascular medicine},
   Volume = {15},
   Number = {6},
   Pages = {195-202},
   Year = {2005},
   Month = {August},
   ISSN = {1050-1738},
   url = {},
   Keywords = {Animals • Defensins • Environment • Humans
             • Immunity, Cellular • Immunity, Innate •
             Lung • Lung Diseases • immunology •
             immunology* • metabolism • physiology •
   Abstract = {The lung serves as a major interface between the host and
             the external environment. As such, numerous lines of defense
             protect the host from inhaled potential pathogens. A breach
             in pulmonary innate immunity can lead to deleterious
             outcomes, such as pneumonia and disseminated infection.
             Pulmonary innate immunity, the first line of defense, is
             mediated by airway and alveolar epithelial cells as well as
             resident and recruited leukocytes. This article will discuss
             the key cellular and secreted components of the pulmonary
             innate immune system.},
   Language = {eng},
   Doi = {10.1016/j.tcm.2005.07.001},
   Key = {fds191207}

   Author = {AK Zaas and BD Alexander},
   Title = {Echinocandins: role in antifungal therapy,
   Journal = {Expert opinion on pharmacotherapy},
   Volume = {6},
   Number = {10},
   Pages = {1657-68},
   Year = {2005},
   Month = {August},
   ISSN = {1744-7666},
   url = { },
   Keywords = {Animals • Antifungal Agents • Echinocandins •
             Fungal Proteins • Humans • Mycoses •
             Peptides, Cyclic • chemistry • drug therapy •
             microbiology • pharmacology • therapeutic
   Abstract = {Novel therapies to treat invasive fungal infections have
             revolutionised the care of patients with candidiasis,
             aspergillosis and other less common fungal infections.
             Physicians in the twenty first century have access to safer
             versions of conventional drugs (i.e., lipid amphotericin B
             products), extended-spectrum versions of established drugs
             (i.e., voriconazole), as well as a new class of antifungal
             agents; the echinocandins. The increased number of options
             in the antifungal armamentarium is well timed, as the
             incidence of both invasive candidiasis and invasive
             aspergillosis, and the financial burden associated with
             these infections, have increased significantly in the past
             several decades. The increasing incidence of fungal
             infections has risen in parallel with the increase in
             critically ill and immunocompromised patients. Candida is
             the fourth most common bloodstream isolate, approximately
             50% of which are non-albicans species. Estimates suggest
             there to be 9.8 episodes of invasive candidiasis per 1000
             admissions to surgical intensive care units, with
             attributable mortality at 30% and cost per episode of
             US44,000 dollars. The burden of candidiasis is even higher
             in the paediatric population, with Candida being the second
             most common bloodstream infection. The increase in
             non-albicans candidiasis mandates the introduction of new
             antifungal agents capable of treating these often
             azole-resistant isolates. In addition, there has been a rise
             in the incidence of invasive aspergillosis, the most common
             invasive mould infection following haematopoietic stem cell
             transplantation, with an estimated incidence of 10 - 20%.
             The mortality associated with invasive aspergillosis has
             increased by 357% since 1980. Unfortunately, the overall
             survival rate among patients treated with amphotericin B,
             and even voriconazole, remains suboptimal, as evidenced by
             the failure of treatment in 47% of patients in the landmark
             voriconazole versus amphotericin B trial. Given the
             increasing incidence and suboptimal outcomes of these
             serious fungal infections, novel therapies represent an
             opportunity for significant advancement in clinical care.
             The current challenge is to discover the optimal place for
             the echinocandins in the treatment of invasive fungal
   Language = {eng},
   Doi = {10.1517/14656566.6.10.1657 },
   Key = {fds191225}

   Author = {AK Zaas and WJ Steinbach},
   Title = {Micafungin: the US perspective.},
   Journal = {Expert review of anti-infective therapy},
   Volume = {3},
   Number = {2},
   Pages = {183-90},
   Year = {2005},
   Month = {April},
   ISSN = {1744-8336},
   url = {},
   Keywords = {Animals • Antifungal Agents • Clinical Trials as
             Topic • Echinocandins • Humans • Lipopeptides
             • Lipoproteins • Mycoses • Peptides, Cyclic
             • Safety • drug therapy* • standards •
             therapeutic use*},
   Abstract = {Invasive fungal infections cause considerable morbidity and
             mortality in nosocomial settings and amongst
             immunocompromised hosts. Invasive candidiasis and
             aspergillosis remain the most common invasive fungal
             infections, with Candida spp. constituting the fourth most
             common bloodstream infection in the USA. Currently available
             antifungal therapies include the polyene, antimetabolite,
             allylamine, azole and echinocandin drug classes. Micafungin,
             approved in March 2005 by the Food and Drug Administration
             for use in the USA, has shown safety and efficacy for the
             treatment of candidiasis and aspergillosis in clinical
             trials in Japan, Europe and South Africa. Micafungin holds
             promise as a first-line treatment option for candidiasis, as
             well as prophylaxis against invasive fungal infections
             during periods of neutropenia in high-risk
   Language = {eng},
   Doi = {10.1586/14787210.3.2.183},
   Key = {fds191222}

   Author = {AK Zaas and BD Alexander},
   Title = {New developments in the diagnosis and treatment of
             infections in lung transplant recipients.},
   Journal = {Respiratory care clinics of North America},
   Volume = {10},
   Number = {4},
   Pages = {531-47},
   Year = {2004},
   Month = {December},
   ISSN = {1078-5337},
   url = {},
   Keywords = {Adult • Female • Graft Rejection • Graft
             Survival • Humans • Incidence • Lung
             Diseases, Fungal • Lung Transplantation • Male
             • Middle Aged • Pneumonia, Bacterial •
             Pneumonia, Viral • Postoperative Complications •
             Prognosis • Risk Assessment • Severity of Illness
             Index • Survival Analysis • adverse effects*
             • diagnosis* • epidemiology • methods •
             mortality • therapy},
   Abstract = {Infections remain a serious and common problem in lung
             transplant recipients. Recent years have seen an explosion
             in the knowledge regarding this major cause of morbidity and
             mortality. Novel diagnostic and therapeutic techniques are
             revolutionizing the approach to infectious diseases in
             transplant recipients. Multicenter trials will expand the
             scope of diagnosis and management of these infections. A
             team approach by transplant physicians and infectious
             diseases experts is critical to the success of managing
             these complex patients.},
   Language = {eng},
   Doi = {10.1016/j.rcc.2004.06.001},
   Key = {fds191214}

   Author = {WJ Steinbach and DK Benjamin Jr and SA Trasi and JL Miller and WA
             Schell, AK Zaas and WM Foster, JR Perfect},
   Title = {Value of an inhalational model of invasive
   Journal = {Medical mycology : official publication of the International
             Society for Human and Animal Mycology},
   Volume = {42},
   Number = {5},
   Pages = {417-25},
   Year = {2004},
   Month = {October},
   ISSN = {1369-3786},
   Keywords = {Administration, Inhalation • Animals •
             Aspergillosis* • Aspergillus fumigatus • Disease
             Models, Animal* • Humans • Lung • Lung
             Diseases, Fungal* • Male • Mice • drug
             effects • drug therapy • microbiology •
             pathogenicity* • pathology},
   Abstract = {Animal models of invasive aspergillosis have been used for
             virulence studies and antifungal efficacy evaluations but
             results have been inconsistent. In an attempt to reproduce
             human infection, many Aspergillus animal models have
             utilized a 'pulmonary route' for delivery of conidia,
             largely through intranasal instillation. However, several
             radiolabeled particle studies have shown that aerosol
             delivery is preferable to intranasal instillation to create
             a more homogenous delivery to the lungs. We hypothesized
             that an inhalational model would be more robust for studies
             of invasive aspergillosis pathogenesis and antifungal
             therapy. We developed an inhalational model of Aspergillus
             fumigatus infection using a Hinners inhalation chamber and
             demonstrated by quantitative polymerase chain reaction that
             this new inhalational model creates a more homogenous murine
             pneumonia, facilitating analysis of mutant strains and
             treatment regimens.},
   Language = {eng},
   Key = {fds191212}

   Author = {AK Zaas and M Boyce and W Schell and BA Lodge and JL Miller, JR
   Title = {Risk of fungemia due to Rhodotorula and antifungal
             susceptibility testing of Rhodotorula isolates.},
   Journal = {Journal of clinical microbiology},
   Volume = {41},
   Number = {11},
   Pages = {5233-5},
   Year = {2003},
   Month = {November},
   ISSN = {0095-1137},
   Keywords = {Antifungal Agents • Humans • Microbial Sensitivity
             Tests • Mycoses • Rhodotorula • drug effects*
             • isolation & purification • microbiology* •
             pathogenicity* • pharmacology*},
   Abstract = {Rhodotorula infections occur among patients with
             immunosuppression and/or central venous catheters. Using
             standardized methods (NCCLS M27-A), we determined the
             antifungal susceptibilities of 10 Rhodotorula bloodstream
             infection isolates. Patient information was collected for
             clinical correlation. The MICs of amphotericin B and
             posaconazole were the lowest, and the MICs of triazoles and
             echinocandins were higher than those of other antifungal
   Language = {eng},
   Key = {fds191219}

   Author = {R Toonkel and A Zaas},
   Title = {Cases from the Osler Medical Service at Johns Hopkins
   Journal = {The American journal of medicine},
   Volume = {115},
   Number = {6},
   Pages = {497-500},
   Year = {2003},
   Month = {October},
   ISSN = {0002-9343},
   Keywords = {Aged • Carcinoma, Hepatocellular • Humans •
             Imaging, Three-Dimensional • Liver • Liver
             Neoplasms • Male • Neoplastic Cells, Circulating*
             • Portal Vein* • Tomography, X-Ray Computed •
             complications* • diagnosis • pathology},
   Language = {eng},
   Key = {fds191237}

   Author = {J Piccini and A Zaas},
   Title = {Cases from the Osler Medical Service at Johns Hopkins
             University. Diffuse colonic angiodysplasia with chronic iron
             deficiency anemia.},
   Journal = {The American journal of medicine},
   Volume = {115},
   Number = {3},
   Pages = {245-8},
   Year = {2003},
   Month = {August},
   ISSN = {0002-9343},
   Keywords = {Anemia, Iron-Deficiency • Angiodysplasia • Chronic
             Disease • Colonic Diseases • Colonoscopy •
             Dyspnea • Female • Hematologic Tests • Humans
             • Iron • Middle Aged • Physical Examination
             • blood • complications* • diagnosis •
             etiology • etiology* • methods •
   Language = {eng},
   Key = {fds191224}

   Author = {J Piccini and A Zaas},
   Title = {Cases from the Osler Medical Service at Johns Hopkins
             University. Digitalis toxicity with bidirectional
             ventricular tachycardia.},
   Journal = {The American journal of medicine},
   Volume = {115},
   Number = {1},
   Pages = {70-1},
   Year = {2003},
   Month = {July},
   ISSN = {0002-9343},
   Keywords = {Aged • Anti-Arrhythmia Agents • Atrial
             Fibrillation • Digitalis Glycosides •
             Electrocardiography • Female • Humans • Risk
             Factors • Tachycardia, Ventricular • Telemetry
             • adverse effects* • blood • chemically
             induced* • diagnosis • drug therapy •
   Language = {eng},
   Key = {fds191226}

   Author = {C Passaretti and A Zaas},
   Title = {Cases from the Osler medical service at Johns Hopkins
   Journal = {The American journal of medicine},
   Volume = {114},
   Number = {7},
   Pages = {613-6},
   Year = {2003},
   Month = {May},
   ISSN = {0002-9343},
   Keywords = {Endocytosis • Female • Humans • Middle Aged
             • Multiple Myeloma • Plasma Cells •
             diagnosis* • physiology* • physiopathology*},
   Abstract = {A 56-year-old black woman with diabetes mellitus was
             admitted for hypoglycemia and confusion. Her past medical
             history included breast cancer, for which she had undergone
             a left lumpectomy and then mastectomy for in-breast
             recurrence. Her oral intake had decreased during the past
             month because of increasing discomfort from left-sided chest
             pain. During this period, she continued to take pioglitazone
             for diabetes at her originally prescribed dose. The
             patient's mental status improved quickly after taking orange
             juice and intravenous glucose, but the chest pain persisted.
             The pain, which was described as an ache along the left
             costal margin, increased with palpation, deep inspiration,
             or coughing. She had recently presented with similar
             complaints at another hospital where she had been prescribed
             a muscle relaxant that provided no relief from the pain. She
             also reported a 14-lb weight loss during the previous 3
             months, as well as fatigue, weakness, and aches in her legs
             and arms. She denied fevers, chills, sweats, abdominal pain,
             nausea, or recent trauma. Laboratory values at the time of
             admission were: calcium, 11.8 mg/dL; total protein, 11.1
             mg/dL; albumin, 3.2 g/dL; creatinine, 1.0 mg/dL; and
             hematocrit, 29.3%, with a mean corpuscular volume of 89.3.
             Chest radiography revealed a lytic lesion in the left
             lateral fourth rib and left humerus (). Serum and urine
             protein electrophoresis revealed a monoclonal spike in the
             gamma region consistent with monoclonal gammopathy. The
             serum spike was quantified at 3.78 g/dL. A skeletal survey
             showed many small well-defined lytic lesions in the skull
             (with one 1.5-cm lytic lesion in the upper posterior
             parietal bone), arms, and legs. A bone scan showed multiple
             foci of increased uptake in the right and left ribs as well
             as the proximal portion of the left femur. The peripheral
             blood smear revealed rouleaux formation () and plasma cells
             (). What is the diagnosis?},
   Language = {eng},
   Key = {fds191217}

   Author = {MJ McGirt and A Zaas and HE Fuchs and TM George and K Kaye and DJ
   Title = {Risk factors for pediatric ventriculoperitoneal shunt
             infection and predictors of infectious pathogens.},
   Journal = {Clinical infectious diseases : an official publication of
             the Infectious Diseases Society of America},
   Volume = {36},
   Number = {7},
   Pages = {858-62},
   Year = {2003},
   Month = {April},
   ISSN = {1537-6591},
   url = {},
   Keywords = {Adolescent • Child • Child, Preschool •
             Humans • Infant • Infant, Newborn •
             Prosthesis-Related Infections • Risk Factors •
             Staphylococcal Infections • Staphylococcus aureus*
             • Ventriculoperitoneal Shunt • adverse effects*
             • epidemiology • microbiology*},
   Abstract = {Identification of risk factors for shunt infection and
             predictors of infectious pathogens may improve current
             methods to prevent and treat shunt infections. We reviewed
             data on 820 consecutive ventriculoperitoneal (VP) shunt
             placement procedures in 442 pediatric patients at our
             institution during 1992-1998. Ninety-two shunts (11%)
             developed infection a median of 19 days (interquartile
             range, 11-35 days) after insertion. Premature birth
             (relative risk [RR], 4.81; 95% confidence interval [CI],
             2.19-10.87), previous shunt infection (RR, 3.83; 95% CI,
             2.40-6.13), and intraoperative use of the neuroendoscope
             (RR, 1.58; 95% CI, 1.01-2.50) were independent risk factors
             for shunt infection. The bacterial organisms early after
             shunt surgery (<14 days) were the same as those late after
             shunt surgery (>14 days). As determined by an analysis of
             the 92 infected shunts, hospital stay of >3 days at the time
             of shunt insertion (odds ratio [OR], 5.27; 95% CI,
             1.15-25.3) and prior Staphylococcus aureus shunt infection
             (OR, 5.91; 95% CI, 1.35-25.9) independently increased the
             odds that S. aureus was the causal pathogen.},
   Language = {eng},
   Doi = {10.1086/368191},
   Key = {fds191229}

   Author = {RW Grow and A Zaas},
   Title = {Cases from the Osler Medical Service at Johns Hopkins
   Journal = {The American journal of medicine},
   Volume = {114},
   Number = {2},
   Pages = {153-5},
   Year = {2003},
   Month = {February},
   ISSN = {0002-9343},
   Keywords = {Abdominal Pain • Acute Disease • Adult •
             Chronic Disease • Diagnosis, Differential •
             Diarrhea • Female • Hepatitis, Alcoholic •
             Hepatorenal Syndrome • Humans • Jaundice •
             Liver • Liver Diseases • complications* •
             diagnosis* • etiology • etiology* • pathology
             • pathology*},
   Abstract = {A 37-year-old woman presented with increasing abdominal pain
             and jaundice. Six weeks before admission, she developed
             persistent diarrhea and jaundice of the skin. She also
             bruised easily, and her gums bled. In the subsequent weeks,
             her appetite decreased, she was fatigued, and she had
             nausea, vomiting, and abdominal distension. She had a
             history of drinking 1 quart of vodka every day for 20 years,
             with brief periods of abstinence; she stopped consuming
             alcohol 11 days before admission because it no longer
             provided symptomatic relief. Her past medical history was
             also notable for depression, including a suicide attempt 4
             years earlier. She did not smoke, use illicit drugs, or have
             unprotected sexual intercourse. She had received no blood
             transfusions and had not traveled recently. She took no
             medications, except for occasional ibuprofen. On physical
             examination, she was thin and deeply jaundiced, and she
             trembled and responded slowly to questions. She was afebrile
             but tachypneic, and she had orthostatic hypotension. Her
             HEENT examination was notable for scleral and sublingual
             icterus, as well as crusted blood on her gums and teeth. The
             jugular veins were flat. The cardiac examination revealed
             tachycardia (heart rate, 103 beats per minute) without
             murmurs, rubs, or gallops. The abdomen was nontender and
             protuberant, with hypoactive bowel sounds; the spleen was
             not palpable, and there was no fluid wave or caput medusae.
             The liver percussed to 18 cm, with a smooth edge extending
             10 cm below the costal margin. She had cutaneous
             telangiectases on her chest and bilateral palmar erythema.
             There was no peripheral edema. The neurologic examination
             was notable for asterixis. Her stool was guaiac positive.
             Laboratory studies revealed the following values:
             hematocrit, 21.2%; white blood cells, 17,310/mm(3); ammonia,
             42 micromol/L; serum creatinine, 3.9 mg/dL; serum urea
             nitrogen, 70 mg/dL; albumin, 2.1 g/dL; total bilirubin, 26.8
             mg/dL; alanine aminotransferase, 14 U/L; aspartate
             aminotransferase, 77 U/L; alkaline phosphatase, 138 U/L;
             prothrombin time, 103 seconds (international normalized
             ratio, 10.6); and urinary sodium, <5 mg/dL. Urinalysis
             revealed an elevated specific gravity and numerous muddy
             granular casts. Hepatitis A, B, and C serologies were
             negative. On abdominal ultrasound examination, there was no
             ascites, and the liver was echogenic. The portal and hepatic
             veins were patent, and the hepatic arteries were normal. The
             spleen measured 14 cm. What is the diagnosis?},
   Language = {eng},
   Key = {fds191211}

   Author = {D Le and A Zaas},
   Title = {Cases from the Osler Medical Service at Johns Hopkins
             University. Left atrial myxoma.},
   Journal = {The American journal of medicine},
   Volume = {113},
   Number = {8},
   Pages = {694-6},
   Year = {2002},
   Month = {December},
   ISSN = {0002-9343},
   Keywords = {Biopsy, Needle • Cardiac Surgical Procedures •
             Echocardiography, Transesophageal • Follow-Up Studies
             • Heart Atria • Heart Catheterization • Heart
             Neoplasms • Humans • Immunohistochemistry •
             Male • Middle Aged • Myxoma • Thoracotomy
             • Tomography, X-Ray Computed • methods •
             methods* • pathology • surgery* •
   Language = {eng},
   Key = {fds191221}

   Author = {AK Zaas and X Song and P Tucker and TM Perl},
   Title = {Risk factors for development of vancomycin-resistant
             enterococcal bloodstream infection in patients with cancer
             who are colonized with vancomycin-resistant
   Journal = {Clinical infectious diseases : an official publication of
             the Infectious Diseases Society of America},
   Volume = {35},
   Number = {10},
   Pages = {1139-46},
   Year = {2002},
   Month = {November},
   ISSN = {1537-6591},
   url = {},
   Keywords = {Bacteremia • Enterococcus faecium* • Female •
             Gram-Positive Bacterial Infections • Humans • Male
             • Middle Aged • Neoplasms • Risk Factors
             • Vancomycin Resistance • complications* •
             epidemiology • etiology • microbiology •
             microbiology* • physiology*},
   Abstract = {Vancomycin-resistant Enterococcus faecium (VRE) is a common
             nosocomial isolate, especially among patients with cancer.
             VRE infections have substantial attributable mortality among
             patients with cancer. The purpose of this study was to
             identify risk factors for developing bloodstream infection
             with VRE in patients with cancer who are colonized with VRE.
             VRE colonization was prospectively identified in 197
             patients with cancer during 4-year period, of whom 179 (91%)
             had complete records for evaluation. Of these 179 patients,
             24 (13.4%) developed hospital-acquired VRE bloodstream
             infections. Risk factors for VRE bloodstream infection
             included vancomycin use (relative risk [RR], 1.98; 95%
             confidence interval [CI], 1.25-3.14), diabetes mellitus (RR,
             3.91; 95% CI, 1.20-12.77), gastrointestinal procedures (RR,
             4.56; 95% CI, 1.05-19.7), and acute renal failure (RR, 3.10;
             95% CI, 1.07-8.93). Strategies for preventing VRE
             bloodstream infection in VRE-colonized patients with cancer
             should include limiting vancomycin use and, perhaps,
             gastrointestinal procedures.},
   Language = {eng},
   Doi = {10.1086/342904},
   Key = {fds191215}

   Author = {A Zaas and P Scheel and A Venbrux and DB Hellmann},
   Title = {Large artery vasculitis following recombinant hepatitis B
             vaccination: 2 cases.},
   Journal = {The Journal of rheumatology},
   Volume = {28},
   Number = {5},
   Pages = {1116-20},
   Year = {2001},
   Month = {May},
   ISSN = {0315-162X},
   Keywords = {Adult • Angiography, Digital Subtraction • Female
             • Hepatitis B • Hepatitis B Vaccines • Humans
             • Middle Aged • Renal Artery Obstruction •
             Subclavian Artery* • Takayasu Arteritis •
             Vaccines, Synthetic • adverse effects • adverse
             effects* • etiology* • prevention & control •
   Abstract = {We describe 2 women who developed large artery vasculitis
             shortly after receiving recombinant hepatitis B vaccination.
             One patient developed Takayasu's arteritis, the other a
             vasculitis involving subclavian and renal arteries. Both
             developed renal failure. Whether the vasculitis was caused
             by the vaccination is not known. Although small vessel
             vasculitis following hepatitis B vaccination has been
             reported a number of times, large vessel vasculitis
             associated with hepatitis B vaccination has been reported
             only once. These cases suggest that large artery vasculitis
             should be added to the list of possible side effects of
             hepatitis B vaccination.},
   Language = {eng},
   Key = {fds191204}

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