Hachem, R. Y., Langston, A. A., Graybill, J. R., Perfect, J. R., Pedicone, L. D., Patino, H., ...
Objectives The aim of this study is to determine the efficacy and safety of posaconazole in patients with underlying renal impairment. Patients and methods We analysed the efficacy and safety of...
Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak (2005)
Fraser, J. A., Giles, S. S., Wenink, E. C., Geunes-Boyer, S. G., Wright, J. R., Diezmann, S., ...
Genealogy can illuminate the evolutionary path of important human pathogens. In some microbes, strict clonal reproduction predominates, as with the worldwide dissemination of Mycobacterium leprae,...
Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak (2005)
Fraser, J. A., Giles, S. S., Wenink, E. C., Geunes-Boyer, S. G., Wright, J. R., Diezmann, S., ...
Genealogy can illuminate the evolutionary path of important human pathogens. In some microbes, strict clonal reproduction predominates, as with the worldwide dissemination of Mycobacterium leprae,...
Lodge, J K, Jackson-Machelski, E, Toffaletti, D L, Perfect, J R, Gordon, J I
Cryptococcus neoformans is a major cause of systemic fungal infection in immunocompromised patients. Myristoyl-CoA:protein N-myristoyltransferase (Nmt) catalyzes the transfer of myristate (C14:0)...
Fungal virulence genes as targets for antifungal chemotherapy.
Fungal virulence genes have now met the age of molecular pathogenesis. The definition of virulence genes needs to be broad so that it encompasses the focus on molecular antifungal targets and vaccine...
In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans.
Perfect, J R, Cox, G M, Dodge, R K, Schell, W A
Multiple isolates of Cryptococcus neoformans were tested to compare the in vitro activity of a new triazole, SCH56592, with those of amphotericin B, fluconazole, and itraconazole, MICs of each drug...
Del Poeta, M, Schell, W A, Perfect, J R
The in vitro activity of the new antifungal drug pneumocandin L-743,872 against 55 isolates of clinically important molds was examined by an adapted macrobroth dilution method for yeasts....
Treatment of experimental cryptococcal meningitis and disseminated candidiasis with SCH39304.
Perfect, J R, Wright, K A, Hobbs, M M, Durack, D T
We studied the pharmacokinetics and in vivo antifungal action of SCH39304, a new antifungal azole compound, in rabbits. It crossed the blood-cerebrospinal fluid barrier in the presence or absence of...
Treatment of experimental disseminated candidiasis with cilofungin.
Perfect, J R, Hobbs, M M, Wright, K A, Durack, D T
The efficacy of cilofungin treatment of experimental disseminated candidiasis in rabbits was examined. Cilofungin treatment reduced yeast counts, especially in the kidney, with activity comparable to...
Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans.
Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the...
Savani, D V, Perfect, J R, Cobo, L M, Durack, D T
We studied the penetration of three azole compounds, ketoconazole, itraconazole, and fluconazole, into the ocular tissues and fluids of rabbits in the presence and absence of ocular inflammation....
Perfect, J R, Rude, T H, Wong, B, Flynn, T, Chaturvedi, V, Niehaus, W
The Mtl gene from Cryptococcus neoformans, which confers the ability of Saccharomyces cerevisiae Sc4l YJO to grow on mannitol with substantial NAD-dependent mannitol dehydrogenase activity, was...
Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with...
Perfect, J R, Savani, D V, Durack, D T
Itraconazole and fluconazole, two new triazoles, were examined for their antifungal activity in rabbits. Fluconazole easily crossed the blood-cerebrospinal fluid barrier, and active drug was...
Uptake of itraconazole by alveolar macrophages.
Perfect, J R, Savani, D V, Durack, D T
Itraconazole is a broad-spectrum potent triazole antifungal agent. Its efficacy in treatment cannot always be explained by body fluid drug levels. In this study, itraconazole was shown to accumulate...
Cameron, M L, Schell, W A, Bruch, S, Bartlett, J A, Waskin, H A, Perfect, J R
Yeast strains isolated from the oropharynx of 87 consecutive patients infected with human immunodeficiency virus type 1 were examined for in vitro susceptibility to fluconazole. Candida albicans was...
Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA.
Toffaletti, D L, Rude, T H, Johnston, S A, Durack, D T, Perfect, J R
A transformation scheme for Cryptococcus neoformans to yield high-frequency, integrative events was developed. Adenine auxotrophs from a clinical isolate of C. neoformans serotype A were complemented...
Fatal, disseminated Acremonium strictum infection in a neutropenic host.
Disseminated Acremonium strictum infection in a neutropenic patient is reported. Positive fecal cultures preceded positive cutaneous and blood cultures by 18 and 21 days, respectively, which suggests...
Wong, B, Perfect, J R, Beggs, S, Wright, K A
We studied the ability of Cryptococcus neoformans to produce the hexitol D-mannitol in vitro and in rabbits with experimental meningitis. Twelve of twelve human isolates of C. neoformans produced...
Opsonic activity of cerebrospinal fluid in experimental cryptococcal meningitis.
Hobbs, M M, Perfect, J R, Granger, D L, Durack, D T
The role of antibody in protection against infection with Cryptococcus neoformans is undefined. In this paper we describe the development of opsonic activity in the cerebrospinal fluid (CSF) of...
Perfect, J R, Hobbs, M M, Granger, D L, Durack, D T
The functional abilities of macrophages from cerebrospinal fluid (CSF) have so far been little studied. We examined the acquisition of activation characteristics by CSF macrophages during the course...
Efficacy of immune therapy in early experimental Naegleria fowleri meningitis.
Lallinger, G J, Reiner, S L, Cooke, D W, Toffaletti, D L, Perfect, J R, Granger, D L, ...
Naegleria fowleri meningoencephalitis is usually fatal in humans despite treatment. As a new approach, we tested intracisternal passive immune therapy in rabbits with amebic meningoencephalitis by...
Effects of cyclosporine in experimental cryptococcal meningitis.
We studied the effects of cyclosporine on experimental cryptococcal meningitis. Like cortisone, cyclosporine depressed the highly effective defense mechanisms of normal rabbits against inoculated...
First report of involvement of Nodulisporium species in human disease.
Cox, G M, Schell, W A, Scher, R L, Perfect, J R
Allergic fungal sinusitis is a common disease that results from a hypersensitivity reaction mounted by the host against fungi living in the paranasal sinuses. We have recently treated a patient with...
Karyotyping of Cryptococcus neoformans as an epidemiological tool.
Perfect, J R, Ketabchi, N, Cox, G M, Ingram, C W, Beiser, C L
Karyotyping of Cryptococcus neoformans var. neoformans can be used as an epidemiological tool for C. neoformans infections. In this study of over 40 isolates from both clinical and environmental...
Perfect, J R, Toffaletti, D L, Rude, T H
A cryptococcal meningitis model in corticosteroid-treated rabbits was used to assess the requirement for the phosphoribosylaminoimidazole gene (ADE2) for virulence of Cryptococcus neoformans. A...
Perfect, J R, Lang, S D, Durack, D T
To evaluate cotrimoxazole in the treatment of bacterial meningitis, we compared its action with that of ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis. Both...
Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages.
Granger, D L, Hibbs, J B, Perfect, J R, Durack, D T
L-arginine is required for the fungistatic action of murine macrophages in vitro. To further investigate this requirement, L-arginine metabolism by macrophages was measured under conditions where...
Separation of chromosomes of Cryptococcus neoformans by pulsed field gel electrophoresis.
Perfect, J R, Magee, B B, Magee, P T
Chromosomes from Cryptococcus neoformans, an encapsulated yeast pathogen, were separated by contour-clamped homogeneous field gel electrophoresis. Seven strains representing all four serotypes were...
In Vitro and In Vivo Efficacies of the New Triazole Albaconazole against Cryptococcus neoformans
Miller, J. L., Schell, W. A., Wills, E. A., Toffaletti, D. L., Boyce, M., Benjamin, D. K., ...
The activity of albaconazole (UR-9825; J. Uriach & Cía. S.A., Barcelona, Spain) was compared to that of fluconazole against 12 isolates of Cryptococcus neoformans in vitro and against 1 isolate in...
Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis
Steen, B. R., Zuyderduyn, S., Toffaletti, D. L., Marra, M., Jones, S. J. M., Perfect, J. R., ...
Cryptococcus neoformans, an encapsulated basidiomycete fungus of medical importance, is capable of crossing the blood-brain barrier and causing meningitis in both immunocompetent and...
Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages.
Granger, D L, Hibbs, J B, Perfect, J R, Durack, D T
The microbiostatic action of macrophages was studied in vitro employing peritoneal cytotoxic macrophages (CM) from mice acting against Cryptococcus neoformans cultured in Dulbecco's medium with 10%...
Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide.
Granger, D L, Perfect, J R, Durack, D T
Cryptococcus neoformans is variably encapsulated in vitro, whereas in tissues it develops a large capsule. We observed that cells of a strain with thin capsules, when growing in a standard fungal...
Identification and Characterization of an SKN7 Homologue in Cryptococcus neoformans
Wormley, F. L., Heinrich, G., Miller, J. L., Perfect, J. R., Cox, G. M.
Cryptococcus neoformans is an encapsulated fungal pathogen that primarily infects the central nervous system of immunocompromised individuals, causing life-threatening meningoencephalitis. The...
Del Poeta, M, Toffaletti, D L, Rude, T H, Dykstra, C C, Heitman, J, Perfect, J R
Topisomerase I is the target of several toxins and chemotherapy agents, and the enzyme is essential for viability in some organisms, including mice and drosophila. We have cloned the TOP1 gene...
Yue, C, Cavallo, L M, Alspaugh, J A, Wang, P, Cox, G M, Perfect, J R, ...
Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised hosts. The organism has a known sexual cycle, and strains of the MATalpha mating type are more virulent than...
Lodge, J K, Jackson-Machelski, E, Toffaletti, D L, Perfect, J R, Gordon, J I
Cryptococcus neoformans is a major cause of systemic fungal infection in immunocompromised patients. Myristoyl-CoA:protein N-myristoyltransferase (Nmt) catalyzes the transfer of myristate (C14:0)...
Fungal virulence genes as targets for antifungal chemotherapy.
Fungal virulence genes have now met the age of molecular pathogenesis. The definition of virulence genes needs to be broad so that it encompasses the focus on molecular antifungal targets and vaccine...
In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans.
Perfect, J R, Cox, G M, Dodge, R K, Schell, W A
Multiple isolates of Cryptococcus neoformans were tested to compare the in vitro activity of a new triazole, SCH56592, with those of amphotericin B, fluconazole, and itraconazole, MICs of each drug...
Del Poeta, M, Schell, W A, Perfect, J R
The in vitro activity of the new antifungal drug pneumocandin L-743,872 against 55 isolates of clinically important molds was examined by an adapted macrobroth dilution method for yeasts....
Treatment of experimental cryptococcal meningitis and disseminated candidiasis with SCH39304.
Perfect, J R, Wright, K A, Hobbs, M M, Durack, D T
We studied the pharmacokinetics and in vivo antifungal action of SCH39304, a new antifungal azole compound, in rabbits. It crossed the blood-cerebrospinal fluid barrier in the presence or absence of...
Treatment of experimental disseminated candidiasis with cilofungin.
Perfect, J R, Hobbs, M M, Wright, K A, Durack, D T
The efficacy of cilofungin treatment of experimental disseminated candidiasis in rabbits was examined. Cilofungin treatment reduced yeast counts, especially in the kidney, with activity comparable to...
Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans.
Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the...
Savani, D V, Perfect, J R, Cobo, L M, Durack, D T
We studied the penetration of three azole compounds, ketoconazole, itraconazole, and fluconazole, into the ocular tissues and fluids of rabbits in the presence and absence of ocular inflammation....
Perfect, J R, Rude, T H, Wong, B, Flynn, T, Chaturvedi, V, Niehaus, W
The Mtl gene from Cryptococcus neoformans, which confers the ability of Saccharomyces cerevisiae Sc4l YJO to grow on mannitol with substantial NAD-dependent mannitol dehydrogenase activity, was...
Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with...
Perfect, J R, Savani, D V, Durack, D T
Itraconazole and fluconazole, two new triazoles, were examined for their antifungal activity in rabbits. Fluconazole easily crossed the blood-cerebrospinal fluid barrier, and active drug was...
Uptake of itraconazole by alveolar macrophages.
Perfect, J R, Savani, D V, Durack, D T
Itraconazole is a broad-spectrum potent triazole antifungal agent. Its efficacy in treatment cannot always be explained by body fluid drug levels. In this study, itraconazole was shown to accumulate...
Cameron, M L, Schell, W A, Bruch, S, Bartlett, J A, Waskin, H A, Perfect, J R
Yeast strains isolated from the oropharynx of 87 consecutive patients infected with human immunodeficiency virus type 1 were examined for in vitro susceptibility to fluconazole. Candida albicans was...
Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA.
Toffaletti, D L, Rude, T H, Johnston, S A, Durack, D T, Perfect, J R
A transformation scheme for Cryptococcus neoformans to yield high-frequency, integrative events was developed. Adenine auxotrophs from a clinical isolate of C. neoformans serotype A were complemented...
Fatal, disseminated Acremonium strictum infection in a neutropenic host.
Disseminated Acremonium strictum infection in a neutropenic patient is reported. Positive fecal cultures preceded positive cutaneous and blood cultures by 18 and 21 days, respectively, which suggests...
Wong, B, Perfect, J R, Beggs, S, Wright, K A
We studied the ability of Cryptococcus neoformans to produce the hexitol D-mannitol in vitro and in rabbits with experimental meningitis. Twelve of twelve human isolates of C. neoformans produced...
Opsonic activity of cerebrospinal fluid in experimental cryptococcal meningitis.
Hobbs, M M, Perfect, J R, Granger, D L, Durack, D T
The role of antibody in protection against infection with Cryptococcus neoformans is undefined. In this paper we describe the development of opsonic activity in the cerebrospinal fluid (CSF) of...
Perfect, J R, Hobbs, M M, Granger, D L, Durack, D T
The functional abilities of macrophages from cerebrospinal fluid (CSF) have so far been little studied. We examined the acquisition of activation characteristics by CSF macrophages during the course...
Efficacy of immune therapy in early experimental Naegleria fowleri meningitis.
Lallinger, G J, Reiner, S L, Cooke, D W, Toffaletti, D L, Perfect, J R, Granger, D L, ...
Naegleria fowleri meningoencephalitis is usually fatal in humans despite treatment. As a new approach, we tested intracisternal passive immune therapy in rabbits with amebic meningoencephalitis by...
Effects of cyclosporine in experimental cryptococcal meningitis.
We studied the effects of cyclosporine on experimental cryptococcal meningitis. Like cortisone, cyclosporine depressed the highly effective defense mechanisms of normal rabbits against inoculated...
First report of involvement of Nodulisporium species in human disease.
Cox, G M, Schell, W A, Scher, R L, Perfect, J R
Allergic fungal sinusitis is a common disease that results from a hypersensitivity reaction mounted by the host against fungi living in the paranasal sinuses. We have recently treated a patient with...
Karyotyping of Cryptococcus neoformans as an epidemiological tool.
Perfect, J R, Ketabchi, N, Cox, G M, Ingram, C W, Beiser, C L
Karyotyping of Cryptococcus neoformans var. neoformans can be used as an epidemiological tool for C. neoformans infections. In this study of over 40 isolates from both clinical and environmental...
Perfect, J R, Toffaletti, D L, Rude, T H
A cryptococcal meningitis model in corticosteroid-treated rabbits was used to assess the requirement for the phosphoribosylaminoimidazole gene (ADE2) for virulence of Cryptococcus neoformans. A...
Perfect, J R, Lang, S D, Durack, D T
To evaluate cotrimoxazole in the treatment of bacterial meningitis, we compared its action with that of ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis. Both...
Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages.
Granger, D L, Hibbs, J B, Perfect, J R, Durack, D T
L-arginine is required for the fungistatic action of murine macrophages in vitro. To further investigate this requirement, L-arginine metabolism by macrophages was measured under conditions where...
Separation of chromosomes of Cryptococcus neoformans by pulsed field gel electrophoresis.
Perfect, J R, Magee, B B, Magee, P T
Chromosomes from Cryptococcus neoformans, an encapsulated yeast pathogen, were separated by contour-clamped homogeneous field gel electrophoresis. Seven strains representing all four serotypes were...
In Vitro and In Vivo Efficacies of the New Triazole Albaconazole against Cryptococcus neoformans
Miller, J. L., Schell, W. A., Wills, E. A., Toffaletti, D. L., Boyce, M., Benjamin, D. K., ...
The activity of albaconazole (UR-9825; J. Uriach & Cía. S.A., Barcelona, Spain) was compared to that of fluconazole against 12 isolates of Cryptococcus neoformans in vitro and against 1 isolate in...
Cryptococcus neoformans Gene Expression during Experimental Cryptococcal Meningitis
Steen, B. R., Zuyderduyn, S., Toffaletti, D. L., Marra, M., Jones, S. J. M., Perfect, J. R., ...
Cryptococcus neoformans, an encapsulated basidiomycete fungus of medical importance, is capable of crossing the blood-brain barrier and causing meningitis in both immunocompetent and...
Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages.
Granger, D L, Hibbs, J B, Perfect, J R, Durack, D T
The microbiostatic action of macrophages was studied in vitro employing peritoneal cytotoxic macrophages (CM) from mice acting against Cryptococcus neoformans cultured in Dulbecco's medium with 10%...
Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide.
Granger, D L, Perfect, J R, Durack, D T
Cryptococcus neoformans is variably encapsulated in vitro, whereas in tissues it develops a large capsule. We observed that cells of a strain with thin capsules, when growing in a standard fungal...
Identification and Characterization of an SKN7 Homologue in Cryptococcus neoformans
Wormley, F. L., Heinrich, G., Miller, J. L., Perfect, J. R., Cox, G. M.
Cryptococcus neoformans is an encapsulated fungal pathogen that primarily infects the central nervous system of immunocompromised individuals, causing life-threatening meningoencephalitis. The...
Del Poeta, M, Toffaletti, D L, Rude, T H, Dykstra, C C, Heitman, J, Perfect, J R
Topisomerase I is the target of several toxins and chemotherapy agents, and the enzyme is essential for viability in some organisms, including mice and drosophila. We have cloned the TOP1 gene...
Yue, C, Cavallo, L M, Alspaugh, J A, Wang, P, Cox, G M, Perfect, J R, ...
Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised hosts. The organism has a known sexual cycle, and strains of the MATalpha mating type are more virulent than...
Comparative Pharmacokinetics of Voriconazole Administered Orally as either Crushed or Whole Tablets▿
Dodds Ashley, E. S., Zaas, A. K., Fang, A. F., Damle, B., Perfect, J. R.
Voriconazole is a triazole antifungal agent used to treat serious, invasive fungal infections including aspergillosis and candidemia. Limitations with existing formulations of voriconazole including...
Chronic cryptococcal meningitis: a new experimental model in rabbits.
Perfect, J. R., Lang, S. D., Durack, D. T.
This paper describes the salient features of a new model for chronic cryptococcal meningitis in cortisone-treated rabbits. Normal rabbits soon recovered after intracisternal inoculation of...