H J Lo

National Health Research Institutes, Miao-li-chieh, Taiwan, Taiwan

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Publications (9)24.02 Total impact

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    ABSTRACT: Ndt80p is an important transcription modulator to various stress-response genes in Candida albicans, the most common human fungal pathogen in systemic infections. We found that Ndt80p directly regulated its target genes, such as YHB1, via the mid-sporulation element (MSE). Furthermore, the ndt80(R432A) allele, with a reduced capability to bind MSE, failed to complement the defects caused by null mutations of NDT80. Thus, the R432 residue in the Ndt80p DNA-binding domain is involved in all tested functions, including cell separation, drug resistance, nitric oxide inactivation, germ tube formation, hyphal growth, and virulence. Hence, the importance of the R432 residue suggests a novel approach for designing new antifungal drugs by blocking the interaction between Ndt80p and its targets.
    Cellular and Molecular Life Sciences CMLS 03/2012; 69(6):1011-23. · 5.62 Impact Factor
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    ABSTRACT: A total of 35 Trichosporon isolates were collected from the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) project from 1999 to 2006, and their identifications as well as drug susceptibilities were determined. The most frequently isolated species was T. asahii (62.9%), and the most common clinical sample that yielded Trichosporon isolates was urine (37.1%). The etiology of all seven invasive trichosporonosis was T. asahii. For the 22 T. asahii isolates, the MIC(50) and MIC(90) for amphotericin B were 0.25 and 1 μg/mL, respectively. Those for fluconazole were 2 and 4 μg/mL, respectively, and for voriconazole 0.031 and 0.063 μg/mL, respectively. When the intraclass correlation coefficients (ICCs) and agreements were calculated, we found that the MICs of fluconazole obtained from different methods were similar and the inter-method discrepancies were low. Nevertheless, no unanimous MIC of amphotericin B and voriconazole was obtained among different methods.
    Mycopathologia 02/2012; 174(2):121-30. · 1.65 Impact Factor
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    ABSTRACT: Opportunistic yeast pathogens may switch from harmless commensal to pathogenic relationships with the host under different conditions. They usually cause superficial infections, but may be the agents of more significant infections in immunocompromised patients. To investigate yeast colonization in the oral cavities of clinically healthy individuals, we collected oral swabs from 323 students and staff at the National Health Research Institutes, Taiwan. A total of 49 (15.2%) volunteers were colonized by low levels of yeasts and of these, only 3 (6.1%) were co-colonized by more than one species. Among the 52 isolates, comprising seven fungal genera and 13 species, Candida albicans (57.7%) was the dominant species, followed by Candida parapsilosis (15.4%). There was only one isolate of C. parapsilosis that showed, in vitro, a high (2 μg/ml) minimum inhibitory concentration (MIC) to amphotericin B. There were six (11.5%) isolates with fluconazole MICs ≥ 64 μg/ml and all of them were non-Candida species. With the exception of Cryptococcus albidus, the remaining five isolates had voriconazole MICs ≥ 4 μg/ml. In addition, there was one C. albicans isolate with relatively high fluconazole (32 μg/ml) and voriconazole (4 μg/ml) MICs.
    Medical mycology: official publication of the International Society for Human and Animal Mycology 01/2011; 49(1):103-6. · 2.13 Impact Factor
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    ABSTRACT: To study the demographic changes of yeasts causing invasive infections in Taiwan, especially with respect to species distribution and antifungal susceptibility, we analyzed isolates obtained from four sterile sites of patients in 19 hospitals in 2002 (155 strains) and again from the same hospitals in 2006 (208 strains). Blood was the most common source of the yeasts, accounting for 73.8% of the total isolates, followed by ascites (21.5%), cerebrospinal fluid (3%), and synovia (1.7%). Candida albicans was the most frequently recovered species (50.1% of the total), followed by Candida tropicalis (20.7%), Candida glabrata (11.6%), Candida parapsilosis (8.5%), Cryptococcus neoformans (3.9%), Candida krusei (0.8%), and nine other species (4.3%). There were one (0.3%) and seven (1.9%) isolates with minimum inhibitory concentrations (MICs) of amphotericin B > or =2 mg/l after 24 h and 48 h incubation, respectively. In addition, there were 15 (4.3%) and 31 (8.6%) isolates with MICs of fluconazole > or =64 mg/l under the same conditions. The MIC(90) value of amphotericin B was 1 mg/l. The MIC(90) values of fluconazole were 4 mg/l after 24 h incubation and 32 mg/l after 48 h incubation. Interestingly, MICs for fluconazole > or =64 mg/l after 24 h were significantly higher for isolates obtained in 2006 than those in 2002 after 24 h (7.1% vs. 0.7%, p =0.009) and 48 h (13.5% vs. 2%, p =0.0003) incubations. The demographic difference between these two surveys is mainly due to one species, C. tropicalis.
    Medical mycology: official publication of the International Society for Human and Animal Mycology 03/2010; 48(2):328-34. · 2.13 Impact Factor
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    ABSTRACT: To study the demographic changes of yeasts causing invasive infections in Taiwan, especially with respect to species distribution and antifungal susceptibility, we analyzed isolates obtained from four sterile sites of patients in 19 hospitals in 2002 (155 strains) and again from the same hospitals in 2006 (208 strains). Blood was the most common source of the yeasts, accounting for 73.8% of the total isolates, followed by ascites (21.5%), cerebrospinal fluid (3%), and synovia (1.7%). Candida albicans was the most frequently recovered species (50.1% of the total), followed by Candida tropicalis (20.7%), Candida glabrata (11.6%), Candida parapsilosis (8.5%), Cryptococcus neoformans (3.9%), Candida krusei (0.8%), and nine other species (4.3%). There were one (0.3%) and seven (1.9%) isolates with minimum inhibitory concentrations (MICs) of amphotericin B >/=2 mg/l after 24 h and 48 h incubation, respectively. In addition, there were 15 (4.3%) and 31 (8.6%) isolates with MICs of fluconazole >/=64 mg/l under the same conditions. The MIC(90) value of amphotericin B was 1 mg/l. The MIC(90) values of fluconazole were 4 mg/l after 24 h incubation and 32 mg/l after 48 h incubation. Interestingly, MICs for fluconazole >/=64 mg/l after 24 h were significantly higher for isolates obtained in 2006 than those in 2002 after 24 h (7.1% vs. 0.7%, p=0.009) and 48 h (13.5% vs. 2%, p=0.0003) incubations. The demographic difference between these two surveys is mainly due to one species, C. tropicalis.
    Medical mycology: official publication of the International Society for Human and Animal Mycology 08/2009; · 2.13 Impact Factor
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    ABSTRACT: Twenty-one Candida albicans isolates from three HIV-infected patients were collected over a period of 3 years and characterized for fluconazole susceptibility, infectivity and genetic relatedness. Fluconazole resistance was found in five isolates, four exhibited dose-dependent susceptibility and the remainder were fully susceptible to this agent. Pulsed-field gel electrophoresis of SfiI restriction digests of the genomic DNA from the isolates revealed that isolates from the same swab specimen were identical despite differences in susceptibility to fluconazole and isolates recovered over time from the three patients retained clonally related DNA fingerprints within each patient. This small-scale study confirms the persistence of oral colonization of C. albicans strains in HIV-infected patients. Clinical data also suggests that the primary infecting strain may become a persistent colonist in the oral cavity once the immune function of the patient has been restored.
    Epidemiology and Infection 05/2006; 134(2):265-9. · 2.87 Impact Factor
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    ABSTRACT: The cph1/cph1 efg1/efg1 Candida albicans mutant cells were non-lethal in a mouse model of systemic infection. We investigated in vivo proliferation and invasion of C. albicans cells in infected mice to elucidate the interaction between the host and the pathogen. Homogenates of kidneys from the mice infected with the wild-type and the mutant C. albicans cells yielded a mean of 2.1 x 10 7 CFU/g and 2.2 x 10 6 CFU/g, respectively. The kidneys from the mice infected with the wild-type cells showed extensive renal cortical necrosis associated with neutrophilic infiltration. There were also wild-type hyphal cells present in abundance. Hence, tubular necrosis leading to renal failure in the mice may be the cause of death. Although the cph1/cph1 efg1/efg1 mutant cells were not lethal, they were capable of establishing restricted zones of infection and colonization near the renal pelvis instead of simply being cleared by the immune system in mice.
    International journal of immunopathology and pharmacology 01/2006; 19(3):561-5. · 2.99 Impact Factor
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    ABSTRACT: Susceptibilities to amphotericin B and fluconazole of 628 clinical yeast strains collected from 22 hospitals in Taiwan were determined. A total of 53 isolates (8.4%) were resistant to fluconazole. Each hospital had different resistance rate to fluconazole ranging from 0% to 24%. None of the 186 isolates from eight of the 22 hospitals was resistant to fluconazole. In contrast, isolates from nine of the remaining 14 hospitals had greater than 10% resistance rate to fluconazole. Consistently, 88.9% (8/9) fluconazole-resistant C. albicans isolates were from hospitals having a high resistance rate to fluconazole. The prevalence of various Candida spp. in each hospital was different. A positive association was found between the prevalence of C. tropicalis and the resistance rate to fluconazole for individual hospitals. Although only three isolates (0.5%) were resistant to amphotericin B, a co-resistance to both amphotericin B and fluconazole was observed, which highlights the emerging problem of drug resistance.
    Epidemiology and Infection 05/2005; 133(2):325-30. · 2.87 Impact Factor
  • Y L Yang, H J Lo
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    ABSTRACT: During the past decade, yeast infections have had an important role in nosocomial infections due to alterations in the immune status of patients. Coincidentally with the increased usage of antifungal agents, the number of reports of drug resistance has increased, which highlights the need for understanding the molecular mechanisms of antifungal agent resistance. This review describes the mechanisms of action of antifungal agents, cellular factors contributing to drug resistance, the known molecular mechanisms of drug resistance, and proposed but unproved molecular mechanisms of drug resistance. This review also proposes possible strategies for preventing drug resistance.
    Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 07/2001; 34(2):79-86. · 1.63 Impact Factor

Publication Stats

84 Citations
24.02 Total Impact Points

Institutions

  • 2006–2012
    • National Health Research Institutes
      • National Institute of Infectious Diseases and Vaccinology
      Miao-li-chieh, Taiwan, Taiwan
  • 2001–2012
    • National Chiao Tung University
      • • Department of Biological Science and Technology
      • • Institute of Molecular Medicine and Bioengineering
      Hsinchu, Taiwan, Taiwan