bluuebunny/crossref_metadata_2025_split huggingface dataset:
International Surveillance of Bloodstream Infections Due to
Candida
Species: Frequency of Occurrence and In Vitro Susceptibilities to Fluconazole, Ravuconazole, and Voriconazole of Isolates Collected from 1997 through 1999 in the SENTRY Antimicrobial Surveillance Program
Authors: Pfaller M. A. , Diekema D. J. , Jones R. N. , Sader H. S. , Fluit A. C. , Hollis R. J. , Messer S. A. ,   The SENTRY Participant Group
Published: July 2002

ABSTRACT

A surveillance program (SENTRY) of bloodstream infections (BSI) in the United States, Canada, Latin America, and Europe from 1997 through 1999 detected 1,184 episodes of candidemia in 71 medical centers (32 in the United States, 23 in Europe, 9 in Latin America, and 7 in Canada). Overall, 55% of the yeast BSIs were due to
Candida albicans
, followed by
Candida glabrata
and
Candida parapsilosis
(15%),
Candida tropicalis
(9%), and miscellaneous
Candida
spp. (6%). In the United States, 45% of candidemias were due to non-
C. albicans
species.
C. glabrata
(21%) was the most common non-
C. albicans
species in the United States, and the proportion of non-
C. albicans
BSIs was highest in Latin America (55%).
C. albicans
accounted for 60% of BSI in Canada and 58% in Europe.
C. parapsilosis
was the most common non-
C. albicans
species in Latin America (25%), Canada (16%), and Europe (17%). Isolates of
C. albicans, C. parapsilosis
, and
C. tropicalis
were all highly susceptible to fluconazole (97 to 100% at ≤8 μg/ml). Likewise, 97 to 100% of these species were inhibited by ≤1 μg/ml of ravuconazole (concentration at which 50% were inhibited [MIC
50
], 0.007 to 0.03 μg/ml) or voriconazole (MIC
50
, 0.007 to 0.06 μg/ml). Both ravuconazole and voriconazole were significantly more active than fluconazole against
C. glabrata
(MIC
90
s of 0.5 to 1.0 μg/ml versus 16 to 32 μg/ml, respectively). A trend of increased susceptibility of
C. glabrata
to fluconazole was noted over the three-year period. The percentage of
C. glabrata
isolates susceptible to fluconazole increased from 48% in 1997 to 84% in 1999, and MIC
50
s decreased from 16 to 4 μg/ml. A similar trend was documented in both the Americas (57 to 84% susceptible) and Europe (22 to 80% susceptible). Some geographic differences in susceptibility to triazole were observed with Canadian isolates generally more susceptible than isolates from the United States and Europe. These observations suggest susceptibility patterns and trends among yeast isolates from BSI and raise additional questions that can be answered only by continued surveillance and clinical investigations of the type reported here (SENTRY Program).
Evaluation of a New Combined Antigen and Antibody Human Immunodeficiency Virus Screening Assay, VIDAS HIV DUO Ultra
Authors: Weber Bernard , Berger Annemarie , Rabenau Holger , Doerr Hans Wilhelm 
Published: July 2002

ABSTRACT
Combined antigen and antibody screening (fourth-generation) assays reduce the diagnostic window period between the time of human immunodeficiency virus (HIV) infection and laboratory diagnosis by 4 days, on average, in comparison to antibody-only (third generation) enzyme immunoassays (EIAs). The aim of the present study was to assess whether the new VIDAS HIV DUO Ultra (Biomérieux, Marcy-l'Etoile, France) showed an improved sensitivity and specificity in comparison to licensed fourth-generation assays. A total of 16 seroconversion panels, 15 cell culture supernatants infected with different HIV type 1 (HIV-1) subtypes, and 257 potentially cross-reactive serum samples were tested with VIDAS DUO HIV Ultra, Genscreen Plus HIV Ag-Ab, Enzygnost HIV Integral, Enzymun-Test HIV Combi, Genscreen HIV 1/2, version 2 (third-generation EIA), and Genetic Systems HIV-1 Ag EIA (p24 antigen assay). VIDAS HIV DUO Ultra showed a comparable sensitivity to the single p24 antigen assay in seroconversion panels and a dilution series of virus lysates. The diagnostic window was reduced with VIDAS HIV DUO Ultra by 3.82 days, on average, in comparison with the fourth-generation assay with the lowest sensitivity of the antigen detection module. HIV-1 infection was detected 5.88 days earlier than with third-generation EIA. The mean time delay between reverse transcription-PCR and VIDAS HIV DUO Ultra was only 2.31 days. The specificity of fourth-generation assays after retesting ranged between 98.1 and 100%. In conclusion, VIDAS HIV DUO Ultra can replace single-antigen screening for laboratory diagnosis and screening of HIV infection in blood donors. There was no evidence for a second diagnostic window due to impaired sensitivity of the antibody detection module of all the fourth-generation EIAs evaluated in the present study. The specificity after initial and/or repeated testing of VIDAS HIV DUO Ultra was equivalent to that of a third-generation assay.
Epidemiologic Genotyping of Methicillin-Resistant
Staphylococcus aureus
by Pulsed-Field Gel Electrophoresis at a University Hospital and Comparison with Antibiotyping and Protein A and Coagulase Gene Polymorphisms
Authors: Montesinos I. , Salido E. , Delgado T. , Cuervo M. , Sierra A. 
Published: July 2002

ABSTRACT

A total of 124 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates were ascertained at the University Hospital of the Canary Islands between January 1997 and April 2000. Genotyping included pulsed-field gel electrophoresis (PFGE) (
Sma
I digestion) and PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for the coagulase (
coa
) and protein A (
spa
) genes. Antibiotic resistance was the main phenotypic marker correlated with genotyping results. Three main PFGE types were detected: A (with 12 subtypes), B (with 2 subtypes), and C. PFGE type A1 was the most commonly found (61% of isolates) and the one responsible for all the epidemic outbreaks. Other genetics markers used (
coa
and
spa
RFLPs) were significantly correlated with the PFGE types detected (
P
< 0.001). These PCR-RFLP assays were useful as molecular markers for a quick, preliminary study of MRSA outbreaks.
Prolonged Dominance of Clonally Restricted CD4+T Cells in Macaques Infected with Simian Immunodeficiency Viruses
Authors: Chen Zheng W. , Shen Yun , Kou Zhongchen , Ibegbu Chris , Zhou Dejiang , Shen Ling , Morrison Paul , Bogle Christine , McClure Harold M. , Nahmias Andre J. , Sehgal Prahbat K. , Letvin Norman L. 
Published: July 2002

ABSTRACTThe repertoire of functional CD4+T lymphocytes in human immunodeficiency virus type 1-infected individuals remains poorly understood. To explore this issue, we have examined the clonality of CD4+T cells in simian immunodeficiency virus (SIV)-infected macaques by assessing T-cell receptor complementarity-determining region 3 (CDR3) profiles and sequences. A dominance of CD4+T cells expressing particular CDR3 sequences was identified within certain Vβ-expressing peripheral blood lymphocyte subpopulations in the infected monkeys. Studies were then done to explore whether these dominant CD4+T cells represented expanded antigen-specific cell subpopulations or residual cells remaining in the course of virus-induced CD4+T-cell depletion. Sequence analysis revealed that these selected CDR3-bearing CD4+T-cell clones emerged soon after infection and dominated the CD4+T-cell repertoire for up to 14 months. Moreover, inoculation of chronically infected macaques with autologous SIV-infected cell lines to transiently increase plasma viral loads in the monkeys resulted in the dominance of these selected CDR3-bearing CD4+T cells. Both the temporal association of the detection of these clonal cell populations with infection and the dominance of these cell populations following superinfection with SIV suggest that these cells may be SIV specific. Finally, the inoculation of staphylococcal enterotoxin B superantigen into SIV-infected macaques uncovered a polyclonal background underlying the few dominant CDR3-bearing CD4+T cells, demonstrating that expandable polyclonal CD4+T-cell subpopulations persist in these animals. These results support the notions that a chronic AIDS virus infection can induce clonal expansion, in addition to depletion of CD4+T cells, and that some of these clones may be SIV specific.
Adeno-Associated Virus Type 2 Rep78 Induces Apoptosis through Caspase Activation Independently of p53
Authors: Schmidt Michael , Afione Sandra , Kotin Robert M. 
Published: July 2002

ABSTRACT

Adeno-associated virus (AAV) type 2 Rep78 is a multifunctional protein required for AAV DNA replication, integration, and gene regulation. The biochemical activities of Rep78 have been described, but the effects of Rep proteins on the cell have not been characterized. We have analyzed Rep-mediated cytotoxicity. We demonstrated that Rep78 expression is sufficient to induce cell death and disruption of the cell cycle. Cell death was found to be mediated by apoptosis. Rep78 expression resulted in the activation of caspase-3, a terminal caspase directly involved in the execution of cell death. A peptidic inhibitor of caspase-3, Z-Asp-Glu-Val-Asp-fluoromethylketone (Z-DEVD-FMK), abrogated Rep78-induced apoptosis, indicating that Rep78-mediated apoptosis is caspase-3 dependent. Rep78 induced apoptosis in wild-type p53-containing human embryonal carcinoma NT-2 cells and in p53-null promyelocytic human HL-60 cells, indicating that at least one pathway of Rep78-induced apoptosis is p53 independent. Apoptosis was shown to occur during the G
1
and early S phases of the cell cycle. By analyzing the effects of Rep78 mutations on cell viability, the cause of cell death was attributed in part to two biochemical activities of Rep78, DNA binding and ATPase/helicase activity. The endonuclease activity of Rep78 did not contribute to apoptosis induction.
In Vitro Reconstitution of a Functional Duck Hepatitis B Virus Reverse Transcriptase: Posttranslational Activation by Hsp90
Authors: Hu Jianming , Anselmo Dana 
Published: July 2002

ABSTRACT
Reverse transcription in hepatitis B viruses is initiated through a unique protein priming mechanism whereby the viral reverse transcriptase (RT) first assembles into a ribonucleoprotein (RNP) complex with its RNA template and then initiates DNA synthesis de novo using the RT itself as a protein primer. RNP formation and protein priming require the assistance of host cell factors, including the molecular chaperone heat shock protein 90 (Hsp90). To better understand the mechanism of RT activation by Hsp90, we have now mapped the minimal RT sequences of the duck hepatitis B virus that are required for chaperone binding, RNP formation, and protein priming. Furthermore, we have reconstituted in vitro both RNP formation and protein priming using purified RT proteins and host factors. Our results show that (i) Hsp90 recognizes two independent domains of the RT, both of which are necessary for RNP formation and protein priming; (ii) Hsp90 function is required not only to establish, but also to maintain, the RT in a state competent for RNA binding; and (iii) Hsp90 is not required during RT synthesis and can activate the RT posttranslationally. Based on these findings, we propose a model for Hsp90 function whereby the chaperone acts as an active interdomain bridge to bring the two RT domains into a poised but labile conformation competent for RNP formation. It is anticipated that the reconstitution system established here will facilitate the isolation of additional host factors required for RT functions and further elucidation of the mechanisms of RT activation.
Characterization of Gammaherpesvirus 68 Gene 50 Transcription
Authors: Liu Shaofan , Pavlova Iglika V. , Virgin Herbert W. , Speck Samuel H. 
Published: July 2002

ABSTRACT
Gene 50 is the only immediate-early gene that appears to be conserved among the characterized gammaherpesviruses. It has recently been demonstrated for the human viruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) that ectopic expression of the gene 50-encoded product in some latently infected cell lines can lead to the induction of virus replication, indicating that gene 50 is likely to play a pivotal role in regulating gammaherpesvirus reactivation. Here we demonstrate that the murine gammaherpesvirus 68 (γHV68) gene 50 is an immediate-early gene and that transcription of γHV68 gene 50 leads to the production of both spliced and unspliced forms of the gene 50 transcript. Splicing of the transcript near the 5′ end serves to extend the gene 50 open reading frame, as has been observed for the gene 50 transcripts encoded by KSHV and herpesvirus saimiri (Whitehouse et al., J. Virol. 71:2550–2554, 1997; Lukac et al., Virology 252:304–312, 1998; Sun et al., Proc. Natl. Acad. Sci. USA 95:10866–10871, 1998). Reverse transcription-PCR analyses, coupled with S1 nuclease protection assays, provided evidence that gene 50 transcripts initiate at several sites within the region from bp 66468 to 66502 in the γHV68 genome. Functional characterization of the region upstream of the putative gene 50 transcription initiation site demonstrated orientation-dependent promoter activity and identified a 110-bp region (bp 66442 to 66552) encoding the putative gene 50 promoter. Finally, we demonstrate that the γHV68 gene 50 can transactivate the γHV68 gene 57 promoter, a known early gene target of the gene 50-encoded transactivator in other gammaherpesviruses. These studies show that the γHV68 gene 50 shares several important molecular similarities with the gene 50 homologs in other gammaherpesviruses and thus provides an impetus for future studies analyzing the role of the γHV68 gene 50-encoded protein in acute virus replication and reactivation from latency in vivo.
Detection of Hepatitis B Virus Infection in Wild-Born Chimpanzees (
Pan troglodytes verus
): Phylogenetic Relationships with Human and Other Primate Genotypes
Authors: MacDonald D. M. , Holmes E. C. , Lewis J. C. M. , Simmonds P. 
Published: July 2002

ABSTRACT

Infection with hepatitis B virus (HBV) was detected by serological testing for HBV surface antigen and by PCR assay for HBV DNA in serum samples from two common chimpanzees (
Pan troglodytes
subsp.
verus
) born in West Africa. The complete genome sequences obtained by nucleotide sequencing of overlapping DNA fragments amplified by PCR were compared with HBV variants recovered from other primates and with human genotypes A to F. Both chimpanzee sequences were 3,182 nucleotides in length, and the surface gene sequence predicted the existence of
a
,
d
, and
w
serological determinants. Neither sequence contained stop codons in the precore region. On phylogenetic analysis, the HBV variants infecting the chimpanzees clustered together with a third chimpanzee HBV isolate independently obtained from an infected captive animal (A. J. Zuckerman, A. Thornton, C. R. Howard, K. N. Tsiquaye, D. M. Jones, and M. R. Brambell, Lancet ii:652–654, 1978), with an overall sequence similarity of >94%. This provides strong evidence for a chimpanzee-specific genotype of HBV which circulates in nature. These findings add to the recent evidence for infection in the wild of other Old and New World primates (gibbon, orangutan, and woolly monkey) with species-specific variants of HBV. There is no evidence for close phylogenetic clustering of variants found so far in primates with any of the established HBV genotypes from humans. With the new evidence for the widespread distribution of HBV in primates, hypotheses for the origins of human infection are reviewed.
Regulation of Human Immunodeficiency Virus Type 1 Replication in Human T Lymphocytes by Nitric Oxide
Authors: Jiménez Jose Luis , González-Nicolás Josefa , Alvarez Susana , Fresno Manuel , Muñoz-Fernández M. Angeles 
Published: July 2002

ABSTRACTAddition of nitric oxide (NO) donors to mitogen-activated human immunodeficiency virus type 1 (HIV-1)-infected peripheral blood mononuclear cultures produced a significant increase in virus replication, and this effect was not associated with a change in cell proliferation. This effect was only observed with T-tropic X4 or X4R5 virus but not with R5 virus. Moreover, HIV-1 replication in mitogen-stimulated cultures was partially prevented by the specific inhibitors of the inducible nitric oxide synthase (iNOS). NO donors also enhanced HIV-1 infection of the human T-cell lines, Jurkat and MT-2. We have also observed that NO leads to an enhancement of HIV-1 replication in resting human T cells transfected with a plasmid carrying the entire HIV-1 genome and activated with phorbol ester plus ionomycin. Thus, in those cultures NO donors strongly potentiated HIV-1 replication in a dose-dependent manner, up to levels comparable to those with tumor necrosis factor alpha (TNF-α) stimulation. Furthermore, iNOS inhibitors decreased HIV-1 replication in HIV-1-transfected T cells to levels similar to those obtained with neutralizing anti-TNF-α antibodies. Moreover, HIV-1 replication induced iNOS and TNF-α transcription in T cells and T-cell lines. Interestingly, NO donors also stimulated long terminal repeat (LTR)-driven transcription whereas iNOS inhibitors partially blocked TNF-α-induced LTR transcription. Therefore, our results suggest that NO is involved in HIV-1 replication, especially that induced by TNF-α.
Mapping the Determinants of the CCR5 Amino-Terminal Sulfopeptide Interaction with Soluble Human Immunodeficiency Virus Type 1 gp120-CD4 Complexes
Authors: Cormier Emmanuel G. , Tran Diep N. H. , Yukhayeva Liyana , Olson William C. , Dragic Tatjana 
Published: July 2002

ABSTRACT
CD4 and CCR5 mediate fusion and entry of R5 human immunodeficiency virus type 1 (HIV-1) strains. Sulfotyrosine and other negatively charged residues in the CCR5 amino-terminal domain (Nt) are crucial for gp120 binding and viral entry. We previously showed that a soluble gp120-CD4 complex specifically binds to a peptide corresponding to CCR5 Nt residues 2 to 18, with sulfotyrosines in positions 10 and 14. This sulfopeptide also inhibits soluble gp120-CD4 binding to cell surface CCR5 as well as infection by an R5 virus. Here we show that residues 10 to 18 constitute the minimal domain of the CCR5 Nt that is able to specifically interact with soluble gp120-CD4 complexes. In addition to sulfotyrosines in positions 10 and 14, negatively charged residues in positions 11 and 18 participate in this interaction. Furthermore, the CCR5 Nt binds to a CD4-induced surface on gp120 that is composed of conserved residues in the V3 loop stem and the C4 domain. Binding of gp120 to cell surface CCR5 is further influenced by residues in the crown of the V3 loop, C1, C2, and C3. Our data suggest that gp120 docking to CCR5 is a multistep process involving several independent regions of the envelope glycoprotein and the coreceptor.
In Vitro Human Immunodeficiency Virus Eradication by Autologous CD8+T Cells Expanded with Inactivated-Virus-Pulsed Dendritic Cells
Authors: Lu Wei , Andrieu Jean-Marie 
Published: July 2002

ABSTRACTDespite significant immune recovery with potent highly active antiretroviral therapy (HAART), eradication of human immunodeficiency virus (HIV) from the bodies of infected individuals represents a challenge. We hypothesized that an inadequate or inappropriate signal in virus-specific antigen presentation might contribute to the persistent failure to mount efficient anti-HIV immunity in most HIV-infected individuals. Here, we conducted an in vitro study with untreated (n= 10) and HAART-treated (n= 20) HIV type 1 (HIV-1) patients which showed that pulsing of monocyte-derived dendritic cells (DC) with aldrithiol-2-inactivated autologous virus resulted in the expansion of virus-specific CD8+T cells which were capable of killing HIV-1-infected cells and eradicating the virus from cultured patient peripheral blood mononuclear cells independently of the disease stages and HAART response statuses of the patients. This in vitro anti-HIV effect was further enhanced by the HIV protease inhibitor indinavir (at a nonantiviral concentration), which has been shown previously to be able to up-regulate directly patient T-cell proliferation following immune stimulation. However, following a 2-day treatment with culture supernatant derived from immune-activated T cells (which mimics an in vivo environment of HIV-disseminated and immune-activated lymphoid tissues), DC lost their capacity to present de novo inactivated-virus-derived antigens. These findings provide important information for understanding the establishment of chronic HIV infection and indicate a perspective for clinical use of DC-based therapeutic vaccines against HIV.
Kaposi's Sarcoma-Associated Herpesvirus Latent and Lytic Gene Expression as Revealed by DNA Arrays
Authors: Jenner Richard G. , Albà M. Mar , Boshoff Chris , Kellam Paul 
Published: July 2002

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) is associated with three human tumors, Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. KSHV encodes a number of homologs of cellular proteins involved in the cell cycle, signal transduction, and modulation of the host immune response. Of the virus complement of over 85 open reading frames (ORFs), the expression of only a minority has been characterized individually. We have constructed a nylon membrane-based DNA array which allows the expression of almost every ORF of KSHV to be measured simultaneously. A PEL-derived cell line, BC-3, was used to study the expression of KSHV during latency and after the induction of lytic replication. Cluster analysis, which arranges genes according to their expression profile, revealed a correlation between expression and assigned gene function that is consistent with the known stages of the herpesvirus life cycle. Furthermore, latent and lytic genes thought to be functionally related cluster into groups. The correlation between gene expression and function also infers possible roles for KSHV genes yet to be characterized.
Rapid Appearance of Secondary Immune Responses and Protection from Acute CD4 Depletion after a Highly Pathogenic Immunodeficiency Virus Challenge in Macaques Vaccinated with a DNA Prime/Sendai Virus Vector Boost Regimen
Authors: Matano Tetsuro , Kano Munehide , Nakamura Hiromi , Takeda Akiko , Nagai Yoshiyuki 
Published: July 2002

ABSTRACT

Heterologous prime/boost regimens are AIDS vaccine candidates because of their potential for inducing cellular immune responses. Here, we have developed a prime/boost regimen leading to rapid control of highly pathogenic immunodeficiency virus infection in macaques. The strategy, priming by an
env
and
nef
deletion-containing simian-human immunodeficiency virus (SHIV) proviral DNA followed by a single booster with a Gag-expressing Sendai virus (SeV-Gag), efficiently induced virus-specific T cells, which were maintained for more than 3 months until challenge. While all naive control macaques showed acute CD4
+
T-cell depletion at week 2 after an intravenous SHIV89.6PD challenge, all the macaques vaccinated with the prime/boost regimen were protected from depletion and showed greatly reduced peak viral loads compared with controls. Vaccination with the DNA alone or SeV-Gag alone was not enough to confer the consistent protection from the depletion, although it led to efficient secondary CD8
+
T-cell responses at week 2 after challenge. At week 1, a difference in the secondary responses between the protected and the unprotected macaques was clear; rapid augmentation of virus-specific CD8
+
T cells was detected in the former but not in the latter. Thus, our results indicate the importance of rapid secondary responses for reduction in the peak viral loads and protection from acute CD4
+
T-cell depletion.