bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Amoxicillin-Clavulanic Acid on Human Fecal Flora in a Gnotobiotic Mouse Model Assessed with Fluorescence Hybridization Using Group-Specific 16S rRNA Probes in Combination with Flow Cytometry
Authors: Barc Marie Claude , Bourlioux François , Rigottier-Gois Lionel , Charrin-Sarnel Céline , Janoir Claire , Boureau Hélène , Doré Joël , Collignon Anne 
Published: March 2004

ABSTRACTPredominant groups of bacteria from a human fecal flora-associated mouse model challenged with amoxicillin-clavulanic acid were quantified with fluorescence in situ hybridization combined with flow cytometry using specific 16S rRNA targeted oligonucleotide probes. This approach provides a useful tool with high throughput to evaluate fecal microflora under antibiotic treatment.
Molecular Characterization of the Gene Encoding a New AmpC β-Lactamase in a Clinical Strain of
Acinetobacter
Genomic Species 3
Authors: Beceiro Alejandro , Dominguez Lourdes , Ribera Anna , Vila Jordi , Molina Francisca , Villanueva Rosa , Eiros Jose Maria , Bou German 
Published: March 2004

ABSTRACT

A presumptive chromosomal cephalosporinase (pI, 9.0) from a clinical strain of
Acinetobacter
genomic species 3 (AG3) is reported. The nucleotide sequence of this β-lactamase shows for the first time the gene encoding an AmpC enzyme in AG3. In addition, the biochemical properties of the novel AG3 AmpC β-lactamase are reported
In Vitro Antimicrobial Activity of Doripenem, a New Carbapenem
Authors: Ge Yigong , Wikler Matthew A. , Sahm Daniel F. , Blosser-Middleton Renée S. , Karlowsky James A. 
Published: March 2004

ABSTRACT

The doripenem MICs at which 90% of the tested strains were inhibited ranged from 0.03 to 1 μg/ml for 10 species of
Enterobacteriaceae
(
n
= 351), from 0.03 to 0.12 μg/ml for oxacillin-susceptible staphylococci (
n
= 119), from 4 to 32 μg/ml for oxacillin-resistant staphylococci (
n
= 64), from ≤0.008 to 0.06 μg/ml for penicillin-susceptible streptococci (
n
= 132), and from 1 to 4 μg/ml for penicillin-resistant streptococci (
n
= 51). Overall, doripenem demonstrated in vitro activity similar to that of meropenem against gram-negative pathogens and to that of imipenem against gram-positive pathogens.
Reduced Triclosan Susceptibility in Methicillin-Resistant
Staphylococcus epidermidis
Authors: Schmid Molly B. , Kaplan Nachum 
Published: March 2004

ABSTRACT

Triclosan MIC determination showed that recent
Staphylococcus aureus
clinical isolates (
n
= 100) were highly susceptible to triclosan, with a 50% minimal inhibitory concentration (MIC
50
) of 0.12 μg/ml and a MIC
90
of 0.25 μg/ml.
Staphylococcus epidermidis
isolates (
n
= 96) were less susceptible, with a MIC
50
of 0.12 μg/ml and a MIC
90
of 8 μg/ml. Decreased susceptibility to triclosan was more prevalent among methicillin-resistant
S. epidermidis
than among methicillin-sensitive
S. epidermidis
isolates.
Human Immunodeficiency Virus Type 1 Reverse Transcriptase Mutation Selection during In Vitro Exposure to Tenofovir Alone or Combined with Abacavir or Lamivudine
Authors: Stone Chris , Ait-Khaled Mounir , Craig Charles , Griffin Philip , Tisdale Margaret 
Published: March 2004

ABSTRACTMutations selected or deselected during passage of human immunodeficiency virus strain HXB2 or resistant variants with tenofovir (TFV), abacavir (ABC), and lamivudine (3TC) differed depending on the drug combination and virus genotype. In the wild-type virus, TFV-ABC and TFV-3TC selected K65R (with reduced susceptibility to all three inhibitors) and then Y115F. TFV-containing regimens might increase K65R selection, which confers multiple nucleoside reverse transcriptase inhibitor resistance.
Identification of the
Haemophilus influenzae tolC
Gene by Susceptibility Profiles of Insertionally Inactivated Efflux Pump Mutants
Authors: Trepod Catherine M. , Mott John E. 
Published: March 2004

ABSTRACT

Isogenic strains containing insertional disruptions of 10
Haemophilus influenzae
Rd genes were investigated for their effects on the susceptibility of the organism to various classes of antimicrobial compounds. MIC results show that HI1462, which encodes an
Escherichia coli
TolC homolog, is the third component of the
H. influenzae
AcrAB pump.
2′-Fluoro-2′-Deoxycytidine Inhibits Borna Disease Virus Replication and Spread
Authors: Bajramovic Jeffrey J. , Volmer Romain , Syan Sylvie , Pochet Sylvie , Gonzalez-Dunia Daniel 
Published: March 2004

ABSTRACT

Borna disease virus (BDV) causes neurological diseases in a variety of warm-blooded animal species, possibly including humans. To date, there is no effective treatment against BDV infection. Recently, we reported on the antiviral activity of 1-β-
d
-arabinofuranosylcytosine (Ara-C). However, Ara-C's cytotoxic side effects are a major obstacle for its therapeutic use. Herein, we demonstrate that the nucleoside analog 2′-fluoro-2′-deoxycytidine (2′-FdC) exhibits potent antiviral activity against BDV. Importantly, 2′-FdC-associated cytotoxicity is negligible, indicating 2′-FdC as an excellent candidate for the development of antiviral therapy against BDV.
Genogroup II Noroviruses Efficiently Bind to Heparan Sulfate Proteoglycan Associated with the Cellular Membrane
Authors: Tamura Masaru , Natori Katsuro , Kobayashi Masahiko , Miyamura Tatsuo , Takeda Naokazu 
Published: March 2004

ABSTRACTNorovirus(NV), a member of the familyCaliciviridae, is one of the important causative agents of acute gastroenteritis. In the present study, we found that virus-like particles (VLPs) derived from genogroup II (GII) NV were bound to cell surface heparan sulfate proteoglycan. Interestingly, the VLPs derived from GII were more than ten times likelier to bind to cells than were those derived from genogroup I (GI). Heparin, a sulfated glycosaminoglycan, and suramin, a highly sulfated derivative of urea, efficiently blocked VLP binding to mammalian cell surfaces. The reagents known to bind to cell surface heparan sulfate, as well as the enzymes that specifically digest heparan sulfate, markedly reduced VLP binding to the cells. Treatment of the cells with chlorate revealed that sulfation of heparan sulfate plays an important role in the NV-heparan sulfate interaction. The binding efficiency of NV to undifferentiated Caco-2 (U-Caco-2) cells differed largely between GI NV and GII NV, whereas the efficiency of binding to differentiated Caco-2 (D-Caco-2) cells did not differ significantly between the two genogroups, although slight differences between strains were observed. Digestion with heparinase I resulted in a reduction of up to 90% in U-Caco-2 cells and a reduction of up to only 50% in D-Caco-2 cells, indicating that heparan sulfate is the major binding molecule for U-Caco-2 cells, while it contributed to only half of the binding in the case of D-Caco-2 cells. The other half of those VLPs was likely to be associated with H-type blood antigen, suggesting that GII NV has two separate binding sites. The present study is the first to address the possible role of cell surface glycosaminoglycans in the binding of recombinant VLPs of NV.
Live, Attenuated Coronavirus Vaccines through the Directed Deletion of Group-Specific Genes Provide Protection against Feline Infectious Peritonitis
Authors: Haijema Bert Jan , Volders Haukeline , Rottier Peter J. M. 
Published: March 2004

ABSTRACT
Feline infectious peritonitis (FIP) is a fatal immunity-mediated disease caused by mutants of a ubiquitous coronavirus. Since previous attempts to protect cats under laboratory and field conditions have been largely unsuccessful, we used our recently developed system of reverse genetics (B. J. Haijema, H. Volders, and P. J. M. Rottier, J. Virol. 77:4528-4538, 2003) for the development of a modified live FIP vaccine. With this objective, we deleted the group-specific gene cluster open reading frame 3abc or 7ab and obtained deletion mutant viruses that not only multiplied well in cell culture but also showed an attenuated phenotype in the cat. At doses at which the wild-type virus would be fatal, the mutants with gene deletions did not cause any clinical symptoms. They still induced an immune response, however, as judged from the high levels of virus-neutralizing antibodies. The FIP virus (FIPV) mutant lacking the 3abc cluster and, to a lesser extent, the mutant missing the 7ab cluster, protected cats against a lethal homologous challenge; no protection was obtained with the mutant devoid of both gene clusters. Our studies show that the deletion of group-specific genes from the coronavirus genome results in live attenuated candidate vaccines against FIPV. More generally, our approach may allow the development of vaccines against infections with other pathogenic coronaviruses, including that causing severe acute respiratory syndrome in humans.
Dissection of Antiviral and Immune Regulatory Functions of Tumor Necrosis Factor Receptors in a Chronic Lymphocytic Choriomeningitis Virus Infection
Authors: Suresh M. , Gao Xiaoyan , Fischer Christopher , Miller Nicole E. , Tewari Kavita 
Published: March 2004

ABSTRACTThe effector function of CD8 T cells is mediated via cell-mediated cytotoxicity and production of cytokines like gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). While the roles of perforin-dependent cytotoxicity, IFN-γ, and TNF-α in controlling acute viral infections are well studied, their relative importance in defense against chronic viral infections is not well understood. Using mice deficient for TNF receptor (TNFR) I and/or II, we show that TNF-TNFR interactions have a dual role in mediating viral clearance and downregulating CD8 and CD4 T-cell responses during a chronic lymphocytic choriomeningitis virus (LCMV) infection. While wild-type (+/+) and TNFR II-deficient (p75−/−) mice cleared LCMV from the liver and lung, mice deficient in TNFR I (p55−/−) or both TNFR I and TNFR II (double knockout [DKO]) exhibited impaired viral clearance. The inability of p55−/−and DKO mice to clear LCMV was not a sequel to either suboptimal activation of virus-specific CD8 or CD4 T cells or impairment in trafficking of LCMV-specific CD8 T cells to the liver and lung. In fact, the expansion of LCMV-specific CD8 and CD4 T cells was significantly higher in DKO mice compared to that in +/+, p55−/−, and p75−/−mice. TNFR deficiency did not preclude the physical deletion of CD8 T cells specific for nucleoprotein 396 to 404 but delayed the contraction of CD8 T-cell responses to the epitopes GP33-41 and GP276-285 in the viral glycoprotein. The antibody response to LCMV was not significantly altered by TNFR deficiency. Taken together, these findings have implications in development of immunotherapy in chronic viral infections of humans.
NFI-Ski Interactions Mediate Transforming Growth Factor β Modulation of Human Papillomavirus Type 16 Early Gene Expression
Authors: Baldwin Amy , Pirisi Lucia , Creek Kim E. 
Published: March 2004

ABSTRACTHuman papillomaviruses (HPVs) are present in virtually all cervical cancers. An important step in the development of malignant disease, including cervical cancer, involves a loss of sensitivity to transforming growth factor β (TGF-β). HPV type 16 (HPV16) early gene expression, including that of the E6 and E7 oncoprotein genes, is under the control of the upstream regulatory region (URR), and E6 and E7 expression in HPV16-immortalized human epithelial cells is inhibited at the transcriptional level by TGF-β. While the URR contains a myriad of transcription factor binding sites, including seven binding sites for nuclear factor I (NFI), the specific sequences within the URR or the transcription factors responsible for TGF-β modulation of the URR remain unknown. To identify potential transcription factors and binding sites involved in TGF-β modulation of the URR, we performed DNase I footprint analysis on the HPV16 URR using nuclear extracts from TGF-β-sensitive HPV16-immortalized human keratinocytes (HKc/HPV16) treated with and without TGF-β. Differentially protected regions were found to be located around NFI binding sites. Electrophoretic mobility shift assays, using the NFI binding sites as probes, showed decreased binding upon TGF-β treatment. This decrease in binding was not due to reduced NFI protein or NFI mRNA levels. Mutational analysis of individual and multiple NFI binding sites in the URR defined their role in TGF-β sensitivity of the promoter. Overexpression of the NFI family members in HKc/HPV16 decreased the ability of TGF-β to inhibit the URR. Since the oncoprotein Ski has been shown to interact with and increase the transcriptional activity of NFI and since cellular Ski levels are decreased by TGF-β treatment, we explored the possibility that Ski may provide a link between TGF-β signaling and NFI activity. Anti-NFI antibodies coimmunoprecipitated endogenous Ski in nuclear extracts from HKc/HPV16, confirming that NFI and Ski interact in these cells. Ski levels dramatically decreased upon TGF-β treatment of HKc/HPV16, and overexpression of Ski eliminated the ability of TGF-β to inhibit the URR. Based on these studies, we propose that TGF-β inhibition of HPV16 early gene expression is mediated by a decrease in Ski levels, which in turn dramatically reduces NFI activity.
Gamma Interferon/Interleukin 10 Balance in Tissue Lymphocytes Correlates with Down Modulation of Mucosal Feline Immunodeficiency Virus Infection
Authors: Avery Paul R. , Hoover Edward A. 
Published: March 2004

ABSTRACTUnderstanding the early cytokine response to lentiviral infections may be critical to the design of prevention and treatment strategies. By using the feline immunodeficiency virus (FIV) model, we have documented an interleukin 10 (IL10)-dominated response in lymphoid tissue CD4+and CD8+T lymphocytes within the first 4 weeks after mucosal FIV infection. This profile coincided with the period of high tissue viral replication. By 10 weeks postinfection, tissue viral levels decreased significantly, and gamma interferon (IFNγ) production in CD8+T cells had increased to restore the IL10/IFNγ ratio to control levels. Concurrently, increased production of IL6 and viral RNA was detected in macrophages. These temporal associations of viral replication with cytokine balance in tissues suggest roles for IL10 in the permissive stage of infection and IFNγ in the subsequent down modulation of lentiviral infection.
Protection from Bacterial Infection by a Single Vaccination with Replication-Deficient Mutant Herpes Simplex Virus Type 1
Authors: Lauterbach Henning , Kerksiek Kristen M. , Busch Dirk H. , Berto Elena , Bozac Aleksandra , Mavromara Penelope , Manservigi Roberto , Epstein Alberto L. , Marconi Peggy , Brocker Thomas 
Published: March 2004

ABSTRACTAdaptive immune responses in which CD8+T cells recognize pathogen-derived peptides in the context of major histocompatibility complex class I molecules play a major role in the host defense against infection with intracellular pathogens. Cells infected with intracellular bacteria such asListeria monocytogenes,Salmonella entericaserovar Typhimurium, orMycobacterium tuberculosisare directly lysed by cytotoxic CD8+T cells. For this reason, current vaccines for intracellular pathogens, such as subunit vaccines or viable bacterial vaccines, aim to generate robust cytotoxic T-cell responses. In order to investigate the capacity of a herpes simplex virus type 1 (HSV-1) vector to induce strong cytotoxic effector cell responses and protection from infection with intracellular pathogens, we developed a replication-deficient, recombinant HSV-1 (rHSV-1) vaccine. We demonstrate in side-by-side comparison with DNA vaccination that rHSV-1 vaccination induces very strong CD8+effector T-cell responses. While both vaccines provided protection from infection withL. monocytogenesat low, but lethal doses, only rHSV-1 vaccines could protect from higher infectious doses; HSV-1 induced potent memory cytotoxic T lymphocytes that, upon challenge by pathogens, efficiently protected the animals. Despite the stimulation of relatively low humoral and CD4-T-cell responses, rHSV-1 vectors are strong candidates for future vaccine strategies that confer efficient protection from subsequent infection with intracellular bacteria.
Impact of Human Cytomegalovirus Latent Infection on Myeloid Progenitor Cell Gene Expression
Authors: Slobedman Barry , Stern J. Lewis , Cunningham Anthony L. , Abendroth Allison , Abate Davide A. , Mocarski Edward S. 
Published: March 2004

ABSTRACTHerpesviruses establish lifelong latent infections in their hosts. Human cytomegalovirus (CMV) targets a population of bone marrow-derived myeloid lineage progenitor cells that serve as a reservoir for reactivation; however, the mechanisms by which latent CMV infection is maintained are unknown. To gain insights into mechanisms of maintenance and reactivation, we employed microarrays of ∼26,900 sequence-verified human cDNAs to assess global changes in cellular gene expression during experimental CMV latent infection of granulocyte-macrophage progenitors (GM-Ps). This analysis revealed at least 29 host cell genes whose expression was increased and six whose expression was decreased during CMV latency. These changes in transcript levels appeared to be authentic, judging on the basis of further analysis of a subset by semiquantitative reverse transcription-PCR. This study provides a comprehensive snapshot of changes in host cell gene expression that result from latent infection and suggest that CMV regulates genes that encode proteins involved in immunity and host defense, cell growth, signaling, and transcriptional regulation. The host genes whose expression we found altered are likely to contribute to an environment that sustains latent infection.
Role of NF-κB in Cell Survival and Transcription of Latent Membrane Protein 1-Expressing or Epstein-Barr Virus Latency III-Infected Cells
Authors: Cahir-McFarland Ellen D. , Carter Kara , Rosenwald Andreas , Giltnane Jena M. , Henrickson Sarah E. , Staudt Louis M. , Kieff Elliott 
Published: March 2004

ABSTRACTEpstein-Barr virus (EBV) latency III infection converts B lymphocytes into lymphoblastoid cell lines (LCLs) by expressing EBV nuclear and membrane proteins, EBNAs, and latent membrane proteins (LMPs), which regulate transcription through Notch and tumor necrosis factor receptor pathways. The role of NF-κB in LMP1 and overall EBV latency III transcriptional effects was investigated by treating LCLs with BAY11-7082 (BAY11). BAY11 rapidly and irreversibly inhibited NF-κB, decreased mitochondrial membrane potential, induced apoptosis, and altered LCL gene expression. BAY11 effects were similar to those of an NF-κB inhibitor, ΔN-IκBα, in effecting decreased JNK1 expression and in microarray analyses. More than 80% of array elements that decreased with ΔN-IκBα expression decreased with BAY11 treatment. Newly identified NF-κB-induced, LMP1-induced, and EBV-induced genes included pleckstrin, Jun-B, c-FLIP, CIP4, and IκBε. Of 776 significantly changed array elements, 134 were fourfold upregulated in EBV latency III, and 74 were fourfold upregulated with LMP1 expression alone, whereas only 28 were more than fourfold downregulated by EBV latency III. EBV latency III-regulated gene products mediate cell migration (EBI2, CCR7, RGS1, RANTES, MIP1α, MIP1β, CXCR5, and RGS13), antigen presentation (major histocompatibility complex proteins and JAW1), mitogen-activated protein kinase pathway (DUSP5 and p62Dok), and interferon (IFN) signaling (IFN-γRα, IRF-4, and STAT1). Comparison of EBV latency III LCL gene expression to immunoglobulin M (IgM)-stimulated B cells, germinal-center B cells, and germinal-center-derived lymphomas clustered LCLs with IgM-stimulated B cells separately from germinal-center cells or germinal-center lymphoma cells. Expression of IRF-2, AIM1, ASK1, SNF2L2, and components of IFN signaling pathways further distinguished EBV latency III-infected B cells from IgM-stimulated or germinal-center B cells.
Adenovirus Type 7 Induces Interleukin-8 in a Lung Slice Model and Requires Activation of Erk
Authors: Booth J. L. , Coggeshall K. M. , Gordon B. E. , Metcalf J. P. 
Published: March 2004

ABSTRACTAdenovirus (Ad), particularly Ad type 7 (Ad7), causes severe lung infection and pneumonia. Initially, Ad causes neutrophilic inflammation of the distal airways and alveoli. Interleukin-8 (IL-8) is the major lung neutrophil chemotaxin, and we have shown that Ad7 induces IL-8 release from the A549 alveolar epithelial cell line. We sought to determine whether ex vivo human and bovine lung tissue containing primary pneumocytes could be used as a more accurate and relevant model to study Ad acute inflammation. We found that cultured lung tissue preserved normal lung architecture for more than 10 days. IL-8 was generated upon exposure of the lung organ culture to Ad7. IL-8 production required activation of the Ras/Erk pathway, since a pharmacological inhibitor blocked the appearance of IL-8 in the medium. Both human and bovine lung explants supported replication of Ad7, and immunohistochemistry experiments demonstrated the presence of the Ad hexon antigen within alveolar epithelial cells. These findings show that our novel human lung organ culture accurately reproduces the in vivo infectious disease process. Thus, this organ culture model represents a valuable tool for studying the acute innate immune response to respiratory infections.
Fatty Acid Synthase Expression Is Induced by the Epstein-Barr Virus Immediate-Early Protein BRLF1 and Is Required for Lytic Viral Gene Expression
Authors: Li Yuling , Webster-Cyriaque Jennifer , Tomlinson Christine C. , Yohe Marielle , Kenney Shannon 
Published: March 2004

ABSTRACT
The Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 (R) is a transcription factor that induces the lytic form of EBV infection. R activates certain early viral promoters through a direct binding mechanism but induces transcription of the other EBV IE gene, BZLF1 (Z), indirectly through cellular factors binding to a CRE motif in the Z promoter (Zp). Here we demonstrate that R activates expression of the fatty acid synthase (FAS) cellular gene through a p38 stress mitogen-activated protein kinase-dependent mechanism. B-cell receptor engagement of Akata cells also increases FAS expression. The FAS gene product is required for de novo synthesis of the palmitate fatty acid, and high-level FAS expression is normally limited to liver, brain, lung, and adipose tissue. We show that human epithelial tongue cells lytically infected with EBV (from oral hairy leukoplakia lesions) express much more FAS than uninfected cells. Two specific FAS inhibitors, cerulenin and C75, prevent R activation of IE (Z) and early (BMRF1) lytic EBV proteins in Jijoye cells. In addition, cerulenin and C75 dramatically attenuate IE and early lytic gene expression after B-cell receptor engagement in Akata cells and constitutive lytic viral gene expression in EBV-positive AGS cells. However, FAS inhibitors do not reduce lytic viral gene expression induced by a vector in which the Z gene product is driven by a strong heterologous promoter. In addition, FAS inhibitors do not reduce R activation of a naked DNA reporter gene construct driven by the Z promoter (Zp). These results suggest that cellular FAS activity is important for induction of Z transcription from the intact latent EBV genome, perhaps reflecting the involvement of lipid-derived signaling pathways or palmitoylated proteins. Furthermore, using FAS inhibitors may be a completely novel approach for blocking the lytic form of EBV replication.