bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrase Inhibitors Effective against Human T-Cell Leukemia Virus Type 1
Authors: Seegulam Muhammad Esa , Ratner Lee 
Published: February 2011

ABSTRACT

Drugs targeting the viral enzyme integrase have been in use for several years as part of the treatment regimen for patients with human immunodeficiency virus type 1 (HIV-1), and similar classes of compounds have been shown to inhibit human T-cell leukemia virus type 1 (HTLV-1) integration
in vitro
. The current study shows that the clinically approved HIV-1 integrase inhibitor, raltegravir, as well as the more recent diketo acid derivative, MK-2048, are active inhibitors of HTLV-1 infection
in vitro
. These agents were effective in inhibiting cell-free and cell-to-cell transmission of HTLV-1 in lymphoid and nonlymphoid cells. The drugs also inhibited HTLV-1 immortalization of human peripheral blood mononuclear cells. A novel adaptation of the
Alu
assay for viral integration was used to show that the drugs inhibit viral integration without affecting reverse transcription. These data support the administration of raltegravir and other integrase inhibitors as treatments for patients with HTLV-1-associated diseases.
Association of Composite IS
26-sul3
Elements with Highly Transmissible IncI1 Plasmids in Extended-Spectrum-β-Lactamase-Producing Escherichia coli Clones from Humans
Authors: Curiao Tânia , Cantón Rafael , Garcillán-Barcia M. Pilar , de la Cruz Fernando , Baquero Fernando , Coque Teresa M. 
Published: February 2011

ABSTRACT

The association of an IS
440-sul3
platform with Tn
21
class 1 integrons carried by IncI1 plasmids encoding extended-spectrum β-lactamases (ESBLs; mainly SHV-12 and CTX-M-14) among worldwide
Escherichia coli
clones of phylogroups A (ST10, ST23, and ST46), B1 (ST155, ST351, and ST359), and D/B2 (ST131) is reported. An
in silico
comparative analysis of
sul3
elements available in the GenBank database shows the evolution of
sul3
platforms by hosting different transposable elements facilitating the potential genesis of IS
26
composite transposons and further insertion element-mediated promoted arrangements.
Outbreak of OXA-48-Positive Carbapenem-Resistant Klebsiella pneumoniae Isolates in France
Authors: Cuzon Gaelle , Ouanich Jocelyne , Gondret Remy , Naas Thierry , Nordmann Patrice 
Published: February 2011

ABSTRACT

Seventeen
Klebsiella pneumoniae
isolates producing the OXA-48 carbapenemase, obtained from 10 patients hospitalized from April to June 2010, mostly in the medical intensive care unit of the Villeneuve-Saint-Georges Hospital in a suburb of Paris, France, were analyzed. Seven patients were infected, of whom five were treated at least with a carbapenem, and five patients died. Molecular analysis showed that the isolates belonged to a single clone that harbored a 70-kb plasmid carrying the
bla
OXA-48
gene and coproduced CTX-M-15 and TEM-1 β-lactamases. This is the first reported outbreak of OXA-48-producing
K. pneumoniae
isolates in France.
In Vitro
Activity of Proveblue (Methylene Blue) on Plasmodium falciparum Strains Resistant to Standard Antimalarial Drugs
Authors: Pascual Aurélie , Henry Maud , Briolant Sébastien , Charras Serge , Baret Eric , Amalvict Rémy , Huyghues des Etages Emilie , Feraud Michel , Rogier Christophe , Pradines Bruno 
Published: February 2011

ABSTRACT

The geometric mean 50% inhibitory concentration (IC
50
) for Proveblue, a methylene blue complying with the European Pharmacopoeia, was more active on 23
P. falciparum
strains than chloroquine, quinine, mefloquine, monodesethylamodiaquine, and lumefantrine. We did not find significant associations between the Proveblue IC
50
and polymorphisms in the
pfcrt
,
pfmdr1
,
pfmdr2
,
pfmrp
, and
pfnhe-1
genes or the copy numbers of the
pfmdr1
and
pfmdr2
genes, all of which are involved in antimalarial resistance.
Evolution of Clonal and Susceptibility Profiles of Serotype 19A Streptococcus pneumoniae among Invasive Isolates from Children in Spain, 1990 to 2008
Authors: Tarragó David , Aguilar Lorenzo , García Raquel , Gimenez María-José , Granizo Juan-José , Fenoll Asunción 
Published: February 2011

ABSTRACT

The genetic structure and antibiotic nonsusceptibility of all serotype 19A
Streptococcus pneumoniae
pediatric pneumococcal isolates received at the Spanish Pneumococcal Reference Laboratory (1990 to 2008) were analyzed. Of them, 410 (79.8%) isolates belonged to 14 sequence types (STs) with >10 isolates each, and 104 to 73 STs (with 21 new STs, ST5141 to ST5161, with one isolate each). Time trends in 2000 to 2008 (
n
= 471) were explored by lineal regression. Serotype 19A increased from 5.7% in 2000 to 16.8% in 2008 (
R
2
= 0.872;
P
= 0.001). Decreasing trends (
P
< 0.03) were found for ST202 (
R
2
= 0.774) and ST81 (
R
2
= 0.559), and increasing trends (
P
< 0.03) for ST878 (
R
2
= 0.544) and ST320 (
R
2
= 0.530), both belonging to the clonal complex (CC) Denmark
14
-32 and first detected in 2003 and 2007, respectively, and ST2013 (
R
2
= 0.704) and ST4461 (
R
2
= 0.707), both appearing in 2004. Penicillin nonsusceptibility was clustered in ST81, ST276, ST320, ST878, ST2013, and ST4461 (>90% nonsusceptibility), and amoxicillin and cefotaxime nonsusceptibility in ST320: 87% amoxicillin (MIC
50
/MIC
90
= 8/8 μg/ml) and 43.5% cefotaxime (MIC
50
/MIC
90
= 1/2 μg/ml) nonsusceptibility. No trends were found for erythromycin nonsusceptibility (ranging from 38.5% to 66.7%) and cefotaxime nonsusceptibility (ranging from 0.0% to 7.8%), but increasing trends (
P
< 0.02) were found for oral penicillin (from 16.7% in 2000 to 56.3% in 2008;
R
2
= 0.628) and amoxicillin (from 0.0% before 2007 to 13.8% in 2008;
R
2
= 0.628) nonsusceptibility. This study warns about the emergence of serotype 19A STs associated with high-level antibiotic nonsusceptibility, with a role for ST320 and ST878 occupying the niche left by some pneumococcal 7-valent conjugate vaccine (PCV7)-related resistant STs. The rapid expansion of serotype 19A and STs related to antibiotic resistance indicates that vaccines covering serotype 19A present advantages in countering invasive disease.
Effect of Ceftobiprole Treatment on Growth of and Toxin Production by Clostridium difficile in Cecal Contents of Mice
Authors: Nerandzic Michelle M. , Donskey Curtis J. 
Published: February 2011

ABSTRACT

Ceftobiprole and ceftobiprole medocaril did not promote growth of or toxin production by
Clostridium difficile
in mouse cecal contents, whereas ceftazidime, cefoxitin, ceftriaxone, cefotaxime, and ertapenem did. The relatively low propensity of ceftobiprole to promote
C. difficile
was attributable to inhibitory activity against
C. difficile
and sparing of anaerobic microflora.
CTX-M-93, a CTX-M Variant Lacking Penicillin Hydrolytic Activity
Authors: Djamdjian Laura , Naas Thierry , Tandé Didier , Cuzon Gaelle , Hanrotel-Saliou Catherine , Nordmann Patrice 
Published: February 2011

ABSTRACT

Extended-spectrum β-lactamases (ESBLs) of the CTX-M type are increasingly being reported worldwide, with more than 90 known variants. Clinical
Escherichia coli
isolate Bre-1 was isolated in 2009 and displayed an unusual ESBL phenotype, made of a synergy image between expanded cephalosporins and clavulanic acid discs and susceptibility to penicillins.
E. coli
Bre-1 harbored a novel CTX-M-encoding gene, designated
bla
CTX-M-93
. CTX-M-93 differed from CTX-M-27 by only a single L169Q substitution. Compared to CTX-M-27, CTX-M-93 conferred higher MICs of ceftazidime for
E. coli
(MIC of 8 versus 1.5 μg/ml) and decreased MICs of other expanded-cephalosporins (MIC of cefotaxime of 1 versus 32 μg/ml) and penicillins (MIC of ticarcillin of 0.5 versus >256 μg/ml). A comparison of enzymatic properties revealed that the L169Q substitution led to a decreased

K
m

for ceftazidime (25.5 versus 330 μM) but decreased hydrolytic activity against good substrates, such as cefotaxime (
k
cat
of 0.6 versus 113 s
−1
), probably owing to the alteration of the omega loop positioning during the catalytic process. The
bla
CTX-M-93
gene was surrounded by the IS
Ecp1
and IS
903
elements and inserted onto a 150-kb non-self-transferrable IncF-type plasmid.
E. coli
Bre-1 belongs to phylogroup D and is of multilocus sequence type (MLST) 624, a sequence type found only in rare Spanish CTX-M-14-producing
E. coli
isolates. We have characterized a novel CTX-M variant, CTX-M-93, lacking significant penicillin hydrolysis but with increased ceftazidime hydrolysis.
Case Report of a Successful Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia and MRSA/Vancomycin-Resistant Enterococcus faecium Cholecystitis by Daptomycin
Authors: Tascini Carlo , Di Paolo Antonello , Polillo Marialuisa , Ferrari Mauro , Lambelet Paola , Danesi Romano , Menichetti Francesco 
Published: February 2011

ABSTRACT

A 72-year-old man, receiving 8 mg daptomycin/kg body weight/day for methicillin-resistant
Staphylococcus aureus
(MRSA) bacteremia, was diagnosed with MRSA/vancomycin-resistant
Enterococcus faecium
(VRE) cholecystitis (daptomycin MIC values, 1 and 2 mg/liter, respectively). After the fifth drug dose, the bile concentration of daptomycin was 66 mg/liter 5 min after drug administration, with the biliary concentration/MIC values higher than 30 for both bacterial strains. Therefore, daptomycin achieved therapeutic levels in bile, hence suggesting a role for the drug in the treatment of MRSA/VRE cholecystitis.
Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes
Authors: Manque Patricio A. , Probst Christian , Pereira Mirian C. S. , Rampazzo Rita C. P. , Ozaki L. Shozo , Pavoni Daniela P. , Silva Neto Dayse T. , Carvalho M. Ruth , Xu Ping , Serrano Myrna G. , Alves João M. P. , Meirelles Maria de Nazareth S. L. , Goldenberg Samuel , Krieger Marco A. , Buck Gregory A. 
Published: February 2011

ABSTRACT

Chagas' disease, caused by the hemoflagellate protozoan
Trypanosoma cruzi
, affects millions of people in South and Central America. Chronic chagasic cardiomyopathy, the most devastating manifestation of this disease, occurs in approximately one-third of infected individuals. Events associated with the parasite's tropism for and invasion of cardiomyocytes have been the focus of intense investigation in recent years. In the present study, we use murine microarrays to investigate the cellular response caused by invasion of primary murine cardiomyocytes by
T. cruzi
trypomastigotes. These studies identified 353 murine genes that were differentially expressed during the early stages of invasion and infection of these cells. Genes associated with the immune response, inflammation, cytoskeleton organization, cell-cell and cell-matrix interactions, apoptosis, cell cycle, and oxidative stress are among those affected during the infection. Our data indicate that
T. cruzi
induces broad modulations of the host cell machinery in ways that provide insight into how the parasite survives, replicates, and persists in the infected host and ultimately defines the clinical outcome of the infection.
Thymopoietic and Bone Marrow Response to Murine Pneumocystis Pneumonia
Authors: Shi Xin , Zhang Ping , Sempowski Gregory D. , Shellito Judd E. 
Published: February 2011

ABSTRACTCD4+T cells play a key role in host defense againstPneumocystisinfection. To define the role of naïve CD4+T cell production through the thymopoietic response in host defense againstPneumocystisinfection,Pneumocystis murinainfection in the lung was induced in adult male C57BL/6 mice with and without prior thymectomy.Pneumocystisinfection caused a significant increase in the number of CCR9+multipotent progenitor (MPP) cells in the bone marrow and peripheral circulation, an increase in populations of earliest thymic progenitors (ETPs) and double negative (DN) thymocytes in the thymus, and recruitment of naïve and total CD4+T cells into the alveolar space. The level of murine signal joint T cell receptor excision circles (msjTRECs) in spleen CD4+cells was increased at 5 weeks post-Pneumocystisinfection. In thymectomized mice, the numbers of naïve, central memory, and total CD4+T cells in all tissues examined were markedly reduced followingPneumocystisinfection. This deficiency of naïve and central memory CD4+T cells was associated with delayed pulmonary clearance ofPneumocystis. Extracts ofPneumocystisresulted in an increase in the number of CCR9+MPPs in the cultured bone marrow cells. Stimulation of cultured bone marrow cells with ligands to Toll-like receptor 2 ([TLR-2] zymosan) and TLR-9 (ODN M362) each caused a similar increase in CCR9+MPP cells via activation of the Jun N-terminal protein kinase (JNK) pathway. These results demonstrate that enhanced production of naïve CD4+T lymphocytes through the thymopoietic response and enhanced delivery of lymphopoietic precursors from the bone marrow play an important role in host defense againstPneumocystisinfection.
Involvement of Epidermal Growth Factor Receptor-Linked Signaling Responses in Pseudomonas fluorescens-Infected Alveolar Epithelial Cells
Authors: Choi Hye Jin , Seo Chan Hee , Park Seong Hwan , Yang Hyun , Do Kee Hun , Kim Juil , Kim Hyung-Kab , Chung Duk-Hwa , Ahn Jung Hoon , Moon Yuseok 
Published: February 2011

ABSTRACTPseudomonas fluorescensis an opportunistic indoor pathogen that can cause severe airway proinflammatory responses. Pulmonary epithelium, like other mucosal epithelial linings of the body, constitutes the first line of defense against airway microbial pathogens. Mucosal epithelial cells can be a sentinel of pathogenic bacteria via stimulation of specific cell surface receptors, including the epidermal growth factor receptor (EGFR) and Toll-like receptor (TLR). This study addressed the involvement of EGFR in airway epithelial pathogenesis byP. fluorescens. Human A549 pneumocytes showed prolonged production of proinflammatory interleukin-8 (IL-8) in response to infection withP. fluorescens, which was via the nuclear factor-kappa B (NF-κB) signaling pathway. Production of proinflammatory cytokine IL-8 was not mediated byP. fluorescenslipopolysaccharide, a representative TLR4 agonist, but was mediated through EGFR-linked signals activated by the opportunistic bacteria. Moreover, EGFR signals were involved in NF-κB signal-mediated production of proinflammatory cytokines. Along with persistent NF-κB activation,P. fluorescensenhanced the EGFR phosphorylation and subsequent activation of downstream mediators, including protein kinase B or extracellular-signal-regulated kinases 1/2. Blocking of EGFR-linked signals increased epithelial susceptibility to pathogen-induced epithelial cell death, suggesting protective roles of EGFR signals. Thus, airway epithelial exposure toP. fluorescenscan trigger antiapoptotic responses via EGFR and proinflammatory responses via TLR4-independent NF-κB signaling pathway in human pneumocytes.
Pneumocystis Infection in an Immunocompetent Host Can Promote Collateral Sensitization to Respiratory Antigens
Authors: Swain Steve D. , Meissner Nicole , Han Soo , Harmsen Allen 
Published: February 2011

ABSTRACTInfection with the opportunistic fungal pathogenPneumocystisis assumed to pass without persistent pathology in immunocompetent hosts. However, when immunocompetent BALB/c mice were inoculated withPneumocystis, a vigorous Th2-like pulmonary inflammation ensued and peaked at 14 days postinfection. This coincided with a 10-fold increase in the number of antigen-presenting cells (APCs) in the lung, and these cells were capable of presenting antigenin vitro, as well as greater uptake of antigenin vivo. When mice were presented with exogenous antigen at the 14-day time point of the infection, they developed respiratory sensitization to that antigen, in the form of increased airway hyperresponsiveness upon a later challenge, whereas mice not infected but presented with antigen did not. Like other forms of collateral sensitization, this response was dependent on interleukin-4 receptor signaling. This ability to facilitate sensitization to exogenous antigen has been previously reported for other infectious disease agents; however,Pneumocystisappears to be uniquely capable in this respect, as a single intranasal dose without added adjuvant, when it was administered at the appropriate time, was sufficient to initiate sensitization.Pneumocystisinfection probably occurs in most humans during the first few years of life, and in the vast majority of cases, it fails to cause any overt direct pathology. However, as we show here,Pneumocystiscan be an agent of comorbidity at this time by facilitating respiratory sensitization that may relate to the later development or exacerbation of obstructive airway disease.
The Cellular Protein La Functions in Enhancement of Virus Release through Lipid Rafts Facilitated by Murine Leukemia Virus Glycosylated Gag
Authors: Nitta Takayuki , Tam Raymond , Kim Jung Woo , Fan Hung 
Published: February 2011

ABSTRACT

Murine leukemia viruses (MuLVs) encode two forms of Gag polyprotein: the precursor for the viral core proteins (Pr65

gag

for Moloney MuLV [M-MuLV]) and a longer glycosylated form (glyco-gag, or gPr80

gag

). gPr80

gag

is translated from the same unspliced viral RNA as Pr65

gag

, from an upstream in-frame CUG initiation codon. As a result, gPr80

gag

contains 88 unique N-terminal amino acids that include a signal peptide that conducts gPr80

gag

into the rough endoplasmic reticulum, where it is glycosylated, exported to the cell surface, and cleaved into two proteins of 55 and 40 kDa. The amino-terminal 55-kDa protein remains cell associated with the 88 unique amino acids exposed to the cytosol. We previously showed that gPr80

gag

facilitates efficient M-MuLV release through lipid rafts. In this report, we found that the unique N-terminal domain of gPr80

gag

is sufficient to facilitate enhanced M-MuLV particle release from transfected 293T cells. A search for cellular proteins involved in gPr80

gag

function led to cellular La protein. Overexpression of mouse or human La enhanced M-MuLV particle release in the absence of glyco-gag, and the released virus had a reduced buoyant density characteristic of increased cholesterol content. Moreover, small interfering RNA (siRNA) knockdown of human La abolished glyco-gag enhancement of M-MuLV release. These results implicate La as a cellular protein involved in M-MuLV glyco-gag function. We also found that overexpression of mouse or human La could enhance HIV-1 release in the absence of gPr80

gag

. Therefore, M-MuLV and HIV-1 may share a pathway for release through lipid rafts involving La.

IMPORTANCE
Retroviruses cause diseases such as leukemia and AIDS. An important aspect of viral replication is how viruses are released from infected cells. We previously found that a unique protein encoded by murine leukemia viruses (MuLVs), glyco-gag (or gPr80

gag

), enhances efficient virus release through cholesterol-rich membrane subdomains called lipid rafts. In this study, we found that the N-terminal domain of gPr80

gag

is sufficient to enhance viral release. A search for cellular proteins that participate in gPr80

gag

function led to cellular La protein. Overexpression of La phenocopied glyco-gag in enhancing M-MuLV release, and knockdown of La abolished glyco-gag function. M-MuLV glyco-gag also enhanced release of HIV-1, as did overexpression La in the absence of glyco-gag. Thus, M-MuLV and HIV-1 may share a cellular pathway for release through lipid rafts involving La. These results may also be relevant for other viruses that are released through lipid rafts.
Ultrasound-guided injections of hyperosmolar dextrose for overuse patellar tendinopathy: a pilot study
Authors: Ryan Michael , Wong Anthony , Rabago David , Lee Kenneth , Taunton Jack 
Published: February 2011

PurposeTo evaluate whether ultrasound-guided injection of hyperosmolar dextrose for treatment of patellar tendinopathy decreases pain scores and normalises the appearance of the patellar tendon on ultrasound.MethodsSubjects were referred from primary care clinics and failed conservative treatment. Subjects received a diagnostic ultrasound examination, then ultrasound-guided injection of 25% dextrose with lidocaine into the area of tendinopathy until they were satisfied with treatment. The primary outcome measure was a three-part visual analogue scale (VAS; baseline and mean of 45 weeks after start of treatment) for pain at rest, activities of daily living (ADL) and during sport. Secondary outcomes included segmental ultrasound examinations assessing tendon hypoechogenicity (area and severity score), neovascularity (severity score) and the presence or absence of intratendinous tearing and calcification, irregularities of cortical bone and thickness.Results47 consecutive referrals were included. Subjects received a mean of four (±3) injection sessions. At mean 45 weeks post-enrollment, subjects reported a reduction in pain across the three VAS items (rest 38.4±25–18.7±18.4; ADL 51.1±22.9–25.8±20.1; sport 78.1±15.7–38.8±26.1; p<0.01). There was improvement in neovascularity following the dextrose injection. A significant correlation between hypoechogenicity severity scores and pain at follow-up is reported.ConclusionThere was a reduction in pain and an improvement in ultrasound appearance following ultrasound-guided dextrose injections for refractory patellar tendinopathy. An improved hypoechoic appearance of the tendon was associated with decreased pain scores, suggesting that dextrose injections may modify patellar tendinopathy at the tissue level and that fibrillar changes may play a role in tendon nociception.
Activation of TYRO3/AXL Tyrosine Kinase Receptors in Thyroid Cancer
Authors: Avilla Elvira , Guarino Valentina , Visciano Carla , Liotti Federica , Svelto Maria , Krishnamoorthy GnanaPrakasam , Franco Renato , Melillo Rosa Marina 
Published: February 2011

Abstract
Thyroid cancer is the most common endocrine cancer, but its key oncogenic drivers remain undefined. In this study we identified the TYRO3 and AXL receptor tyrosine kinases as transcriptional targets of the chemokine CXCL12/SDF-1 in CXCR4-expressing thyroid cancer cells. Both receptors were constitutively expressed in thyroid cancer cell lines but not normal thyroid cells. AXL displayed high levels of tyrosine phosphorylation in most cancer cell lines due to constitutive expression of its ligand GAS6. In human thyroid carcinoma specimens, but not in normal thyroid tissues, AXL and GAS6 were often coexpressed. In cell lines expressing both receptors and ligand, blocking each receptor or ligand dramatically affected cell viability and decreased resistance to apoptotic stimuli. Stimulation of GAS6-negative cancer cells with GAS6 increased their proliferation and survival. Similarly, siRNA-mediated silencing of AXL inhibited cancer cell viability, invasiveness, and growth of tumor xenografts in nude mice. Our findings suggest that a TYRO3/AXL-GAS6 autocrine circuit sustains the malignant features of thyroid cancer cells and that targeting the circuit could offer a novel therapeutic approach in this cancer. Cancer Res; 71(5); 1792–804. ©2011 AACR.