bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐6 concentration changes in plasma and saliva in bisphosphonate‐related osteonecrosis of the jaws
Authors: Bagan J , Sáez GT , Tormos MC , Hens E , Terol MJ , Bagan L , Diaz‐Fernández JM , Lluch A , Camps C 
Published: June 2013

AimTo determine the plasma and saliva levels of IL‐6 in patients with bisphosphonate‐related osteonecrosis of the jaws (BRONJ) and to investigate whether there is a correlation between more advanced stages of BRONJ and levels of IL‐6.Material and MethodsWe studied three groups: group 1 consisted of 30 patients with BRONJ due to intravenous bisphosphonates (ivBP), group 2 consisted of 25 patients treated with ivBP but without BRONJ, and group 3 consisted of 15 healthy controls. In each case, we assayed plasma and saliva IL‐6 samples using an ELISA test.ResultsSignificantly, higher IL‐6 values were found in both saliva and plasma in group 1 vs groups 2 and 3 (P < 0.01). Group 1 showed no differences in plasma or saliva IL‐6 according to patient gender (P > 0.05), type of tumor, BRONJ location, etiology of BRONJ, or disease stage (P > 0.05). We found higher plasma and saliva IL‐6 values in the more advances stages of BRONJ, although the differences were not statistically significant.ConclusionsPlasma and saliva IL‐6 values were higher in our patients with BRONJ than in controls and therefore might be a useful tool for monitoring the severity of BRONJ.
Risk factors for respiratory symptoms in adults: The Busselton Health Study
Authors: James Alan L. , Knuiman Matthew W. , Divitini Mark L. , Hui Jennie , Hunter Michael L. , Mulrennan Siobhain A. , Musk A. W. ‘Bill’ 
Published: June 2013

AbstractBackground and objectiveThe prevalence of reported doctor‐diagnosed ‘asthma’ increased between 1990 and 2005–2007 in Busselton, Western Australia, accompanied by increased reported cough and phlegm but not recent wheeze. Possible reasons for the increase in diagnosed asthma include environmental exposures and diagnostic transfer. The aim of this study was to relate subject characteristics and exposures to the presence of wheeze and/or current cough/phlegm in the 2005–2007 survey.MethodsA gender‐ and age‐stratified random sample of 2862 adults from the Busselton shire completed questionnaires regarding doctor‐diagnosed asthma, respiratory symptoms and environmental exposures; and measures of anthropometry, spirometry, exhaled nitric oxide (eNO), airway hyperresponsiveness (AHR) and atopy. Associations between respiratory symptoms and subject characteristics were assessed in 2656 subjects.ResultsWheeze was reported by 23% of subjects, cough/phlegm by 22% and both by 9%. The significant and independent correlates of wheeze were reflux symptoms, lung function, AHR, eNO, atopy, body mass index and smoking. The significant and independent correlates of cough/phlegm were reflux symptoms, lung function, smoking and dusty job. Subjects more likely to report only wheeze than only cough/phlegm were female, aged <40 years, atopic, had lower percentage predicted forced expiratory volume in one second (FEV1) or higher percentage predicted force vital capacity.ConclusionsA variety of risk factors was associated with wheeze or cough/phlegm or both. Increased non‐allergic exposures may account for increased prevalence of reported cough and phlegm and may contribute to increased reported asthma in adults.
Molecular diagnostic algorithm for epidermal growth factor receptor mutation detection in Asian lung adenocarcinomas: Comprehensive analyses of 445 Taiwanese patients with immunohistochemistry, PCR‐direct sequencing and Scorpion/ARMS methods
Authors: Ho Hsiang‐Ling , Chang Fu‐Pang , Ma Hsiu‐Hsun , Liao Li‐Rung , Chuang Yu‐Ting , Chang‐Chien Yi‐Chun , Lin Kun‐Yang , Chou Teh‐Ying 
Published: June 2013

AbstractBackground and objectiveTherapeutic responses of lung adenocarcinoma patients to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) are closely associated with activating mutations within the EGFR tyrosine kinase domain. Screening activating EGFR mutations prior to selection for therapeutic strategy has been considered extremely valuable for clinical management of lung adenocarcinoma patients in Asian countries including Taiwan, where the EGFR mutation rate is higher than in the rest of the world. Currently there is no consensus on the method of choice to assess EGFR mutations in tumour tissue.MethodsWe enrolled 445 lung adenocarcinoma patients for analysis of tumour EGFR mutations using polymerase chain reaction (PCR)‐direct sequencing, scorpion/amplified refractory mutation system (ARMS) technology and immunohistochemistry with mutation‐specific antibodies.ResultsTwo hundred forty‐five patients (245/445; 55%) were found to harbour activating EGFR mutations using PCR‐direct sequencing method, with a majority of patients (233/245; 95%) carrying exon 19 deletion or p.L858R point mutations. One hundred three of 200 patients were negative for EGFR mutations from PCR‐direct sequencing were further analysed using Scorpion/ARMS technology. Up to 30% of the PCR‐direct sequencing negative patients turned out to be positive in the Scorpion/ARMS EGFR mutation tests. For immunohistochemistry analysis of EGFR mutations, the p.E746_A750del specific antibody showed a sensitivity of 57% and a specificity of 100% for exon 19 deletions while the p.L858R point mutation specific antibody showed a sensitivity of 68% and a specificity of 95%.ConclusionsBased on this study, we proposed an algorithm for comprehensive and efficient testing of EGFR mutations on lung adenocarcinoma patients in Asia.
Influence of skin extension upon the epidermal morphometry, an in vivo study
Authors: Lévêque Jean‐Luc , Fanian Ferial , Humbert Philippe 
Published: June 2013

BackgroundThe Dermal–Epidermal Junction (DEJ) is characterized by undulations whose apices are called papillae. With aging, epidermis becomes thinner, together with a flattening of the DEJ, leading to a decreased density of papillae. The causes of these modifications are likely as multiple as uncertain. The present paper deals with in vivo morphometric characterization of the DEJ and its changes following a skin surface deformation.MethodsLiving epidermis of human adults was examined by means of in vivo Reflectance Confocal Microscopy. Distances between skin surface and papillae apex and pegs of the DEJ were, respectively, recorded in both relaxed and stretched skin situation. The number of papillae present within a single image (field of view, 500 × 500 μm) was also measured.ResultsSkin extension has no effect upon the distance between skin surface and the apex of papillae. In contrast, the distance between skin surface and the pegs of papillae decreases. On the other hand, skin extension leads to a significant decrease in the number of papillae within a single image.ConclusionEpidermal atrophy and structural changes observed in the DEJ with aging may be, by some extent, related to daily and repetitive skin deformations all along the life span.
The coupling of plasma membrane calcium entry to calcium uptake by endoplasmic reticulum and mitochondria
Authors: García‐Sancho Javier 
Published: June 2013

Key points
Cross‐talk between organelles and plasma membrane Ca2+ channels modulates cytosolic Ca2+ signals in different ways.
In chromaffin cells Ca2+ entry through voltage‐operated channels is amplified by Ca2+ release from the endoplasmic reticulum (ER) and generates subplasmalemmal high Ca2+ microdomains (HCMDs) as high as 20–50 μm, which trigger exocytosis. Subplasmalemmal mitochondria take up Ca2+ from HCMDs and avoid progression of the Ca2+ wave towards the cell core.
In non‐excitable HEK293 cells activation of store‐operated Ca2+ entry triggered by ER Ca2+ emptying also generates subplasmalemmal HCMDs of about 2 μm. In this case most of the Ca2+ is taken up by the ER rather than by mitochondria. This outcome may be explained because sarco‐endoplasmic reticulum Ca2+ ATPase (SERCA) has much higher Ca2+ affinity than mitochondria. The relative positioning of organelles, channels and accessory proteins may also play a role.
AbstractCross‐talk between organelles and plasma membrane Ca2+ channels is essential for modulation of the cytosolic Ca2+ ([Ca2+]C) signals, but such modulation may differ among cells. In chromaffin cells Ca2+ entry through voltage‐operated channels induces calcium release from the endoplasmic reticulum (ER) that amplifies the signal. [Ca2+]C microdomains as high as 20–50 μm are sensed by subplasmalemmal mitochondria, which accumulate large amounts of Ca2+ through the mitochondrial Ca2+ uniporter (MCU). Mitochondria confine the high‐Ca2+ microdomains (HCMDs) to beneath the plasma membrane, where exocytosis of secretory vesicles happens. Cell core [Ca2+]C is much smaller (1–2 μm). By acting as a Ca2+ sink, mitochondria stabilise the HCMD in space and time. In non‐excitable HEK293 cells, activation of store‐operated Ca2+ entry, triggered by ER Ca2+ emptying, also generated subplasmalemmal HCMDs, but, in this case, most of the Ca2+ was taken up by the ER rather than by mitochondria. The smaller size of the [Ca2+]C peak in this case (about 2 μm) may contribute to this outcome, as the sarco‐endoplasmic reticulum Ca2+ ATPase has much higher Ca2+ affinity than MCU. It is also possible that the relative positioning of organelles, channels and effectors, as well as cytoskeleton and accessory proteins plays an important role.
Fitness Consequences of
Plasmodium falciparum pfmdr1
Polymorphisms Inferred from
Ex Vivo
Culture of Ugandan Parasites
Authors: Ochong Edwin , Tumwebaze Patrick K. , Byaruhanga Oswald , Greenhouse Bryan , Rosenthal Philip J. 
Published: June 2013

ABSTRACT

Polymorphisms in the
Plasmodium falciparum
multidrug resistance 1 (
pfmdr1
) gene impact sensitivity to multiple antimalarials. In Africa, polymorphisms at N86Y and D1246Y are common and have various impacts on sensitivity to different drugs. To gain insight into the fitness consequences of these polymorphisms, we cultured parasites isolated from children with malaria in Tororo, Uganda, where the multiplicity of infection is high, and used pyrosequencing to follow polymorphism prevalences in culture over time. Of 71 cultures, parasites in 69 were successfully analyzed at N86Y and parasites in 68 were successfully analyzed at D1246Y over 3 to 36 days of culture. For position 86, the sequences of 39/69 (56.5%) parasites remained stable (>90% prevalence over 2 to 17 time points), with 82.1% of these being stable for the 86Y mutation. For position 1246, the sequences of 31/68 (45.6%) parasites remained stable, with 64.5% of these being stable for the wild-type D1246 sequence (
P
= 0.0002 for comparison of stable mutant genotypes for the two alleles). Defining allele selection as a ≥15% change in prevalence between the first and last samples assessed, for position 86, 11 samples showed selection, with selection toward 86Y occurring in 72.7% of alleles; for position 1246, 14 samples showed selection, with selection toward D1246 occurring in 64.3% of alleles (
P
= 0.11 for comparison of selection of mutations at the two alleles). Among the 7 samples with selection at both alleles, 5 showed selection for both 86Y and D1246. Overall, consistent trends in the direction of selection were seen, although differences were not statistically significant. Our results suggest fitness advantages for parasites with the
pfmdr1
86Y mutation and wild-type D1246, highlighting the complex interplay between drug resistance and fitness in malaria parasites. (This study has been registered at ClinicalTrials.gov under registration no. NCT00948896 and NCT00993031.)
Evaluation of Combinations of 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine with Clinically Used Antiretroviral Drugs
Authors: Hachiya Atsuko , Reeve Aaron B. , Marchand Bruno , Michailidis Eleftherios , Ong Yee Tsuey , Kirby Karen A. , Leslie Maxwell D. , Oka Shinichi , Kodama Eiichi N. , Rohan Lisa C. , Mitsuya Hiroaki , Parniak Michael A. , Sarafianos Stefan G. 
Published: June 2013

ABSTRACTDrug combination studies of 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) with FDA-approved drugs were evaluated by two different methods, MacSynergy II and CalcuSyn. Most of the combinations, including the combination of the two adenosine analogs EFdA and tenofovir, were essentially additive, without substantial antagonism or synergism. The combination of EFdA and rilpivirine showed apparent synergism. These studies provide information that may be useful for the design of EFdA combination regimens for initial and salvage therapy assessment.
Nasal Carriage of Epidemic Methicillin-Resistant Staphylococcus aureus 15 (EMRSA-15) Clone Observed in Three Chicago-Area Long-Term Care Facilities
Authors: Das Sanchita , Anderson Christopher J. , Grayes Althea , Mendoza Katherine , Harazin Maureen , Schora Donna M. , Peterson Lance R. 
Published: June 2013

ABSTRACT

The spread of pandemic methicillin-resistant
Staphylococcus aureus
(MRSA) clones such as USA300 and EMRSA-15 is a global health concern. As a part of a surveillance study of three long-term care facilities in the Greater Chicago area, phenotypic and molecular characterization of nasal MRSA isolates was performed. We report a cluster of pandemic EMRSA-15, an MRSA clone rarely reported from the United States, detected during this study.
Amphiphilic Antimony(V) Complexes for Oral Treatment of Visceral Leishmaniasis
Authors: Fernandes Flaviana R. , Ferreira Weverson A. , Campos Mariana A. , Ramos Guilherme S. , Kato Kelly C. , Almeida Gregório G. , Corrêa José D. , Melo Maria N. , Demicheli Cynthia , Frézard Frédéric 
Published: June 2013

ABSTRACTThe need for daily parenteral administration is an important limitation in the clinical use of pentavalent antimonial drugs against leishmaniasis. In this study, amphiphilic antimony(V) complexes were prepared from alkylmethylglucamides (L8 and L10, with carbon chain lengths of 8 and 10, respectively), and their potential for the oral treatment of visceral leishmaniasis (VL) was evaluated. Complexes of Sb and ligand at 1:3 (SbL8 and SbL10) were obtained from the reaction of antimony(V) with L8 and L10, as evidenced by elemental and electrospray ionization-tandem mass spectrometry (ESI-MS) analyses. Fluorescence probing of hydrophobic environment and negative-staining transmission electron microscopy showed that SbL8 forms kinetically stabilized nanoassemblies in water. Pharmacokinetic studies with mice in which the compound was administered by the oral route at 200 mg of Sb/kg of body weight indicated that the SbL8 complex promoted greater and more sustained Sb levels in serum and liver than the levels obtained for the conventional antimonial drug meglumine antimoniate (Glucantime [Glu]). The efficacy of SbL8 and SbL10 administered by the oral route was evaluated in BALB/c mice infected withLeishmania infantumafter a daily dose of 200 mg of Sb/kg for 20 days. Both complexes promoted significant reduction in the liver and spleen parasite burdens in relation to those in the saline-treated control group. The extent of parasite suppression (>99.96%) was similar to that achieved after Glu given intraperitoneally at 80 mg of Sb/kg/day. As expected, there was no significant reduction in the parasitic load in the group treated orally with Glu at 200 mg of Sb/(kg day). In conclusion, amphiphilic antimony(V) complexes emerge as an innovative and promising strategy for the oral treatment of VL.
Restrictive Streptomycin Resistance Mutations Decrease the Formation of Attaching and Effacing Lesions in Escherichia coli O157:H7 Strains
Authors: Chen Chun , Blumentritt Carla A. , Curtis Meredith M. , Sperandio Vanessa , Torres Alfredo G. , Dudley Edward G. 
Published: June 2013

ABSTRACT

Streptomycin binds to the bacterial ribosome and disrupts protein synthesis by promoting misreading of mRNA. Restrictive mutations on the ribosomal subunit protein S12 confer a streptomycin resistance (Str
r
) phenotype and concomitantly increase the accuracy of the decoding process and decrease the rate of translation. Spontaneous Str
r
mutants of
Escherichia coli
O157:H7 have been generated for
in vivo
studies to promote colonization and to provide a selective marker for this pathogen. The locus of enterocyte effacement (LEE) of
E. coli
O157:H7 encodes a type III secretion system (T3SS), which is required for attaching and effacing to the intestinal epithelium. In this study, we observed decreases in both the expression and secretion levels of the T3SS translocated proteins EspA and EspB in
E. coli
O157:H7 Str
r
restrictive mutants, which have K42T or K42I mutations in S12. However, mildly restrictive (K87R) and nonrestrictive (K42R) mutants showed slight or indistinguishable changes in EspA and EspB secretion. Adherence and actin staining assays indicated that restrictive mutations compromised the formation of attaching and effacing lesions in
E. coli
O157:H7. Therefore, we suggest that
E. coli
O157:H7 strains selected for Str
r
should be thoroughly characterized before
in vivo
and
in vitro
experiments that assay for LEE-directed phenotypes and that strains carrying nonrestrictive mutations such as K42R make better surrogates of wild-type strains than those carrying restrictive mutations.
Species-Dependent Blood-Brain Barrier Disruption of Lipopolysaccharide: Amelioration by ColistinIn VitroandIn Vivo
Authors: Jin Liang , Nation Roger L. , Li Jian , Nicolazzo Joseph A. 
Published: June 2013

ABSTRACTThe aim of this study was to usein vitroandin vivomodels to assess the impact of lipopolysaccharide (LPS) from two different bacterial species on blood-brain barrier (BBB) integrity and brain uptake of colistin. Following repeated administration of LPS fromPseudomonas aeruginosa, the brain-to-plasma ratio of [14C]sucrose in Swiss outbred mice was not significantly increased. Furthermore, while the brain uptake of colistin in mice increased 3-fold following administration of LPS fromSalmonella enterica, LPS fromP. aeruginosahad no significant effect on colistin brain uptake. This apparent species-dependent effect did not appear to correlate with differences in plasma cytokine levels, as the concentrations of tumor necrosis factor alpha and interleukin-6 following administration of each LPS were not different (P> 0.05). To clarify whether this species-specific effect of LPS was due to direct effects on the BBB, human brain capillary endothelial (hCMEC/D3) cells were treated with LPS fromP. aeruginosaorS. entericaand claudin-5 expression was measured by Western blotting.S. entericaLPS significantly (P< 0.05) reduced claudin-5 expression at a concentration of 7.5 μg/ml. In contrast,P. aeruginosaLPS decreased (P< 0.05) claudin-5 expression only at the highest concentration tested (i.e., 30 μg/ml). Coadministration of therapeutic concentrations of colistin ameliorated theS. entericaLPS-induced reduction in claudin-5 expression in hCMEC/D3 cells and the perturbation in BBB function in mice. This study demonstrates that BBB disruption induced by LPS is species dependent, at least betweenP. aeruginosaandS. enterica, and can be ameliorated by colistin.
In Vivo
Effects of Cefazolin, Daptomycin, and Nafcillin in Experimental Endocarditis with a Methicillin-Susceptible Staphylococcus aureus Strain Showing an Inoculum Effect against Cefazolin
Authors: Nannini Esteban C. , Singh Kavindra V. , Arias Cesar A. , Murray Barbara E. 
Published: June 2013

ABSTRACT

Several reports have implicated the inoculum effect that some strains of type A beta-lactamase (Bla)-producing, methicillin-susceptible
Staphylococcus aureus
(MSSA) show against cefazolin as the cause for clinical failures in certain serious deep-seated infections. Here, using a previously reported MSSA strain displaying this phenotype (TX0117), we obtained a Bla-cured derivative (TX0117c) with a combination of novobiocin and high temperature. Both isolates were then used in a rat endocarditis model and treated with cefazolin, nafcillin, and daptomycin, given to simulate human dosing. Animals were treated for 3 days and either sacrificed at 24 h after the last antibiotic dose (standard group) or left untreated for an additional 3 days (relapse group). With TX0117 in the standard treatment group, daptomycin and nafcillin were both significantly better than cefazolin in reducing CFU/g of vegetations, achieving mean log
10
reductions compared to levels in untreated rats of 7.1, 5.3, and 1.8, respectively (cefazolin versus daptomycin,
P
< 0.0001; cefazolin versus nafcillin,
P
= 0.005; daptomycin versus nafcillin,
P
= 0.053). In addition, cefazolin was significantly more effective in reducing vegetation titers of TX0117c than of TX0117 (mean log
10
reduction of 1.4 versus 5.5, respectively;
P
= 0.0001). Similar results were observed with animals in the relapse group. Thus, these data show that there can be an
in vivo
consequence of the
in vitro
inoculum effect that some MSSA strains display against cefazolin and indicate a specific role for Bla production using a Bla-cured derivative strain against which cefazolin regained both
in vitro
and
in vivo
activity.
Synergistic and Additive Effects of Chromosomal and Plasmid-Encoded Hemolysins Contribute to Hemolysis and Virulence in Photobacterium damselae subsp. damselae
Authors: Rivas Amable J. , Balado Miguel , Lemos Manuel L. , Osorio Carlos R. 
Published: June 2013

ABSTRACT

Photobacterium damselae
subsp.
damselae
causes infections and fatal disease in marine animals and in humans. Highly hemolytic strains produce damselysin (Dly) and plasmid-encoded HlyA (HlyA
pl
). These hemolysins are encoded by plasmid pPHDD1 and contribute to hemolysis and virulence for fish and mice. In this study, we report that all the hemolytic strains produce a hitherto uncharacterized chromosome-encoded HlyA (HlyA
ch
). Hemolysis was completely abolished in a single

hlyA
ch

mutant of a plasmidless strain and in a

dly hlyA
pl
hlyA
ch

triple mutant. We found that Dly, HlyA
pl
, and HlyA
ch
are needed for full hemolytic values in strains harboring pPHDD1, and these values are the result of the additive effects between HlyA
pl
and HlyA
ch
, on the one hand, and of the synergistic effect of Dly with HlyA
pl
and HlyA
ch
, on the other hand. Interestingly, Dly-producing strains produced synergistic effects with strains lacking Dly production but secreting HlyA, constituting a case of the CAMP (
C
hristie,
A
tkins, and
M
unch-
P
etersen) reaction. Environmental factors such as iron starvation and salt concentration were found to regulate the expression of the three hemolysins. We found that the contributions, in terms of the individual and combined effects, of the three hemolysins to hemolysis and virulence varied depending on the animal species tested. While Dly and HlyA
pl
were found to be main contributors in the virulence for mice, we observed that the contribution of hemolysins to virulence for fish was mainly based on the synergistic effects between Dly and either of the two HlyA hemolysins rather than on their individual effects.