bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt5a: its signalling, functions and implication in diseases
Authors: Kikuchi A. , Yamamoto H. , Sato A. , Matsumoto S. 
Published: March 2011

AbstractWnt5a is a representative ligand that activates the β‐catenin‐independent pathways. Because the β‐catenin‐independent pathway includes multiple signalling cascades in addition to the planar cell polarity and Ca2+ pathway, Wnt5a regulates a variety of cellular functions, such as proliferation, differentiation, migration, adhesion and polarity. Consistent with the multiple functions of Wnt5a signalling, Wnt5a knockout mice show various phenotypes, including an inability to extend the embryonic anterior–posterior and proximal–distal axes in outgrowth tissues. Thus, many important roles of Wnt5a in developmental processes have been demonstrated. Moreover, recent reports suggest that the postnatal abnormalities in the Wnt5a signalling are involved in various diseases, such as cancer, inflammatory diseases and metabolic disorders. Therefore, Wnt5a and its signalling pathways could be important targets for the diagnosis and therapy for human diseases.
Computed tomographic findings in canine pyothorax and correlation with findings at exploratory thoracotomy
Authors: Swinbourne F. , Baines E. A. , Baines S. J. , Halfacree Z. J. 
Published: March 2011

Objectives: To describe computed tomographic (CT) findings in canine spontaneous pyothorax and compare them to surgical findings and to assess the utility of CT in guiding case management.Methods: Records from 2003 to 2010 were reviewed to identify dogs, with spontaneous pyothorax, which had undergone CT. Cases were managed medically or surgically. CT images and surgery reports were reviewed and compared for surgical cases.Results: Twelve dogs were included. Eight were managed surgically, three were managed medically and one died before management. Pleural fluid was present in all dogs on CT (n=12) and at surgery (n=8). Pleural gas was identified in five dogs on CT. Pleural thickening was detected in eight dogs on CT (seven visceral, one parietal and six mediastinal) and eight dogs at surgery (seven visceral, eight parietal and six mediastinal), six of which were identified by CT. Abnormal pulmonary parenchyma was detected in 10 dogs on CT and 5 dogs at surgery, all of which were identified by CT. Mediastinal involvement was detected in 10 dogs on CT and 6 dogs at surgery, 5 of which were identified by CT.Conclusions: CT and surgical findings are similar in most cases of canine spontaneous pyothorax. CT may be a useful diagnostic tool for guiding case management.
Is the Indispensability Argument Dispensable?
Authors: BUSCH JACOB 
Published: March 2011

AbstractWhen the indispensability argument for mathematical entities (IA) is spelled out, it would appear confirmational holism is needed for the argument to work. It has been argued that confirmational holism is a dispensable premise in the argument if a construal of naturalism, according to which it is denied that we can take different epistemic attitudes towards different parts of our scientific theories, is adopted. I argue that the suggested variety of naturalism will only appeal to a limited number of philosophers. I then suggest that if we allow for some degree of separation between different component parts of theories, IA can be formulated as an argument aimed at more than a limited number of philosophers, but in implementing this strategy the notion of indispensability needs spelling out. The best way of spelling out indispensability is in terms of theory contribution, but doing so requires adopting inference to the best explanation (IBE). IBE is however sufficient for establishing the conclusion that IA is supposed to establish. Thus, IA is a redundant argument.
Changes in hepatitis B virus DNA levels and liver function after transcatheter arterial chemoembolization of hepatocellular carcinoma
Authors: Lao Xiang‐Ming , Wang Dian , Shi Ming , Liu Guipeng , Li Shengping , Guo Rongping , Yuan Yunfei , Chen Minshan , Li Jinqing , Zhang Yaqi , Lin Xiaojun 
Published: March 2011

Aim:  Reports concerning changes in hepatitis B virus (HBV) status and liver function in hepatocellular carcinoma (HCC) during or after transcatheter arterial chemoembolization (TACE) have been rare and the results inconsistent. The objective of this retrospective study was to evaluate these parameters in a large cohort of HBV‐related HCC patients.Methods:  One hundred and seventy‐two hepatitis B surface antigen positive HCC patients with Child–Pugh grade A or B liver disease who underwent 228 sessions of TACE were enrolled, and related clinical and laboratory data were analyzed.Results:  In total, HBV reactivated in 33 (14.5%), remained stable in 152 (66.7%) and decreased in 43 (18.8%) sessions. Univariate analysis revealed that sex and HBV DNA levels correlated with changes in HBV DNA status after TACE, while hepatitis B e‐antigen (HBeAg), prothrombin time and chemotherapeutic agents were marginally significant factors. Multivariate analysis demonstrated that the major factors that influenced the HBV DNA status were baseline HBV DNA levels(P = 0.0002) and HBeAg (P = 0.0387). A comparison of the post‐TACE (30–90 days) liver function to the baseline revealed no significant differences. The reactivation group has the highest rate of exacerbation (12.1%) compared with the stable group (5.9%) and downregulation group (4.7%).Conclusion:  HBV DNA changes after TACE included reactivated, decreased and stable HBV DNA levels. Although HBV reactivation did not necessarily result in exacerbation of liver damage and most HCC patients with Child–Pugh grade A and B tolerated TACE well, careful post‐procedure monitoring and managing is needed.
Classification of scattering media within benign and malignant breast tumors based on ultrasound texture‐feature‐based and Nakagami‐parameter images
Authors: Liao Yin‐Yin , Tsui Po‐Hsiang , Li Chia‐Hui , Chang King‐Jen , Kuo Wen‐Hung , Chang Chien‐Cheng , Yeh Chih‐Kuang 
Published: March 2011

Purpose:Benign and malignant tumors can be classified by using texture analysis of the ultrasound B‐scan image to describe the variation in the echogenicity of scatterers. The recently proposed ultrasonic Nakagami parametric image has also been used to detect the concentrations and arrangements of scatterers for tumor characterization applications. B‐scan‐based texture analysis and the Nakagami parametric image are functionally complementary in ultrasonic tissue characterizations and this study aimed to combine these methods in order to improve the ability to characterize breast tumors.Methods:To validate this concept, radio‐frequency data obtained from 130 clinical cases were used to construct the texture‐feature parametric image and the Nakagami parametric image. Four texture‐feature parameters based on a gray‐level co‐occurrence matrix (homogeneity, contrast, energy, and variance) and the Nakagami parameters of the benign and malignant tumors were calculated. The usefulness of an individual parameter was determined and scatter graphs indicated the relationship between two selected texture‐feature parameters. Fisher's linear discriminant analysis was used to combine the selected texture‐feature parameters with the Nakagami parameter. The performance in classifying tumors was evaluated based on the receiver operating characteristic curve.Results:The results indicated that there is a trade‐off between sensitivity and specificity when using an individual texture‐feature parameter or when combining two such correlated parameters to discriminate benign and malignant cases. However, the best performance was obtained when combining selected texture‐feature parameters with the Nakagami parameter.Conclusions:The study findings suggest that combining B‐scan‐based texture analysis and the Nakagami parametric image could improve the ability to classify benign and malignant breast tumors.
Accuracies of the synthesized monochromatic CT numbers and effective atomic numbers obtained with a rapid kVp switching dual energy CT scanner
Authors: Goodsitt Mitchell M. , Christodoulou Emmanuel G. , Larson Sandra C. 
Published: March 2011

Purpose:This study was performed to investigate the accuracies of the synthesized monochromatic images and effective atomic number maps obtained with the new GE Discovery CT750 HD CT scanner.Methods:A Gammex‐RMI model 467 tissue characterization phantom and the CT number linearity section of a Phantom Laboratory Catphan 600 phantom were scanned using the dual energy (DE) feature on the GE CT750 HD scanner. Synthesized monochromatic images at various energies between 40 and 120 keV and effective atomic number maps were generated. Regions of interest were placed within these images/maps to measure the average monochromatic CT numbers and average of the materials within these phantoms. The true values were either supplied by the phantom manufacturer or computed using Mayneord's equation. The linear attenuation coefficients for the true CT numbers were computed using the NIST XCOM program with the input of manufacturer supplied elemental compositions and densities. The effects of small variations in the assumed true densities of the materials were also investigated. Finally, the effect of body size on the accuracies of the synthesized monochromatic CT numbers was investigated using a custom lumbar section phantom with and without an external fat‐mimicking ring.Results:Other than the of the simulated lung inserts in the tissue characterization phantom, which could not be measured by DECT, the values of all of the other materials in the tissue characterization and Catphan phantoms were accurate to 15%. The accuracies of the synthesized monochromatic CT numbers of the materials in both phantoms varied with energy and material. For the 40–120 keV range, RMS errors between the measured and true CT numbers in the Catphan are 8–25 HU when the true CT numbers were computed using the nominal plastic densities. These RMS errors improve to 3–12 HU for assumed true densities within the nominal density range. The RMS errors between the measured and true CT numbers of the tissue mimicking materials in the tissue characterization phantom over the 40–120 keV range varied from about 6 HU–248 HU and did not improve as dramatically with small changes in assumed true density.Conclusions:Initial tests indicate that the values computed with DECT on this scanner are reasonably accurate; however, the synthesized monochromatic CT numbers can be very inaccurate, especially for dense tissue mimicking materials at low energies. Furthermore, the synthesized monochromatic CT numbers of materials still depend on the amount of the surrounding tissues especially at low keV, demonstrating that the numbers are not truly monochromatic. Further research is needed to develop DE methods that produce more accurate synthesized monochromatic CT numbers.
Emergence of NDM-1-Producing Enterobacteriaceae in Belgium
Authors: Bogaerts Pierre , Bouchahrouf Warda , de Castro Roberta Rezende , Deplano Ariane , Berhin Catherine , Piérard Denis , Denis Olivier , Glupczynski Youri 
Published: March 2011

ABSTRACT

Five multidrug-resistant nonclonally related
Enterobacteriaceae
isolates were recovered in Belgium in 2010 from three patients who had been hospitalized in Pakistan, Montenegro, and Serbia/Kosovo. New Delhi metallo-β-lactamase (NDM-1) was detected in each of the isolates in addition to several extended-spectrum β-lactamases (CTX-M-15, SHV-12), plasmidic cephalosporinases (CMY-16, CMY-58), rRNA methylases (ArmA, RmtB), and Qnr genes (
qnrA6
,
qnrB1
,
qnrB2
). One patient died from uncontrolled sepsis, while the two others recovered. No secondary cases occurred in any of the hospitals.
Inactivation of the Indigenous Methyltransferase RlmN in Staphylococcus aureus Increases Linezolid Resistance
Authors: LaMarre Jacqueline M. , Howden Benjamin P. , Mankin Alexander S. 
Published: March 2011

ABSTRACT

The indigenous methyltransferase RlmN modifies A2503 in 23S rRNA. A recently described
rlmN
mutation in a clinical
Staphylococcus aureus
isolate decreases susceptibility to linezolid and was thought to increase the extent of A2503 modification. However, we show that the mutation in fact abolishes RlmN activity, resulting in a lack of A2503 modification. Since many mutations could inactivate the
rlmN
gene, our findings unveil a potential mechanism for future linezolid resistance in clinical strains.
Molecular Drug Susceptibility Testing and Genotyping of Mycobacterium leprae Strains from South America
Authors: Singh Pushpendra , Busso Philippe , Paniz-Mondolfi Alberto , Aranzazu Nacarid , Monot Marc , Honore Nadine , de Faria Fernandes Belone Andrea , Virmond Marcos , Villarreal-Olaya Maria Esther , Rivas Carlos , Cole Stewart T. 
Published: March 2011

ABSTRACTPossible drug resistance inMycobacterium lepraestrains from Venezuela and three other South American countries was surveyed by molecular methods. None of the 230 strains from new leprosy cases exhibited drug resistance-associated mutations. However, two of the three strains from relapsed cases contained dapsone resistance mutations, and one strain also harbored a rifampin resistance mutation. Single nucleotide polymorphism analysis of these strains revealed five subtypes: 3I (73.8%), 4P (11.6%), 1D (6.9%), 4N (6%), and 4O (1.7%).
Pharmacokinetics and Safety of FV-100, a Novel Oral Anti-Herpes Zoster Nucleoside Analogue, Administered in Single and Multiple Doses to Healthy Young Adult and Elderly Adult Volunteers
Authors: Pentikis Helen S. , Matson Mark , Atiee George , Boehlecke Brian , Hutchins Jeff T. , Patti Joseph M. , Henson Geoffrey W. , Morris Amy 
Published: March 2011

ABSTRACT
FV-100 is the prodrug of the highly potent anti-varicella zoster virus bicyclic nucleoside analogue CF-1743. To characterize the pharmacokinetics and safety of oral FV-100, 3 randomized, double-blind, placebo-controlled clinical trials were conducted: (i) a single-ascending-dose study in 32 healthy subjects aged 18 to 55 years (100-, 200-, 400-, and 800-mg doses) with an evaluation of the food effect in the 400-mg group; (ii) a multiple-ascending-dose study in 48 subjects aged 18 to 55 years (100 mg once daily [QD], 200 mg QD, 400 mg QD, 400 mg twice a day, and 800 mg QD for 7 days); and (iii) a 2-part study in subjects aged 65 years and older with a single 400-mg dose in 15 subjects and a 400-mg QD dosing regimen for 7 days in 12 subjects. FV-100 was rapidly and extensively converted to CF-1743, the concentration of which remained above that required to reduce viral activity by 50% for the 24-hour dosing period. Renal excretion of CF-1743 was very low. A high-fat meal reduced exposure to CF-1743; a low-fat meal did not. Pharmacokinetic parameters for the elderly subjects were comparable to those for the younger subjects. FV-100 was well tolerated by all subjects. The pharmacokinetic and safety profiles of FV-100 support its continued investigation for the treatment of herpes zoster and prevention of postherpetic neuralgia with once-daily dosing and without dose modifications for elderly or renally impaired patients.
Raltegravir Concentrations in the Genital Tract of HIV-1-Infected Women Treated with a Raltegravir-Containing Regimen (DIVA 01 Study)
Authors: Clavel Cyril , Peytavin Gilles , Tubiana Roland , Soulié Cathia , Crenn-Hebert Catherine , Heard Isabelle , Bissuel François , Ichou Houria , Ferreira Claudia , Katlama Christine , Marcelin Anne-Geneviève , Mandelbrot Laurent 
Published: March 2011

ABSTRACT
We studied the penetration of raltegravir and HIV shedding in the genital tract among 14 HIV-1-infected women receiving a raltegravir-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median raltegravir concentrations were 235 ng/ml in BP and 93 ng/ml in CVF, with a CVF/BP ratio of approximately 2.3. This good penetration of raltegravir may contribute to the control of viral replication in the female genital tract.
Gentian Violet Exhibits Activity against Biofilms Formed by Oral Candida Isolates Obtained from HIV-Infected Patients
Authors: Traboulsi Rana S. , Mukherjee Pranab K. , Chandra Jyotsna , Salata Robert A. , Jurevic Richard , Ghannoum Mahmoud A. 
Published: March 2011

ABSTRACT

The effect of gentian violet against
Candida albicans
and non
-Candida albicans
biofilms formed on polymethylmethacrylate strips was evaluated using a dry weight assay and confocal laser scanning microscopy. The ability of gentian violet to inhibit
Candida albicans
germination was also assessed. Gentian violet activity against
Candida
biofilms was demonstrated by a reduction in dry weight, disruption of biofilm architecture, and reduced biofilm thickness. Additionally, gentian violet inhibited
Candida
germination in a concentration-dependent manner.
Detection of the KPC Gene in Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii during a PCR-Based Nosocomial Surveillance Study in Puerto Rico
Authors: Robledo Iraida E. , Aquino Edna E. , Vázquez Guillermo J. 
Published: March 2011

ABSTRACT

A 6-month, PCR-based, island-wide hospital surveillance study of beta-lactam resistance in
Escherichia coli
,
Klebsiella pneumoniae
,
Pseudomonas aeruginosa
, and
Acinetobacter baumannii
was conducted in Puerto Rico. Of 10,507 isolates, 1,239 (12%) unique, multi-beta-lactam-resistant isolates from all geographical regions were identified. The KPC gene was detected in 61
E. coli
, 333
K. pneumoniae
, 99
P. aeruginosa
, and 41
A. baumannii
isolates, indicating the widespread dissemination of the KPC gene in clinically significant nosocomial isolates.
Pharmacokinetics and Safety of MP-376 (Levofloxacin Inhalation Solution) in Cystic Fibrosis Subjects
Authors: Geller David E. , Flume Patrick A. , Griffith David C. , Morgan Elizabeth , White Dan , Loutit Jeffery S. , Dudley Michael N. 
Published: March 2011

ABSTRACT

The pharmacokinetics and tolerability of nebulized MP-376 (levofloxacin inhalation solution [Aeroquin]) were determined in cystic fibrosis (CF) subjects. Ten CF subjects received single 180-mg doses of two formulations of MP-376, followed by a multiple-dose phase of 240 mg once daily for 7 days. Serum and expectorated-sputum samples were assayed for levofloxacin content. Safety was evaluated following the single- and multiple-dose study phases. Nebulized MP-376 produced high concentrations of levofloxacin in sputum. The mean maximum plasma concentration (
C
max
) ranged between 2,563 and 2,932 mg/liter for 180-mg doses of the 50- and 100-mg/ml formulations, respectively. After 7 days of dosing, the mean
C
max
for the 240-mg dose was 4,691 mg/liter. The mean serum levofloxacin
C
max
ranged between 0.95 and 1.28 for the 180-mg doses and was 1.71 for the 240-mg dose. MP-376 was well tolerated. Nebulized MP-376 produces high sputum and low serum levofloxacin concentrations. The pharmacokinetics, safety, and tolerability were similar for the two formulations. MP-376 240 mg (100 mg/ml) is being advanced into late-stage clinical development.
Duodenal Helminth Infection Alters Barrier Function of the Colonic Epithelium via Adaptive Immune Activation
Authors: Su Chien-wen , Cao Yue , Kaplan Jess , Zhang Mei , Li Wanglin , Conroy Michelle , Walker W. Allan , Shi Hai Ning 
Published: March 2011

ABSTRACTChronic infection with intestinal helminth parasites is a major public health problem, particularly in the developing world, and can have significant effects on host physiology and the immune response to other enteric infections and antigens. The mechanisms underlying these effects are not well understood. In the current study, we investigated the impact of infection with the murine nematode parasiteHeligmosomoides polygyrus, which resides in the duodenum, on epithelial barrier function in the colon. We found thatH. polygyrusinfection produced a significant increase in colonic epithelial permeability, as evidenced by detection of elevated serum levels of the tracer horseradish peroxidase following rectal administration. This loss of normal barrier function was associated with clear ultrastructural changes in the tight junctions of colonic epithelial cells and an alteration in the expression and distribution of the junctional protein E-cadherin. These parasite-induced abnormalities were not observed in SCID mice but did occur in SCID mice that were adoptively transferred with wild-type T cells, indicating a requirement for adaptive immunity. Furthermore, the helminth-induced increase in gut permeability was not seen in STAT6 knockout (KO) mice. Taken together, the results demonstrate that one of the mechanisms by which helminths exert their effects involves the lymphocyte- and STAT6-dependent breakdown of the intestinal epithelial barrier. This increase in epithelial permeability may facilitate the movement of lumenal contents across the mucosa, thus helping to explain how helminth infection can alter the immune response to enteric antigens.
Blastomyces dermatitidis Yeast Cells Inhibit Nitric Oxide Production by Alveolar Macrophage Inducible Nitric Oxide Synthase
Authors: Rocco Nicole M. , Carmen John C. , Klein Bruce S. 
Published: March 2011

ABSTRACTThe ability of pathogens to evade host antimicrobial mechanisms is crucial to their virulence. The dimorphic fungal pathogenBlastomyces dermatitidiscan infect immunocompetent patients, producing a primary pulmonary infection that can later disseminate to other organs.B. dermatitidispossesses a remarkable ability to resist killing by alveolar macrophages. To date, no mechanism to explain this resistance has been described. Here, we focus on macrophage production of the toxic molecule nitric oxide as a potential target of subversion byB. dermatitidisyeast cells. We report thatB. dermatitidisyeast cells reduce nitric oxide levels in the supernatants of activated alveolar macrophages. This reduction is not due to detoxification of nitric oxide, but rather to suppression of macrophage nitric oxide production. We show thatB. dermatitidisyeast cells do not block upregulation of macrophage inducible nitric oxide synthase (iNOS) expression or limit iNOS access to its arginine substrate. Instead,B. dermatitidisyeast cells appear to inhibit iNOS enzymatic activity. Further investigation into the genetic basis of this potential virulence mechanism could lead to the identification of novel antifungal drug targets.