bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelin attenuates endothelium‐dependent platelet inhibition in man
Authors: Malmström R. E. , Settergren M. , Pernow J. 
Published: November 2009

AbstractAim: The vascular endothelium produces several substances, including nitric oxide (NO) and endothelin‐1 (ET‐1), which participate in the regulation of vascular tone in humans. Both these substances may exert other actions of importance for cardiovascular disease, e.g. effects on vascular smooth muscle cell proliferation and inflammation, and NO inhibits platelet function. Experiments were designed to investigate the effect of ET‐1 on endothelium‐dependent vasodilatation and attenuation of platelet activation.Methods: In 25 healthy male subjects (25 ± 1 years), forearm blood flow was measured by venous occlusion plethysmography, and platelet activity was assessed by whole blood flow cytometry (platelet fibrinogen binding and P‐selectin expression) in unstimulated and adenosine diphosphate (ADP)‐stimulated samples during administration of ET‐1, the endothelium‐dependent vasodilator acetylcholine and the NO synthase inhibitorl‐NMMA.Results: Acetylcholine increased forearm blood flow and significantly inhibited platelet activation in both unstimulated and ADP‐stimulated samples. In samples stimulated with 0.3 μmADP, fibrinogen binding decreased from 41 ± 4% to 31 ± 3% (P < 0.01,n = 11) after acetylcholine administration. The vasodilator response to acetylcholine was significantly impaired during infusions of ET‐1 andl‐NMMA. ET‐1 did not affect platelet activityper se, whereasl‐NMMA increased platelet P‐selectin expression. Both ET‐1 andl‐NMMA attenuated the acetylcholine‐induced inhibition of platelet activity.Conclusions: Our study indicates that, further to inhibiting endothelium‐dependent vasodilatation, ET‐1 may also attenuate endothelium‐dependent inhibition of platelet activation induced by acetylcholine. An enhanced ET‐1 activity, as suggested in endothelial dysfunction, may affect endothelium‐dependent platelet modulation and thereby have pathophysiological implications.
Gall bladder mucoceles and their association with endocrinopathies in dogs: a retrospective case‐control study
Authors: Mesich M. L. L. , Mayhew P. D. , Paek M. , Holt D. E. , Brown D. C. 
Published: December 2009

Objective: To investigate the relationship between endocrinopathies and diagnosis of gall bladder mucocele in dogs via a retrospective case‐control study. Methods: Records of 78 dogs with a surgical or ultrasonographic diagnosis of gall bladder mucocele were examined for the presence or absence of hyperadrenocorticism, hypothyroidism and diabetes mellitus. Two age‐ and breed‐matched controls for each gall bladder mucocele dog (156 total control dogs) were examined for the same concurrent diseases. A matched case‐control analysis was performed using conditional logistic regression. Results: The odds of mucocele in dogs with hyperadrenocorticism were 29 times that of dogs without hyperadrenocorticism (P=0·001; 95 per cent CI 3·8, 219·9). No difference was found between dogs with and without diabetes mellitus. Although a significant association was found between gall bladder mucocele and hypothyroidism, potential observation bias was also identifi ed. Clinical Significance: Hyperadrenocorticoid dogs that were presented for acute illness with laboratory evidence of hepatobiliary disease should undergo evaluation for the presence of a biliary mucocele. Dogs diagnosed with a gall bladder mucocele should be screened for concurrent hyperadrenocorticism if clinical suspicion exists.
Prognostic significance of specific magnetic resonance imaging features in canine nasal tumours treated by radiotherapy
Authors: Agthe P. , Caine A. R. , Gear R. N. A. , Dobson J. M. , Richardson K. J. , Herrtage M. E. 
Published: December 2009

Objectives:To investigate the prognostic significance of the magnetic resonance (MR) findings of meningeal hyperintensity of the olfactory bulbs and tumour extension into the caudal nasal recess (CNR) in dogs with nasal tumours treated by radiotherapy.Methods:MR images of 41 dogs with nasal tumours treated with radiotherapy were reviewed. The occurrence of neurological signs and survival of patients with and without meningeal hyperintensity of the olfactory bulbs and tumour extension into the CNR were analysed together with possible confounding factors including intracranial extension and patient age.Results:There was no significant association between the presence of meningeal hyperintensity or CNR involvement and the occurrence of neurological signs. Although there was a tendency towards shorter survival in dogs with tumour extension into the CNR, multivariable analysis showed no significant difference in survival between dogs with/without CNR involvement, meningeal hyperintensity or intracranial tumour extension (P=0·12, 0·50 and 0·57, respectively).ClinicalSignificance:In dogs with nasal tumours treated with radiotherapy, tumour extension into the cranium is not necessarily associated with shorter survival in patients without neurological signs at time of diagnosis. Although a definite influence of CNR involvement on case outcome could not be demonstrated, studies with a larger population are warranted.
Oesophageal and gastric endoscopic foreign body removal: complications and follow‐up of 102 dogs
Authors: Gianella P. , Pfammatter N. S. , Burgener I. A. 
Published: December 2009

Objectives:To assess complication rate, risk factors for complications and outcome in dogs with oesophageal and gastric endoscopic foreign body (FB) removal.Methods:Medical records of 102 dogs undergoing endoscopic removal of oesophageal and/or gastric FBs from March 2001 to November 2006 were retrospectively reviewed. All owners were contacted by telephone to provide follow‐up information.Results:West Highland white terriers, Yorkshire terriers and Bernese mountain dogs were over‐represented compared to the hospital population. Endoscopy alone was successful in 92/102 dogs (90·2 per cent), whereas gastrotomy (but no oesophagotomy) was required in 10 dogs (9·8 per cent). Complications in 13/102 dogs (12·7 per cent) were perforation (8), oesophageal stricture (1), oesophageal diverticula (1), perioesophageal abscess (1), pneumothorax and pleural effusion (1) and respiratory arrest (1). Six dogs (all weighing <10 kg) had complications resulting in death or euthanasia. Bone FBs, bodyweight of less than 10 kg, and oesophageal or gastric FB in place for more than three days were significant risk factors for complications. Of the dogs available for follow‐up (75/96), 92 per cent had no complications after discharge.ClinicalSignificance:Endoscopic FB removal is associated with a low overall complication rate with bone FBs and bodyweight of less than 10 kg as significant risk factors.
Expression of KIT Receptor Tyrosine Kinase in Endothelial Cells of Juvenile Brain Tumors
Authors: Puputti Marjut , Tynninen Olli , Pernilä Paula , Salmi Marko , Jalkanen Sirpa , Paetau Anders , Sihto Harri , Joensuu Heikki 
Published: December 2009

AbstractKIT receptor tyrosine kinase is expressed in tumor endothelial cells of adult glioblastomas, but its expression in pediatric brain tumor endothelial cells is unknown. We assessed expression of KIT, phosphorylated KIT, stem cell factor (SCF) and vascular endothelial growth factor receptor‐2 (VEGFR‐2) in 35 juvenile pilocytic astrocytomas and 49 other pediatric brain tumors using immunohistochemistry, and KIT messenger RNA (mRNA) using in situ hybridization. KIT and phospho‐KIT were moderately or strongly expressed in tumor endothelia of 37% and 35% of pilocytic astrocytomas, respectively, whereas marked SCF and VEGFR‐2 expression was uncommon. KIT mRNA was detected in tumor endothelial cells. Tumor endothelial cell KIT expression was strongly (P < 0.01) associated with endothelial cell phospho‐KIT and SCF expression, and with tumor KIT (P = 0.0011) and VEGFR‐2 expression (P = 0.022). KIT and phospho‐KIT were present in endothelia of other pediatric brain tumors, notably ependymomas. Endothelial cell KIT expression was associated with a young age at diagnosis of pilocytic astrocytoma or ependymoma, and it was occasionally present in histologically normal tissue of the fetus and children. We conclude that KIT is commonly present in endothelial cells of juvenile brain tumors and thus may play a role in angiogenesis in these neoplasms.
Comparative Pharmacokinetics of Ceftaroline in Rats, Rabbits, and Monkeys following a Single Intravenous or Intramuscular Injection
Authors: Ge Yigong , Maynard David , Rickert Douglas E. 
Published: December 2009

ABSTRACT
This study assessed the pharmacokinetic profiles for intramuscular and intravenous ceftaroline treatment for rats, rabbits, and monkeys. Ceftaroline, a novel cephalosporin with broad-spectrum activity against Gram-positive and Gram-negative pathogens, demonstrated favorable pharmacokinetic profiles following intramuscular administration in all 3 animal species, comparable to the levels for intravenous dosing. The areas under the plasma concentration-time curve obtained after intramuscular administration were increased in rats and similar in rabbits and monkeys, compared with the levels obtained after intravenous dosing (129%, 7.29%, and 12.7% greater in rats, rabbits, and monkeys, respectively). The data reported here support the development of an intramuscular formulation for ceftaroline.
Ex Vivo
Comparison of Microbicide Efficacies for Preventing HIV-1 Genomic Integration in Intraepithelial Vaginal Cells
Authors: McElrath M. Juliana , Ballweber Lamar , Terker Andrew , Kreger Allison , Sakchalathorn Polachai , Robinson Barry , Fialkow Michael , Lentz Gretchen , Hladik Florian 
Published: December 2009

ABSTRACT

Vaginally applied microbicides hold promise as a strategy to prevent sexual HIV transmission. Several nonspecific microbicides, including the polyanion cellulose sulfate, have been evaluated in large-scale clinical trials but have failed to show significant efficacy. These findings have prompted a renewed search for preclinical testing systems that can predict negative outcomes of microbicide trials. Moreover, the pipeline of potential topical microbicides has been expanded to include antiretroviral agents, such as reverse transcriptase, fusion, and integrase inhibitors. Using a novel
ex vivo
model of vaginal HIV-1 infection, we compared the prophylactic potentials of two forms of the fusion inhibitor T-20, the CCR5 antagonist TAK-778, the integrase inhibitor 118-D-24, and cellulose sulfate (Ushercell). The T-20 peptide with free N- and C-terminal amino acids was the most efficacious compound, causing significantly greater inhibition of viral genomic integration in intraepithelial vaginal leukocytes, measured by an optimized real-time PCR assay, than the more water-soluble N-acetylated T-20 peptide (Fuzeon) (50% inhibitory concentration [IC
50
], 0.153 μM versus 51.2 μM [0.687 ng/ml versus 230 ng/ml];
P
< 0.0001). In contrast, no significant difference in IC
50
s was noted in peripheral blood cells (IC
50
, 13.58 μM versus 7.57 μM [61 ng/ml versus 34 ng/ml];
P
= 0.0614). Cellulose sulfate was the least effective of all the compounds tested (IC
50
, 1.8 μg/ml). These results highlight the merit of our model for screening the mucosal efficacies of novel microbicides and their formulations and potentially rank ordering candidates for clinical evaluation.
Bortezomib Inhibits Hepatitis B Virus Replication in Transgenic Mice
Authors: Bandi Prasanthi , Garcia Mayra L. , Booth Carmen J. , Chisari Francis V. , Robek Michael D. 
Published: December 2009

ABSTRACTPharmacological modulation of cellular proteins as a means to block virus replication has been proposed as an alternative antiviral strategy that may be less susceptible than others to the development of viral drug resistance. Recent evidence indicates that the ubiquitin-proteasome pathway interacts with different aspects of the hepatitis B virus (HBV) life cycle in cell culture models of virus replication. We therefore examined the effect of proteasome inhibition on HBV replicationin vivousing HBV transgenic mice. The proteasome inhibitor bortezomib (Velcade) inhibits proteasome activityin vivoand is used therapeutically for the clinical treatment of multiple myeloma. We found that a single intravenous dose of 1 mg of bortezomib/kg of body weight reduced virus replication for as long as 6 days. The inhibition of HBV by bortezomib was dose dependent and occurred at a step in replication subsequent to viral RNA and protein expression. The reduction in HBV replication did not result from nonspecific hepatocellular toxicity and was not mediated indirectly through the induction of an intrahepatic interferon response. Thus, pharmacological manipulation of the ubiquitin-proteasome pathway may represent an alternative therapeutic approach for the treatment of chronic HBV infection.
In Vitro
Adsorption of Gentamicin and Netilmicin by Polyacrylonitrile and Polyamide Hemofiltration Filters
Authors: K.N. Lam Philip , Tian Qi , Ip Margaret , Gomersall Charles D. 
Published: December 2009

ABSTRACT

Adsorption of gentamicin and netilmicin by new polyacrylonitrile and polyamide hemofiltration filters was studied over 4 h, using a single-compartment
in vitro
continuous venovenous hemofiltration model. After the first dose (16.6 mg of gentamicin, 19.3 mg of netilmicin), 14.9 mg of gentamicin and 19.2 mg of netilmicin were adsorbed to polyacrylonitrile filters
in vitro
. Adsorption by polyacrylonitrile filters was rapid and irreversible and could be increased by repeated dosing. Adsorption by polyamide filters was substantially less.
Detection and Characterization of Heterogeneous Vancomycin-Intermediate
Staphylococcus aureus
Isolates in Canada: Results from the Canadian Nosocomial Infection Surveillance Program, 1995-2006
Authors: Adam Heather J. , Louie Lisa , Watt Christine , Gravel Denise , Bryce Elizabeth , Loeb Mark , Matlow Anne , McGeer Allison , Mulvey Michael R. , Simor Andrew E. 
Published: December 2009

ABSTRACT

We describe the epidemiology of heterogeneously resistant
Staphylococcus aureus
(hVISA) identified in Canadian hospitals between 1995 and 2006. hVISA isolates were confirmed by the population analysis profiling-area under the curve method. Only 25 hVISA isolates (1.3% of all isolates) were detected. hVISA isolates were more likely to have been health care associated (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.9 to 14.2) and to have been recovered from patients hospitalized in central Canada (OR, 3.0; 95% CI, 1.2 to 7.4). There has been no evidence of vancomycin “MIC creep” in Canadian strains of methicillin (meticillin)-resistant
S. aureus
, and hVISA strains are currently uncommon.
Deep Sequencing of a Dimethylsulfoniopropionate-Degrading Gene (dmdA) by Using PCR Primer Pairs Designed on the Basis of Marine Metagenomic Data
Authors: Varaljay Vanessa A. , Howard Erinn C. , Sun Shulei , Moran Mary Ann 
Published: December 2009

ABSTRACTIn silicodesign and testing of environmental primer pairs with metagenomic data are beneficial for capturing a greater proportion of the natural sequence heterogeneity in microbial functional genes, as well as for understanding limitations of existing primer sets that were designed from more restricted sequence data. PCR primer pairs targeting 10 environmental clades and subclades of the dimethylsulfoniopropionate (DMSP) demethylase protein, DmdA, were designed using an iterative bioinformatic approach that took advantage of thousands ofdmdAsequences captured in marine metagenomic data sets. Using the bioinformatically optimized primers,dmdAgenes were amplified from composite free-living coastal bacterioplankton DNA (from 38 samples over 5 years and two locations) and sequenced using 454 technology. An average of 6,400 amplicons per primer pair represented more than 700 clusters of environmentaldmdAsequences across all primers, with clusters defined conservatively at >90% nucleotide sequence identity (∼95% amino acid identity). Degenerate and inosine-based primers did not perform better than specific primer pairs in determiningdmdArichness and sometimes captured a lower degree of richness of sequences from the same DNA sample. A comparison ofdmdAsequences in free-living versus particle-associated bacteria in southeastern U.S. coastal waters showed that sequence richness in somedmdAsubgroups differed significantly between size fractions, though most gene clusters were shared (52 to 91%) and most sequences were affiliated with the shared clusters (∼90%). The availability of metagenomic sequence data has significantly enhanced the design of quantitative PCR primer pairs for this key functional gene, providing robust access to the capabilities and activities of DMSP demethylating bacteriain situ.
Lineage and Host Source Are Both Correlated with Levels of Shiga Toxin 2 Production by
Escherichia coli
O157:H7 Strains
Authors: Zhang Yongxiang , Laing Chad , Zhang Zhengzhong , Hallewell Jennyka , You Chunping , Ziebell Kim , Johnson Roger P. , Kropinski Andrew M. , Thomas James E. , Karmali Mohamed , Gannon Victor P. J. 
Published: December 2009

ABSTRACT

Escherichia coli
O157:H7 strains fall into three major genetic lineages that differ in their distribution among humans and cattle. Several recent studies have reported differences in the expression of virulence factors between
E. coli
O157:H7 strains from these two host species. In this study, we wished to determine if important virulence-associated “mobile genetic elements” such as Shiga toxin 2 (Stx2)-encoding prophage are lineage restricted or are host source related and acquired independently of the pathogen genotype. DNA sequencing of the
stx
2
flanking region from a lineage II (LII) strain, EC970520, revealed that the transcriptional activator gene Q in LI strain EDL933 (upstream of
stx
2
) is replaced by a
pphA
(serine/threonine phosphatase) homologue and an altered Q gene in this and all other LII strains tested. In addition, nearly all LI strains carried
stx
2
, whereas all LII strains carried variant
stx
2c
and 4 of 14 LI/II strains had copies of both
stx
2
and variant
stx
2c
. Real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that LI and LI/II strains produce significantly more
stx
2
mRNA and Stx2 than LII strains. However, among LI strains significantly more Stx2 is also produced by strains from humans than from cattle. Therefore, lineage-associated differences among
E. coli
O157:H7 strains such as prophage content, toxin type, and toxin expression may contribute to host isolation bias. However, the level of Stx2 production alone may also play an important role in the within-lineage association of
E. coli
O157:H7 strains with human clinical disease.
Searching for a “Hidden” Prophage in a Marine Bacterium
Authors: Zhao Yanlin , Wang Kui , Ackermann Hans-Wolfgang , Halden Rolf U. , Jiao Nianzhi , Chen Feng 
Published: December 2009

ABSTRACTProphages are common in many bacterial genomes. Distinguishing putatively viable prophages from nonviable sequences can be a challenge, since some prophages are remnants of once-functional prophages that have been rendered inactive by mutational changes. In some cases, a putative prophage may be missed due to the lack of recognizable prophage loci. The genome of a marine roseobacter,Roseovarius nubinhibensISM (hereinafter referred to as ISM), was recently sequenced and was reported to contain no intact prophage based on customary bioinformatic analysis. However, prophage induction experiments performed with this organism led to a different conclusion. In the laboratory, virus-like particles in the ISM culture increased more than 3 orders of magnitude following induction with mitomycin C. After careful examination of the ISM genome sequence, a putative prophage (ISM-pro1) was identified. Although this prophage contains only minimal phage-like genes, we demonstrated that this “hidden” prophage is inducible. Genomic analysis and reannotation showed that most of the ISM-pro1 open reading frames (ORFs) display the highest sequence similarity withRhodobacteralesbacterial genes and some ORFs are only distantly related to genes of other known phages or prophages. Comparative genomic analyses indicated that ISM-pro1-like prophages or prophage remnants are also present in otherRhodobacteralesgenomes. In addition, the lysis of ISM by this previously unrecognized prophage appeared to increase the production of gene transfer agents (GTAs). Our study suggests that a combination ofin silicogenomic analyses and experimental laboratory work is needed to fully understand the lysogenic features of a given bacterium.
Mechanism of Degradation of Immunogenic Gluten Epitopes from
Triticum turgidum
L. var.
durum
by Sourdough Lactobacilli and Fungal Proteases
Authors: De Angelis Maria , Cassone Angela , Rizzello Carlo G. , Gagliardi Francesca , Minervini Fabio , Calasso Maria , Di Cagno Raffaella , Francavilla Ruggero , Gobbetti Marco 
Published: December 2009

ABSTRACT

As shown by R5 antibody-based sandwich and competitive enzyme-linked immunosorbent assay (ELISA), selected sourdough lactobacilli, in combination with fungal proteases, hydrolyzed gluten (72 h at 37°C) of various cultivars of
Triticum turgidum
L. var.
durum
to less than 20 ppm. Complementary electrophoretic, chromatography, and mass spectrometry techniques were used to characterize the gluten and epitope hydrolysis. Nine peptidases were partially purified from the pooled cytoplasmic extract of the sourdough lactobacilli and used to hydrolyze the 33-mer epitope, the most immunogenic peptide generated during digestion of
Triticum
species. At least three peptidases (general aminopeptidase type N [PepN], X-prolyl dipeptidyl aminopeptidase [PepX], and endopeptidase PepO) were necessary to detoxify the 33-mer without generation of related immunogenic epitopes. After 14 h of incubation, the combination of all or at least six different peptidases totally hydrolyzed the 33-mer (200 mM) into free amino acids. The same results were found for other immunogenic epitopes, such as fragments 57-68 of α9-gliadin, 62-75 of A-gliadin, and 134-153 of γ-gliadin. When peptidases were used for fermentation of durum wheat semolina, they caused the hydrolysis of gluten to
ca
. 2 ppm. The
in vivo
digestion was simulated, and proteins/peptides extracted from pepsin-trypsin (PT) digestion of durum wheat semolina fermented with selected sourdough lactobacilli induced the expression of gamma interferon and interleukin 2 at levels comparable to those of the negative control. Durum wheat semolina fermented with sourdough lactobacilli was freeze-dried and used for making Italian-type pasta. The scores for cooking and sensory properties for this pasta were higher that those of conventional gluten-free pasta.