bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective Comparison of Caffeine and Doxapram for the Treatment of Hypercapnia in Foals with Hypoxic‐Ischemic Encephalopathy
Authors: Giguère S. , Slade J.K. , Sanchez L.C. 
Published: December 2008

Background: Despite a lack of data regarding their efficacy, both caffeine and doxapram have been recommended for treatment of hypercapnia in equine neonates with central nervous system damage.Hypothesis: Caffeine and doxapram alleviate hypercapnia in foals with hypoxic‐ischemic encephalopathy.Animals: Sixteen foals treated with either caffeine (n = 8) or doxapram (n = 8).Methods: Information on age, body temperature, heart rate, respiratory rate, arterial blood gas parameters, duration of therapy, and outcome was abstracted from each medical record.Results: Therapy with doxapram resulted in a significant decrease in partial pressure of carbon dioxide (PaCO2 [P= .004]), bicarbonate concentration (P= .002), and base excess (P= .005) compared with baseline values but failed to correct acidemia. In contrast, administration of caffeine did not result in significant changes from baseline values. The percentage decrease in PaCO2 and bicarbonate concentration was significantly greater in foals treated with doxapram than in foals treated with caffeine (P= .004). The proportions of foals that achieved the targeted PaCO2 (≤ 50 mmHg) were significantly higher in foals treated with doxapram than in foals treated with caffeine (P= .029). The proportion of survivors in the 2 treatment groups was not significantly different.Conclusions and Clinical Importance: Doxapram is more effective than caffeine for rapid correction of hypercapnia in foals with hypoxic‐ischemic encephalopathy.
Effect of Age, Feeding, and Omeprazole Administration on Gastric Tonometry in Healthy Neonatal Foals
Authors: Sanchez L.C. , Giguère S. , Javsicas L.H. , Bier J. , Walrond C.J. , Womble A.Y. 
Published: December 2008

Background:Gastric tonometry is commonly used in humans as an assessment of intestinal mucosal perfusion. Values in healthy foals are currently unknown.Hypothesis:Age, enteral feeding, and omeprazole administration would significantly alter gastric tonometry measurements in neonatal foals.Animals:Nine clinically normal foals were used to assess the effect of age and feeding, and 8 similar foals were used to assess the effect of omeprazole.Methods:At 1, 7, and 14 days of age, gastric intramucosal PCO2(PgCO2) and arterial blood gas samples were obtained at baseline, immediately after feeding milk, and 1 and 2 hours after fasting for calculation of the intramucosal‐arterial PCO2difference (ΔCO2). To evaluate the effect of omeprazole, foals were evaluated twice as above, 2 hours after fasting, comparing administration of omeprazole to no drug.Results:There was a significant effect of age and feeding on PgCO2and ΔCO2, whereas arterial PCO2was not significantly affected by these factors. Postfeeding ΔCO2values were significantly lower than fasted values. Baseline and postfeeding ΔCO2increased with age. There was no significant effect of age on data collected after 1 or 2 hours of fasting. The 90% reference interval for ΔCO2data collected after fasting was 0–54 mmHg. Foals had a significantly higher mean gastric pH and significantly higher ΔCO2and PgCO2following omeprazole relative to no treatment.Conclusions and Clinical Importance:Because of the high and variable ΔCO2, which is exacerbated by omeprazole administration, the reference interval in foals is extremely wide.
Plasma Asymmetric Dimethylarginine, Symmetric Dimethylarginine,l‐Arginine, and Nitrite/Nitrate Concentrations in Cats with Chronic Kidney Disease and Hypertension
Authors: Jepson R.E. , Syme H.M. , Vallance C. , Elliott J. 
Published: December 2008

Background:Chronic kidney disease (CKD) and hypertension have been associated with decreased bioavailability of nitric oxide (NO) and endothelial dysfunction. Increased concentrations of the endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) are implicated.Hypothesis:Plasma ADMA concentration is increased in cats with CKD and systemic hypertension corresponding to a decrease in total plasma nitrate/nitrite (NOx) availability. Decrease in systolic blood pressure (SBP) and proteinuria during treatment of hypertension with amlodipine besylate may be associated with increased NOxavailability.Animals:Sixty‐nine client‐owned normotensive and hypertensive cats with variable azotemia.Methods:Plasma ADMA, symmetric dimethylarginine (SDMA), andl‐arginine were measured simultaneously by hydrophilic‐interaction liquid chromatography‐electrospray tandem mass spectrometry in cats from 6 groups: normotensive nonazotemic (n = 10), normotensive mildly azotemic (n = 10), hypertensive mildly azotemic with hypertensive retinopathy (n = 20), hypertensive mildly azotemic without hypertensive retinopathy (n = 10), normotensive moderately azotemic cats (n = 10), and hypertensive nonazotemic cats (n = 9). Plasma NOxconcentrations were measured.Results:A moderate correlation between plasma creatinine and ADMA (n = 69,r= .608,P< .001), SDMA (n = 69,r= .741,P< .001), and NOxconcentrations (n = 69,r= .589,P< .001) was observed. There was no association among plasma ADMA, SDMA, and NOxconcentrations and SBP.Conclusions and Clinical Importance:Plasma ADMA and SDMA concentrations are increased in cats with CKD and correlate with plasma creatinine concentration. This may imply the presence of endothelial dysfunction in cats with CKD. Plasma ADMA concentrations were not associated with systemic hypertension. Treatment of systemic hypertension with amlodipine besylate did not affect plasma ADMA or NOxconcentrations.
Risk of Hemolytic Anemia with Intravenous Administration of Famotidine to Hospitalized Cats
Authors: De Brito Galvao J.F. , Trepanier L.A. 
Published: December 2008

Background: Famotidine administered IV has been associated anecdotally with hemolysis in cats, and some veterinarians recommend using injectable famotidine only by the subcutaneous (SC) route for cats. However, the actual risk of such a reaction is not known.Hypothesis: We hypothesized that famotidine, when given IV slowly, would not be associated with a clinically significant drop in packed cell volume (PCV) in hospitalized cats.Animals: One hundred and forty‐two hospitalized cats.Methods: A retrospective medical record review was performed for hospitalized cats prescribed famotidine IV (n = 56), famotidine SC (n = 48), or no famotidine (n = 38) at a veterinary medical teaching hospital over the period from January 2004 through December 2006.Results: Baseline signalment, observation times, and famotidine dosage (in treated cats) were similar among groups. Median baseline PCVs were significantly lower in the IV (31.5%) and SC (32.0%) groups compared with the control group (35.0%; P= .04). The median percent drop in PCV (3–4%), however, was no different in cats that received famotidine by either route compared with the control group (P= .90), and no cats in either famotidine group were observed to have any clinical signs of hemolysis.Conclusions and Clinical Importance: We conclude from this retrospective study that famotidine IV was given to 56 hospitalized cats without evidence of hemolysis, and that the IV route appeared safe when famotidine was administered over 5 minutes. We could not document a safety advantage of SC versus IV administration in this group of cats.
Risk Factors for Owner‐Reported Occurrence of Equine Protozoal Myeloencephalitis in the US Equine Population
Authors: Morley P.S. , Traub‐Dargatz J.L. , Benedict K.M. , Saville W.J.A. , Voelker L.D. , Wagner B.A. 
Published: December 2008

Background:Equine protozoal myeloencephalitis (EPM) is a serious and often fatal neurologic disease of horses, but few studies have investigated risk factors.Objectives:To evaluate operation‐ and individual‐level factors associated with likelihood of the occurrence of EPM.Animals:Data were collected as part of a study of the US equine industry from 1,178 operations representing 83.9% of horses and 51.6% of operations with ≥3 horses in 28 states.Methods:Probability‐based sampling was used to enroll representative operations in a cross‐sectional study. Interviews were conducted to collect information regarding health and management of horses. A nested case‐control study was used to investigate risk factors among individual horses. Interview data were combined with climate data, human population density, and opossum regional ecology categories. Data were analyzed using logistic regression to identify risk factors for the occurrence of EPM.Results:Owners reported that 95% of EPM cases included in this study were diagnosed by veterinarians. Variables associated with EPM occurrence on premises included opossum regional ecology, reported exposure to small wildlife, climate, terrain, housing, choice of bedding material, method of storing feeds, equine stocking density, and primary use of horses. Among individual horses, age was most strongly associated with disease risk. Associations also were identified with sex, breed, primary use, and participation in competitions.Conclusions and Clinical Importance:Because the risk of EPM occurrence on operations is closely tied to factors that impact exposure to opossums, their feces, and their environment, controlling these exposures may be important in preventing the occurrence of EPM.
Comparison of 3 Ultrasound Methods for Quantifying Left Ventricular Systolic Function: Correlation with Disease Severity and Prognostic Value in Dogs with Mitral Valve Disease
Authors: Serres F. , Chetboul V. , Tissier R. , Poujol L. , Gouni V. , Carlos Sampedrano C. , Pouchelon J.‐L. 
Published: December 2008

Background: End‐systolic volume index (ESVI) is a marker of systolic function, which can be assessed by the geometric (GM, based on Teichholz formula) or 2 planimetric methods (PM, Simpson's derived and length area methods).Hypothesis: Systolic dysfunction (SyD) may be observed in dogs with mitral valve disease (MVD) and is better assessed by PM than GM, which does not take into account the longitudinal left ventricular systolic shortening.Animals: Six healthy dogs were used to determine the variability of the tested variables (Study 1). These variables were then prospectively assessed (Study 2) in 101 small breed dogs: 77 dogs with MVD and 24 healthy controls (CD).Methods: ESVI was measured by GM and PM in awake dogs.Results: All within‐ and between‐day coefficients of variation were <11% (Study 1). For Study 2, a nonlinear overestimation of ESVI was observed by GM compared with PM. PM‐derived ESVI was significantly increased in ISACHC class 3 dogs compared with ISACHC class 1 dogs and exerted a significant influence on cardiac events at 5 months in dogs with MVD from ISACHC classes 2 and 3 (P < .05).Conclusions and Clinical Importance: ESVI can be calculated by GM and PM with good repeatability and reproducibility. However, GM overestimates ESVI in a nonlinear way. Therefore, PM‐derived ESVI should be preferred for the detection of SyD that is present at the late stages of the disease.
Evaluation of Boronic Acid Disk Tests for Differentiating KPC-Possessing
Klebsiella pneumoniae
Isolates in the Clinical Laboratory
Authors: Tsakris Athanassios , Kristo Ioulia , Poulou Aggeliki , Themeli-Digalaki Katerina , Ikonomidis Alexandros , Petropoulou Dimitra , Pournaras Spyros , Sofianou Danai 
Published: December 2008

ABSTRACT

The worldwide increase in the occurrence and dissemination of KPC β-lactamases among gram-negative pathogens makes critical the early detection of these enzymes. Boronic acid disk tests using different antibiotic substrates were evaluated for detection of KPC-possessing
Klebsiella pneumoniae
isolates. A total of 57 genotypically confirmed KPC-possessing
K. pneumoniae
isolates with varying carbapenem MICs were examined. To measure the specificity of the tests, 106 non-KPC-possessing isolates (89
K. pneumoniae
and 17
Escherichia coli
isolates) were randomly selected among those exhibiting reduced susceptibility to cefoxitin, expanded-spectrum cephalosporins, or carbapenems. As many as 56, 53, and 40 of the non-KPC-possessing isolates harbored extended-spectrum β-lactamases, metallo-β-lactamases, and plasmid-mediated AmpC β-lactamases, respectively. By use of CLSI methodology and disks containing imipenem, meropenem, or cefepime, either alone or in combination with 400 μg of boronic acid, all 57 KPC producers gave positive results (sensitivity, 100%) whereas all 106 non-KPC producers were negative (specificity, 100%). The meropenem duplicate disk with or without boronic acid demonstrated the largest differences in inhibition zone diameters between KPC producers and non-KPC producers. By use of disks containing ertapenem, all isolates were correctly differentiated except for five AmpC producers that gave false-positive results (sensitivity, 100%; specificity, 95.3%). These practical and simple boronic acid disk tests promise to be very helpful for the accurate differentiation of KPC-possessing
K. pneumoniae
isolates, even in regions where different broad-spectrum β-lactamases are widespread.
Comparison of Commercial and In-House Real-Time PCR Assays Used for Detection of
Mycoplasma pneumoniae
Authors: Dumke Roger , Jacobs Enno 
Published: December 2008

ABSTRACT

We tested two commercial and three in-house PCR assays under standardized conditions to detect
Mycoplasma pneumoniae
. All five procedures were able to demonstrate
M. pneumoniae
DNA in a concentration comparable to 1 CFU/μl, but the mean crossing points resulted in differences in the concentration of the genome copies of a factor of 20.
Herpes Simplex Virus Type 1 Thymidine Kinase Sequence Fused to the
lacZ
Gene Increases Levels of β-Galactosidase Activity per Genome of High-Capacity but Not First-Generation Adenoviral Vectors In Vitro and In Vivo
Authors: Puntel M. , Barrett R. J. , Mondkar S. , Saxena V. , Kroeger K. M. , Muhammad A. K. M. , Liu C. , Bondale N. , Sciascia S. , Xiong W. , Shi Y. , Salem A. , Zadmehr A. , Huynh P. , Palmer D. , Ng P. , Castro M. G. , Lowenstein P. R. 
Published: December 2008

ABSTRACT

Increased transgene expression per vector genome is an important goal in the optimization of viral vectors for gene therapy. Herein we demonstrate that herpes simplex virus type 1 (HSV1) thymidine kinase (TK) gene sequences (1,131 bp) fused to the 3′ end of
lacZ
increase transgene expression from high-capacity adenoviral vectors (HCAd), but not from first-generation (Ad) vectors. The woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), in contrast, increased transgene expression levels from Ad but not HCAd vectors. The differential activity of the HSV1 TK gene and WPRE sequences was detected both in vitro and in vivo and suggests potentially different mechanisms of action or the interaction of these elements with vector genomic sequences.
Template Usage Is Responsible for the Preferential Acquisition of the K65R Reverse Transcriptase Mutation in Subtype C Variants of Human Immunodeficiency Virus Type 1
Authors: Coutsinos Dimitrios , Invernizzi Cédric F. , Xu Hongtao , Moisi Daniela , Oliveira Maureen , Brenner Bluma G. , Wainberg Mark A. 
Published: December 2008

ABSTRACTWe propose that a nucleotide template-based mechanism facilitates the acquisition of the K65R mutation in subtype C human immunodeficiency virus type 1 (HIV-1). Different patterns of DNA synthesis were observed using DNA templates from viruses of subtype B or C origin. When subtype C reverse transcriptase (RT) was employed to synthesize DNA from subtype C DNA templates, preferential pausing was seen at the nucleotide position responsible for the AAG-to-AGG K65R mutation. This did not occur when the subtype B RT and template were used. Template factors can therefore increase the probability of K65R development in subtype C HIV-1.
Binding and Relocalization of Protein Kinase R by Murine Cytomegalovirus
Authors: Child Stephanie J. , Geballe Adam P. 
Published: December 2008

ABSTRACT
Many viruses have evolved mechanisms to evade the repression of translation mediated by protein kinase R (PKR). In the case of murine cytomegalovirus (MCMV), the protein products of two essential genes, m142 and m143, bind to double-stranded RNA (dsRNA) and block phosphorylation of PKR and eukaryotic initiation factor 2α. A distinctive feature of MCMV is that two proteins are required to block PKR activation whereas other viral dsRNA-binding proteins that prevent PKR activation contain all the necessary functions in a single protein. In order to better understand the mechanism by which MCMV evades the PKR response, we investigated the associations of pm142 and pm143 with each other and with PKR. Both pm142 and pm143 interact with PKR in infected and transfected cells. However, the ∼200-kDa pm142-pm143 complex that forms in these cells does not contain substantial amounts of PKR, suggesting that the interactions between pm142-pm143 and PKR are unstable or transient. The stable, soluble pm142-pm143 complex appears to be a heterotetramer consisting of two molecules of pm142 associated with each other, and each one binds to and stabilizes a monomer of pm143. MCMV infection also causes relocalization of PKR into the nucleus and to an insoluble cytoplasmic compartment. These results suggest a model in which the pm142-pm143 multimer interacts with PKR and causes its sequestration in cellular compartments where it is unable to shut off translation and repress viral replication.
ISG15 Arg151 and the ISG15-Conjugating Enzyme UbE1L Are Important for Innate Immune Control of Sindbis Virus
Authors: Giannakopoulos Nadia V. , Arutyunova Elena , Lai Caroline , Lenschow Deborah J. , Haas Arthur L. , Virgin Herbert Whiting 
Published: December 2008

ABSTRACTInterferon (IFN)-stimulated gene 15 (ISG15) is a ubiquitin-like molecule that conjugates to target proteins via a C-terminal LRLRGG motif and has antiviral function in vivo. We used structural modeling to predict human ISG15 (hISG15) residues important for interacting with its E1 enzyme, UbE1L. Kinetic analysis revealed that mutation of arginine 153 to alanine (R153A) ablated hISG15-hUbE1L binding and transthiolation of UbcH8. Mutation of other predicted UbE1L-interacting residues had minimal effects on the transfer of ISG15 from UbE1L to UbcH8. The capacity of hISG15 R153A to form protein conjugates in 293T cells was markedly diminished. Mutation of the homologous residue in mouse ISG15 (mISG15), arginine 151, to alanine (R151A) also attenuated protein ISGylation following transfection into 293T cells. We assessed the role of ISG15-UbE1L interactions in control of virus infection by constructing double subgenomic Sindbis viruses that expressed the mISG15 R151A mutant. While expression of mISG15 protected alpha/beta-IFN-receptor-deficient (IFN-αβR−/−) mice from lethality following Sindbis virus infection, expression of mISG15 R151A conferred no survival benefit. The R151A mutation also attenuated ISG15's ability to decrease Sindbis virus replication in IFN-αβR−/−mice or prolong survival of ISG15−/−mice. The importance of UbE1L was confirmed by demonstrating that mice lacking this ISG15 E1 enzyme were highly susceptible to Sindbis virus infection. Together, these data support a role for protein conjugation in the antiviral effects of ISG15.
Leader-Induced Phosphorylation of Nucleoporins Correlates with Nuclear Trafficking Inhibition by Cardioviruses
Authors: Porter Frederick W. , Palmenberg Ann C. 
Published: December 2008

ABSTRACT

Picornaviruses disrupt nucleocytoplasmic trafficking pathways during infection. Poliovirus and rhinovirus inhibit nuclear protein import/export through a series of 2A protease-dependent cleavages within nuclear pore proteins (nucleoporins [Nups]), including Nup62, Nup98, and Nup153. Cardioviruses lack the same protease and instead affect trafficking inhibition through an activity mapped to their leader (L) protein, a 67- to 76-amino acid (aa) polypeptide with no known enzymatic activity. We have shown that L from encephalomyocarditis virus (EMCV) binds and inhibits the activity of Ran-GTPase, a key regulator of nucleocytoplasmic transport. We now report that recombinant EMCV L triggers the unregulated efflux of protein cargo from preloaded HeLa cell nuclei in cell-free reactions dependent upon
Xenopus
egg cytosol or HeLa cell-derived cytosol. Recombinant L was the only viral protein necessary for this activity or for nuclear protein import inhibition. Mutational disruption of the L protein zinc finger domain (C
19
A) abrogated the inhibitory activity for both import and efflux in cell extracts, but mutations in the C-terminal acidic domain of L (aa 37 to 61) did not. Notably, HeLa cell nuclei treated with L, or those from EMCV-infected cells, showed reproducibly altered patterns of nucleoporin phosphorylation. Nup62, Nup153, and Nup214 each became hyperphosphorylated in an L-dependent manner. Staurosporine, a broad-spectrum kinase inhibitor, blocked this phosphorylation and rescued nuclear import/export activity from L-dependent inhibition. Therefore, cardioviruses target the same group of nucleoporins as enteroviruses, but the effector mechanism triggered by L (or L-Ran complexes) involves a unique cytosol-dependent phosphorylation cascade rather than proteolysis.
Replication of Equine Infectious Anemia Virus in Engineered Mouse NIH 3T3 Cells
Authors: Zhang Baoshan , Montelaro Ronald C. 
Published: December 2008

ABSTRACT
We employed the equine lentivirus equine infectious anemia virus (EIAV) to investigate the cellular restrictions for lentivirus replication in murine NIH 3T3 cells. The results of these studies demonstrate that NIH 3T3 cells expressing the EIAV receptor ELR1 and equine cyclin T1 supported productive replication of EIAV and produced infectious virions at levels similar to those found in a reference permissive equine cell line. The studies presented here demonstrate, for the first time, differential levels of restriction for EIAV and human immunodeficiency virus type 1 (HIV-1) replication in murine cells and suggest that these differences can be exploited to reveal critical virus-cell interactions required for HIV-1 assembly and budding of lentivirus particles.
The Hepatitis C Virus NS4B Protein Can
trans
-Complement Viral RNA Replication and Modulates Production of Infectious Virus
Authors: Jones Daniel M. , Patel Arvind H. , Targett-Adams Paul , McLauchlan John 
Published: December 2008

ABSTRACT

Studies of the hepatitis C virus (HCV) life cycle have been aided by development of in vitro systems that enable replication of viral RNA and production of infectious virus. However, the functions of the individual proteins, especially those engaged in RNA replication, remain poorly understood. It is considered that NS4B, one of the replicase components, creates sites for genome synthesis, which appear as punctate foci at the endoplasmic reticulum (ER) membrane. In this study, a panel of mutations in NS4B was generated to gain deeper insight into its functions. Our analysis identified five mutants that were incapable of supporting RNA replication, three of which had defects in production of foci at the ER membrane. These mutants also influenced posttranslational modification and intracellular mobility of another replicase protein, NS5A, suggesting that such characteristics are linked to focus formation by NS4B. From previous studies, NS4B could not be
trans
-complemented in replication assays. Using the mutants that blocked RNA synthesis, defective NS4B expressed from two mutants could be rescued in
trans
-complementation replication assays by wild-type protein produced by a functional HCV replicon. Moreover, active replication could be reconstituted by combining replicons that were defective in NS4B and NS5A. The ability to restore replication from inactive replicons has implications for our understanding of the mechanisms that direct viral RNA synthesis. Finally, one of the NS4B mutations increased the yield of infectious virus by five- to sixfold. Hence, NS4B not only functions in RNA replication but also contributes to the processes engaged in virus assembly and release.