bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐Insulin Antibodies in Diabetic Dogs Before and After Treatment with Different Insulin Preparations
Authors: Davison L.J. , Walding B. , Herrtage M.E. , Catchpole B. 
Published: January 2009

Background:Anti‐insulin antibodies (AIA) occur in diabetic dogs after insulin therapy, although their clinical significance is unclear.Hypothesis:Treatment of diabetic dogs with heterologous insulin is more likely to stimulate production of AIA than is treatment with homologous insulin.Animals:Diabetic dogs sampled before insulin therapy (n = 40), diabetic dogs sampled following treatment with porcine (homologous) insulin (n = 100), bovine (heterologous) lente insulin (n = 100), or bovine protamine zinc (PZI) insulin (n = 20), and nondiabetic control dogs (n = 120).Methods:Prospective observational study. Sera were analyzed by ELISA for antibodies against porcine insulin, bovine insulin, insulin A, B, or C peptides, and control antigens; canine distemper virus (CDV) and canine thyroglobulin (TG). Canine isotype‐specific antibodies were used to determine total and anti‐insulin IgG1 : IgG2 ratios.Results:There was no difference in CDV or TG reactivity among the groups. AIA were detected in 5 of 40 newly diagnosed (untreated) diabetic dogs. There was no significant difference in AIA (ELISA optical density reactivity) comparing control and porcine insulin‐treated diabetic dogs (P> .05). Anti‐insulin reactivity was most prevalent in bovine PZI insulin‐treated dogs (90%;P< .01), and bovine lente insulin‐treated dogs (56%;P< .01). AIA induced by treatment were enriched for the IgG1 isotype.Conclusions and Clinical Importance:This study indicates that bovine insulin is more immunogenic than porcine insulin when used for treatment of diabetic dogs.
Ventricular Tachyarrhythmias in 106 Cats: Associated Structural Cardiac Disorders
Authors: Côté E. , Jaeger R. 
Published: January 2009

Background:Ventricular tachyarrhythmias occur in association with cardiac and extracardiac disorders in many species of animals, but information identifying concurrent disorders in cats with such arrhythmias is scarce.Methods:We investigated coexisting diseases by retrospectively evaluating medical records of cats with ventricular tachyarrhythmias seen during a 51‐month period at 1 institution. For comparative purposes, we evaluated records of dogs with similar arrhythmias during the same time period. All cats and dogs had premature ventricular complexes, accelerated idioventricular rhythm, ventricular tachycardia, or some combination of these arrhythmias, and all had undergone echocardiography during the same visit that led to the diagnosis of ventricular tachyarrhythmia.Results and Conclusions:Most (102/106; 96%) cats had at least 1 echocardiographically apparent abnormality concurrent with ventricular tachyarrhythmias. Ventricular tachyarrhythmias in cats were most commonly associated with myocardial disease (eg, left ventricular concentric hypertrophy [n = 66], restrictive or unclassified cardiomyopathy [n = 17], and dilated cardiomyopathy [n = 6]). When comparing dogs and cats that had ventricular tachyarrhythmias and were diagnosed on the same clinical service of the same institution, an echocardiographically apparent cardiac lesion was seen more often in cats (102/106, 96%) than in dogs (95/138, 69%) (P< .001).
Use of a Surface Plasmon Resonance Method To Investigate Antibiotic and Plasma Protein Interactions
Authors: Banères-Roquet Françoise , Gualtieri Maxime , Villain-Guillot Philippe , Pugnière Martine , Leonetti Jean-Paul 
Published: January 2009

ABSTRACTThe pharmacologic effect of an antibiotic is directly related to its unbound concentration at the site of infection. Most commercial antibiotics have been selected in part for their low propensity to interact with serum proteins. These nonspecific interactions are classically evaluated by measuring the MIC in the presence of serum. As higher-throughput technologies tend to lose information, surface plasmon resonance (SPR) is emerging as an informative medium-throughput technology for hit validation. Here we show that SPR is a useful automatic tool for quantification of the interaction of model antibiotics with serum proteins and that it delivers precise real-time kinetic data on this critical parameter.
Daptomycin versus Friulimicin B: In-Depth Profiling of
Bacillus subtilis
Cell Envelope Stress Responses
Authors: Wecke Tina , Zühlke Daniela , Mäder Ulrike , Jordan Sina , Voigt Birgit , Pelzer Stefan , Labischinski Harald , Homuth Georg , Hecker Michael , Mascher Thorsten 
Published: January 2009

ABSTRACT

The related lipo(depsi)peptide antibiotics daptomycin and friulimicin B show great potential in the treatment of multiply resistant gram-positive pathogens. Applying genome-wide in-depth expression profiling, we compared the respective stress responses of
Bacillus subtilis
. Both antibiotics target envelope integrity, based on the strong induction of extracytoplasmic function σ factor-dependent gene expression. The cell envelope stress-sensing two-component system LiaRS is exclusively and strongly induced by daptomycin, indicative of different mechanisms of action in the two compounds.
β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli
Authors: Al-Hasan Majdi N. , Wilson John W. , Lahr Brian D. , Thomsen Kristine M. , Eckel-Passow Jeanette E. , Vetter Emily A. , Tleyjeh Imad M. , Baddour Larry M. 
Published: January 2009

ABSTRACT

The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of <4, combination therapy was associated with lower 28-day mortality than single therapy (4.2% [9 of 214] versus 8.8% [28 of 319]; adjusted HR, 0.44; 95% confidence interval [CI], 0.20 to 0.98;
P
= 0.044). In critically ill patients with Pitt bacteremia scores of ≥4, there was no difference in 28-day mortality between combination and single therapy (25.6% [23 of 90] versus 27.8% [22 of 79]; adjusted HR, 0.87; 95% CI, 0.47 to 1.62;
P
= 0.660). These findings were consistent for 14-day all-cause mortality. In this large cohort, we found for the first time that combination therapy with beta-lactams and fluoroquinolones was associated with a reduction in 28-day all-cause mortality among less severely ill patients with bacteremia caused by gram-negative bacilli.
Two Clinical Strains of
Klebsiella pneumoniae
Carrying Plasmid-Borne
bla
IMP-4
,
bla
SHV-12
, and
armA
Isolated at a Pediatric Center in Shanghai, China
Authors: Liu Ying , Zhang Bei , Cao Qing , Huang Weichun , Shen Lisong , Qin Xuan 
Published: January 2009

ABSTRACT

Two cases of pulmonary infection due to strains of multidrug-resistant
Klebsiella pneumoniae
were investigated. Beta-lactamase determinants, such as
bla
IMP-4
and
bla
SHV-12
, and the 16S rRNA methyltransferase-encoding gene
armA
were detected in these plasmid-bearing organisms. The integron-borne
bla
IMP-4
and
armA
contained intervening sequences highly related to those of a
Vibrio cholerae
O139 plasmid found in Hangzhou, China.
Genetic Analysis of Factors Affecting Susceptibility ofBacillus subtilisto Daptomycin
Authors: Hachmann Anna-Barbara , Angert Esther R. , Helmann John D. 
Published: January 2009

ABSTRACTDaptomycin is the first of a new class of cyclic lipopeptide antibiotics used against multidrug-resistant, gram-positive pathogens. The proposed mechanism of action involves disruption of the functional integrity of the bacterial membrane in a Ca2+-dependent manner. We have used transcriptional profiling to demonstrate that treatment ofBacillus subtiliswith daptomycin strongly induces theliaoperon including the autoregulatory LiaRS two-component system (homologous toStaphylococcus aureusVraSR). Theliaoperon protects against daptomycin, and deletion ofliaH, encoding a phage-shock protein A (PspA)-like protein, leads to threefold increased susceptibility. Since daptomycin interacts with the membrane, we tested mutants with altered membrane composition for effects on susceptibility. Deletion mutations ofmprF(lacking lysyl-phosphatidylglycerol) ordes(lipid desaturase) increased daptomycin susceptibility, whereas overexpression of MprF decreased susceptibility. Conversely, depletion of the cell for the anionic lipid phosphatidylglycerol led to increased resistance. Fluorescently labeled daptomycin localized to the septa and in a helical pattern around the cell envelope and was delocalized upon the depletion of phosphatidylglycerol. Together, these results indicate that the daptomycin-Ca2+complex interacts preferentially with regions enriched in anionic phospholipids and leads to membrane stresses that can be ameliorated by PspA family proteins.
Engineered
Streptomyces platensis
Strains That Overproduce Antibiotics Platensimycin and Platencin
Authors: Smanski Michael J. , Peterson Ryan M. , Rajski Scott R. , Shen Ben 
Published: January 2009

ABSTRACT

Platensimycin, which is isolated from
Streptomyces platensis
MA7327, and platencin, which is isolated from
S. platensis
MA7339, are two recently discovered natural products that serve as important antibiotic leads. Here we report on the identification of
S. platensis
MA7327 as a dual producer of both platensimycin and platencin. A PCR-based approach was used to locate and clone the locus involved in platensimycin and platencin production, including
ptmR1
, which encodes a putative GntR-like transcriptional regulator. Deletion of this gene from the producing organism allowed us to isolate strains that overproduce platensimycin and platencin with yields of 323 ± 29 mg/liter and 255 ± 30 mg/liter, respectively. These results illustrate the effectiveness of genetic manipulation for the rational engineering of improvements in titers.
Decline in Cases of Rotavirus Gastroenteritis Presenting to The Children's Hospital of Philadelphia after Introduction of a Pentavalent Rotavirus Vaccine
Authors: Clark H Fred , Lawley Diane , Mallette Laura A. , DiNubile Mark J. , Hodinka Richard L. 
Published: January 2009

ABSTRACT
A pentavalent rotavirus vaccine for infants became available in the United States in February 2006. By 2007, vaccination rates nationwide were estimated to be ∼50%. We studied the effectiveness of the vaccine in a real-world setting outside of a clinical trial. All children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by enzyme-linked immunosorbent assay (ELISA [followed by genotyping if ELISA positive]) since the 1994-1995 epidemic season, presenting a unique opportunity to assess the impact of the recently introduced vaccine. The annual number of community-acquired cases over the preceding 13 years had approached or exceeded 100, with 271 cases in 2005 to 2006 and 167 cases in 2006 to 2007. In the 2007-2008 season, only 36 community-acquired cases were identified, representing an 87% reduction from the same period in 2005 to 2006. G3 was the predominant serotype, accounting for 15 community cases (42%). Our study is limited by its observational design using historical comparisons. Nonetheless, the abrupt decline in rotavirus gastroenteritis cases during the 2007-2008 season likely resulted from vaccination. Because protection rates appeared to have exceeded vaccination rates, herd immunity may have contributed to some degree to the effectiveness of the vaccine.
Incidence, Virulence Factors, and Clonality among Clinical Strains of Non-O1, Non-O139
Vibrio cholerae
Isolates from Hospitalized Diarrheal Patients in Kolkata, India
Authors: Chatterjee S. , Ghosh K. , Raychoudhuri A. , Chowdhury G. , Bhattacharya M. K. , Mukhopadhyay A. K. , Ramamurthy T. , Bhattacharya S. K. , Klose Karl E. , Nandy R. K. 
Published: January 2009

ABSTRACT

The incidence of
Vibrio cholerae
non-O1, non-O139 strains from hospitalized patients with acute diarrhea constituted 27.4% (
n
= 54) of the total 197
V. cholerae
strains isolated from patients in Kolkata, India, in 2003. Of 197 strains, 135 were identified as O1 serotype Ogawa and 2 were identified as O139. In the same time period, six O1 background rough strains that possessed all known virulence factors were identified. Serotype analysis of the non-O1, non-O139 strains placed 42 strains into 19 serogroups, while 12 remained O nontypeable (ONT); the existing serotyping scheme involved antisera to 206 serogroups. Detection of a good number of ONT strains suggested that additional serogroups have arisen that need to be added to the current serotyping scheme. The non-O1, non-O139 strains were nontoxigenic except for an O36 strain (SC124), which regulated expression of cholera toxin as O1 classical strains did. Additionally, strain SC124 carried alleles of
tcpA
and
toxT
that were different from those of the O1 counterpart, and these were also found in five clonally related strains belonging to different serogroups. Strains carrying
tcpA
exhibited higher colonization in an animal model compared to those lacking
tcpA
. PCR-based analyses revealed remarkable variations in the distribution of other virulence factors, including
hlyA
,
rtxA
,
Vibrio
seventh pandemic island I (VSP-I), VSP-II, and type III secretion system (TTSS). Most strains contained
hlyA
(87%) and
rtxA
(81.5%) and secreted cytotoxic factors when grown in vitro. Approximately one-third of the strains (31.5%) contained the TTSS gene cluster, and most of these strains were more motile and hemolytic against rabbit erythrocytes. Partial nucleotide sequence analysis of the TTSS-containing strains revealed silent nucleotide mutations within
vcsN2
(type III secretion cytoplasmic ATPase), indicating functional conservation of the TTSS apparatus.
Herpesvirus gB-Induced Fusion between the Virion Envelope and Outer Nuclear Membrane during Virus Egress Is Regulated by the Viral US3 Kinase
Authors: Wisner Todd W. , Wright Catherine C. , Kato Akihisa , Kawaguchi Yasushi , Mou Fan , Baines Joel D. , Roller Richard J. , Johnson David C. 
Published: January 2009

ABSTRACT
Herpesvirus capsids collect along the inner surface of the nuclear envelope and bud into the perinuclear space. Enveloped virions then fuse with the outer nuclear membrane (NM). We previously showed that herpes simplex virus (HSV) glycoproteins gB and gH act in a redundant fashion to promote fusion between the virion envelope and the outer NM. HSV mutants lacking both gB and gH accumulate enveloped virions in herniations, vesicles that bulge into the nucleoplasm. Earlier studies had shown that HSV mutants lacking the viral serine/threonine kinase US3 also accumulate herniations. Here, we demonstrate that HSV gB is phosphorylated in a US3-dependent manner in HSV-infected cells, especially in a crude nuclear fraction. Moreover, US3 directly phosphorylated the gB cytoplasmic (CT) domain in in vitro assays. Deletion of gB in the context of a US3-null virus did not add substantially to defects in nuclear egress. The majority of the US3-dependent phosphorylation of gB involved the CT domain and amino acid T887, a residue present in a motif similar to that recognized by US3 in other proteins. HSV recombinants lacking gH and expressing either gB substitution mutation T887A or a gB truncated at residue 886 displayed substantial defects in nuclear egress. We concluded that phosphorylation of the gB CT domain is important for gB-mediated fusion with the outer NM. This suggested a model in which the US3 kinase is incorporated into the tegument layer (between the capsid and envelope) in HSV virions present in the perinuclear space. By this packaging, US3 might be brought close to the gB CT tail, leading to phosphorylation and triggering fusion between the virion envelope and the outer NM.
Robust In Vivo Transduction of a Genetically Stable Epstein-Barr Virus Episome to Hepatocytes in Mice by a Hybrid Viral Vector
Authors: Gallaher Sean D. , Gil Jose S. , Dorigo Oliver , Berk Arnold J. 
Published: January 2009

ABSTRACT
To make a safe, long-lasting gene delivery vehicle, we developed a hybrid vector that leverages the relative strengths of adenovirus and Epstein-Barr virus (EBV). A fully gene-deleted helper-dependent adenovirus (HDAd) is used as the delivery vehicle for its scalability and high transduction efficiency. Upon delivery, a portion of the HDAd vector is recombined to form a circular plasmid. This episome includes two elements from EBV: an EBV nuclear antigen 1 (EBNA1) expression cassette and an EBNA1 binding region. Along with a human replication origin, these elements provide considerable genetic stability to the episome in replicating cells while avoiding insertional mutagenesis. Here, we demonstrate that this hybrid approach is highly efficient at delivering EBV episomes to target cells in vivo. We achieved nearly 100% transduction of hepatocytes after a single intravenous injection in mice. This is a substantial improvement over the transduction efficiency of previously available physical and viral methods. Bioluminescent imaging of vector-transduced mice demonstrated that luciferase transgene expression from the hybrid was robust and compared well to a traditional HDAd vector. Quantitative PCR analysis confirmed that the EBV episome was stable at approximately 30 copies per cell for up to 50 weeks and that it remained circular and extrachromosomal. Approaches for adapting the HDAd-EBV hybrid to a variety of disease targets and the potential benefits of this approach are discussed.
Self-Assembly of Epstein-Barr Virus Capsids
Authors: Henson Brandon W. , Perkins Edward M. , Cothran Jonathan E. , Desai Prashant 
Published: January 2009

ABSTRACT

Epstein-Barr virus (EBV), a member of the
Gammaherpesvirus
family, primarily infects B lymphocytes and is responsible for a number of lymphoproliferative diseases. The molecular genetics of the assembly pathway and high-resolution structural analysis of the capsid have not been determined for this lymphocryptovirus. As a first step in studying EBV capsid assembly, the baculovirus expression vector (BEV) system was used to express the capsid shell proteins BcLF1 (major capsid protein), BORF1 (triplex protein), BDLF1 (triplex protein), and BFRF3 (small capsid protein); the internal scaffold protein, BdRF1; and the maturational protease (BVRF2). Coinfection of insect cells with the six viruses expressing these proteins resulted in the production of closed capsid structures as judged by electron microscopy and sedimentation methods. Therefore, as shown for other herpesviruses, only six proteins are required for EBV capsid assembly. Furthermore, the small capsid protein of EBV (BFRF3), like that of Kaposi's sarcoma-associated herpesvirus, was found to be required for assembly of a stable structure. Localization of the small capsid protein to nuclear assembly sites required both the major capsid (BcLF1) and scaffold proteins (BdRF1) but not the triplex proteins. Mutational analysis of BFRF3 showed that the N-terminal half (amino acids 1 to 88) of this polypeptide is required and sufficient for capsid assembly. A region spanning amino acids 65 to 88 is required for the concentration of BFRF3 at a subnuclear site and the N-terminal 65 amino acids contain the sequences required for interaction with major capsid protein. These studies have identified the multifunctional role of the gammaherpesvirus small capsid proteins.
Olfactory System Involvement in Natural Scrapie Disease
Authors: Corona Cristiano , Porcario Chiara , Martucci Francesca , Iulini Barbara , Manea Barbara , Gallo Marina , Palmitessa Claudia , Maurella Cristiana , Mazza Maria , Pezzolato Marzia , Acutis Pierluigi , Casalone Cristina 
Published: January 2009

ABSTRACTThe olfactory system (OS) is involved in many infectious and neurodegenerative diseases, both human and animal, and it has recently been investigated in regard to transmissible spongiform encephalopathies. Previous assessments of nasal mucosa infection by prions following intracerebral challenge suggested a potential centrifugal spread along the olfactory nerve fibers of the pathological prion protein (PrPSc). Whether the nasal cavity may be a route for centripetal prion infection to the brain has also been experimentally studied. With the present study, we wanted to determine whether prion deposition in the OS occurs also under field conditions and what type of anatomical localization PrPScmight display there. We report here on detection by different techniques of PrPScin the nasal mucosa and in the OS-related brain areas of sheep affected by natural scrapie. PrPScwas detected in the perineurium of the olfactory nerve bundles in the medial nasal concha and in nasal-associated lymphoid tissue. Olfactory receptor neurons did not show PrPScimmunostaining. PrPScdeposition was found in the brain areas of olfactory fiber projection, chiefly in the olfactory bulb and the olfactory cortex. The prevalent PrPScdeposition patterns were subependymal, perivascular, and submeningeal. This finding, together with the discovery of an intense PrPScimmunostaining in the meningeal layer of the olfactory nerve perineurium, at the border with the subdural space extension surrounding the nerve rootlets, strongly suggests a probable role of cerebrospinal fluid in conveying prion infectivity to the nasal submucosa.
Coagulation Factors IX and X Enhance Binding and Infection of Adenovirus Types 5 and 31 in Human Epithelial Cells
Authors: Jonsson Mari I. , Lenman Annasara E. , Frängsmyr Lars , Nyberg Cecilia , Abdullahi Mohamed , Arnberg Niklas 
Published: January 2009

ABSTRACT
Most adenoviruses bind directly to the coxsackie and adenovirus receptor (CAR) on target cells in vitro, but recent research has shown that adenoviruses can also use soluble components in body fluids for indirect binding to target cells. These mechanisms have been identified upon addressing the questions of how to de- and retarget adenovirus-based vectors for human gene and cancer therapy, but the newly identified mechanisms also suggest that the role of body fluids and their components may also be of importance for natural, primary infections. Here we demonstrate that plasma, saliva, and tear fluid promote binding and infection of adenovirus type 5 (Ad5) in respiratory and ocular epithelial cells, which corresponds to the natural tropism of most adenoviruses, and that plasma promotes infection by Ad31. By using a set of binding and infection experiments, we also found that Ad5 and Ad31 require coagulation factors IX (FIX) or X (FX) or just FIX, respectively, for efficient binding and infection. The concentrations of these factors that were required for maximum binding were 1/100th of the physiological concentrations. Preincubation of virions with heparin or pretreatment of cells with heparinase I indicated that the role of cell surface heparan sulfate during FIX- and FX-mediated adenovirus binding and infection is mechanistically serotype specific. We conclude that the use of coagulation factors by adenoviruses may be of importance not only for the liver tropism seen when administering adenovirus vectors to the circulation but also during primary infections by wild-type viruses of their natural target cell types.