FeMV is a cathepsin-dependent unique morbillivirus infecting the kidneys of domestic cats.

Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the family. We determined the complete sequence of FeMV directly from an FeMV-positive urine sample without virus isolation or cell passage. Sequence analysis of the viral genome revealed potential divergence from characteristics of archetypal morbilliviruses.

Bias, Repeatability and Reproducibility of Liver T Mapping With Variable Flip Angles.

Background: Three-dimensional variable flip angle (VFA) methods are commonly used for T mapping of the liver, but there is no data on the accuracy, repeatability, and reproducibility of this technique in this organ in a multivendor setting.

Purpose: To measure bias, repeatability, and reproducibility of VFA T mapping in the liver.

Study Type: Prospective observational.

Patient adaptive maximal resolution magnetic resonance myocardial stress perfusion imaging.

Purpose: To demonstrate the feasibility of an automatic adaptive acquisition sequence. Magnetic resonance perfusion pulse sequences often leave potential acquisition time unused in patients with lower heart-rates (HR) and smaller body size.

Materials And Methods: A perfusion technique was developed that automatically adapts to HR and field-of-view by maximizing in-plane spatial resolution while maintaining temporal resolution every cardiac cycle.

Characterisation of a novel Fc conjugate of macrophage colony-stimulating factor.

We have produced an Fc conjugate of colony-stimulating factor (CSF) 1 with an improved circulating half-life. CSF1-Fc retained its macrophage growth-promoting activity, and did not induce proinflammatory cytokines in vitro. Treatment with CSF1-Fc did not produce adverse effects in mice or pigs.

In vitro functional characterization of feline IgGs.

Very little is known about the functional properties of feline IgGs. Here we report the in vitro characterization of cloned feline IgGs. Rapid amplification of cDNA ends (RACE) and full-length PCR of cat splenic cDNA were used to identify feline sequences encoding IgG heavy chain constant regions (IGHC).

Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice.

Complementarity determining regions (CDR) are responsible for binding antigen and provide substantial diversity to the antibody repertoire, with VH CDR3 of the immunoglobulin variable heavy (VH) domain playing a dominant role. In this study, we examined 1200 unique canine VH and 500 unique variable light (VL) sequences of large and small canine breeds derived from peripheral B cells. Unlike the human and murine repertoire, the canine repertoire is heavily dominated by the Canis lupus familiaris IGHV1 subgroup, evolutionarily closest to the human IGHV3 subgroup.

Comparative functional characterization of canine IgG subclasses.

To date, very little is known about the functional characteristics of the four published canine IgG subclasses. It is not clear how each subclass engages the immune system via complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC), or how long each antibody may last in serum. Such information is critical for understanding canine immunology and for the discovery of canine therapeutic monoclonal antibodies.

Thermodynamic and structure guided design of statin based inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2-7% of patients may experience statin-induced myalgia that limits compliance with a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors with improved HMGR affinity and therapeutic index relative to statin-induced myalgia. These studies facilitated the identification of imidazole 1 as a potent (IC 50 = 7.

Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors.

This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models.

Design and synthesis of novel, conformationally restricted HMG-CoA reductase inhibitors.

Using structure-based design, a novel series of conformationally restricted, pyrrole-based inhibitors of HMG-CoA reductase were discovered. Leading analogs demonstrated potent inhibition of cholesterol synthesis in both in vitro and in vivo models and may be useful for the treatment of hypercholesterolemia and related lipid disorders.

Myocardial T1 mapping for detection of left ventricular myocardial fibrosis in chronic aortic regurgitation: pilot study.

Objective: The aim of this study was to identify diffuse myocardial fibrosis secondary to chronic aortic regurgitation by comparing the T1 relaxation times of left ventricular myocardium in a pilot patient group with a previously established normal range of times.

Subjects And Methods: Eight patients with chronic aortic regurgitation and normal coronary arteries awaiting surgical valve replacement underwent a comprehensive MRI examination that included assessment of left ventricular function, severity of valvular regurgitation, and presence of overt myocardial scar evidenced by delayed enhancement. For each patient, myocardial T1 relaxation times determined with a modified Look-Locker technique before and after contrast administration were compared with values previously established for 15 healthy volunteers.

The structure of the carboxyltransferase component of acetyl-coA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme.

Acetyl-coA carboxylase (ACC) is a central metabolic enzyme that catalyzes the committed step in fatty acid biosynthesis: biotin-dependent conversion of acetyl-coA to malonyl-coA. The bacterial carboxyltransferase (CT) subunit of ACC is a target for the design of novel therapeutics that combat severe, hospital-acquired infections resistant to the established classes of frontline antimicrobials. Here, we present the structures of the bacterial CT subunits from two prevalent nosocomial pathogens, Staphylococcus aureus and Escherichia coli, at a resolution of 2.

Assessment of regional left ventricular function: accuracy and reproducibility of positioning standard short-axis sections in cardiac MR imaging.

The assessment of regional left ventricular (LV) function with cardiac magnetic resonance (MR) cine techniques requires a standardized section positioning. A simple selective short-axis method for selective positioning of three short-axis sections (basal, midcavity, apical) was tested for its accuracy, compared with accepted criteria, in 21 volunteers (mean age, 32 years +/- 11) and in 23 patients with myocardial infarction (mean age, 56 years +/- 12). Reproducibility of section positioning and of regional LV parameters was tested in the volunteers.

A comparison of left ventricular mass between two-dimensional echocardiography, using fundamental and tissue harmonic imaging, and cardiac MRI in patients with hypertension.

Purpose: To compare left ventricular mass (LVM) as measured by two-dimensional (2D) echocardiography using two different calculation methods: truncated ellipse (TE) and area length (AL), in both fundamental and tissue harmonic imaging frequencies, to LVM as measured by, the current gold standard, cardiac magnetic resonance imaging (MRI). Turbo gradient echo (TGE) pulse sequence was utilized for MRI.

Materials And Methods: Thirty-two subjects with history of hypertension were recruited.

Left ventricle mass index and the common, functional, X-linked angiotensin II type-2 receptor gene polymorphism (-1332 G/A) in patients with systemic hypertension.

A common intronic polymorphism, (-1332 G/A) of the angiotensin type-2 receptor gene, located on the X-chromosome, has been reported to be functional. The aim of our study was to evaluate this polymorphism for an association with left ventricular hypertrophy. Left ventricle (LV) mass was measured in 197 patients with systemic hypertension and 60 normal volunteers using a 1.

Cardiac MR imaging with external respirator: synchronizing cardiac and respiratory motion--feasibility study.

The feasibility of electrocardiography (ECG)-synchronized respiration with an external cuirass-type respirator in cardiac magnetic resonance (MR) imaging was evaluated. Cardiac MR imaging was performed in 10 nonsedated healthy volunteers with an ECG-triggered external respirator that was modified for use in the MR environment. Coronary MR angiograms and multiphase gradient-echo cine images were acquired with one respiratory cycle performed per cardiac cycle.

Comparison of right ventricular volume measurement between segmented k-space gradient-echo and steady-state free precession magnetic resonance imaging.

Purpose: To compare right ventricular volume measurements and their reproducibility between steady-state free precession (SSFP) and conventional turbo gradient-echo (TGE) imaging.

Materials And Methods: Right ventricular volumes and observer variabilities were compared between SSFP and TGE in 31 subjects (21 normal volunteers and 10 subjects with heart failure). For further internal validation of the right ventricular volumes, the left ventricle (LV) and right ventricle (RV) stroke volumes were compared for the normal volunteers.

Steady-state free precession magnetic resonance imaging of the heart: comparison with segmented k-space gradient-echo imaging.

Steady-state free precession imaging is a promising technique for cardiac magnetic resonance imaging (MRI), as it provides improved blood/myocardial contrast in shorter acquisition times compared with conventional gradient-echo acquisition. The better contrast could improve observer agreement and automatic detection of cardiac contours for volumetric assessment of the ventricles, but measurements might differ from those obtained using conventional methods. We compared volumetric measurements, observer variabilities, and automatic contour detection between a steady-state free precession imaging sequence (BFFE = balanced fast field echo) and segmented k-space gradient-echo acquisition (TFE = turbo field echo) in 41 subjects.

Colicin pore-forming domains bind to Escherichia coli trimeric porins.

Colicin N kills sensitive Escherichia coli cells by first binding to its trimeric receptor (OmpF) via its receptor binding domain. It then uses OmpF to translocate across the outer membrane and in the process it also needs domains II and III of the protein TolA. Recent studies have demonstrated sodium dodecyl sulfate- (SDS) dependent complex formation between trimeric porins and TolA-II.

Effect of mutation of lysine-128 of the large subunit of ribulose bisphosphate carboxylase/oxygenase from Anacystis nidulans.

The contribution of lysine-128 within the active site of Anacystis nidulans d-ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.

Displacement of OmpF loop 3 is not required for the membrane translocation of colicins N and A in vivo.

The pore-forming colicins N and A require the porin, OmpF, in order to translocate across the outer membrane of Escherichia coli. We investigated the hypothesis that in vivo, colicins N and A may traverse the outer membrane through the OmpF channel. In order to accommodate a polypeptide in the pore, the mid-channel constriction loop of OmpF, L3, would need to undergo a conformational change.

Voltage gating is a fundamental feature of porin and toxin beta-barrel membrane channels.

Beta-barrel pores are found in outer membrane porins of gram-negative bacteria, bacterial toxins and mitochondrial channels. Apart from the beta-barrel the three groups show no close sequence or structural homology but these pores exhibit symmetrical voltage gating when reconstituted into planar lipid bilayers. The structures of several of these are known and many site-directed mutants have been examined.

Discovery of critical Tol A-binding residues in the bactericidal toxin colicin N: a biophysical approach.

Colicins translocate across the Escherichia coli outer membrane and periplasm by interacting with several receptors. After first binding to outer membrane surface receptors via their central region, they interact with TolA or TonB proteins via their N-terminal regions. Finally, the toxic C-terminal region is inserted into or across the cytoplasmic membrane.