Biomedical subjects

William P Taylor

Publications and source records attributed to William P Taylor.

4 recordsLinked to original sources

PubMed2006

Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease.

VX-950 is a potent, selective, peptidomimetic inhibitor of the hepatitis C virus (HCV) NS3-4A serine protease, and it demonstrated excellent antiviral activity both in genotype 1b HCV replicon cells (50% inhibitory concentration [IC50] = 354 nM) and in human fetal hepatocytes infected with genotype 1a HCV-positive patient sera (IC50 = 280 nM). VX-950 forms a covalent but reversible complex with the genotype 1a HCV NS3-4A protease in a slow-on, slow-off process with a steady-state inhibition constant (K(i)*) of 7 nM. Dissociation of the covalent enzyme-inhibitor complex of VX-950 and genotype 1a HCV protease has a half-life of almost an hour. A >4-log10 reduction in the HCV RNA levels was observed after a 2-week incubation of replicon cells with VX-950, with no rebound of viral RNA observed after withdrawal of the inhibitor. In several animal species, VX-950 exhibits a favorable pharmacokinetic profile with high exposure in the liver. In a recently developed HCV protease mouse model, VX-950 showed excellent inhibition of HCV NS3-4A protease activity in the liver. Therefore, the overall preclinical profile of VX-950 supports its candidacy as a novel oral therapy against hepatitis C.

Administration, Oral↗

PubMed2003

Laminectomy contributes to cervical spine deformity demonstrated by holographic interferometry.

Multiple factors contribute to the pathogenesis of postlaminectomy deformity and instability of the cervical spine. The complex alterations in both static and dynamic biomechanics after laminectomy are incompletely defined. We sought to examine the role of the lamina in compressive load bearing across the vertebral body. Holographic interferometry was used to study the surface deformation of single axially loaded cervical vertebral bodies before and after hemilaminotomy, hemilaminectomy, and experimental acrylic laminar reconstruction. Our results showed that hemilaminotomy did not alter the surface deformation because of axial loading across the cervical vertebral body. However, gross alterations in surface deformation across the cervical vertebral body were consistently observed after hemilaminectomy. Experimental reconstruction of the laminar arch using acrylic restored the deformation pattern to the prelaminectomized baseline. Our results support a role for the lamina and the integrity of the laminar arch in axial load bearing across the cervical vertebral body. The altered axial load bearing may be a significant contributor to postlaminectomy deformity and instability. These findings offer an additional biomechanical advantage to minimal bony intervention for cervical spine pathology.

Acrylic Resins↗

PubMed2002

KpsF is the arabinose-5-phosphate isomerase required for 3-deoxy-D-manno-octulosonic acid biosynthesis and for both lipooligosaccharide assembly and capsular polysaccharide expression in Neisseria meningitidis.

We have identified and defined the function of kpsF of Neisseria meningitidis and the homologues of kpsF in encapsulated K1 and K5 Escherichia coli. KpsF was shown to be the arabinose-5-phosphate isomerase, an enzyme not previously identified in prokaryotes, that mediates the interconversion of ribulose 5-phosphate and arabinose 5-phosphate. KpsF is required for 3-deoxy-d-manno-octulosonic acid (Kdo) biosynthesis in N. meningitidis. Mutation of kpsF or the gene encoding the CMP-Kdo synthetase (kpsU/kdsB) in N. meningitidis resulted in expression of a lipooligosaccharide (LOS) structure that contained only lipid A and reduced capsule expression in the five invasive disease-associated meningococcal serogroups (A, B, C, Y, and W-135). The step linking meningococcal capsule and LOS biosynthesis was shown to be Kdo production as the expression of capsule was wild type in a Kdo transferase (kdtA) mutant. Thus, in addition to lipooligosaccharide assembly, Kdo is required for meningococcal capsular polysaccharide expression. Furthermore, N. meningitidis, unlike enteric Gram-negative bacteria, can survive and synthesize only unglycosylated lipid A.

Aldose-Ketose Isomerases↗

PubMed2002

Rinderpest.

Rinderpest, also known as cattle plague, was for centuries the most dreaded bovine plague known and one that changed the course of history and still seriously compromises trade. It can lay waste not only to farming communities but the wildlife heritage of countries also is threatened because its broad host spectrum extends across cattle, Asian buffaloes, yaks, and many other artiodactyls, both domesticated and wild, including swine. This article provides a brief history of rinderpest before describing its clinical, pathologic, epidemiologic, and diagnostic features. In dealing with control, the prospects for total eradication are described in the context of the Global Rinderpest Eradication Programme, which is on target to achieve that goal by 2010--the first time that an animal disease will have been eradicated.

Animals↗