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Biomedical subjects

John West

Publications and source records attributed to John West.

14 recordsLinked to original sources
PubMed2006

Role of a conserved tripeptide in the endodomain of Sindbis virus glycoprotein E2 in virus assembly and function.

Envelopment of Sindbis virus (SV) at the plasma membrane begins with the interaction of the E2 glycoprotein endodomain with a hydrophobic cleft in the surface of the pre-assembled nucleocapsid. The driving force for this budding event is thought to reside in this virus type-specific association at the surface of the cell. The specific amino acids involved in this interaction have not been identified; however, it has been proposed that a conserved motif (TPY) at aa 398-400 in the E2 tail plays a critical role in this interaction. This interaction has been examined with virus containing mutations at two positions in this conserved domain, T398A and Y400N. The viruses produced have very low infectivity (as determined by particle : p.f.u. ratios); however, there appears to be no defect in assembly, as the virus has wild-type density and electron microscopy shows assembled particles with no obvious aberrant structural changes. The loss of infectivity in the double mutant is accompanied by the loss of the ability to fuse cells after brief exposure to acid pH. These data support the idea that these residues are vital for production of infectious/functional virus; however, they are dispensable for assembly. These results, combined with other published observations, expand our understanding of the interaction of the E2 endodomain with the capsid protein.

Acids↗
PubMed2006

Endodontic update 2006.

The past 10 years have witnessed more significant changes in the art and science of endodontics than the previous 100 years. This observation is no surprise, given that change is our only constant. The rate of change, however, has been anything but constant. The rate has accelerated so fast that all clinicians in the field of dentistry need a reliable source to guide us in what works. What works today in endodontics is the theme of this update. The discoveries and advancements in endodontic technology, instruments, and materials enable practitioners to achieve treatment outcomes that were previously considered unattainable. For example, in nonsurgical endodontic treatment, nickel titanium technology consistently can produce predictable radicular preparations that can be easily obturated. In nonsurgical re-treatment, the previous endodontic obturation attempt frequently can be removed and successfully re-treated largely because of enhanced vision and coaxial lighting from the operating microscope. Importantly, careful nonsurgical re-treatment usually can be accomplished without disruption to the existing restorations and without risk to ferrule integrity. In endodontic surgery underfilled foramina, and the isthmi between them, predictably can be connected and obturated with state-of-the-art miniature instruments. CLINICAL SIGNIFICANCE This article reviews the clinical endodontic breakthroughs encountered during the last decade and focuses on three primary topics: (1) finding canals; (2) following canals; and (3) finishing canals. Every day, dentists are faced with the interdisciplinary treatment planning question of to "save or not to save a tooth?" Dentists must routinely make the decision of whether to remove or restore the tooth based on biology, structure, function, esthetics, and value.(1) Occasionally, the endodontically treated tooth can be the weakest link in the restorative and esthetic sequence. This article examines the current state of endodontic technology, as well as the fundamentals of endodontic mechanics needed to achieve the most predictable endodontic outcome with the highest degree of success.

Dental Equipment↗
PubMed2006

Mutations in the endodomain of Sindbis virus glycoprotein E2 define sequences critical for virus assembly.

Envelopment of Sindbis virus at the plasma membrane is a multistep process in which an initial step is the association of the E2 protein via a cytoplasmic endodomain with the preassembled nucleocapsid. Sindbis virus is vectored in nature by blood-sucking insects and grows efficiently in a number of avian and mammalian vertebrate hosts. The assembly of Sindbis virus, therefore, must occur in two very different host cell environments. Mammalian cells contain cholesterol which insect membranes lack. This difference in membrane composition may be critical in determining what requirements are placed on the E2 tail for virus assembly. To examine the interaction between the E2 tail and the nucleocapsid in Sindbis virus, we have produced substitutions and deletions in a region of the E2 tail (E2 amino acids 408 to 415) that is initially integrated into the endoplasmic reticulum. This sequence was identified as being critical for nucleocapsid binding in an in vitro peptide protection assay. The effects of these mutations on virus assembly and function were determined in both vertebrate and invertebrate cells. Amino acid substitutions (at positions E2: 408, 410, 411, and 413) reduced infectious virus production in a position-dependent fashion but were not efficient in disrupting assembly in mammalian cells. Deletions in the E2 endodomain (delta406-407, delta409-411, and delta414-417) resulted in the failure to assemble virions in mammalian cells. Electron microscopy of BHK cells transfected with these mutants revealed assembly of nucleocapsids that failed to attach to membranes. However, introduction of these deletion mutants into insect cells resulted in the assembly of virus-like particles but no assayable infectivity. These data help define protein interactions critical for virus assembly and suggest a fundamental difference between Sindbis virus assembly in mammalian and insect cells.

Amino Acid Sequence↗
PubMed2006

Rules of engagement: mastering the endodontic game, part 2.

The rules of engagement are an overview of the essential elements needed to reconstruct endodontically volved teeth back to successful, healthy members of the dental arch that function and are biologically healthy, structurally strong, aesthetic, and valuable. Endodontics just keeps getting better and better, and the future of endodontic success is bright. Now more than ever patients value and appreciate dental aesthetics. Everyone wants to look good, smell good, and appear successful. Teeth will always play a major role in these human desires. The endodontic tooth can either be the "weakest link" or it can be as strong a link as any other healthy tooth. The choice is ours...if we play by the rules.

Edetic Acid↗
PubMed2006

Progressive taper technology: rationale and clinical technique for the new ProTaper universal system.

ProTaper Universal has produced a comprehensive yet simple solution for dentists in search of a single, versatile system that solves major endodontic problems from access to obturation. The key in high-performance endodontics is to produce the most and the best while doing the least. We know this as leverage. Breakthrough safety and simplicity features, combined with optimum efficiency, are at the heart of ProTaper Universal. The net intentional result of these newest endodontic technologies is that the practitioner can predictably and consistently produce exceptional patient outcomes (Figures 15 to 20).

Dental Alloys↗
PubMed2005

The drop-jump screening test: difference in lower limb control by gender and effect of neuromuscular training in female athletes.

BACKGROUND: A valgus lower limb alignment has been noted during noncontact anterior cruciate ligament injuries. A video drop-jump test can indicate an athlete's ability to control lower limb axial alignment in the coronal plane. HYPOTHESES: Female athletes have decreased knee separation distances on landing and acceleration; male athletes have a neutrally aligned lower limb position. A neuromuscular training program will significantly increase knee separation distance in female athletes. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The authors tested 325 female and 130 male athletes aged 11 to 19 years. The distance between the hips, knees, and ankles was measured during a drop-jump test. The separation distance between the knees and ankles was normalized by the hip separation distance. A neuromuscular training program (Sportsmetrics) was completed by 62 female athletes, and their jump-landing characteristics were reexamined. RESULTS: A marked decrease in knee separation distance was found on takeoff in 80% of female athletes and in 72% of male athletes. There was no difference between male and female athletes in the normalized knee and ankle separation distance during the landing and takeoff phases. The knee separation distance on landing was 23 +/- 9 cm in the female athletes and 22 +/- 8 cm in the male athletes. The normalized knee separation distance was 51% +/- 19% in the female athletes and 51% +/- 15% in the male athletes. After training, statistically significant increases were found in the female athletes in the knee separation distance on landing (29 +/- 8 cm, P < .0001) and in the normalized knee separation distance (68% +/- 18%, P < .0001). The trained female athletes had significantly greater knee separation distance and normalized knee separation distance than did the males (P < .0001). CONCLUSIONS: The majority of untrained female and male athletes demonstrated a valgus alignment appearance on the video test. After neuromuscular training, female athletes had improved knee separation distances and a more neutral lower limb alignment on landing and takeoff.

Adolescent↗
PubMed2005

Opening wedge tibial osteotomy: the 3-triangle method to correct axial alignment and tibial slope.

BACKGROUND: Although a change in tibial slope may occur during a medial opening wedge osteotomy, calculations have not been defined to address this problem. The authors investigated geometric factors important to correct axial alignment and tibial slope during osteotomy. PURPOSE: To calculate, through 3-dimensional analysis of the proximal tibia, how the angle of the opening wedge along the anteromedial tibial cortex influences the tibial slope (sagittal plane) and valgus correction (coronal plane) during osteotomy, and to analyze the different radiographic methods reported in the literature to measure medial and lateral tibial slope. The authors postulated that differences in reported normal values of tibial slope in the sagittal plane were technique dependent. STUDY DESIGN: Descriptive laboratory study. METHODS: The proximal anteromedial tibial cortex obliquity on magnetic resonance imaging was measured in 35 knees. Serial computed tomography images of the proximal tibia were digitized, allowing a series of virtual opening wedge osteotomies to be performed. Algebraic calculations defined the effect of an opening wedge osteotomy on the anteromedial tibial cortex opening wedge angle, sagittal tibial slope angle, and coronal valgus alignment. RESULTS: The anteromedial tibial cortex oblique angle at the medial osteotomy site was 45 degrees +/- 6 degrees and determined, along with the degrees of valgus correction, the degrees of the opening wedge angle in the oblique plane. The anterior osteotomy gap at the tibial tubercle was generally one half of the posteromedial gap to maintain the normal sagittal tibial slope. Every millimeter of gap error at the tibial tubercle resulted in approximately 2 degrees of change in the tibial slope. The width of the buttress plate along the anteromedial tibial cortex was 2 to 3 mm less than the computed coronal valgus posteromedial osteotomy gap to achieve tibiofemoral valgus correction. CONCLUSIONS: A series of measurements preoperatively and intraoperatively are required to obtain the desired correction of tibial slope and valgus alignment.

Adolescent↗
PubMed2004

Conformational and substituent effects in the 19F spectra of C7-C10 straight-chain chlorofluoroalkanes.

One- and two-dimensional fluorine NMR spectra of straight-chain chlorofluoroalkanes having 7-10 carbons were obtained and interpreted. Spectral assignments were based primarily on indirect spin-spin correlations. A scale of chlorine substituent effects was developed. The effects of asymmetric CFCl centers on chemical-shift differences in nearby CF2 groups were analyzed in terms of molecular conformational effects. Spin-spin coupling patterns of CF3 groups were elucidated.

Journal Article↗
PubMed2004

Response of antioxidant enzymes and redox metabolites to cadmium-induced oxidative stress in CRL-1439 normal rat liver cells.

Cadmium is a non-physiological heavy metal released into the environment and workplace as a result of industrial, municipal, and agricultural activities. The association of Cd with pulmonary, prostatic and testicular cancer may be related to the ability of Cd to induce oxidative stress, which could in turn cause oxidative damage to DNA. This study examines the response of antioxidant enzymes and metabolites to Cd-induced oxidative stress in normal liver cells. We found a definite concentration-dependent increase in ROS when CRL-1439 normal liver cells were exposed to various concentrations of Cd2+ (100-300 microM). An increase in ROS production is an indication of oxidative stress, which is known to impact on the performance of antioxidant enzymes and metabolites in the cell. In fact, we found that superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) lost activities upon a 4-h exposure of liver cells to levels of Cd2+ ranging from 100 to 300 microM. After exposure of cells for 8 h, the activity of SOD and GPx increased while those of CAT and GR decreased substantially. The metabolites glutathione (GSH), oxidized glutathione (GSSG) and total thiols showed a decrease in concentration after 4 or 8 h of incubation of liver cells with Cd (100-300 microM). Malondialdehyde (MDA) on the other hand, showed an increase in concentration after 4-8 h of incubation of liver cells with Cd due to lipid peroxidation. The relationships of these fluxes to oxidative stress as well as intracellular redox homeostasis are discussed.

Animals↗
PubMed2003

Progressive truncations C terminal to the membrane-spanning domain of simian immunodeficiency virus Env reduce fusogenicity and increase concentration dependence of Env for fusion.

The simian immunodeficiency virus (SIV) transmembrane (TM) protein, gp41, has multiple functions, which include anchoring the glycoprotein complex in the lipid envelope of the virus and mediating fusion of the virus and host cell membranes. Recently, a series of mutants of the SIVmac239 TM protein that have truncations at the carboxyl terminus of the membrane-spanning domain (MSD) have been characterized (J. T. West, P. Johnston, S. R. Dubay, and E. Hunter, J. Virol. 75:9601-9612, 2001). These mutants retained membrane anchorage but demonstrated reduced fusogenicity and infectivity as the MSD length was shortened. We have established a novel three-color fluorescence assay, which allows qualitative confocal and quantitative flow cytometric analyses, to further characterize the nature of the fusion defect in five of the MSD mutants: TM185, TM186, TM187, TM188, and TM189. Our analysis showed that each mutant could mediate complete lipid and aqueous dye transfer at early time points after effector and target cell mixing. No hemifusion with only lipid dye flux was detected. However, another intermediate fusion stage, which appears to involve small-fusion-pore formation that allowed small aqueous dye transfer but prevented the exchange of large cytoplasmic components, was identified infrequently in mutant-Env-expressing cell and target cell mixtures. Quantitative flow cytometric analysis of these mutants demonstrated that the TM187, TM188, and TM189 mutants were significantly more fusogenic than TM185 and TM186 but remained significantly impaired compared to the wild type. Moreover, fusion efficiency showed an increased dependence on the expression level of glycoproteins, suggesting that, for these mutants, formation of an active fusion complex was an increasingly stochastic event.

Animals↗
PubMed2002

The angiotensin-converting enzyme gene I/D polymorphism and heart rate variability following acute myocardial infarction.

AIMS: Heart rate variability (HRV) is a measure of cardiac autonomic control and is therefore subject to regulation by the renin-angiotensin system. The primary objective of this study was to determine the effect of an insertion/deletion polymorphism within the angiotensin-converting enzyme (ACE) gene on HRV in the early stages after a myocardial infarction at a time when cardiac autonomic control is deranged. The secondary objective was to determine whether this polymorphism affected the HRV response to inhibition of ACE. MAJOR FINDINGS: 149 Caucasian subjects were studied 25 +/- 16 h following MI using time and frequency domain measures of HRV derived from two 5-minute ECG recordings. Recordings were repeated at 182 +/- 65 h following MI, when subjects had been stabilised on ramipril 2.5 mg bd. The study included 46 subjects with the DD genotype, 69 with the ID genotype, and 34 with the II genotype. No effect of the I/D polymorphism on short-term recordings of HRV was found. There was no difference in HRV response to the introduction of ramipril according to the genotypes. PRINCIPAL CONCLUSIONS: The I/D polymorphism within the ACE gene does not influence HRV after MI or the HRV response to ACE inhibitor therapy with ramipril. These findings may reflect the relative lack of importance of the I/D polymorphism and ACE activity in determining plasma and tissue angiotensin II concentration after a major stimulus to the renin-angiotensin system as occurs after myocardial infarction.

Aged↗