Biomedical subjects

N B Wood

Publications and source records attributed to N B Wood.

At least 19 recordsLinked to original sources

PubMed2006

Curvature and tortuosity of the superficial femoral artery: a possible risk factor for peripheral arterial disease.

Atherosclerosis in the superficial femoral artery (SFA) resulting in peripheral arterial disease is more common in men than women and shows a predilection for the region of the adductor canal. Blood flow patterns are related to development of atherosclerosis, and we investigated if curvature and tortuosity of the femoral artery differed between young men and women and if differences resulted in adverse flow patterns. Magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) were combined in 18 young adult volunteers (9 men) to assess the relationship of flow features to likely sites of future atherosclerosis formation. Subjects underwent MRI of the right SFA, three-dimensional vascular geometry was reconstructed, and measures of tortuosity and curvature were calculated. Tortuosity and curvature were significantly greater for men than women, and this was related to increased body surface area, body mass index, or weight in men. In both sexes, "tortuosity" increased from the midthigh to the popliteal fossa. The greatest curvature was found within the distal quarter of the SFA. CFD modeling was undertaken on MRI-based reconstructions of the SFA. Wall shear stresses (WSS) were extracted from the computations. WSS showed greater spatial variation in the men than in the women, and the men exhibited lower mean WSS. These data indicate that sex differences related to body size and anatomical course of the femoral artery may contribute to the enhanced risk of focal atherosclerosis in the adductor canal.

Adult↗

PubMed2004

Ultrasound image-based computer model of a common carotid artery with a plaque.

Ultrasound scans were acquired from a common carotid artery in a patient with an early atherosclerotic plaque forming a mild asymmetrical stenosis. The 3D vascular geometry of the diseased arterial segment was reconstructed from a series of 2D cross-sectional images, and computational meshes for the flow and wall domains were developed. Numerical flow simulations incorporating coupled fluid-solid interaction were implemented using flow and pressure waveforms measured in vivo. The effects of wall distensibility were investigated by comparing the predictions obtained with different wall compliance, one with 'natural' compliance and another with a stiffer wall. Limited flow separation was predicted in the post-stenotic zone. The non-uniform thickness of the diseased wall restricted the wall motion locally and re-distributed the stress, giving raised concentrations at the plaque shoulders.

Blood Flow Velocity↗

PubMed2001

Combined MR imaging and CFD simulation of flow in the human descending aorta.

A combined MR and computational fluid dynamics (CFD) study is made of flow in the upper descending thoracic aorta. The aim was to investigate further the potential of CFD simulations linked to in vivo MRI scans. The three-dimensional (3D) geometrical images of the aorta and the 3D time-resolved velocity images at the entry to the domain studied were used as boundary conditions for the CFD simulations of the flow. Despite some measurement uncertainties, comparisons between simulated and measured flow structures at the exit from the domain demonstrated encouraging levels of agreement. Moreover, the CFD simulation allowed the flow structure throughout the domain to be examined in more detail, in particular the flow separation region in the distal aortic arch and its influence on the downstream flow during late systole. Additional information such as relative pressure and wall shear stress, which could not be measured via MRI, were also extracted from the simulation. The results have encouraged further applications of the methods described. J. Magn. Reson. Imaging 2001;13:699-713.

Adult↗

PubMed2001

Computational flow modeling of the left ventricle based on in vivo MRI data: initial experience.

A combined computational fluid dynamics (CFD) and magnetic resonance imaging (MRI) methodology has been developed to simulate blood flow in heart chambers, with specific application in the present study to the human left ventricle. The proposed framework employs MRI scans of a human heart to obtain geometric data, which are then used for the CFD simulations. These latter are accomplished by geometrical modeling of the ventricle using time-resolved anatomical slices of the ventricular geometry and imposition of inflow/outflow conditions at orifices notionally representing the mitral and aortic valves. The predicted flow structure evolution and physiologically relevant flow characteristics were examined and compared to existing information. The CFD model convincingly captures the three-dimensional contraction and expansion phases of endocardial motion in the left ventricle, allowing simulation of dominant flow features, such as the vortices and swirling structures. These results were qualitatively consistent with previous physiological and clinical experiments on in vivo ventricular chambers, but the accuracy of the simulated velocities was limited largely by the anatomical shortcomings in the valve region. The study also indicated areas in which the methodology requires improvement and extension.

Adult↗

PubMed1999

Aspects of fluid dynamics applied to the larger arteries.

A review is given of some of the ideas from fluid mechanics which are considered essential background for researchers in cardiovascular flows. The paper links the topics discussed at a fundamental level with real problems which, in the experience of the author, occur in research. In particular, approximate equations governing the principal phenomena, and which help with understanding, are introduced. A description is given of the equations of motion and the significance of similarity parameters is discussed: it is shown how Reynolds number and the Womersley parameter arise from dimensionless forms of the equations. Steady flow equations and approximations are commented on, including illustrations of their use. Unsteady flow phenomena are introduced and it is shown how Stokes' first and second problems illustrate key aspects of unsteady viscous diffusion and boundary layers in the circulation. Important features of pulsatile pipe flow, as analysed by both Uchida and Womersley, are discussed and linked to Stokes' two-dimensional results. Entrance effects in steady and unsteady pipe flow are compared and contrasted. Other phenomena discussed include the effects of bends in vessels, transition to turbulence and the different time-scales associated with unsteady flows. Computational methods, which are assuming increasing importance in biological fluid mechanics, also receive a brief description. Finally, comments are made on pressure and other measurements and the need for an understanding of various fluid flow phenomena when planning measurements and interpreting the resulting data.

Animals↗

PubMed1998

Tumor angiogenesis and p53 mutations: prognosis in head and neck cancer.

OBJECTIVES: To assess how p53 gene mutations and microvessel density (MVD) may be used as prognostic markers for the study and management of head and neck squamous cell carcinomas and to investigate putative associations between p53 gene mutations and MVD and the relationship of these factors to tumor response to radiotherapy and/or chemotherapy at 6 weeks. PATIENTS AND DESIGN: Thirty-nine patients with squamous cell carcinoma of the head and neck, stages I to IV, who were examined at Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill, and its affiliated hospitals between 1993 and 1995 were monitored. Mutations in the p53 gene were identified by microdissection of tumor cells on frozen sections, followed by single-strand conformation polymorphism analysis of the products of polymerase chain reaction amplification of exons 5 to 9. The microvessels were immunostained with monoclonal antibodies to factor VIII and/or CD31. Microvessel counts were done by 2 investigators blinded to each other's counts and to the p53 gene status. Intratumoral or peritumoral microvascular "hot spots" were assessed and counts were done with an ocular grid in 3 x 200 fields of hot spots by each investigator. The mean of the highest values was considered. Statistical analysis was done with the Wilcoxon rank sum test, the log-rank test, and proportional hazard models. RESULTS: Of the 39 patients, 13 had mutations in exons 5 to 9. Mutations in the p53 gene were associated with unfavorable overall (P=.003) and disease-free (P=.02) survival. A strong inverse relationship was seen between MVD and p53 mutations (P=.01). No statistically significant relationship was seen between mean MVD and overall and disease-free survival. The response to therapy differed significantly (P=.03) by p53 mutations, whereas there was no statistical significance with MVD counts. CONCLUSION: In this study a strong inverse relationship was seen between MVD and p53 mutations. p53 Mutations in exons 5 through 9 were associated with unfavorable survival, whereas MVD showed no association with survival.

Adult↗

PubMed1998

Regulators of proliferation and apoptosis in carcinoma of the larynx.

Expression of interrelated gene products regulating cell proliferation and apoptosis may be disordered in squamous cell carcinoma (SCC) of the larynx compared with normal squamous mucosa. Certain of these abnormalities, alone or in combination, may be of prognostic significance in low-stage carcinomas of the larynx. A retrospective study of archival material was made. Expression of the Bcl-2 family of apoptosis-related genes (bcl-2, bcl-X, mcl-1, and bax) and the proliferation- and apoptosis-related genes p53 and cyclin D-1 were determined in 40 low-T-stage laryngeal carcinomas and in uvular epithelium from patients without SCC. Among the antiapoptotic members of the Bcl-2 family, Bcl-X and Mcl-1 showed more intense and widespread staining than Bcl-2 itself in both normal squamous mucosa and SCC. The well-ordered expression patterns of Bcl-2-related proteins found in normal epithelium were lost in SCC, and patterns of expression varied widely among individual tumors. Also, mean expression levels for Bax and cyclin D-1 were significantly lower than in normal epithelium (P = .036 and P = .009, respectively), whereas expression of p53 was higher in tumors (P = .034). Expression of Bcl-X and Mcl-1 was greater in poorly differentiated than in well-differentiated tumors (P = .014 and P = .031, respectively). No associations were seen between marker expression patterns and clinical outcome in this group of patients. Bcl-x and Mcl-1 appear to be the most abundantly expressed antiapoptotic proteins of the Bcl-2 family in both normal squamous mucosa and SCC of the larynx. Multiple genes regulating proliferation and apoptosis are expressed abnormally in laryngeal SCC compared with normal epithelium. In particular, loss or measurable decrease in expression of the proapoptotic protein Bax in tumors may contribute to the deranged growth control of SCC. Further study is needed to evaluate the prognostic significance of particular patterns of disordered expression of proteins regulating proliferation and apoptosis in SCC of different head and neck sites.

Adult↗

PubMed1997

Mutation of p53 in squamous cell cancer of the head and neck: relationship to tumor cell proliferation.

Rapid proliferation of squamous cell carcinomas of the head and neck (SCCHN) during therapy may contribute to treatment failure. We have investigated the presence of p53 abnormalities in patients with SCCHN as a correlate of proliferation rate and other pathologic and clinical variables. p53 Mutation, as determined by polymerase chain reaction and single-strand conformation polymorphism analysis of microdissected frozen sections of tumor biopsies, was significantly associated with a high labeling index, as determined by in vivo infusion of IUdR and BrdU (P = 0.017). p53 Protein expression was detected by immunohistochemistry with two different antibodies, followed by quantitative image analysis. Many cases exhibited strong p53 protein expression in the absence of mutations within the conserved region of the gene, and expression was not related to proliferation. The presence of p53 mutations was related to tumor differentiation in this group of patients.

Adult↗

PubMed1996

Computation of flow pressure fields from magnetic resonance velocity mapping.

Magnetic resonance phase velocity mapping has unrivalled capacities for acquiring in vivo multi-directional blood flow information. In this study, the authors set out to derive both spatial and temporal components of acceleration, and hence differences of pressure in a flow field using cine magnetic resonance velocity data. An efficient numerical algorithm based on the Navier-Stokes equations for incompressible Newtonian fluid was used. The computational approach was validated with in vitro flow phantoms. This work aims to contribute to a better understanding of cardiovascular dynamics and to serve as a basis for investigating pulsatile pressure/flow relationships associated with normal and impaired cardiovascular function.

Algorithms↗

PubMed1994

PCR production of a digoxigenin-labeled probe for the detection of human cytomegalovirus in tissue sections.

In situ hybridization (ISH) provides a means for identifying viral genomes in the context of tissue pathology. We have developed a specific and sensitive ISH probe for the detection of cytomegalovirus (CMV) DNA in formalin-fixed, paraffin-embedded tissue sections. Digoxigenin-11-dUTP was incorporated into a 435-base pair fragment of the CMV Major Immediate Early (MIE) gene with use of the polymerase chain reaction (PCR). Hybridized probe was detected by reaction with antidigoxigenin antibody coupled to alkaline phosphatase and chromogenic substrates. This method has detected CMV infection in routine clinical specimens from a variety of tissue types, including colon, kidney, liver, and stomach. Infection in cells with and without characteristic inclusions is revealed with this probe. The background is so low that single infected cells are detected unambiguously. No cross-hybridization was observed with cells infected with other viruses of Herpesviridae. This approach may be useful for producing probes for the detection of other viral genomes in tissue sections.

Base Sequence↗

PubMed1989

Growth and characterization of epithelial cells from normal human uterine ectocervix and endocervix.

The human uterine cervix consists of an endocervical canal lined with a single layer of columnar mucus-secreting cells and an outer ectocervix covered by a stratified squamous epithelium. We report here the culture of human endocervical epithelial cells (HEnE) and human ectocervical epithelial cells (HEcE) in serum-free medium (KGM). Both HEnE and HEcE cultures were composed of keratinocytelike cells which formed desmosomal contacts and stratified in the presence of high concentrations of calcium ions. Cells with a pleomorphic epithelial morphology were observed in HEnE cultures, but not in HEcE cultures. Keratin 18, which is characteristic of endocervix in vivo, was detected by indirect immunofluorescent staining in all HEnE cells but was never detected in cultured HEcE. HEcE expressed keratin 13 which is characteristic of ectocervix in vivo. Although keratin 13 was never detected in primary HEnE cultures, it was expressed in passaged HEnE cultures grown in medium with high concentrations of calcium and in late passage HEnE cultures. HEnE underwent an average of 15.1 population doublings during serial culture. Mean colony-forming efficiency during Passages 2 to 3 was 14.7% and mean population doubling time was 17.8 h. HEcE cultures underwent significantly more population doublings (29.0) than HEnE cultures, whereas colony-forming efficiencies and doubling times were similar to those determined for HEnE. HEnE and HEcE cells may be useful in developing in vitro models of cervical squamous metaplasia and for exploring the interactions between target cell differentiation, carcinogens, and papillomaviruses in the development of cervical neoplasia.

Antibodies, Monoclonal↗

PubMed1980

Control of phycobiliprotein proteolysis and heterocyst differentiation in Anabaena.

Phycobiliprotein degradation can be initiated in cultures of the cyanobacterium Anabaena by removal of combined nitrogen from the medium. Certain strains of Anabaena differentiate cells specialized for aerobic nitrogen fixation (heterocysts) under such conditions. We describe here a procedure for the preparation of extracts from heterocysts or vegetative cells that contain an activity capable of degrading only the phycobiliproteins in a mixture of soluble Anabaena proteins in vitro. This activity increased under nitrogen starvation conditions or in ammonia-replete cultures treated with the glutamine synthetase inhibitor methionine sulfoximine. The increase in activity induced by nitrogen starvation was prevented by chloramphenicol or by carbon starvation. Under all these conditions, phycobiliprotein degradative activity assayed in vitro was correlated with the loss of phycobiliprotein absorbance in vivo. Finally, starvation of a met auxotroph of Anabaena for methionine (in the presence of ammonia) did not induce phycobiliprotein degradation in vivo or the increase in proteinase activity. Together with direct measurements of ppGpp, these results indicate that proteolysis in Anabaena is not controlled by compounds associated with the stringent response in Escherichia coli. Since the increase in proteinase activity appears to be regulated by the same variables that control heterocyst differentiation, the activity should provide a useful biochemical marker for the early events of differentiation.

Adenosine Triphosphate↗

PubMed1976

Structure of Caulobacter deoxyribonucleic acid.

The deoxyribonucleic acid of the dimorphic bacterium Caulobacter crescentus contains a component that renatures with rapid, unimolecular kinetics. This component was present in both swarmer and stalked cells and exhibited the sensitivity to endonuclease S1 expected for hairpin loops. Double-stranded side branches between 100 and 600 nucleotide pairs in length were visible in electron micrographs of rapidly reassociating deoxyribonucleic acid isolated by hydroxyapatite chromatography. No extrachromosomal elements were found in spite of systematic attempts to detect their presence. These results indicate that the rapidly reassociating fraction derives from inverted repeat sequences within the chromosome and not from cross-links or plasmids. We estimate that there are approximately 350 inverted repeat regions per Caulobacter genome. The kinetic complexity of Caulobacter deoxyribonucleic acid, however, is no greater than that of other bacteria.

Bacteria↗

PubMed1971