Biomedical subjects

T McInerney

Publications and source records attributed to T McInerney.

9 recordsLinked to original sources

PubMed2000

Immunogenic and antigenic dominance of a nonneutralizing epitope over a highly conserved neutralizing epitope in the gp41 envelope glycoprotein of human immunodeficiency virus type 1: its deletion leads to a strong neutralizing response.

The Kennedy peptide, (731)PRGPDRPEGIEEEGGERDRDRS(752), from the cytoplasmic domain of the gp41 transmembrane envelope glycoprotein of HIV-1 contains a conformationally dependent neutralizing epitope (ERDRD) and a linear nonneutralizing epitope (IEEE). No recognized murine T cell epitope is present. The peptide usually stimulates virus-specific antibody, but this is not always neutralizing. Here we show that IEEE (or possibly IEEE plus adjacent sequence) is immunogenically and antigenically dominant over the ERDRD neutralizing epitope. Thus rabbits immunized in a variety of routes, doses, and adjuvants with a chimeric cowpea mosaic virus (CPMV) expressing the Kennedy peptide on its surface (CPMV-HIV/1) synthesized IEEE-specific serum antibody but no ERDRD-specific or HIV-1-neutralizing antibody. To test if this resulted from immunodominance or from a hole in the antibody repertoire, we immunized rabbits with chimera CPMV-HIV/29, which expresses the GERDRDR part of the Kennedy sequence. This chimera readily stimulated ERDRD-specific, neutralizing antibody. In mice the situation was less extreme, but individual animals with low neutralizing titers had a high ratio of IEEE-specific:ERDRD-specific antibody. Data are consistent with immunodominance of IEEE over ERDRD in the Kennedy peptide. IEEE-specific antibody was also antigenically dominant and prevented ERDRD-specific antibody from binding to its epitope and from neutralizing HIV-1. It may be that HIV-1 has evolved a nonneutralizing immunodominant epitope that allows it to possess a neutralizing epitope without suffering the consequences, and this idea is supported by the covariance of both epitope sequences. To our knowledge this is the first example of a defined sequence that controls the activity of an adjacent epitope.

Amino Acid Sequence↗

PubMed2000

T-snakes: topology adaptive snakes.

We present a new class of deformable contours (snakes) and apply them to the segmentation of medical images. Our snakes are defined in terms of an affine cell image decomposition (ACID). The 'snakes in ACID' framework significantly extends conventional snakes, enabling topological flexibility among other features. The resulting topology adaptive snakes, or 'T-snakes', can be used to segment some of the most complex-shaped biological structures from medical images in an efficient and highly automated manner.

Brain↗

PubMed1999

Topology adaptive deformable surfaces for medical image volume segmentation.

Deformable models, which include deformable contours (the popular snakes) and deformable surfaces, are a powerful model-based medical image analysis technique. We develop a new class of deformable models by formulating deformable surfaces in terms of an affine cell image decomposition (ACID). Our approach significantly extends standard deformable surfaces, while retaining their interactivity and other desirable properties. In particular, the ACID induces an efficient reparameterization mechanism that enables parametric deformable surfaces to evolve into complex geometries, even modifying their topology as necessary. We demonstrate that our new ACID-based deformable surfaces, dubbed T-surfaces, can effectively segment complex anatomic structures from medical volume images.

Algorithms↗

PubMed1998

Approaching physician recruitment systematically.

Physician recruitment has become increasingly competitive. Organizations that recruit physicians need to establish a systematic recruitment approach that includes determining the organization's recruitment objectives, using various recruiting sources, assessing the skills and "fit" of all candidates, explaining the benefits to candidates early in the process, checking references carefully, and acting quickly to make an offer. Following a systematic physician recruitment plan can help healthcare organizations hire the best person for the job.

Databases, Factual↗

PubMed1997

Deformable models and the analysis of medical images.

Deformable models are a popular and vigorously researched model-based approach to computer-assisted medical image analysis. The widely recognized efficacy of deformable models stem from their ability to segment, match and track images of anatomic structures by exploiting (bottom-up) constraints derived from the image data together with (top-down) a priori knowledge about the location, size and shape of structures of interest. Deformable models are capable of accommodating the often significant variability of biological structures over time and across different individuals. Furthermore, they support highly intuitive interaction mechanisms that allow medical scientists and practitioners to bring their expertise to bear on the model-based image interpretation task as necessary. In this paper we will review deformable models and present some recent developments in the methodology, including topologically adaptable deformable models, an approach that permits segmentation and reconstruction of topologically complex anatomical structures.

Computer Simulation↗

PubMed1996

Deformable models in medical image analysis: a survey.

This article surveys deformable models, a promising and vigorously researched computer-assisted medical image analysis technique. Among model-based techniques, deformable models offer a unique and powerful approach to image analysis that combines geometry, physics and approximation theory. They have proven to be effective in segmenting, matching and tracking anatomic structures by exploiting (bottom-up) constraints derived from the image data together with (top-down) a priori knowledge about the location, size and shape of these structures. Deformable models are capable of accommodating the significant variability of biological structures over time and across different individuals. Furthermore, they support highly intuitive interaction mechanisms that, when necessary, allow medical scientists and practitioners to bring their expertise to bear on the model-based image interpretation task. This article reviews the rapidly expanding body of work on the development and application of deformable models to problems of fundamental importance in medical image analysis, including segmentation, shape representation, matching and motion tracking.

Animals↗

PubMed1991

Probing the idiotype/anti-idiotype antibody interaction with a set of synthetic peptide homologues.

Anti-idiotypic (anti-Id) antibodies were raised against two murine monoclonal antibodies (mAb 1/1 and mAb 2/1) which recognise two distinct and well-characterised epitopes on a 24-residue synthetic peptide representing part of the haemagglutinin (HA) of influenza virus. A monoclonal anti-Id antibody, specific for mAb 2/1, could bind to mAb 2/1 when the paratope of the latter was occupied with peptide, indicating that this anti-Id antibody is directed to a framework idiotope. In contrast, an anti-Id mAb derived from mAb 1/1-immunised mice was inhibited in its binding to Id by the parent peptide and also by the heptapeptide NVPEKQT which constitutes the epitope recognised by mAb 1/1. The small size of this synthetic peptide eliminates the possibility of significant steric inhibition in the system, and establishes that this mAb is a true paratope-directed anti-Id antibody. The interaction of this anti-Id mAb with the paratope of mAb 1/1 in the presence of a set of peptide homologues of the epitope was also examined. A peptide as short as 5 residues, which contains two of the three irreplaceable residues of the epitope, could inhibit binding between the two mAbs.

Amino Acid Sequence↗

PubMed1989

Cross-reactions of nucleic acids with monoclonal antibodies to phosphatidylinositol phosphate and cholesterol.

Four monoclonal IgM antibodies to phosphatidylinositol phosphate (PIP), four antibodies to cholesterol and one antibody to liposomes containing phosphatidylcholine, cholesterol and dicetyl phosphate were tested for reactivity with denatured DNA. Three of four antibodies to PIP cross-reacted strongly with denatured DNA. The other antibodies did react with denatured DNA but only very weakly. The binding to DNA was competed by synthetic polynucleotides. In competitive assays, one of the anti-PIP antibodies was particularly reactive with poly(dT) and another with poly(I) and poly(dG). Binding of an anti-cholesterol antibody to ssDNA was also inhibited by poly(I) and poly(dG). Two of the anti-PIP antibodies were also reactive with mononucleotides, and all four bound inositol hexaphosphate. High concns of nucleosides did not compete for binding, indicating that phosphate is involved in the binding site. Phospholipids, particularly those containing inositol phosphate, also competed for binding to DNA, but to varying extents, indicating a variable overlap in the antibody binding site for DNA and phospholipid determinants. These antibodies, induced by immunization with liposomes, showed cross-reactivity characteristics often found with certain types of autoantibodies, but they did not bear the H130 idiotype, which was identified on IgM anti-DNA autoantibodies from MRL-lpr/lpr mice.

Animals↗

PubMedDate not supplied

A dynamic finite element surface model for segmentation and tracking in multidimensional medical images with application to cardiac 4D image analysis.

This paper presents a physics-based approach to anatomical surface segmentation, reconstruction, and tracking in multidimensional medical images. The approach makes use of a dynamic "balloon" model--a spherical thin-plate under tension surface spline which deforms elastically to fit the image data. The fitting process is mediated by internal forces stemming from the elastic properties of the spline and external forces which are produced form the data. The forces interact in accordance with Lagrangian equations of motion that adjust the model's deformational degrees of freedom to fit the data. We employ the finite element method to represent the continuous surface in the form of weighted sums of local polynomial basis functions. We use a quintic triangular finite element whose nodal variables include positions as well as the first and second partial derivatives of the surface. We describe a system, implemented on a high performance graphics workstation, which applies the model fitting technique to the segmentation of the cardiac LV surface in volume (3D) CT images and LV tracking in dynamic volume (4D) CT images to estimate its nonrigid motion over the cardiac cycle. The system features a graphical user interface which minimizes error by affording specialist users interactive control over the dynamic model fitting process.

Animals↗