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Biomedical subjects

K J Myers

Publications and source records attributed to K J Myers.

At least 19 recordsLinked to original sources
PubMed2000

Sensible use of antisense: how to use oligonucleotides as research tools.

In the past decade, there has been a vast increase in the amount of gene sequence information that has the potential to revolutionize the way diseases are both categorized and treated. Old diagnoses, largely anatomical or descriptive in nature, are likely to be superceded by the molecular characterization of the disease. The recognition that certain genes drive key disease processes will also enable the rational design of gene-specific therapeutics. Antisense oligonucleotides represent a technology that should play multiple roles in this process.

Animals↗
PubMed2000

Reconstruction of MR images from data acquired on a general nonregular grid by pseudoinverse calculation.

A minimum-norm least-squares image-reconstruction method for the reconstruction of magnetic resonance images from non-Cartesian sampled data is proposed. The method is based on a general formalism for continuous-to-discrete mapping and pseudoinverse calculation. It does not involve any regridding or interpolation of the data and therefore the methodology differs fundamentally from existing regridding-based methods. Moreover, the method uses a continuous representation of objects in the image domain instead of a discretized representation. Simulations and experiments show the possibilities of the method in both radial and spiral imaging. Simulations revealed that minimum-norm least-squares image reconstruction can result in a drastic decrease of artifacts compared with regridding-based reconstruction. Besides, both in vivo and phantom experiments showed that minimum-norm least-squares image reconstruction leads to contrast improvement and increased signal-to-noise ratio compared with image reconstruction based on regridding. As an appendix, an analytical calculation of the raw data corresponding to the well-known Shepp and Logan software head phantom is presented.

Humans↗
PubMed1998

Interleukin-12-induced adhesion molecule expression in murine liver.

Systemically administered interleukin (IL)-12 causes liver inflammation in mice characterized by Kupffer cell proliferation and hypertrophy, hepatocyte necrosis, and multifocal accumulations of leukocytes in the hepatic parenchyma and around portal tracts and central veins. We have used both immunohistochemical staining and radiolabeled antibody quantitation to examine adhesion molecule expression in the livers of mice dosed daily with murine IL-12. Cells infiltrating livers of IL-12-treated mice were primarily mononuclear leukocytes expressing LFA-1, VLA-4, MAC-1, and CD18 adhesion molecules but little L-selectin. Kupffer cells constitutively expressed LFA-1 and smaller amounts of MAC-1, and high levels of ICAM-1 were constitutively expressed by liver sinusoidal lining cells, portal tract, and central vein endothelia. With IL-12 treatment, existing ICAM-1 expression was up-regulated and de novo expression occurred along bile duct epithelia. VCAM-1 levels were dramatically increased, with induced expression occurring along portal tract and central vein endothelia and scattered bile duct epithelial cells and in aggregations of cells in perivascular areas and the liver parenchyma. Although constitutive expression of E- and P-selectin was negligible, Il-12 induced a moderate rise in E-selectin levels. These increases in adhesion molecule expression may have implications for the therapeutic use of IL-12, especially in patients with liver disease or autoimmune conditions where augmented adhesion molecule expression may be critical to disease pathogenesis.

Animals↗
PubMed1998

Clinical diorama.

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Accidents, Traffic↗
PubMed1998

Clinical diorama.

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AIDS-Related Opportunistic Infections↗
PubMed1997

Constrained reconstruction applied to 2-D chemical shift imaging.

The method of constrained reconstruction, previously applied to magnetic resonance imaging (MRI), is extended to magnetic resonance spectroscopy. This method assumes a model for the MR signal. The model parameters are estimated directly from the phase encoded data. This process obviates the need for the fast Fourier transform (FFT) (which often exhibits limited resolution and ringing artifact). The technique is tested on simulated data, phantom data, and data acquired from human liver in vivo. In each case, constrained reconstruction offers spatial resolution superior to that obtained with the FFT.

Artifacts↗
PubMed1995

Both anti-CD11a (LFA-1) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system (CNS) induced in rodents by activated CD4+ T cells specific for various myelin proteins such as myelin basic protein and proteolipid protein. The disease is characterized by breach of the blood-brain barrier, perivascular infiltration of leukocytes into the CNS, local inflammation and demyelination in the form of plaques. In this study, we evaluated the effect of administration of antibodies to two members of the beta 2 integrin sub-family of adhesion molecules, CD11a and CD11b, on the onset and progression of EAE. CD11a and CD11b are involved in cell-cell interactions leading to T cell and macrophage extravasation to inflammatory sites and T cell activation. Our results show that anti-CD11a antibodies could completely block the induction of EAE and anti-CD11b antibodies significantly delayed the onset and diminished the severity of clinical signs of EAE even when injections were initiated at the first appearance of clinical signs.

Amino Acid Sequence↗
PubMed1995

Toward consensus on quantitative assessment of medical imaging systems.

Consensus has been developing over the past few decades on a number of measurements required for the laboratory assessment of medical imaging modalities. Nevertheless, understanding of the connection between these measurements and human observer performance in a broad range of tasks remains far from complete. Focusing primarily on projection radiography to provide concrete examples, this overview indicates areas in which consensus on methodology for physical image-quality measurement has been established. Concepts such as "noise equivalent quanta" (NEQ) and "detective quantum efficiency" (DQE) have been found useful for normalizing physical measurements on an absolute scale and for relating those measurements to the decision performance of a hypothetical "ideal observer" that effectively performs decision tasks from the image data. The connection between ideal observer performance and human performance, as determined by receiver operating characteristic (ROC) analysis, remains to be understood for many clinically relevant tasks.

Biophysical Phenomena↗
PubMed1995

Objective assessment of image quality. II. Fisher information, Fourier crosstalk, and figures of merit for task performance.

Figures of merit for image quality are derived on the basis of the performance of mathematical observers on specific detection and estimation tasks. The tasks include detection of a known signal superimposed on a known background, detection of a known signal on a random background, estimation of Fourier coefficients of the object, and estimation of the integral of the object over a specified region of interest. The chosen observer for the detection tasks is the ideal linear discriminant, which we call the Hotelling observer. The figures of merit are based on the Fisher information matrix relevant to estimation of the Fourier coefficients and the closely related Fourier crosstalk matrix introduced earlier by Barrett and Gifford [Phys. Med. Biol. 39, 451 (1994)]. A finite submatrix of the infinite Fisher information matrix is used to set Cramer-Rao lower bounds on the variances of the estimates of the first N Fourier coefficients. The figures of merit for detection tasks are shown to be closely related to the concepts of noise-equivalent quanta (NEQ) and generalized NEQ, originally derived for linear, shift-invariant imaging systems and stationary noise. Application of these results to the design of imaging systems is discussed.

Computer Simulation↗
PubMed1993

Model observers for assessment of image quality.

Image quality can be defined objectively in terms of the performance of some "observer" (either a human or a mathematical model) for some task of practical interest. If the end user of the image will be a human, model observers are used to predict the task performance of the human, as measured by psychophysical studies, and hence to serve as the basis for optimization of image quality. In this paper, we consider the task of detection of a weak signal in a noisy image. The mathematical observers considered include the ideal Bayesian, the nonprewhitening matched filter, a model based on linear-discriminant analysis and referred to as the Hotelling observer, and the Hotelling and Bayesian observers modified to account for the spatial-frequency-selective channels in the human visual system. The theory behind these observer models is briefly reviewed, and several psychophysical studies relating to the choice among them are summarized. Only the Hotelling model with channels is mathematically tractable in all cases considered here and capable of accounting for all of these data. This model requires no adjustment of parameters to fit the data and is relatively insensitive to the details of the channel mechanism. We therefore suggest it as a useful model observer for the purpose of assessing and optimizing image quality with respect to simple detection tasks.

Discrimination, Psychological↗
PubMed1993

In vivo antigen presentation by both brain parenchymal cells and hematopoietically derived cells during the induction of experimental autoimmune encephalomyelitis.

A fundamental issue in the etiology of autoimmune diseases of the central nervous system such as multiple sclerosis and its animal counterpart experimental autoimmune encephalomyelitis (EAE) concerns the identity of cells capable of presenting autoantigen to the T cells that mediate these diseases. The prevailing dogma is that only bone marrow-derived cells function as APC during EAE induction. We have addressed this issue by studying EAE induction in mouse bone marrow chimeras, and have found that although bone marrow-derived APC such as macrophages and brain microglial cells are more efficient at presenting autoantigen, brain parenchymal cells such as astrocytes and endothelial cells are also capable of inducing disease. EAE was induced in these chimeras by the adoptive transfer of encephalitogenic T cell lines designed to be MHC-histocompatible with APC contained either within the hematopoietic system of the chimera or with APC resident to the brain of the chimera. The subsequent development of EAE in these chimeras then indicated which population of cells served as in vivo APC during EAE pathogenesis. Possible effects of alloreactivity between the host chimera and the adoptively transferred T cells were eliminated by using encephalitogenic T cell lines made tolerant to the haplotype(s) of the recipient chimera.

Amino Acid Sequence↗
PubMed1993

Phenytoin as a countermeasure for motion sickness in NASA maritime operations.

Seasickness is the most prevalent form of motion sickness and is an operational problem during Space Shuttle Solid-fueled Rocket Booster (SRB) retrieval. Phenytoin has been shown to protect against motion sickness induced by Coriolis stress. We exposed SRB recovery personnel to off-vertical rotation and sea motion after phenytoin or placebo. Phenytoin blood levels of at least 9 micrograms/ml were protective against motion sickness at sea. No change in susceptibility to nitrogen narcosis was seen in divers in chamber tests at 460 KPa. Phenytoin was used during performance of critical and hazardous tasks during training and actual SRB recovery operations. Phenytoin is an effective operational countermeasure for motion sickness for selected SRB crewmembers.

Adult↗
PubMed1992

Synergy between encephalitogenic T cells and myelin basic protein-specific antibodies in the induction of experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an experimentally induced demyelinating disease mediated by CD4+ T cells specific for various myelin proteins including myelin basic protein (MBP) and myelin proteolipid protein (PLP). Although myelin- and other CNS-specific antibodies are produced in EAE, B cells and antibodies are thought by most not to play a decisive role in the induction of EAE. In this report we show that B cells serve as the major antigen-presenting cells (APC) during the T cell activation stage in lymph nodes, and that MBP-specific antibodies can greatly enhance the induction of EAE. The role of B cells as APC is demonstrated in B cell-depleted mice. EAE cannot be induced by antigen/complete Freund's adjuvant immunization unless these mice are locally reconstituted with B cells prior to immunization. The enhancing effect of antibodies is demonstrated in experiments in which EAE is induced by the adoptive transfer of encephalitogenic T cells. The adoptive transfer of large numbers of encephalitogenic T cells induces EAE in 90% of normal recipient mice, but only 33% of B cell-depleted mice get EAE at the same cell dose. The efficiency of EAE induction in B cell-depleted mice can be enhanced if MBP-specific antibodies are simultaneously administered. A similar enhancement is also seen in normal mice when the number of adoptively transferred T cells is limiting. We propose that MBP-specific antibodies enhance the presentation of myelin-derived antigens by APC in the CNS to the adoptively transferred encephalitogenic T cells.

Animals↗