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Biomedical subjects

D G Brown

Publications and source records attributed to D G Brown.

At least 55 records · Page 3Linked to original sources

Crystal and solution structures of the oligonucleotide d(ATGCGCAT)2: a combined X-ray and NMR study.

A combined crystal-structure determination and NMR analysis of the octanucleotide d(ATGCGCAT)2 is reported. The X-ray analysis shows that the structure is A-form duplex in crystal state. The NMR study shows that in solution this sequence is B-type. The conformational results from each technique are presented in detail. The implications of these findings in terms of conformational flexibility and ligand binding are discussed.

Base Sequence↗

Crystal structure of a berenil-dodecanucleotide complex: the role of water in sequence-specific ligand binding.

The three-dimensional structure of a complex between the dodecanucleotide d(CGCGAATTCGCG) and the anti-trypanocidal drug berenil, has been determined to a resolution of 2.5 A. The structure has been solved by molecular replacement and refined to an R factor of 0.177. A total of 49 water molecules have been located. The drug is bound at the 5'-AAT-3' region of the oligonucleotide. At one end of the drug the amidinium group is in hydrogen-bonded contact with N3 of the adenine base complementary to the thymine of the AAT. The other amidinium group does not make direct interactions with the DNA. Instead, a water molecule mediates between them. This is in hydrogen-bonded contact with an amidinium nitrogen atom, N3 of the 5' end adenine base and the ring oxygen atom of an adjacent deoxyribose. Molecular mechanics calculations have been performed on this complex, with the drug at various positions along the sequence. These show that the observed position is only 0.8 kcal/mol higher in energy than the best position. It is suggested that there is a broad energy well in the AATT region for this drug, and that water molecules as well as the neighbouring sequence, will determine precise positioning. More general aspects of minor groove binding are discussed.

Amidines↗

CNR enhancement in the presence of multiple interfering processes using linear filters.

Given several images of the same slice, a linear filter can produce an image in which the contrast-to-noise ratio (CNR) between pathological and normal tissues is greater than in any of the initial images. To distinguish the pathology from more than one tissue, the filter should optimize the set of CNRs between the pathology and each of the interfering tissues. We define the optimal filter as the one which provides the largest value for the minimum CNR in the set and show how it is selected from a field of only four possibilities. The filter is demonstrated with both experimental phantom studies and clinical cases. Filter performance is compared with that of other techniques for distinguishing a desired feature from more than one interfering process.

Image Enhancement↗

High-speed line scan MR angiography.

We describe a system which forms MR angiographic images at high speed. Multiple axial sections are imaged sequentially using a 2DFT GRASS sequence with TR/TE 50/15 ms, 64 phase encodings per image. Reconstruction and projection of each image are performed immediately (within 220 ms) after data for that image are acquired. The projection angiogram is constructed line by line as the scan progresses, thereby totally eliminating any additional time required for reconstruction and projection.

Blood Vessels↗

Magnetic resonance imaging in patients with inflammatory arthritis of the knee.

Magnetic resonance imaging (MRI) permits visualization of anatomic structures not appreciated by conventional radiographic imaging and may quantify inflammatory disease and its progression with greater sensitivity than available techniques. We therefore compared MRI with clinical evaluation and with radiographic examination of 17 patients with inflammatory arthritis of the knee. We sought to determine anatomic integrity of bone, cartilage, menisci, and ligaments, and to quantify joint effusion and synovial proliferation. Patients studied had rheumatoid arthritis (10 patients), juvenile rheumatoid arthritis (4 patients), ankylosing spondylitis (1 patient), and monoarticular arthritis (2 patients). In all patients MRI revealed clinically important abnormalities not detected by physical or conventional radiographic exams. These included proliferative synovitis (13 patients), cartilage thinning (2 patients), cartilage erosion (8 patients), bone infarction (1 patient), meniscal injury (1 patient), and synovial invagination into bone (1 patient). Also MRI indicated inflammatory disease to be quantitatively greater than had been appreciated on clinical examination or routine X-ray studies--proliferative synovitis (12 patients), erosion (7 patients), effusion (8 patients), cartilage thinning (11 patients), and ligamentous/meniscal damage (1 patient). These findings led to reassessment of anatomic staging and influenced therapeutic decision for these patients. Thus MRI provides clinically important information about joint integrity and inflammatory disease, with a sensitivity and resolution considerably beyond conventional techniques.

Adult↗

Phenotypic stability and metastatic behaviour of serially xenografted rat mesotheliomas.

Mesotheliomas induced in rats by intrapleural injection of the fibrous zeolite, erionite, were serially transplanted in nude mice for up to ten generations. The cell phenotypes (epithelial or sarcomatous) were well maintained during passaging, as determined morphologically and by the expression of the cytokeratin markers demonstrated in normal mesothelial cells. Some of the tumours occasionally produced metastasis in nude mice. In contrast, a cloned epithelial cell mesothelioma and sarcomatous cell mesothelioma, the original cells of which were isolated in tissue culture, both produced regular multiple metastases when passaged in nude mice. These metastases were frequently found on the visceral pleura, rather than in the lung parenchyma, in nude mice. The high metastatic rate of the xenograph mesotheliomas derived by in vitro isolation of cells from mesotheliomas is atypical of the usual behaviour of xenografts of mesotheliomas.

Aluminum Silicates↗

Describing small-scale structure in random media using pulse-echo ultrasound.

A method for estimating structural properties of random media is described. The size, number density, and scattering strength of particles are estimated from an analysis of the radio frequency (rf) echo signal power spectrum. Simple correlation functions and the accurate scattering theory of Faran [J.J. Faran, J. Acoust. Soc. Am. 23, 405-418 (1951)], which includes the effects of shear waves, were used separately to model backscatter from spherical particles and thereby describe the structures of the medium. These methods were tested using both glass sphere-in-agar and polystyrene sphere-in-agar scattering media. With the appropriate correlation function, it was possible to measure glass sphere diameters with an accuracy of 20%. It was not possible to accurately estimate the size of polystyrene spheres with the simple spherical and Gaussian correlation models examined because of a significant shear wave contribution. Using the Faran scattering theory for spheres, however, the accuracy for estimating diameters was improved to 10% for both glass and polystyrene scattering media. It was possible to estimate the product of the average scattering particle number density and the average scattering strength per particle, but with lower accuracy than the size estimates. The dependence of the measurement accuracy on the inclusion of shear waves, the wavelength of sound, and medium attenuation are considered, and the implications for describing the structure of biological soft tissues are discussed.

Models, Theoretical↗

MR angiography with oblique gradient-recalled echo technique.

Magnetic resonance (MR) angiography with use of an oblique gradient-recalled echo sequence is discussed. The technique was developed for the efficient acquisition of angiographic data when the desired projection direction is already known. The raw data set is acquired directly at the projection angle; thus, a high-resolution projection is created, despite a decrease in the number of phase-encoding views acquired per axial image. Excessive reduction in the number of views acquired causes a loss of contrast in the projection images rather than a loss of resolution. High-resolution, high-contrast MR projection angiograms can be obtained in 2 1/2 minutes, with 50 3-mm sections and 48 phase encodings per section, a repetition time of 50 msec, an echo time of 15 msec, and a flip angle of 45 degrees. This represents one-fifth the time required for a conventional angiographic image. Venous blood is successfully saturated when the saturation band is placed at a fixed distance from the current imaging section. The method is demonstrated in the imaging of the carotid bifurcation in healthy volunteers and of a patient who had undergone carotid endarterectomy.

Carotid Arteries↗

Physics and statistics of medical imaging.

Extraordinary progress has been made over the last two decades in the development and dissemination of new medical imaging technologies. The development of computed tomography, positron emission tomography, and magnetic resonance imaging, as well as major innovations to the conventional imaging modalities, have revolutionized medical diagnostic imaging. Despite their many differences, all of these modalities can be viewed from a common perspective: being described in terms of the underlying physical properties imaged, the type of radiation/detection system used to produce the images, and the imaging performance that the modality achieves, both in absolute terms and relative to that of a conceptual ideal observer. This is a US government work. There are no restrictions on its use.

Diagnostic Imaging↗

Cardiovascular risk factors among black schoolchildren: comparisons among four Know Your Body studies.

Baseline cardiovascular risk factor variables were obtained from 1,041 black District of Columbia children in Grades 4-6 as part of a Know Your Body evaluation project. Screening included height, weight, triceps skinfold measurements, systolic and diastolic blood pressures, step-test for fitness, serum cholesterol, high-density lipoprotein cholesterol and thiocyanate. Results were compared with those in three other Know Your Body studies, Bronx, New York, Westchester, New York, and Los Angeles, and indicated that District of Columbia black children are more likely to have high cholesterol levels and to fail the fitness test than black children in the other studies. In the District of Columbia, obese children had significantly higher total serum cholesterol, systolic, diastolic, and high-density lipoprotein levels, and were less fit than other District of Columbia children; almost three-fourths of all of the children had one or more risk factors. Socioeconomic status was negatively correlated with diastolic blood pressure, skinfold thickness, and cholesterol levels and was positively correlated with high-density lipoprotein cholesterol. Rates of obesity and diastolic blood pressure were consistent with Bronx and Westchester comparisons suggesting that socioeconomic status interacts with ethnicity to determine risk factor levels. The existence of children with multiple risk factors in all of the Know Your Body studies supports the need for early intervention.

Adolescent↗

Statistical properties of radio-frequency and envelope-detected signals with applications to medical ultrasound.

Both radio-frequency (rf) and envelope-detected signal analyses have lead to successful tissue discrimination in medical ultrasound. The extrapolation from tissue discrimination to a description of the tissue structure requires an analysis of the statistics of complex signals. To that end, first- and second-order statistics of complex random signals are reviewed, and an example is taken from rf signal analysis of the backscattered echoes from diffuse scatterers. In this case the scattering form factor of small scatterers can be easily separated from long-range structure and corrected for the transducer characteristics, thereby yielding an instrument-independent tissue signature. The statistics of the more economical envelope- and square-law-detected signals are derived next and found to be almost identical when normalized autocorrelation functions are used. Of the two nonlinear methods of detection, the square-law or intensity scheme gives rise to statistics that are more transparent to physical insight. Moreover, an analysis of the intensity-correlation structure indicates that the contributions to the total echo signal from the diffuse scatter and from the steady and variable components of coherent scatter can still be separated and used for tissue characterization. However, this analysis is not system independent. Finally, the statistical methods of this paper may be applied directly to envelope signals in nuclear-magnetic-resonance imaging because of the approximate equivalence of second-order statistics for magnitude and intensity.

Humans↗

Anesthetic gas exposure. Protecting the OR environment.

A trace gas study was conducted at The University of Michigan Hospitals to assess levels of anesthetic gas in the OR environment. Samples were collected at various sites associated with anesthesia equipment in 18 operating rooms and three treatment rooms where general anesthesia was used routinely. Waste anesthetic gas levels were found to vary widely and, depending upon anesthesiologists' work practices and equipment design, significant personnel exposures were documented. Although standard turbulent air flow, nonrecirculating systems are used in most ORs, areas of high gas concentration were identified. Such locations included the area between the gas machine and adjacent wall, and along the perimeter of the patient drapes. Gas concentrations were influenced by such variables as the distance from the anesthesia equipment to the exhaust grilles, and personnel movement. Anesthetizing techniques and work practices are the major contributors to waste anesthesia levels in the OR environment.

Air Movements↗

Multipotential behaviour of cloned rat mesothelioma cells with epithelial phenotype.

Reference cultures derived from a transplantable rat mesothelioma were obtained by cloning cells three times in soft agar. Each line, designated "CARM-Lines", was selected on the basis of their epithelial or fibroblastic phenotype, and their uniform morphology. Three epithelial lines were used for more detailed in vitro studies comparing morphological and biological criteria at early and late passages. All three lines exhibited both epithelial and fibroblastic elements after 10-14 passages in vitro, demonstrating that the dimorphic histology of these tumours could be derived from a single aberrant cell. Morphology and growth characteristics of these cells were density-dependent. Anchorage dependent and independent clonogenic assays did not correlate. Anchorage dependent colony formation was the only parameter which differed markedly from the original parent line in the assays described. In vivo evidence of chondrogenesis and attempted ossification support the concept of a multipotential cell contributing to the diverse primary tumour morphology by cellular modulation or differentiation.

Animals↗

Group intervention: a psychosocial and educational approach to open heart surgery patients and their families.

Fear and apprehension usually accompany surgery on the human heart. Experience and research have demonstrated that many patients who have undergone open heart surgery have less than optimal psychological outcomes. This article describes the response of one university hospital to the physiological and psychological needs of the cardiovascular surgery patient during the final phase of hospitalization. To give patients and families an opportunity to deal with their questions and concerns about discharge, one-sessional educational support groups are co-led by a social worker and cardiovascular nurse specialist. The development and implementation of patient and relative groups and the process through which a more comprehensive program evolved are described. An analysis of the experience and conclusions and recommendations for the future are reviewed.

Adaptation, Psychological↗