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Biomedical subjects

D G Brown

Publications and source records attributed to D G Brown.

At least 19 recordsLinked to original sources
PubMed1992

Molecular structure of the B-DNA dodecamer d(CGCAAATTTGCG)2. An examination of propeller twist and minor-groove water structure at 2.2 A resolution.

The crystal structure of the dodecanucleotide duplex d(CGCAAATTTGCG)2 has been solved to 2.2 A resolution and refined to an R-factor of 18.1% with the inclusion of 71 water molecules. The structure shows propeller twists of up to -20 degrees for the A.T base-pairs, although there is probably only one (weak) three-centre hydrogen bond in the six base-pair AT narrow minor-groove region. An extensive ribbon of hydration has been located in this groove that has features distinctive from the classic "spine of hydration". Solvation around phosphate groups is described, with several instances of water molecules bridging between phosphates.

Base Composition↗
PubMed1992

Crystal structure of a berenil-d(CGCAAATTTGCG) complex. An example of drug-DNA recognition based on sequence-dependent structural features.

The AT-selective drug berenil has been co-crystallized with the dodecanucleotide sequence d(CGCAAATTTGCG)2. The crystal structure has been solved to a resolution of 2.0 A and an R factor of 18.3%, with the location of 65 water molecules. The drug is symmetrically bound in the 5'-AATT region of the minor groove, with its amidinium groups hydrogen-bonding to O-2 atoms of the thymine base at each end of the binding site. This arrangement is distinct from that previously found for berenil with the sequence d(CGCGAATTCGCG)2, which has the drug bound to the sequencing 5'-ATT via hydrogen bonds to adenine N-3 atoms with the involvement of a bridging water molecule at one end of the binding site. The reasons for these differences are discussed in terms of changes in helical parameters; in particular propeller twist and base-pair roll are considered to be important. The conformational and base-pair geometry of the dodecanucleotide in the structure reported here, is closely similar to that for the native structure, suggesting that the 5'-AAATTT sequence does not significantly alter during drug binding, either because of its inflexibility or because its geometry is nearly ideal for berenil binding.

Base Sequence↗
PubMed1992

Contrast-to-noise ratios in maximum intensity projection images.

We present a statistical analysis of the maximum intensity projection (MIP) algorithm, which is commonly used for MR angiography (MRA). The analysis explains why MIP projection images display as much as a twofold increase in signal- and contrast-to-noise ratios over those of the source image set. This behavior is demonstrated with simulations and in phantom and MRA image sets.

Algorithms↗
PubMed1992

Effect of light dose on the photodynamic destruction of endobronchial tumors.

The effects of various light power densities (milliwatts per centimeter of diffusing fiber [mW/cf]) and light doses (joules per centimeter of diffusing fiber [J/cf]) on the effectiveness of photodynamic therapy to endobronchial and tracheal tumors were evaluated at 46 different sites. All patients had squamous cell carcinoma or adenocarcinoma. They received 2 mg/kg body weight dihematoporphyrin ether intravenously 2 days before treatment bronchoscopy. Only one light treatment was delivered to the site. Patients were treated with diffusing cylinder light tips and underwent toilet bronchoscopy 2 days after photodynamic therapy. The percentage of obstruction was estimated before and after treatment and before and after toilet bronchoscopy. There was no difference between the effects resulting from power densities of 400 and 500 mW/cf, nor were there differences in the reactions between squamous cell carcinoma and adenocarcinoma. The amount of tumor that could be removed at the end of the treatment bronchoscopy, the amount of reobstruction by secretions and exudate seen at toilet bronchoscopy, and the final percent decrease in obstruction at the end of toilet bronchoscopy were proportional to the light dose. Because the final percentage decrease in obstruction plateaued at light doses of 400 to 500 J/cf and there was no statistically significant difference between 400 and 500 J/cf, we recommend using a power density of 500 mW/cf and a light dose of 400 J/cf during photodynamic therapy.

Adenocarcinoma↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1985

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↗