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Biomedical subjects

D L Weaver

Publications and source records attributed to D L Weaver.

At least 19 recordsLinked to original sources
PubMed1992

Hydrophobic interaction between globin helices.

The interhelical interfaces have been examined in seven high-resolution globin chains. The profiles of hydrophobic contact, as measured by the residue solvent-accessible area loss upon folding, have been calculated. The seven globins studied differ in their overall loss of solvent-accessible area upon packing of their helices, the order being 1MBD greater than 1LH1 greater than 1ECD greater than 2MHBB greater than 2HHBB greater than 2HHBA greater than 2MHBA, which gives a measure of the difference in stability due to the hydrophobic interaction. The five helix-pair packings (AH, BE, BG, FH and GH) examined in detail have qualitative similarities. There are, however, substantial quantitative differences both at the equivalent residue level and at the level of overall helix-helix contact, which has significance in some models of folding. The AH pair has the most uniform area loss over the seven globins and the largest variation in accessible area loss on packing among the five helix pairs is the GH pair. The set of residues required to produce the globin fold has been deduced from the residue area losses.

Animals↗
PubMed1992

DNA signal splitting improves detection and analysis of tetraploid populations.

Detection of DNA tetraploid populations requires a high index of suspicion at the time of data acquisition and frequently requires subsequent off-line analysis for confirmation, including evaluation of the hypertetraploid region. To analyze these specimens, the flow cytometer operator must run all specimens with the G0G1 peak in low channels or rerun specimens in which tetraploidy is suspected with a lower photomultiplier tube (PMT) voltage or lower amplifier gain setting. Re-analysis may not be possible in specimens with few cells. A simple modification to the cytometer allows PMT signal splitting with simultaneous processing of the signal by two different amplifiers. This allows simultaneous acquisition of histograms optimized for both the hypotetraploid and hypertetraploid regions.

DNA, Neoplasm↗
PubMed1992

Beta-sheet coil transitions in a simple polypeptide model.

A simplified model of a polypeptide chain is used to study the dynamics of the beta-sheet-coil transition. Each amino acid residue is treated as a single quasiparticle in an effective potential that approximates the potential of mean force in solution. The model is used to study the equilibrium and dynamic aspects of the sheet-coil transition. Systems studied include ones with both strands free to move (two-strand sheet), and ones with either strand fixed in position (multistrand sheet). The equilibrium properties examined include sheet-coil equilibrium constants and their dependence on chain position. Dynamic properties are investigated by a stochastic simulation of the Brownian motion of the chain in its solvent surroundings. Time histories of the dihedral angles and residue-residue cross-strand distances are used to study the behavior of the sheet structure. Auto- and cross-correlation functions are calculated from the time histories with relaxation times of tens to hundreds of picoseconds. Sheet-coil rate constants of tens of ns-1 were found for the fixed strand cases.

Models, Molecular↗
PubMed1992

Modeling microdomains: the surface area of globin helices.

The accessible surface areas of 53 high-resolution globin helices are correlated with molecular weight. The linear fit is assessed for statistical accuracy using a boot-strap analysis, and by comparison to the areas of 13 ideal polyalanine alpha-helices. The accessible area of the unfolded helices is compared with the folded values before helix-helix packing. An analytical physical model is presented to explain the correlation, and to provide an analytical value for the surface area parameter in the diffusion-collision model of protein folding.

Animals↗
PubMed1991

DNA histogram debris theory and compensation.

In this paper we describe a theory of DNA histogram debris generation and compensation that can be applied to paraffin-embedded frozen tissue preparations. The theory predicts the distribution of fragments generated from single and multiple random sectioning of three-dimensional ellipsoids representing nuclei. The fragment distribution is assumed to be a major component of the underlying debris in DNA histograms. A comparison of S-phase fractions (SPF) from matched tissue prepared by frozen and formalin-fixed paraffin-embedded DNA methods demonstrates the usefulness of the theory.

Cell Cycle↗
PubMed1991

Variation of folded polypeptide surface area with probe size.

Three types of polypeptide surface area (contact, accessible, and molecular) have been studied as a function of the radius of a probe sphere used to map the surface. The surfaces are: (1) three alpha-helices, the H-helix of myoglobin, the E-helix of leghemoglobin, and an artificial polyalanine helix, each with 26 residues; (2) two globins, myoglobin and leghemoglobin, each with 153 residues; and (3) a two-center model system for which the three types of surface area have been calculated analytically. The two globin helices have almost identical surface areas as a function of probe size as do the two globins. The polyalanine helix surface area is smaller but similar in shape to the globin helix areas. All three helix contact areas tend to the same limit as the probe size increases, and the globin contact areas behave similarly. Fractal dimensions were calculated for the helix and globin contact and molecular surfaces. All fractal dimensions showed strong dependence on probe size. The contact fractal dimension peaks at larger values for both the helices and globins. Most residues do not make contact with large probes (15 A).

Models, Molecular↗
PubMed1990

Molecular interactions in protein crystals: solvent accessible surface and stability.

The accessible surface areas of 58 monomeric and dimeric proteins, when measured in the crystalline environment, are found to be simply related to molecular weight. The loss of accessible surface when the proteins go from a free to their crystalline environment is well defined, implying that the hydrophobic interaction, which has been found to contribute to protein folding and stability in living systems, also contributes to protein crystal stability.

Molecular Weight↗
PubMed1990

Hereditary persistence of fetal hemoglobin presenting as fetal-maternal hemorrhage.

This report describes a case of hereditary persistence of fetal hemoglobin (HPFH) presenting initially as a marginal placental abruption in a primiparous woman at 27 weeks gestation. Persistent but erratic elevation of percent hemoglobin F positive cells, as determined by a modified Kleihauer-Betke method, complicated the remainder of her pregnancy. The clinical impression of placental abruption with possible extension could not be documented by ultrasound or examination of the placenta at delivery. Hemoglobin electrophoresis followed by quantitative fetal hemoglobin first suggested the diagnosis of HPFH, which was confirmed seven months postpartum. Furthermore, the magnitude of percent positive F-cells could be profoundly altered by subtle changes in pH of the acid elution reagent. This case demonstrates that positive acid elution tests for maternal-fetal transfusion may be caused by elevated maternal hemoglobin F. Erratic results, elevated quantitative hemoglobin-F and sensitivity to reagent pH should alert the pathologist to this diagnosis and alter clinical management.

Diagnosis, Differential↗
PubMed1990

Improved flow cytometric determination of proliferative activity (S-phase fraction) from paraffin-embedded tissue.

Recent studies suggest that proliferative activity (S-phase fraction [SPF]) may have greater prognostic significance than total nuclear DNA content; however, relatively few studies have examined SPF from paraffin-embedded tissue because of significant contamination of histograms with debris. In this study, cell cycle analysis was performed on 124 matched tissue specimens. Fresh tissue was divided into two equal portions; one portion was frozen, whereas the other portion was processed and embedded in paraffin. S-phase could be determined for both frozen and paraffin-embedded tissue in 81 cases. Correlation between SPF from frozen and paraffin-embedded tissue was demonstrated (r = 0.80) when debris was subtracted from histograms with the use of two new subtraction algorithms referred to as multicut and singlecut. Unlike other debris-subtraction algorithms, the quantity and distribution of debris calculated by these algorithms are dependent on the magnitude and position of histogram peaks. A lesser degree of correlation was demonstrated with the use of a standard exponential debris subtraction algorithm (r = 0.67). Correlation of SPF for aneuploid cases was greater when SPF was calculated as a percentage of the aneuploid cell population rather than as a percentage of the entire cell population. This was attributed to the observation that the proportion of aneuploid cells from paraffin-embedded tissue was less than that from frozen tissue. The results of this study indicate that SPF can be calculated from paraffin-embedded tissue with values comparable to those obtained from frozen tissue. The ability to calculate SPF reliably from paraffin-embedded tissue should allow additional evaluation of this parameter as a prognostic indicator.

Algorithms↗
PubMed1990

The National Health Service Corps: a partner in rural medical education.

Within the United States Public Health Service, the programs of the Bureau of Health Care Delivery and Assistance have played an important role in improving access to primary care services in rural America. In part, this has been accomplished through the administration of grants to assist in establishing systems of care and the assignment of National Health Service Corps (NHSC) health professionals. From a peak of over 1,600 NHSC-obligated scholarship recipients available for service in 1985, the number of available obligated practitioners has decreased to around 120 in 1990. A main focus of the NHSC has, therefore, necessarily changed from the placement of obligated health professionals to the recruitment of volunteers and increased emphasis on the retention of current providers. The systems of care that have been most successful in their retention efforts have been: group practices, composed of a nucleus of individuals who had been at the site for three to five years; community-oriented, utilizing non-physician providers as part of the delivery team; and those committed to continued provider education. The NHSC has initiated programs to help increase the likelihood that medical students will choose a primary care career and spend all or part of that career serving those most in need. These programs include the National Medical Association Minority Mentor Network, the American Medical Student Association Health Promotion/Disease Prevention Program, the Commissioned Officer Student Training and Externship Program, and the American Academy of Family Physicians Residency Advocate Program. To meet the future needs for access to care in rural America, partnerships with academic centers must be enhanced and expanded.

Education, Medical↗
PubMed1989

The surface area of monomeric proteins: significance of power law behavior.

The coefficients in a power law fit of accessible area versus molecular weight for high-resolution monomeric protein structures are assessed with respect to statistical accuracy using bootstrap analyses, and with respect to physical significance using model systems and the concept of roughness or fractal structure of the protein surface.

Models, Statistical↗
PubMed1988

Diffusion-collision model for the folding kinetics of myoglobin.

The diffusion-collision model has been used to analyze the folding kinetics of myoglobin. The microdomains, which are the basic units that coalesce during the folding, are identified with the helices and the stabilizing contacts between helices are determined from the native structure. Both association and dissociation reactions are included and a range of stabilization parameters is investigated to determine the variation in overall rate and the relative contributions made by different intermediates during the folding process. In a comparison of folding to the native state and to the midpoint of the folding transition (i.e., 50% native protein at the completion of the reaction) significant differences in the contributing intermediates are found.

Diffusion↗
PubMed1988

Repeated systemic mercury embolization.

Mercury embolization is an uncommon phenomenon that is easily diagnosed roentgenographically. We have reported a case of repeated self-administration of metallic mercury into the subcutaneous tissues. An intravenous component of the injection occurred, with systemic embolization to the lungs, CNS, pericardium, and diaphragm. These findings were demonstrated by plain films and CT, and were followed over a period of 15 months.

Adult↗
PubMed1988

Morphometry of the thoracic and lumbar spine related to transpedicular screw placement for surgical spinal fixation.

Vertebral transpedicular screws provide secure attachment for posterior spinal fixation devices. Screw design details, biomechanics, and implantation safety depend upon anatomic constraints, especially from the pedicle and body. Previous morphometric data were limited; thus, a retrospective study was undertaken using computerized axial tomograms (CT) of 91 vertebrae (T9-L5). In addition, eight cadaver vertebrae were CT scanned and then cut transversely to compare x-ray measurements with direct physical measurements. Measured parameters included pedicle width, pedicle length, angle of pedicle axis to sagittal plane, and transpedicular cortex-to-cortex chord length. Good correlation is shown to occur between CT scan and direct physical measurements of human vertebrae. Implications for spinal implant screw dimensions and safety of implantation are discussed. Comparison with previously available data is made.

Adolescent↗
PubMed1986

Paraganglioma of urinary bladder in patient with neurofibromatosis.

Pheochromocytoma in patients with von Recklinghausen's neurofibromatosis is a well-known association. However, extra-adrenal pheochromocytoma with this association is rare. Herein we report a case of urinary bladder paraganglioma in a patient with neurofibromatosis.

Aged↗
PubMed1986

Aortic pseudoaneurysm due to ingested foreign body.

We have described a child with pseudoaneurysm of the thoracic aorta caused by an ingested safety pin, who survived this life-threatening injury in which the diagnosis was elusive for four months. Esophageal foreign bodies, especially sharp, pointed ones, can cause such a cardiovascular complication. A high index of suspicion is imperative if the diagnosis is to be made early. Serial chest x-ray films showing an enlarging mediastinal mass should trigger aggressive radiologic evaluation.

Aorta, Thoracic↗