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Biomedical subjects

D L Weaver

Publications and source records attributed to D L Weaver.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

An internal fixator for posterior application to short segments of the thoracic, lumbar, or lumbosacral spine. Design and testing.

A new spinal implant has been designed and biomechanical testing completed, intended for application to "short-segment" spinal defects such as disc degeneration, fracture, spondylolisthesis, or tumor. Major improvements over currently available devices include: only 2-3 vertebrae are spanned, not 5-7 as with Harrington rods; true three-dimensional fixation is achieved, preventing such problems as hook or rod dislocation; three-dimensional adjustment is easily accomplished, allowing fracture or spondylolisthesis reduction to be readily performed; attachment to vertebrae is by means of transpedicular screws eliminating deliberate encroachment into the spinal canal, such as Luque wires or Harrington hooks; no special alignment between screws is needed (such as with holes or slots in a plate), allowing screw placement to fully conform to anatomic structures; and laminectomy sites and lumbosacral junction are readily instrumented. Background investigations presented here for design of this device include: CT-defined pedicle morphometry showing that screws may be larger than those currently used; effect of pitch, minor diameter, and tooth profile on screw pull-out strength; mechanical testing of a compact, three-dimensionally adjustable, strong, nonloosening articulating clamp; and establishing of the relationship between depth of penetration and strength of fixation of transpeduncular screws.

Adolescent↗

Diffusion-collision model for the folding kinetics of the lambda-repressor operator-binding domain.

The operator-binding domain of the lambda-repressor contains five alpha-helices and an extended N-terminal arm in the crystal structure determined by Pabo and Lewis reported in Nature 298, 443, 1982 (1). The four helices form a "box" enclosing a hydrophobic core with the fifth helix interacting with the equivalent helix in a dimer. With a small number of well-defined secondary structure elements (microdomains), the repressor is well suited for an analysis of its folding pathways and kinetics by use of the diffusion-collision model. In this paper, the basic elements of the model appropriate to a several microdomain protein are formulated and applied to a set of folding pathways consistent with the crystal structure of the operator-binding domain. The overall kinetics, as well as the time-dependence of intermediate states are determined as a function of the microdomain stability parameter.

Binding Sites↗

Activation of 2-aminofluorene by cultured plant cells.

Cultured tobacco plant cells activated 2-aminofluorene to an agent mutagenic to Salmonella typhimurium strain TA98. The plant activation of 2-aminofluorene is heat-inactivated and may not involve solely cytochrome P-450. The kinetics of activation demonstrated both time- and concentration-dependent responses.

Biotransformation↗

Diffusion-mediated localization on membrane surfaces.

Using the model of a cell membrane of a spherical surface in which membrane components may diffuse, the rate of localization due to trapping under diffusion control has been estimated by computing an analytical expression for the mean trapping time including the possibilities of a trapping probability less than 1 and/or the establishment of an equilibrium at the trap boundary.

Cell Membrane↗

Neurotransmitter chemistry in feline GM1 gangliosidosis: a model for human ganglioside storage disease.

Assays for synaptosomal high-affinity uptake activity (glutamate, gamma-aminobutyric acid, norepinephrine), neurotransmitter synthesizing enzymes (choline acetyltransferase, glutamate decarboxylase, tyrosine hydroxylase), and endogenous neurotransmitters were performed in cats with advanced inherited GM1 gangliosidosis. A significant reduction in uptake activity, ranging from 24 to 77% of control, was demonstrated in motor, occipital, and cerebellar brain regions. This reduction was unassociated with comparable alterations in neurotransmitter levels or synthesizing enzyme activity. We hypothesize that the defect of neurotransmitter inactivation is part of an overall abnormality of synaptic membrane function that could contribute to the neurological symptoms seen in the hereditary gangliosidoses.

Animals↗