PubMed Health⌕ Search

Biomedical subjects

J L Winslow

Publications and source records attributed to J L Winslow.

10 recordsLinked to original sources
PubMed2001

Collagenous gastritis: a long-term follow-up with the development of endocrine cell hyperplasia, intestinal metaplasia, and epithelial changes indeterminate for dysplasia.

This report reviews the literature pertaining to collagenous gastritis and describes the clinicopathologic evolution of this disease in a patient during a 12-year period. We examined 109 biopsy specimens of gastric mucosa from 19 different endoscopic procedures for the severity and distribution of collagenous gastritis in a single patient. Assessments were undertaken for the presence of endocrine and gastrin cell hyperplasias and dysplastic epithelial changes. Relative to biopsy specimens from age- and sex-matched control subjects, the patient's biopsy specimens showed a significantly lower number of antral gastrin cells, along with a significant corpus endocrine cell hyperplasia, suggesting an increased risk of endocrine neoplasia. Gastric corpus biopsy specimens revealed an active, chronic gastritis, subepithelial collagen deposition, smooth muscle hyperplasia, and mild to moderate glandular atrophy. Additional findings of intestinal metaplasia and reactive epithelial changes indeterminate for dysplasia raise concerns about the potential for adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Rotational changes in the morphology of the vertebral artery at a common site of artery dissection.

OBJECTIVE: Given that vertebral artery dissection and transient vertebrobasilar insufficiency occurs commonly at the C1-C2 junction, the objective was to study, in vivo, the normal rotational anatomy at C1-C2 using magnetic resonance angiography (MRA) with 3-dimensional (3D) reconstructions and to correlate these reconstructions with our experience of dissection location. METHODS: 3D phase-contrast MRAs were obtained from the foramen magnum to C3 in 4 normal volunteers in neutral and rotated (45 degrees) positions. The magnitude images were used as source images for 3D reconstruction. The images from only 1 of the volunteers were completely motion free, and these were subjected to arterial length calculations using image analysis wire frame outline of the vessel. All angiograms of vertebral artery dissection obtained at our institution from 1993 to 1997 were also reviewed. RESULTS: 3D reconstructions document elongation (approximately 7% in quantitatively analyzed case) and slight narrowing of the artery contralateral to the direction of head rotation from C2 to the dural entry point. The artery turns most sharply and is subject to the anterior force of the rotating C1 vertebra as it exits the C1 foramen. Of 14 cases of vertebral artery dissection, 50% occurred between the transverse foramen and the posterior lamina of C1. CONCLUSIONS: With head rotation, the contralateral vertebral artery undergoes the greatest anatomical distortion as it exits the C1 transverse foramen. This increased stress may account for the higher frequency of dissections at this location.

Adult↗
PubMed1999

Signals in stochastically generated neurons.

To incorporate variation of neuron shape in neural models, we developed a method of generating a population of realistically shaped neurons. Parameters that characterize a neuron include soma diameters, distances to branch points, fiber diameters, and overall dendritic tree shape and size. Experimentally measured distributions provide a means of treating these morphological parameters as stochastic variables in an algorithm for production of neurons. Stochastically generated neurons shapes were used in a model of hippocampal dentate gyrus granule cells. A large part of the variation of whole neuron input resistance R(N) is due to variation in shape. Membrane resistivity Rm computed from R(N) varies accordingly. Statistics of responses to synaptic activation were computed for different dendritic shapes. Magnitude of response variation depended on synapse location, measurement site, and attribute of response.

Algorithms↗
PubMed1996

Synaptic structural complexity as a factor enhancing probability of calcium-mediated transmitter release.

1. In a model synaptic system, the excitatory neuromuscular junction of the freshwater crayfish, the nerve terminals possess synapses that vary in structural complexity, with numbers of active zones ranging from zero to five. Active zones on individual synapses show a wide range of separation distances. We tested the hypothesis that two active zones of a single synapse in close proximity can enhance the localized increase in free calcium ion concentration, thus enhancing the probability of neurotransmission at that synapse. We evaluated the increase in calcium ion concentration as a function of distance between adjacent active zones. 2. To test this hypothesis, a reaction-diffusion model for Ca2+ entering the presynaptic terminals was used. This test was used because 1) present measurement techniques are inadequate to resolve quantitatively the highly localized, transient calcium microdomains at synaptic active zones; and 2) there is presently no suitable preparation for physiological recording from isolated synapses with varying distances between active zones. Included in the model were intracellular buffer and a typical distribution of voltage-activated Ca2+ channels for an active zone, estimated from freeze-fracture micrographs. 3. The model indicated that localized Ca2+ clouds from discrete active zones can overlap to create spatial enhancement of Ca2+ concentration. The degree of interaction between two active zones depends on the distance between them. When two typical active zones are separated by < or = 200 nm, the maximum intracellular Ca2+ concentration ([Ca2+]i) is greater at 1) the midpoint between them, and 2) the center of each one, than at the corresponding positions for a single isolated active zone. Enhanced [Ca2+]i at the edge of the active zone where "docked" synaptic vesicles occur would be expected to have an effect on transmitter release. 4. When the model includes no intracellular buffer, the increase in [Ca2+]i is a linear function of calcium channel current, but is a nonlinear function of the number of conducting calcium channels in an active zone. With immobile buffer included, the increase in [Ca2+]i is nonlinear with respect to both channel current and number of conducting channels. 5. Inclusion of immobile buffer in the model provides "released" residual calcium that slowly accumulates during a train of current pulses. Released residual calcium accumulates more rapidly at paired active zones separated by < or = 200 nm that at single isolated active zones. 6. We propose that the probability of release is enhanced at synapses with closely associated active zones. Synapses of this type ("complex" synapses) could be selectively recruited when the neuron is active at low frequencies. At higher frequencies of neuronal activity, more distant active zones may interact and acquire a greater probability of releasing quanta. This would provide the nerve terminal with one component of a mechanism for frequency facilitation, because the number of quanta released by the terminal as a whole would increase with frequency. Thus variation in synaptic complexity in a nerve terminal provides a mechanism for short-term plasticity of transmitter release.

Animals↗
PubMed1994

Stress and adenosine: I. Effect of methylxanthine and amphetamine stimulants on learned helplessness in rats.

In 3 experiments, the authors examined the effect of methylxanthine and amphetamine stimulants on deficits in shuttle-escape responding produced by earlier exposure to inescapable electric shock in rats. Caffeine completely reversed escape deficits in inescapably shocked rats when injected just before shuttle-escape testing but failed to prevent a test deficit when injected before shock pretreatment. Dose-response curves indicated that, whereas caffeine and theophylline were equally effective at reversing escape deficits, amphetamine not only failed to improve performance in preshocked rats but retarded escape in restrained (no-shock) controls. This amphetamine-induced deficit was reversed by cotreatment with caffeine. These data are discussed in terms of the role of adenosine receptor activation in helplessness and conservation-withdrawal.

Amphetamine↗
PubMed1994

Stress and adenosine: II. Adenosine analogs mimic the effect of inescapable shock on shuttle-escape performance in rats.

In 3 experiments, the authors examined the role of adenosine regulation in escape deficits produced by earlier exposure to inescapable shock in rats (learned helplessness). Adenosine analogs injected before escape testing mimicked the effect of earlier inescapable shock, with the magnitude of the deficit varying with dose and drug specificity for A2 adenosine receptors. Agonist-induced and stress-induced escape deficits were eliminated by pretest treatment with the centrally acting adenosine receptor antagonist theophylline but not the peripheral antagonist 8-[p-sulfophenyl]-theophylline. Finally, preexposure to an ineffective number of inescapable shocks interacted in synergy with an ineffective pretest injection of adenosine agonist to maximize deficits in escape performance. These data implicate energy regulation and a central compensatory action by adenosine in the aspects of helplessness related to conservation-withdrawal.

Adenosine↗
PubMed1994

Homosynaptic facilitation of transmitter release in crayfish is not affected by mobile calcium chelators: implications for the residual ionized calcium hypothesis from electrophysiological and computational analyses.

1. Evoked neurotransmitter release at the crayfish neuromuscular junction was measured in the presence of the cell-permeant calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetotoxymethyl (BAPTA-AM). Excitatory post-synaptic potentials were greatly diminished after application of the intracellular chelator, an effect resulting from attenuation of the rise in the concentration of cytoplasmic Ca2+ ([Ca]i) that is necessary for neurotransmission. However, short-term homosynaptic facilitation of release, the magnitude and time course of which is thought to depend on the accumulation and removal of residual Ca ions (Ca2+), was not affected. Application of the cell-permeant form of ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) gave similar results. 2. To interpret these results we developed a reaction-diffusion model in 3D rectangular coordinates for Ca2+ diffusion in the presence of mobile and immobile buffers. Solutions of the model in response to influx of Ca2+ through one or six channels for different diffusion coefficients and no nondiffusable buffer, predict that 1) the time course of residual Ca2+ is very brief, 2) an unrealistically low Ca2+ diffusion coefficient is required for residual calcium, 3) the spatially distributed Ca2+ signal is attenuated by intracellular BAPTA, 4) the rate at which free Ca2+ returns to resting levels, after entry (residual Ca2+) is faster with more mobile buffer, and 5) when pulse trains of Ca2+ channel current are used as input, computed facilitation is comparable to experimental measurements without buffer, but is abolished in the presence of exogenous buffer. 3. When the diffusion coefficient of Ca2+ in water is used, there is no residual Ca2+; however, when 0.1-1.6 mM nondiffusable buffer is present with a fast binding coefficient comparable to BAPTA, there is a very small residual Ca2+ due to the unbinding from the fixed binding sites. The nondiffusable buffer is saturated next to a Ca2+ channel. For this case of the diffusion coefficient of calcium in H2O and nondiffusable buffer, when a moderate amount of diffusable buffer is added to the system containing nondiffusable buffer, the very small residual Ca2+ is substantially reduced. This is because the product of diffusable buffer and Ca2+ is carried away as diffusable product, in contrast to the nondiffusable product releasing Ca2+, after Ca2+ entry ceases. 4. The model predicts that mobile calcium buffers with appropriate physical properties will attenuate facilitation and hasten its decay by removing residual calcium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Resolution limit of serial sections for 3D reconstruction of tubular cristae in rat liver mitochondria.

Following stereo, high resolution scanning electron microscopy (HRSEM) of various rat tissue mitochondria prepared by mild glutaraldehyde fixation followed by freeze cleavage and extraction of the cytosol (Lea and Hollenberg, 1989a), a new model for the ultrastructure of mitochondrial cristae has been developed (Lea and Hollenberg, 1989b). The cristae mitochondriales, previously considered in most cells to have a shelf like structure, were found in many cell types including hepatocytes by HRSEM to be tubes which spanned the mitochondrial matrix and were continuous with the inner mitochondrial membrane at both ends. Despite computer aided, serial, reconstruction of serial thin sections examined in the transmission electron microscope (TEM), tubular cristae in mitochondria have not been resolved entirely, even though circular cross sectional profiles of cristae have been observed in the TEM. The current study was undertaken to probe this deficiency and to understand its cause. In this study, the problems of inherent contrast and resolution loss in the digitized image have been reduced by using a computer based, background, extraction process analogous in the computer to the chemical cytosol extraction process used for HRSEM (Lea and Hollenberg, 1988; Hollenberg et al., 1989). Despite the use of this membrane enhancement algorithm, it was still not possible to reconstruct entire tubular cristae, as observed by HRSEM, even when the micrograph negatives were digitized and reprocessed (Lea and Hollenberg, 1989b). A comparison of serial section thickness deduced from the diffraction colour of the respective section (60 nm) to the measured diameter of tubular cristae profiles (30 nm), with membrane thickness of 10 nm, suggested that this size disparity is responsible for the apparent loss of resolution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Three-dimensional reconstruction of biological objects using a graphics engine.

A common problem in the study of biological material is the determination of three-dimensional structure from serial sections. The large number of sections required to obtain sufficient internal detail of a structure results in enormous processing requirements. These requirements can now be satisfied by current graphics engine technology in combination with image-digitizing hardware. The previously onerous tasks of manipulating and displaying 3D objects become routine with this combination of technologies. We report a computer-assisted reconstruction system on a graphics engine-based workstation. The system accepts images from any video source and includes a utility for aligning adjacent video images. Also available is an editor for geometric object entry and editing. More novel in our approach is the use of video interiors in 3D displays in addition to contours and tiled surfaces. Video interiors is a form of display in which digitized pixels interior to objects are revealed by cutaway blocks.

Algorithms↗