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Biomedical subjects

D Yager

Publications and source records attributed to D Yager.

At least 37 records · Page 2Linked to original sources

Acute histamine-induced flux of airway liquid: role of neuropeptides.

The role of capsaicin-sensitive neuropeptides in the accumulation of airway wall liquid observed 30 s after histamine infusion was investigated in guinea pigs. Two groups were studied: normal animals and animals in which endogenous neuropeptides had been depleted by capsaicin pretreatment. A rapid intravenous infusion of saline or histamine (11 micrograms/kg resulted in marked but similar changes in pulmonary mechanics in normal and capsaicin-pretreated animals. To assess liquid accumulation in airway wall compartments, the lungs were frozen 30 s after histamine infusion; airways from these lungs, 0.15-2.44 mm in internal perimeter, were imaged by low-temperature scanning electron microscopy. There was no difference in average airway surface liquid thickness (hASL) in normal or capsaicin-pretreated airways in response to saline. In capsaicin-pretreated animals, histamine infusion was associated with a significantly decreased hASL (hASL, cap11/hASL,cap0 = 0.58, P < 0.04). Capsaicin pretreatment, without histamine exposure, caused significant increases in epithelial and submucosal areas (Aepi,cap0/Aepi,norm0 = 1.23, P < 0.06; Asub,cap0/Asub,norm0 = 1.40, P < 0.01). The notation cap0 and cap11 indicates capsaicin-pretreated airways given 0 or 11 micrograms/kg histamine, respectively; similarly, norm0 and norm11 indicate normal airways given 0 and 11 micrograms/kg histamine, respectively. Histamine infusion in capsaicin-pretreated animals was associated with liquid shifts from epithelium to lamina propria and from submucosa to adventitia; however, the total wall area was similar to, if not smaller than, that in capsaicin-pretreated animals without histamine treatment. In contrast, histamine infusion in normal animals resulted in significant increases in the areas of the epithelial and lamina propria compartments (Aepi,norm11/Aepi,norm0 = 1.25, P < 0.05; Alp,norm11/Alp,norm0 = 2.19, P < 0.001) as well as a substantial increase in adventitial area, which was significantly attenuated by capsaicin pretreatment (Aadv,cap11/Aadv,norm11 = 0.40, P < 0.001). The resulting total wall area was more than twice that in normal animals without histamine treatment. Our data indicate that histamine-induced accumulation of liquid in the epithelium, lamina propria, and adventitia of normal airways is rapid in onset, most likely derives from a leaky bronchial microvasculature, and is mediated by the secondary release of neurokinins.

Airway Resistance↗

Role of ascorbic acid in procollagen expression and secretion by human intestinal smooth muscle cells.

The role of ascorbate in the production and secretion of procollagen by human intestinal smooth muscle cells and the conditions in culture for optimal ascorbate bioefficacy were studied. Procollagen synthesis and secretion were determined by the incubation of cells with L-[5-3H]proline, and the quantitation of radiolabelled procollagen bands in the cell layer and the culture medium by polyacrylamide slab gel electrophoresis and densitometry. When cells were cultured without ascorbate in the culture medium, procollagen secretion into the medium was 75% less than in cells receiving fresh ascorbate daily. In the cell layer, in contrast, procollagen accumulation was fourfold greater in the scorbutic cells than in the ascorbate-replete cells. These findings contrasted with those in a control line of scorbutic human dermal fibroblasts in which a 95% decrease in procollagen secretion was not associated with any procollagen accumulation in the cells. In the intestinal smooth muscle cells, the absence of ascorbate resulted in a 25 and 50% decrease in steady-state levels of procollagen I and III mRNA, respectively, compared to a 40 and 75% decrease in fibroblasts. Heat inactivation of the serum in the culture medium augmented the promotion of procollagen secretion by ascorbate two- to fourfold. L-ascorbate phosphate did not increase the activity of L-ascorbate when replaced in medium either daily or every 4 days, and its efficacy was not augmented by serum heat inactivation. The changing of culture medium induced collagen secretion in the absence of ascorbate, but this process was markedly enhanced by ascorbate and induced a transient decrease in the steady-state levels of both procollagen and nonprocollagen mRNAs. The predominant action of L-ascorbate on HISM cells in vitro is to promote procollagen secretion and not procollagen synthesis. L-ascorbate-phosphate is not an adequate substitute for L-ascorbate in this cell line.

Ascorbic Acid↗

A labeled lines explanation of the perceived spatial frequency of moderate-, near-threshold- and zero-contrast spatial patterns.

We tested the predictions of a multiple-channels model about the appearance of spatial patterns. Specifically we tested how encoding the perceived spatial frequency of a near-threshold pattern compared with encoding of a zero-contrast or moderate-contrast pattern. For example, the model predicts that the mean perceived spatial frequency of a near-threshold pattern is a weighted average of the response to the stimulus and the noise. Six subjects used the method of adjustment procedure to match a peripherally viewed test stimulus (or a blank) with a foveally viewed grating. For near-threshold patterns we found a smooth perceived spatial-frequency function, with a smaller range of perceived spatial frequencies than obtained for 0.16 contrast patterns. These results are consistent with the predictions of the model: noise can affect the appearance of near-threshold and zero-contrast patterns.

Contrast Sensitivity↗

Accommodation responds to changing contrast of long, middle and short spectral-waveband components of the retinal image.

We simulated the effects of longitudinal (axial) chromatic aberration and defocus on contrast of the long-, middle- and short-wavelength components of the retinal image to determine whether the effects of chromatic aberration are sufficient to drive accommodation. Accommodation was monitored continuously while subjects (12) viewed a 3 c/deg white sine-wave grating (0.92 contrast) in a Badal stimulus system. The contrasts (amplitudes) of the red, green and blue components of the white grating changed independently to simulate a grating oscillating from 1 D behind the retina to 1 D in front of the retina at 0.2 Hz. Subjects responded strongly to the chromatic simulation but poorly to a luminance control. The results support the hypothesis that focus is specified by the contrast of spectral-wavebands of the retinal image, and that conventional color mechanisms, monitoring chromatic contrast at luminance borders (1-8 c/deg), mediate the signals that specify dioptric vergence.

Accommodation, Ocular↗

"The Reading Assistant": user-friendly technology for the visually impaired.

One important way in which optometry must respond to the needs of persons with visual disabilities is to develop innovative applications of technologies that will allow these people to function productively in the workplace, where their performance depends on the ability to read at reasonable rates: to read such documents as letters, memos, contracts, instruction manuals, newspapers, magazines, and the like. In this paper I will describe one example of such an effort, a system that is being developed jointly by the SUNY College of Optometry, the National Eye Institute, and MerlinVision Industries, Inc., a company in Yorktown Heights, NY. I have an interest in what is reported here: I hold a part-time position as Director of Clinical Research at MerlinVision.

Humans↗

Alveolar lining layer is thin and continuous: low-temperature scanning electron microscopy of rat lung.

The low-temperature electron microscope, which preserves aqueous structures as solid water at liquid nitrogen temperature, was used to image the alveolar lining layer, including surfactant and its aqueous subphase, of air-filled lungs frozen in anesthetized rats at 15-cmH2O transpulmonary pressure. Lining layer thickness was measured on cross fractures of walls of the outermost subpleural alveoli that could be solidified with metal mirror cryofixation at rates sufficient to limit ice crystal growth to 10 nm and prevent appreciable water movement. The thickness of the liquid layer averaged 0.14 micron over relatively flat portions of the alveolar walls, 0.89 micron at the alveolar wall junctions, and 0.09 micron over the protruding features (9 rats, 20 walls, 16 junctions, and 146 areas), for an area-weighted average thickness of 0.2 micron. The alveolar lining layer appears continuous, submerging epithelial cell microvilli and intercellular junctional ridges; varies from a few nanometers to several micrometers in thickness, and serves to smooth the alveolar air-liquid interface in lungs inflated to zone 1 or 2 conditions.

Animals↗

Disability glare: effects of temporal characteristics of the glare source and of the visual-field location of the test stimulus.

One of the main early complaints of cataract patients, even when these patients exhibit only mild glare problems as measured by standard tests, is that glare impairs their night driving. To provide a better measure of the patients' impairment, glare tests should include measurements of the glare effect in conditions more similar to those found in night driving. During night driving the ambient light is very low, and oncoming headlights present a transient temporal pattern. Furthermore, the objects of interest often appear initially in the peripheral visual field. Thus three important characteristics of glare in night driving are that the ambient illuminance is in the scotopic-mesopic range, the detection stimulus is in the periphery, and the glare source is transient. Most of the current glare testers measure glare only at photopic levels, and all the glare tests that we know of use only steady sources of glare with foveal discriminations. All these conditions are dealt with. The transient glare source raised thresholds by 0.5-0.75 log unit more than the steady glare source, and the transient glare effect was more pronounced and more long lasting in the periphery. Standard glare testers seriously underestimate disability glare effects in everyday life.

Adaptation, Ocular↗

Airway wall liquid. Sources and role as an amplifier of bronchoconstriction.

Airway liquid balance in asthma is largely determined by active plasma exudation from tracheobronchial microvessels into the interstitial spaces of the mucosa, submucosa, and/or adventitia, and from there into the luminal space. This exuded plasma is rich in proteins and cell mediators capable of initiating several events, including activation of sensory neural pathways, plasma protein cleavage, inflammatory cell recruitment, and inhibition of surfactant function. It can act to amplify the bronchoconstrictor response by increasing mucosal and/or submucosal thickness, altering mechanical properties of airway wall compartments, decoupling the airway wall from parenchymal attachments, filling airway interstices, and by creating an additional inward force because of surface tension, resulting in further airway constriction and possibly closure and thereby significantly increasing airways resistance.

Animals↗

Biology of fetal wound healing: hyaluronate receptor expression in fetal fibroblasts.

Fetal tissue repair is rapid, relatively scarless, and proceeds in an environment rich in hyaluronic acid. Understanding the interaction of hyaluronic acid (HA) with the reparative cells may provide important insight into the remarkable process of fetal wound healing. Therefore, the purpose of this study was to characterize the HA receptor (a member of the CD44 family of cell surface glycoproteins) and its density on the cell surface of fetal fibroblasts. HA receptor expression on both adult and fetal fibroblasts was first studied by Western blot analysis. Autoradiographs of the blots were assessed by densitometry to quantitate the relative amounts of the HA receptor. It appears that the HA receptor expressed on both adult and fetal rabbit dermal fibroblasts is a 56-kd protein. After normalizing for total protein concentration using the Bradford protein assay, the fetal HA receptor density was found to be approximately four-fold greater than that of the adult. The same adult and fetal fibroblasts were then studied by flow cytometry, using a fluorescence-activated cell sorter (FACS). Relative fluorescence was representative of HA receptor density. Corroborating the authors' earlier result with the Western blot analysis, the FACS analysis showed that the fetal fibroblasts had 2.5 times the fluorescence of the adult cells. It is concluded that, in comparison to adult fibroblasts, fetal fibroblasts have an increased density of cell-surface HA receptor.

Animals↗

Age differences in spatial contrast sensitivity are not the result of changes in subjects' criteria or psychophysical performance.

PURPOSE: To analyze separately the sensory and nonsensory aspects of reductions in contrast sensitivity with age. METHODS: Two-alternative forced choice psychometric functions were fitted with a three-parameter Weibull function, which independently estimated threshold, slope, and upper asymptote of the functions. RESULTS: There were no changes in slope or upper asymptote with age, but contrast sensitivity decreased with age. CONCLUSIONS: Most studies of decreased visual function in the elderly are difficult to interpret because possible nonsensory effects are ignored. This paper illustrates a method that can be used to demonstrate a true sensory decline with age.

Adult↗

Contrast detection and discrimination in young and older adults.

PURPOSE: To determine if age differences in contrast detection thresholds extend to suprathreshold contrast discrimination. METHODS: Psychophysical contrast detection and discrimination thresholds were determined in 56 adults ranging in age from 22 to 72 years. In experiment 1, thresholds were measured using a two-interval forced-choice procedure across a range of pedestal grating contrasts. In experiment 2, detection and discrimination thresholds were measured at two spatial frequencies and two luminance levels. RESULTS: When normalized to the contrast detection threshold, contrast discrimination thresholds were similar in young and older adults. This result is akin to previous findings for clinical patients with contrast detection deficits. In addition, contrast discrimination in the elderly is independent of mean display luminance as has been found in young adults. CONCLUSIONS: Normalized contrast discrimination functions have the same shape in young and older adults and show no change with a 4-fold reduction in luminance.

Adult↗

Airway surface liquid thickness as a function of lung volume in small airways of the guinea pig.

The average thickness and distribution of airway surface liquid (ASL) on the luminal surface of peripheral airways were measured in normal guinea pig lungs frozen at functional residual capacity (FRC) and total lung capacity (TLC). Tissue blocks containing cross sections of airways of internal perimeter 0.188-3.342 mm were cut from frozen lungs and imaged by low-temperature scanning electron microscopy (LTSEM). Measurements made from LTSEM images were found to be independent of freezing rate by comparison of measurements at rapid and slow freezing rates. At both lung volumes, the ASL was not uniformly distributed in either the circumferential or longitudinal direction; there were regions of ASL where its thickness was < 0.1 micron, whereas in other regions ASL collected in pools. Discernible liquid on the surfaces of airways frozen at FRC followed the contours of epithelial cells and collected in pockets formed by neighboring cells, a geometry consistent with a low value of surface tension at the air-liquid interface. At TLC airway liquid collected to cover epithelial cells and to form a liquid meniscus, a geometry consistent with a higher value of surface tension. The average ASL thickness (h) was approximately proportional to the square root of airway internal perimeter, regardless of lung volume. For airways of internal perimeter 250 and 1,800 microns, h was 0.9 and 1.8 microns at FRC and 1.7 and 3.7 microns at TLC, respectively. For a given airway internal perimeter, h was 1.99 times thicker at TLC than at FRC; the difference was statistically significant (P < 0.01; 95% confidence interval 1.29-3.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Controlling unwanted sources of threshold change in disability glare studies: a prototype apparatus and procedure.

One of the main purposes of cataract surgery is to reduce the debilitating effects of light scatter by the lens. An important effect of this intraocular forward scatter is to produce a veiling retinal illuminance from a glare source. The retinal contrast of the stimulus is thus reduced, and a quantifiable "disability glare" effect may be measured. A complication is introduced by the fact that intraocular scatter arises from other sources in addition to the lens. All present tests of glare disability fail to eliminate or control for these factors, nor do they control for the light adaptation effect of the glare source. The effects of lens removal may not be predicted accurately by such tests, and patients may report little improvement in visual function after surgery. The goal of this research is to provide the background for developing a method of measuring disability glare due only to light scatter in the lens. Thirty-seven patients with mild to moderate cortical cataracts served as subjects. A disability glare effect (DG) was measured with a Maxwellian-view system that eliminates or controls scatter from the iris, sclera, and retina, and which controls for light-adaptation effects from the glare source. DG with this method showed a significant correlation with objective measures of lens light back scatter. Suggestions were made for improvements in the apparatus and procedures for future clinical studies.

Aged↗

Reduction of foveal desensitization with blurred backgrounds.

Photopic spatial desensitization and sensitization (Westheimer) functions were measured with sharp edged and blurred edged backgrounds. Data show that for 6-min backgrounds, desensitization is reduced for test flashes presented against blurred backgrounds compared to test flashes presented against backgrounds with sharp edges. We suggest that the transients from edges of retinal images, caused by high frequency fixational eye movements, contribute to the mechanisms of spatial desensitization and sensitization; the effect of transients is reduced by blurring the backgrounds.

Adaptation, Ocular↗

Effect of bronchial smooth muscle contraction on lung compliance.

Lung compliance is generally considered to represent a blend of surface and tissue forces, and changes in compliance in vivo are commonly used to indicate changes in surface forces. There are, however, theoretical arguments that would allow contraction of airway smooth muscle to affect substantially the elasticity of the lung. In the present study we evaluated the role of conducting airway contraction on lung compliance in vivo by infusing methacholine (MCh) at a constant rate into the bronchial circulation. With a steady-state MCh infusion of 2.4 micrograms/min into the bronchial perfusate (perfusate concentration = 0.7 microM), there was an approximate doubling of lung resistance and a 50% fall in dynamic compliance. There were also significant decreases in chord compliance measured from the quasi-static pressure-volume curves and in total lung capacity and residual volume. When the same infusion rate was administered into the pulmonary artery, no changes in lung mechanics were observed. These results indicate that the conducting airways may have a major role in regulating lung elasticity. This linkage between airway contraction and lung compliance may account for the common observation that pharmacological challenges given to the lung usually result in similar changes in lung compliance and airway conductance. Our results also suggest the possibility that the lung tissue resistance, which dominates the measurement of lung resistance in many species, might in fact reflect the physical properties of conducting airways.

Airway Resistance↗

Microscopic vs. macroscopic deformation of the pulmonary alveolar duct.

The stretch of the perimeters of alveolar ducts was measured at the surface of saline-filled specimens of human and dog lung parenchyma that were stretched biaxially. The microscopic stretch of these ducts was measured at several levels of isotropic biaxial macroscopic stretch of the parenchyma with stretch ratio (lambda x = lambda y) in the range of 1.20-1.40, which roughly corresponds to tidal breathing in humans and dogs. Alveolar walls were found to be load-carrying elements in the saline-filled lung, as seen by their straightness at all levels of stretch. Quantitatively, let l, A, L, and S denote, respectively, the duct perimeter length and area and the parenchymal target perimeter and area in the deformed state and lo, Ao, Lo, and So the corresponding variables in the undeformed state. The microscopic stretch ratio of the ducts (l/lo) was found to be approximately 4% larger than the macroscopic stretch ratio (L/Lo) in human lung and approximately 10% larger in dog lung. The microscopic area ratio of the ducts (A/Ao) was found to be approximately 10% larger than the macroscopic area ratio (S/So) in human lung and approximately 22% larger in dog lung. Ducts within human parenchyma were seen to be about twice as stiff as ducts within dog parenchyma over the range of macroscopic stretch studied. This correlates with the volume fractions of collagen and elastin being higher in the human lung than in dog lung. The observed nonuniformity in strain field at the microstructural level suggests the need to include a force balance between alveolar ducts and septal walls when modeling the mechanics of saline-filled parenchyma.

Animals↗

What is the utility of the psychophysical 'light scattering factor'?

It has been suggested by Sjöstrand and his colleagues that an index of scatter by the ocular media may be derived from contrast sensitivity measured with and without a glare source. This index was tested under different conditions of stimulus luminance and found not to be constant and thus to not reflect a property of the media.

Adult↗

A model for perceived spatial frequency and spatial frequency discrimination.

The responses of labelled spatial frequency channels are combined to generate an index of perceived spatial frequency. Spatial frequency discrimination thresholds are shown to be inversely related to the slope of the function of the index vs spatial frequency, when it is plotted on log-log co-ordinates.

Discrimination, Psychological↗