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Biomedical subjects

D Whitaker

Publications and source records attributed to D Whitaker.

At least 73 records · Page 4Linked to original sources

Factors affecting light-adapted pupil size in normal human subjects.

PURPOSE: To investigate the effect of age, gender, refractive error, and iris color on light-adapted pupil size in humans. METHODS: Pupil diameters of 91 subjects (age range, 17 to 83 years) with normal, healthy eyes were measured using an objective infrared-based continuous recording technique. Five photopic ocular illuminance levels were used (2.15 to 1050 lumens m-2), and the accommodative status of each subject was precisely controlled at a constant level. RESULTS: Pupil size decreased linearly as a function of age at all illuminance levels. Even at the highest illuminance level, there was still a significant effect of age upon pupil size. The rate of change of pupil diameter with age decreased from 0.043 mm per year at the lowest illuminance level to 0.015 mm per year at the highest. In addition, the variability between pupil sizes of subjects of the same age decreased by a factor of approximately two as luminance was increased over the range investigated. Pupil size was found to be independent of gender, refractive error, or iris color (P > 0.1). CONCLUSIONS: Of the factors investigated, only chronologic age had a significant effect on the size of the pupil. The phenomenon of senile miosis is present over a wide range of ocular illuminance levels.

Accommodation, Ocular↗

Confirmation of the validity of the psychophysical light scattering factor.

PURPOSE: To reevaluate the validity of the light scatter factor (LSF) formula of Paulsson and Sjöstrand, LSF = L/E (M2/M1-1), where L is the target luminance, E is the illuminance of the glare source at the eye, and M2 and M1 are modulation contrast thresholds measured with and without the glare source, respectively. This equation has recently been deemed invalid by Yager, Yuan, and Mathews. METHOD: Ratios of contrast thresholds with and without glare were measured for three glare illuminance levels for each of three stimulus luminances. This results in five different ratios of L/E, spanning a range of 1.60 log units. RESULTS: The data show an excellent fit to the Paulsson and Sjöstrand equation, and the LSF scores conform well to previously published normative values. CONCLUSION: The light scatter factor equation of Paulsson and Sjöstrand is confirmed as valid without resorting to the need for correction factors based on variables such as pupil size.

Adult↗

Cytological diagnosis of Paget's disease of the nipple by scrape smears: a report of five cases.

Five cases of mammary Paget's disease were diagnosed by nipple scrape cytology. The neoplastic material obtained was abundant in two cases, moderate in one, but in two, only a few cell aggregates feature in three cases and this, together with dense tumour cell cytoplasm and the background of keratinous debris, may impart a squamous-like appearance; however, three-dimensional cell aggregates, papillary-like groups, acinar-like collections, and some cells with vacuolated cytoplasm and eccentric nuclei allowed glandular differentiation to be inferred in three cases. In four cases a combination of clinical evaluation, and cytological findings of malignant cells compatible with Paget's disease was used so that mastectomy could proceed, and in one case there was frozen section confirmation of an underlying invasive carcinoma. In the single case in which it was performed, there was positive immunoperoxidase staining for c-erb B2 oncoprotein. Demonstration of this protein, CEA, or mucin, helps distinguish Paget's disease from melanoma or squamous cell carcinoma in-situ.

Aged↗

Evaluation of FASTPAC: a new strategy for threshold estimation with the Humphrey Field Analyser.

A new strategy for threshold estimation, FASTPAC, has been introduced for the Humphrey Field Analyser with the aim of improving the efficiency of visual field examination without loss of accuracy. FASTPAC was compared to the standard 4-2 double staircase strategy in 98 normal volunteers (age 23-83 years). One eye of each subject was examined with both strategies on two visits using Program 30-2. The order of strategy was randomised. FASTPAC examination time was 43% faster than the standard algorithm, but the mean sensitivities were similar. Short-term fluctuation was 24% higher with FASTPAC (P < 0.001). Most parameters were adversely affected by increasing age. FASTPAC offers a valid alternative to the standard strategy in the examination of suspected normal fields and should always be considered as an alternative to the threshold-related screening strategies. The performance of the algorithm in the identification of field loss and in areas of reduced sensitivity awaits further study.

Adult↗

What part of a vernier stimulus determines performance?

Vernier acuity was measured using a pair of long, abutting vertical sinusoidal luminance gratings. Performance was also measured for pairs of thin horizontal strips of grating whose vertical separation was varied in order to represent different parts of the original grating. At small strip separations, performance was equivalent to that for the long gratings only at high spatial frequencies. At moderate spatial frequencies, intermediate strip separations resulted in equivalent performance. This suggests that different parts of a vernier stimulus can mediate performance depending upon the underlying spatial frequency content. Implications for the effect of contrast upon different vernier configurations are examined.

Contrast Sensitivity↗

Detection and discrimination of curvature in foveal and peripheral vision.

Curvature detection and discrimination were measured across the visual field in order to determine whether performance at a given eccentricity could be related to that at another by a simple change of magnification. Both types of task obeyed this concept, the critical variable being the rate at which magnification must increase as a function of eccentricity. The situation can be expressed in terms of the eccentricity (E2) at which magnification must be doubled to retain performance equivalent to that at the fovea. E2 values were 1.84-1.96 deg for the detection task and 1.42-2.27 deg for discrimination. These are similar to E2 values for vernier acuity and orientation discrimination, suggesting that all of these tasks share a common determining feature across the visual field, perhaps the distribution of neural elements selective for stimulus orientation.

Discrimination, Psychological↗

Light scatter in the normal young, elderly, and cataractous eye demonstrates little wavelength dependency.

The purpose of the study was to investigate whether light scatter in normal young, elderly, and cataractous eyes exhibits significant wavelength dependency. Straylight was quantified by calculating light scatter factors (LSF's) based upon the reduction in contrast sensitivity produced by a glare source. The angle of the glare source relative to fixation was varied (3.25 to 26 degrees), as was its wavelength (460 to 660 nm). LSF's increased as a function of age an especially in the presence of media opacities. However, the relation between LSF and glare angle remained approximately the same for each group. Our results suggest that wavelength dependency in normal young, elderly, or cataractous eyes is rather unimportant relative to other factors.

Adult↗

Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells.

The expression of the alpha 6 beta 4 and alpha 6 beta 1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits alpha 6, beta 4, and beta 1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immuno-electron microscopy. The identity of these cells as LC was further established by coincident staining for alpha 6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-alpha (TNF alpha), the predominant cytokine in mast cell granules, also induced LC to express alpha 6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNF alpha antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce alpha 6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNF alpha in the regulation of the integrins alpha 6 beta 4 and alpha 6 beta 1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.

Cell Degranulation↗

Effect of filters on disability glare.

Disability glare is the reduction in visual performance caused by a peripheral glare source. We examined the effect of a long wavelength pass (red) and a short wavelength pass (blue) filter on disability glare in the presence of varying amounts of induced wavelength dependent stray light. Measurements were made in the absence of any filter and then repeated in the presence of the red and blue filters whose luminous transmission factors were equal relative to both the stimulus and the glare source. Neither of the filters had any effect on disability glare. Filters not only reduce the amount of veiling luminance from the glare source, but also reduce the ability to detect the stimulus. Disability glare was not significantly different with the red and blue filters, even in the presence of wavelength dependent scatter. Calculation of the veiling luminance transmitted by each filter revealed that the difference in veiling luminance in the two filter conditions was insufficient to result in a measurable difference in disability glare.

Adult↗

Expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during melanoma-induced angiogenesis in vivo.

Recent ultrastructural data indicate that tumor-induced angiogenesis involves polarized outgrowth of endothelial cells from established vessels into tumor parenchyma and interstitium. Efforts to define the cytoarchitecture of the angiogenic response and to ascertain molecular determinants of polarized endothelial migration have been impeded by lack of sensitive and specific immunologic markers for endothelium and vessel wall components. In this study, we utilized monoclonal antibody to platelet-endothelial cell adhesion molecule-1 (PECAM-1), a cell-cell adhesion molecule belonging to the immunoglobulin superfamily, to determine extent and patterns of angiogenesis in metastatic melanomas before (N = 7) and after (N = 3) induction of tumor-infiltrating lymphocyte responses provoked by administration of experimental melanoma vaccine. PECAM-1 proved to be a more reliable marker for angiogenesis than antibodies to von Willebrand Factor. Although both normal and tumor vessels exhibited prominent staining for PECAM-1, different patterns of endothelial reactivity were observed. Formation of new vessels was associated with i) PECAM-1 redistribution from a constitutive circumferential membrane pattern to a pattern restricted to cell-cell junctions; ii) formation of endothelial cords formed by cell-cell interactions; and iii) eventual development of open lumens. Vessels within inflamed (vaccine-treated) and non-inflamed melanomas did not differ with regard to patterns of PECAM-1 expression. Forming vessels of inflamed melanomas failed to express the cytokine-inducible activation marker, E-selectin. Although normal microvessels and reactive vessels of healing wounds demonstrated prominent staining for alpha 6 laminin receptor, vessels within melanomas showed apparently diminished expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Novel interactions between dermal dendrocytes and mast cells in human skin. Implications for hemostasis and matrix repair.

BACKGROUND: Dermal dendrocytes are a newly-recognized cell type in human skin. They express coagulation Factor XIIIa (FXIIIa), also known as fibrin stabilizing factor, and their number is increased in certain inflammatory dermatoses. Current dogma suggests that these recently described cells may represent a subset of antigen-presenting macrophages. The present study therefore was undertaken to examine further the phenotype and potential function of these novel cells. EXPERIMENTAL DESIGN: Conventional ultrastructure, single and dual label immunofluorescence and immunocytochemistry, confocal laser scanning microscopy, and immunoelectron microscopy were used to define structure and potential heterogeneity among dermal dendrocytes. Human neonatal foreskin organ culture exposed to mast cell secretagogues, inhibitors, and relevant recombinant cytokines (tumor necrosis factors alpha) was employed to gain insight into functional characteristics of FXIIIa expression. RESULTS: We found that dermal dendrocytes are phenotypically unique dermal cells, separate from conventional macrophages, with antigenic heterogeneity of FXIIIa and CD34 expression related to their microanatomical location in the dermis. Moreover, they express specialized membrane-matrix plaques that may stabilize their placement in various dermal strata. Finally, superficial subpopulations of dermal dendrocytes are closely-associated with mast cells and show enhanced FXIIIa expression in response to mast cell degranulation, an event that appears to result from liberation of mast cell tumor necrosis factor in the dendrocyte microenvironment. CONCLUSIONS: These new insights establish dermal dendrocytes as distinctive fixed skin cells with potential functional capacity for mast cell-dependent facilitation of fibrin cross-linking and matrix remodeling. These previously unrecognized phenotypic and functional characteristics of dermal dendrocytes therefore may be relevant to cellular interactions responsible for cutaneous wound healing and hemostasis.

Cell Communication↗

Magnification perimetry.

PURPOSE: The authors used a method of spatial scaling to quantify the eccentricity-related decline in differential light sensitivity as a function of visual field meridian and age. METHODS: Differential light threshold at the fovea was measured in two groups of subjects of differing age (young mean age, 23.6 yr; standard deviation, 2.4 yr; elderly mean age, 69.6 yr; standard deviation, 6.2 yr) using a Goldmann size I stimulus moving across fixation at 1 degree/sec. With luminance kept constant, eccentricity thresholds for kinetic stimuli of increasing magnification were then measured. The results were analyzed in terms of the E2 value, which specifies the eccentricity at which the stimulus size must double to maintain performance equivalent to that at the fovea. RESULTS: For the young subjects, eccentricity thresholds increased linearly with an increase in stimulus diameter for most meridians. E2 varied between 5-12 degrees, depending on the meridian, and showed the same meridional trend as that of retinal ganglion cell distribution, although the magnitudes of E2 were different. For the elderly subjects, the eccentricity thresholds increased in a nonlinear manner with the stimulus diameter. CONCLUSIONS: Further factors, such as spatial summation, must also determine the eccentricity dependence of the differential light threshold because ganglion cell density decreases at a much faster rate than the differential light threshold. The most marked effects of age on differential light sensitivity occur at the fovea and beyond 20 degrees in the peripheral field, with a relative sparing in the pericentral area.

Adult↗

Establishment of a murine model of malignant mesothelioma.

Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with previous asbestos exposure and is generally found to be resistant to conventional forms of therapy. Adequate scientific and clinical assessment of this disease has been severely limited by the relatively low incidence of mesothelioma and the lack of representative cell lines and animal models. The purpose of this study was to develop an asbestos-induced murine model of MM both as an in vivo-passaged malignancy and as in vitro-established cell lines. Such a model system would be invaluable for use in the study of various cellular, molecular and genetic aspects of the disease, and for the pre-clinical evaluation of potential therapeutic agents. BALB/c and CBA mice were injected intraperitoneally with crocidolite asbestos. Seven to 25 months after exposure, 35% of the mice developed mesothelioma (5 BALB/c, 9 CBA), as determined by standard cytological and histological parameters. From these primary tumours, 12 continuously growing cell lines (5 BALB/c, 7 CBA) were established in culture. All have been confirmed as mesothelioma by cytological and ultrastructural (electron microscopy) analyses. These lines have been in culture for 7 to 24 months and have achieved passages above 32 (range 32 to 106). As in the human disease, the murine mesothelioma lines vary in their morphology and growth rates (doubling times ranging from 14 to 30 hr). All cell lines produced tumours when injected into syngeneic mice.

Animals↗

Simulating age-related optical changes in the human eye.

The decline in visual function observed in older adults has been attributed to a deterioration in optical quality, decreased neural function, or a combination of both of these factors. One way of separating their contribution is to design a simulation of the optics of the elderly eye and examine its effect on the visual performance of younger observers. The age-related reduction in pupil size was simulated by the administration of an ophthalmic miotic drug, whilst a neutral density filter was included to account for the increased absorption of the ocular media. An optical cell containing a critical concentration of 500 nm diameter polystyrene microspheres in suspension was used to simulate light scatter. The spatiotemporal contrast sensitivity of an older group of observers was then compared with that of a younger group with and without the optical simulation. The contrast sensitivity of the younger group was consistently better than that of the older, and the presence of the optical simulation produced no significant effect on performance. This suggests that, under normal viewing conditions, it is primarily neural factors which underlie the deterioration in visual quality experienced by older observers.

Adult↗

The influence of eccentricity on position and movement acuities as revealed by spatial scaling.

The rate of decline with increasing eccentricity of several position and movement acuities was measured using a method of spatial scaling. In this method all stimuli at each visual field location are simply magnified versions of each other. The influence of separation and eccentricity were dissociated by presenting stimuli on an iso-eccentric arc. For each task, the rate of decline in performance was quantified by the parameter E2 which represents the eccentricity at which stimulus size must double in order to maintain performance equivalent to that at the fovea. All tasks were found to obey the concept of spatial scaling in that performance at a given field location could be equated with performance at any other location simply by a change of scale. However, the rate at which performance deteriorated with eccentricity varied over an enormous range (over 100-fold) depending on the task itself. The advantage of such diverse peripheral gradients is clear; the goal is to establish the physiological mechanisms which underlie this phenomenon.

Discrimination, Psychological↗

Spatial scaling of vernier acuity tasks.

Vernier acuity thresholds for two abutting lines and for a two-dot stimulus were measured as a function of stimulus magnification at eccentricities of 0, 5, 10 and 15 deg using a spatial scaling technique in which all stimuli are simply magnified versions of each other. The advantage of such a technique is that no prior knowledge of a suitable magnification factor with which to increase the size of peripheral stimuli is required. Thresholds for the line stimulus could be successfully scaled by the application of a magnification factor with an E2 value of 1.23-1.78 deg. Further, provided that the effects of dot separation and eccentricity were dissociated, spatial scaling with an E2 value of 1.06-1.96 deg was also successful in removing eccentricity dependence for two-dot vernier thresholds.

Fovea Centralis↗

An ultrastructural study of the developing urogenital tract in early human fetuses.

OBJECTIVES: This study examines the gonoducts during the ambisexual stage of human fetal development to define their ultrastructural characteristics, including the origin and antomic relationship of the mesonephric and paramesonephric ducts during gonoductal development. STUDY DESIGN: The reproductive tracts from five fetuses ranging in gestational age from 35 to 45 days were processed for ultrastructural examination. The developing mesonephric ducts, paramesonephric ducts, and their surrounding mesenchyme were studied with a Phillips 300 transmission electron microscope. RESULTS: The mesonephric ducts and paramesonephric ducts have distinctive cytoplasmic and cell surface ultrastructural characteristics, as well as different morphologic patterns of epithelial-mesenchymal interaction. Cephalad portions of mesonephric ducts and paramesonephric ducts are separated by mesenchyme, but more caudal aspects move progressively closer until they are juxtaposed but separate. CONCLUSIONS: Early mesonephric ducts and paramesonephric ducts may be distinguished because of their distinctive ultrastructural features; epithelial-mesenchymal interaction may be important in their differentiation and maintenance; both gonoducts retain their morphologic identity throughout, supporting their separate origins.

Cell Nucleolus↗