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Biomedical subjects

S A Klein

Publications and source records attributed to S A Klein.

At least 55 records · Page 3Linked to original sources
PubMed1998

Optimal corneal ablation for eyes with arbitrary Hartmann-Shack aberrations.

New technologies for accurately measuring corneal shape and full eye aberrations are now available. An algorithm that uses these technologies to predict the amount of ablation needed to produce a corneal surface that optimally focuses light is developed. It is found that knowledge of the aberrations is far more important than knowledge of corneal shape. Neglect of corneal shape information introduces an error of less than approximately 0.05 micron in the optimal ablation depth. Neglect of the aberrations is a different story. Small changes in the aberration structure, such as going from the optimal ablation to a spherical ablation, introduce ablation changes of greater than 10 microns. It is argued that there are many occasions when less ablation can lead to improved image quality.

Algorithms↗
PubMed1997

Feature integration in pattern perception.

The human visual system is able to effortlessly integrate local features to form our rich perception of patterns, despite the fact that visual information is discretely sampled by the retina and cortex. By using a novel perturbation technique, we show that the mechanisms by which features are integrated into coherent percepts are scale-invariant and nonlinear (phase and contrast polarity independent). They appear to operate by assigning position labels or "place tags" to each feature. Specifically, in the first series of experiments, we show that the positional tolerance of these place tags in foveal, and peripheral vision is about half the separation of the features, suggesting that the neural mechanisms that bind features into forms are quite robust to topographical jitter. In the second series of experiment, we asked how many stimulus samples are required for pattern identification by human and ideal observers. In human foveal vision, only about half the features are needed for reliable pattern interpolation. In this regard, human vision is quite efficient (ratio of ideal to real approximately 0.75). Peripheral vision, on the other hand is rather inefficient, requiring more features, suggesting that the stimulus may be relatively underrepresented at the stage of feature integration.

Contrast Sensitivity↗
PubMed1997

Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry.

OBJECTIVE: To characterize changes of Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) that occur during the course of HIV infection by cytoplasmic cytokine staining on single cell level. DESIGN AND METHODS: Mitogen-stimulated PBMC from 16 healthy donors, 18 HIV-1-infected individuals without AIDS and 14 patients with AIDS were stained intracellularly with fluorescein-labelled MAb against interleukin (IL)-2, IL-4, IL-10 and interferon (IFN)-gamma. Additionally, co-staining of CD4+ T-cell, CD8+ T-cell, natural killer (NK) cell, B-cell and monocytic markers was performed. Fluorescence staining was analysed by three-colour flow-cytometry. RESULTS: A reduced percentage of IL-2 and IFN-gamma (Th1 type)-producing cells among CD4+ T cells from HIV-1-infected individuals could be demonstrated. There was a continuous decrease of IFN-gamma-producing CD4+ T cells in the course of HIV infection and a dramatic reduction of IL-2-expressing cells among CD4+ T cells in patients with AIDS. In contrast to Th1 cytokines, the frequency of Th2 cytokine expressing cells among CD4+ T cells increased in HIV-infected individuals. The maximum frequency of IL-4-expressing cells among CD4+ T cells was seen in HIV-infected individuals without AIDS, whereas the rate of IL-10-producing cells was highest in patients with AIDS. In HIV-infected individuals no significant proportion of Th0 cells expressing both Th1 and Th2 cytokines was detectable. In CD8+ T cells the percentage of IL-2 was expressing cells decreased continuously accompanied by a strong increase of the frequency of IFN-gamma-producing cells. CONCLUSION: The decreased percentage of cells expressing IL-2 and IFN-gamma in conjunction with an increased proportion of IL-4- and IL-10-producing cells among the CD4+ T cells in HIV-1-infected individuals demonstrate a Th1 to Th2 cytokine shift in the course of HIV infection on a single cell level. There was no evidence of a Th1 to Th0 cytokine shift. In addition to the loss of CD4+ T cells in HIV infection, the qualitative changes of Th1/Th2 cytokine expression may serve as a marker for progressive failure of cell-mediated immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Vernier acuity with non-simultaneous targets: the cortical magnification factor estimated by psychophysics.

The eccentricity at which peripheral thresholds double their foveal value (E2) may relate to the visual system's anatomical organization. Using a variety of experimental approaches, previous estimates of E2 for vernier acuity have ranged from less than 0.1 deg to greater than 15.0 deg. This broad range of values seems to challenge the usefulness of E2 for determining visual topography. We explain that the varying contributions from at least two different regimes, spatial filter and local sign, may explain the broad range of E2 values found previously. We attempt to limit responses to the local sign regime, where it may be possible to determine the psychophysical analog to the gradient of the cortical spatial grain. In our experiments we measure how vernier task performance falls off with eccentricity. We hypothesize that if the vernier features are adequately separated in time, they will fall outside of the spatial filter's temporal integration span and the local sign regime would then predominate for precise positional processing. Using an interstimulus interval ranging from 20 to 200 msec between the two vernier features, we estimate that vernier thresholds in the local sign regime double at about 0.8 +/- 0.2 deg eccentricity, which is similar to anatomical estimates of the eccentricity at which the linear spacing of human cortical units doubles.

Contrast Sensitivity↗
PubMed1997

Resolution acuity is better than vernier acuity.

Our impressive sensitivity to vernier offsets as compared to resolution acuity has long inspired vision researchers to study the phenomena in great detail. In this study we use the test-pedestal framework to compare resolution and vernier acuity. In these experiments the test stimulus is the same for both tasks, only the pedestals differ. When thresholds are expressed in common units of test strength, vernier acuity thresholds are higher (worse) than for resolution and contrast discrimination tasks over the range of pedestal strengths tested. This apparent reversal of sensitivity is actually consistent with expectations based on the presumed underlying visual mechanisms involved in the tasks.

Contrast Sensitivity↗
PubMed1997

Ex vivo induction of apoptosis in lymphocytes is mediated by oxidative stress: role for lymphocyte loss in HIV infection.

Programmed cell death (apoptosis) of T-lymphocytes observed in human immunodeficiency virus (HIV) infected individuals could be linked to oxidative stress. Therefore, we have investigated whether reactive oxygen species (ROS) induce apoptosis, which might contribute to the cell loss during progression of HIV-1 infection. ROS were generated in peripheral blood mononuclear cells (PBMC) obtained from HIV-1-positive patients and from healthy controls by stimulation with bacteria or by treatment with hypoxanthine/xanthine oxidase, which has been shown to generate ROS without direct involvement of cytokines. A dose-dependent inhibition of ROS formation correlated with the reduction of apoptosis induced by both bacterial and hypoxanthine/xanthine oxidase stimulation, suggesting that ROS generation was responsible for the induction of apoptosis. In addition, hydrogen peroxide (H2O2) rather than superoxide (O2.-) was observed to induce apoptosis. ROS-dependent apoptosis was shown to be independent of cytokines such as tumor necrosis factor-alpha (TNF-alpha). ROS-induced apoptosis was significantly enhanced in HIV-infected subjects even in the very early stages after infection. Moreover, ROS-mediated apoptosis was not restricted to a particular lymphocyte subset. In view of the diminished oxidative resistance of HIV-infected individuals, our results suggest that ROS-mediated apoptosis might contribute to the deletion of lymphocytes and to the pathogenesis of the disease.

Acetylcysteine↗
PubMed1997

Factors determining rigid contact lens flexure.

BACKGROUND: Many factors have been demonstrated to influence flexure of rigid contact lenses, but the contributions of surface tension and eyelid forces to flexure are not well understood. METHODS: We placed lenses on a model eye consisting of a polymethyl methacrylate (PMMA) base which could be flexed, and measured resultant flexure with a videokeratoscope. We varied the base toricity, sequence of measurement, and lens base curve. The effects of evaporation of the postlens fluid were also observed. RESULTS: Clinically significant flexure (> 0.50 D) occurred when two conditions were met: (1) the volume of the postlens space would increase if the lens unflexed, and (2) there was a paucity of fluid available to fill that space. Flexure was minimal (< or = 0.50 D) when ample fluid was present. CONCLUSION: Surface tension forces serve more to maintain rather than create rigid lens flexure. Our model helps to explain why steep-fitting lenses flex more and leads to several predictions for flexure, which appear generally to be obeyed.

Contact Lenses↗
PubMed1997

Gaussian power with cylinder vector field representation for corneal topography maps.

The corneal maps displayed on commercially available corneal topography instruments are really one-dimensional, defining quantities only along a meridian, and ignoring shape information along any other direction. Both axial and instantaneous power have the drawbacks that there is a singularity at the center data point on the videokeratograph axis, and the computed powers and appearance of the corneal map change depending on the videokeratograph axis or on the location of asymmetries. We propose a new representation for corneal topography maps, Gaussian power with cylinder vector field, that has no singularity, and faithfully produces power values and corneal map patterns that are independent of videokeratograph axis or location of asymmetries.

Computer Simulation↗
PubMed1997

Axial curvature and the skew ray error in corneal topography.

BACKGROUND: Many intuitions about corneal shape are based on corneas with axial symmetry. In that case, the corneal normal intersects the axis of symmetry and there is an unambiguous definition for axial curvature. If, however, the corneal normal is not in the meridional plane, at least three definitions are available. The present paper defines, analyzes, and makes quantitative comparisons among the different definitions of axial curvature. When Placido rings are used as targets, current algorithms incur an error (the skew ray error) because the axial curvature that is measured is different from the axial curvature used for corneal reconstruction. METHODS: A cylindrical coordinate system is used that greatly simplifies the visualization and mathematics of skew rays. In the process of handling the axial curvature for different shapes, we develop a number of convenient formulas for handling ellipsoids and bispheres such as occur in keratoconus and photorefractive keratectomy (PRK). We also develop a simple approach based on vector cross-products for calculating axial curvature for an arbitrarily placed axis. RESULTS: The skew error is calculated for ellipsoidal and keratoconic corneas, and for corneas that have undergone decentered PRK ablation. For reasonable ellipsoidal and PRK corneas, the skew ray error is found to be negligible. However, for keratoconus and for decentered views of PRK corneas the error can be substantial. The implications of the skew ray ambiguity for instantaneous curvature are also discussed. CONCLUSIONS: The formalism developed in this paper facilitates the interpretation of axial curvature maps for corneas that are not axially symmetric. The skew ray error is negligible except for a small class of distorted corneas.

Cornea↗
PubMed1997

Corneal topography reconstruction algorithm that avoids the skew ray ambiguity and the skew ray error.

BACKGROUND: Because corneal shape is typically measured with Placido ring targets, there is an ambiguity in determining which point on the ring corresponds to which point on the image. This ambiguity is expected to lead to errors (which we call the skew ray error) in reconstructing the corneal shape from Placido ring videokeratoscope (VKS) images. METHODS: A coordinate system based on cylindrical coordinates is developed for handling the case when the corneal normal does not lie in the meridional plane. A simple solution is found for the forward problem of locating the Placido ring object given the VKS image and the corneal slope. RESULTS: Algorithms for solving two inverse problems are developed: (1) the inverse problem of determining the Placido image given the Placido ring object and the corneal shape, and (2) the inverse problem of reconstructing the corneal shape based on knowledge of the Placido ring object and image. The algorithm compensates for the skew ray error and does not assume the cornea to be small. Both inverse algorithms are applied to a corneal shape with eight-fold corrugations similar to what might occur in radial keratotomy (RK). The reconstruction algorithm assumes sufficient smoothness for an arc-step algorithm to be possible. We find that the reconstruction algorithm does an excellent job of obtaining the correct corneal shape without the skew ray error. CONCLUSIONS: The concrete reconstruction algorithm demonstrates that one can recover the correct corneal shape just from the reflection of the Placido rings. A dart board pattern is not necessary for removing the skew ray ambiguity, as long as the cornea has sufficient smoothness in the radial direction, an assumption common to all reconstruction algorithms.

Algorithms↗
PubMed1997

Temperature distributions during thermoradiotherapy: a sensitivity study with a transient numerical model of the rabbit eye.

An approach to the treatment of medium-sized choroidal melanomas combines radiation with ferromagnetic hyperthermia. The study herein discusses results with a numerical thermal model of a choroidal melanoma in the rabbit eye as treated with episcleral, thermoradiotherapy plaques. The sensitivity of a temperature-dependent blood perfusion model is investigated.

Animals↗
PubMed1997

Motion thresholds can be predicted from contrast discrimination.

The detection thresholds for oscillatory motion and flicker were compared across a wide range of pedestal contrasts, spatial frequencies, and temporal frequencies in both foveal and peripheral vision. Motion and flicker stimuli were both generated by summation of a counterphase test grating with a static pedestal grating. For the oscillatory motion task the test and the pedestal were presented 90 deg out of phase to each other, whereas for flicker the two gratings were presented in phase. Since detection of both stimuli would depend on the same test stimulus, detection thresholds could be similar even though the tasks differ. Although there was a slight elevation in flicker detection thresholds compared with motion thresholds, our main finding is that oscillatory motion and flicker thresholds for suprathreshold sinusoidal gratings are similar. This finding supports the idea that motion and flicker have a common underlying detection mechanism. Our finding that flicker thresholds are slightly higher than jitter thresholds indicates that the contrast gain control (or saturating energy transducer) has a weak phase dependence. The ability to discriminate motion from flicker was elevated relative to their detection thresholds, particularly at high temporal frequencies. We offer two models to account for this behavior. The discrimination of motion from flicker may require a temporal comparison of the outputs of directionally selective filters tuned to opposite directions or to the population statistics of a bank of separable mechanisms.

Contrast Sensitivity↗
PubMed1997

Substitution of testosterone in a HIV-1 positive patient with hypogonadism and Wasting-syndrome led to a reduced rate of apoptosis.

Peripheral blood mononuclear cells from HIV infected individuals develop in vitro apoptosis to a much higher extent than healthy donors. Aside from the direct cytopathic effect of HIV, programmed cell death can be induced by such cytokine system imbalance as seen with increased levels of TNF-alpha or the Th1-->Th2-cytokine shift. However, wasting syndrome, which occurs in the majority of AIDS patients is associated with an enhanced expression of TNF-alpha and IL 6 as well. A 37-year-old AIDS patient suffering from wasting syndrome and hypogonadism was treated with 1 alpha-dihydrotestosterone. The rate of apoptotic peripheral blood mononuclear cells was determined before, during and after this therapy. After three weeks of androgen substitution therapy, the rate of spontaneous apoptosis was reduced to 34% and the ionomycin induced apoptosis to 52% of the rate of apoptotic cells at the beginning of the therapy. Moreover, the general and nutritional condition improved remarkably. Thus, we suggest that the use of anabolic drugs for the treatment of AIDS-associated wasting-syndrome would not only improve their general and nutritional condition, but might also prevent the loss of CD4+ T-cells through an inhibition of apoptosis.

Acquired Immunodeficiency Syndrome↗
PubMed1996

TNF-alpha mediated apoptosis of CD4 positive T-lymphocytes. A model of T-cell depletion in HIV infected individuals.

Apoptosis has been suggested to account for loss of CD4+ T-cells in HIV infected individuals. Aside from MHC II dependent superantigens no mediator for preferential apoptosis of CD4+ T-cell has been described. However, the expression of TNF-alpha is increased in HIV+ patients. Additionally, TNF-alpha is known as a potent inducer of apoptosis in a variety of cell types. We therefore investigated the capacity of TNF-alpha to mediate apoptosis in vitro preferentially in CD4+ T-cells from HIV+ individuals. In the presence of TNF-alpha, CD4+ T-cells from HIV+ individuals with more than 200 CD4+ T-cells/microl (classified CDC A1, A2, B1, B2) could be significantly depleted by apoptosis without a reduction of CD8+ T-cells. In cells from patients with less than 100 CD4+ T-cells/microl (classified CDC C3), TNF-alpha mediated apoptosis was not apparent due to an already immensely elevated rate of apoptosis observed in the absence of TNF-alpha. Here we demonstrate cord blood mononuclear cells as a model for apoptosis since these cells develop apoptosis at a similar rate as that of PBMC in HIV+ patients. More than 50% of TNF-alpha stimulated CD4+ cord blood T-cells were depleted within 3 days by apoptosis, whereas CD8+ T-cells, B-cells and NK-cells were not affected. In PBMC from healthy adults, a preferential loss of CD4+ T-cells mediated by TNF-alpha was not observed. A reduced production of IFN-gamma was observed in mononuclear cells from newborns and from HIV+ patients. Moreover, IFN-gamma and IL-2 could prevent TNF-alpha mediated apoptosis. Therefore, a reduced Th1-cell-function may contribute to TNF-alpha mediated apoptosis of CD4+ T-cells from these donor groups. Taken together, the data suggest that TNF-alpha probably is a mediator of the loss of CD4+ T-cells in HIV infected patients in vivo.

Adult↗
PubMed1996

Intrinsic uncertainty and integration efficiency in bisection acuity.

A spatial perturbation paradigm was used to determine equivalent intrinsic uncertainty and spatial integration efficiency in bisection. Specifically, three-line bisection thresholds were measured in the fovea of four normal observers with stimulus lines comprised of discrete dark dots distributed randomly around the mean line position according to a Gaussian function. The standard deviation of the Gaussian distribution (sigma e), the number (N), and the strength (C) of the dots as well as line separation were varied. Bisection thresholds were modeled by an ideal integrator, from which the magnitude of equivalent internal uncertainty (sigma i), the equivalent effective number of dots (k), and equivalent integration efficiency (k/N) were quantified. At the 2 min arc separation, sigma i decreases (down to a few sec arc) as N and/or C increases. The effects of both N and C can be accounted for by the stimulus visibility (V, in multiples of detection threshold). At the 16 min arc separation, sigma i is independent of N, C, or V, and is about 1 min arc. The two different forms of sigma i indicate that bisection judgments are limited by at least two separate sources of limiting noise, consistent with the hypothesis of two separate mechanisms (i.e. spatial filters and local signs). A visibility dependent sigma i at the 2 min arc separation can be explained on the basis of contrast sensitive spatial filter mechanisms. A fixed sigma i at the 16 min arc separation indicates a genuine positional uncertainty, consistent with local-sign mechanisms. Interestingly, equivalent integration efficiency (k/N) is very similar at the two line separations. k/N is critically dependent on, and proportional to C, indicating a common limitation in a detection mechanism.

Depth Perception↗