Biomedical subjects

V Lakshminarayanan

Publications and source records attributed to V Lakshminarayanan.

At least 19 recordsLinked to original sources

PubMed1999

Stimulus-specific regulation of chemokine expression involves differential activation of the redox-responsive transcription factors AP-1 and NF-kappaB.

The promoters of the IL-8, MCP-1, and RANTES genes contain binding sites for the redox-responsive transcription factors AP-1 and NF-kappaB, which have been shown to be important for their expression. In this overview, we present evidence from our laboratories that the stimulus-specific regulation of these chemokines by the reactive oxidant H2O2, the proinflammatory cytokine TNF-alpha, and respiratory syncytial virus (RSV) is mediated in a cell type-specific manner involving different patterns of AP-1 and NF-kappaB binding activity. Our results demonstrate that H2O2 induction of IL-8 gene expression is linked with the selective binding of AP-1 to the IL-8 promoter, whereas TNF-alpha and RSV induction of IL-8 correlates with the activation of NF-kappaB binding. We propose that the differential activation and binding of inducible transcription factors to the promoter regions of chemokine genes provides a critical regulatory mechanism by which the CXC and CC chemokines can be selectively expressed in a cell type-specific and stimulus-specific manner. Such a regulatory mechanism of differential chemokine expression could critically influence the site-specific recruitment of distinct subsets of leukocytes to sites of inflammation and injury.

Animals↗

PubMed1998

H2O2 and tumor necrosis factor-alpha induce differential binding of the redox-responsive transcription factors AP-1 and NF-kappaB to the interleukin-8 promoter in endothelial and epithelial cells.

We previously demonstrated that tumor necrosis factor-alpha (TNFalpha) and H2O2 differentially regulate interleukin-8 (IL-8) and intercellular adhesion molecule (ICAM-1) gene expression in endothelial and epithelial cells. H2O2 induced IL-8 expression in the A549 and BEAS-2B epithelial cell lines, but not in the human microvessel endothelial cell line, HMEC-1 or human umbilical vein endothelial cells. In contrast, H2O2 induced ICAM-1 only in endothelial cells. Unlike H2O2, the proinflammatory cytokine TNFalpha induced IL-8 and ICAM-1 in both cell types. In this study, we examine the role of the redox-responsive transcription factors AP-1 and nuclear factor-kappaB (NF-kappaB) in the differential expression of IL-8. DNA binding studies using nuclear protein extracts from HMEC-1 and A549 cells stimulated with H2O2 or TNFalpha demonstrated differential activation and promoter binding of AP-1 and NF-kappaB. H2O2 activated AP-1 but not NF-kappaB in A549, whereas TNFalpha activated AP-1 as well as NF-kappaB. In HMEC-1, TNFalpha activated NF-kappaB but not AP-1, while H2O2 did not activate either transcription factor. The differential activation of the factors was also reflected in their differential binding to the IL-8 promoter. Moreover, the H2O2 concentration dependent increase in epithelial IL-8 mRNA expression directly corresponded to the H2O2 concentration dependent binding of AP-1 to the IL-8 promoter. Supershift analysis revealed H2O2 as well as TNFalpha induced AP-1 complexes containing c-Fos and JunD. TNFalpha induced NF-kappaB complexes containing Rel A (p65). Immunohistochemical staining of HMEC-1 and A549 cells revealed TNFalpha stimulated nuclear localization of Rel A, whereas no translocation of Rel A was detected in either cell type stimulated by H2O2. These data indicate that the cell type-specific induction of IL-8 gene expression by H2O2 and TNFalpha in HMEC-1 and A549 cells can be explained by the differential binding of AP-1 and NF-kappaB to the IL-8 promoter.

Base Sequence↗

PubMed1998

Choice of reference axis in ocular wave-front aberration measurement.

The geometrical center of the pupil has often been used as the reference axis in ocular wave-front aberration measurement. However, the geometrical center of the pupil may shift when the pupil size changes under different conditions. In particular, for subjective methods, defining the center of the pupil precisely during the actual measurement is not always practical. Furthermore, the geometrical center of the pupil may not define the chief ray of the ocular optics because of the Stiles-Crawford apodization effect, which has a peak location that often deviates from the geometrical center of the pupil. We present the coefficient transformation table of the Taylor polynomial up to the sixth order with respect to reference axis shift. We illustrate the effect of wave-front aberration change with reference axis shift with experimental data. This type of wave-front aberration change could be a true measurement error if there is an error in defining the reference axis. We also propose using the coaxially sighted corneal reflex as a better reference axis in aberration measurement.

Humans↗

PubMed1998

Lie algebraic treatment of dioptric power and optical aberrations.

The dioptric power of an optical system can be expressed as a four-component dioptric power matrix. We generalize and reformulate the standard matrix approach by utilizing the methods of Lie algebra. This generalization helps one deal with nonlinear problems (such as aberrations) and further extends the standard matrix formulation. Explicit formulas giving the relationship between the incident and the emergent rays are presented. Examples include the general case of thick and thin lenses. The treatment of a graded-index medium is outlined.

Humans↗

PubMed1997

Differential regulation of interleukin-8 and intercellular adhesion molecule-1 by H2O2 and tumor necrosis factor-alpha in endothelial and epithelial cells.

The reactive oxygen intermediate H2O2 can function as a signaling molecule to activate gene expression. In this study, we demonstrate that oxidant stress induced by tumor necrosis factor alpha (TNFalpha) or H2O2 differentially regulates intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) gene expression in endothelial and epithelial cells. Northern blot analysis revealed that TNFalpha induced both ICAM-1 and IL-8 expression in either the A549 lung epithelial cell line or the human microvessel endothelial cell line (HMEC-1). In contrast, H2O2 selectively induced only ICAM-1 in HMEC-1 and only IL-8 in A549. This cell type-specific pattern of IL-8 expression was also observed in several other endothelial and epithelial cells. TNFalpha induced greater IL-8 gene expression as compared with H2O2, but the kinetics of induction were similar. The induction of epithelial IL-8 message was accompanied by a corresponding increase in functional IL-8 protein secretion as determined by a neutrophil motility assay. The increased neutrophil motility stimulated by conditioned media from H2O2- or TNFalpha-exposed A549 cells was completely inhibited by an anti-IL-8 antibody. TNFalpha and H2O2 also induced a differential pattern of CC chemokine expression in A549. While TNFalpha induced both RANTES and MCP-1, H2O2 induced only MCP-1. These data suggest that epithelial cells under oxidant stress contribute to the inflammatory cytokine network by selective production of IL-8, MCP-1, and RANTES, which may critically influence the site-specific recruitment of leukocyte subsets.

Animals↗

PubMed1997

Expressions for aberration coefficients using nonlinear transforms.

A matrix method to do nonlinear calculations is described. This is possible only under the special condition when a transformation maps a zero vector onto a zero vector. Geometrical optics conform to this condition and hence matrix methods can be applied to calculate aberrations. Methods to reduce computational complexities using symmetry arguments are provided. The formalism is applied to study refraction by a conic surface. Aberration coefficients, up to fifth order, are obtained as functions of eccentricity and the latus rectum of the conic surface. The method can be used to model corneal aberrations.

Cornea↗

PubMed1997

Photoreceptor orientation and alignment in nasal fundus ectasia.

BACKGROUND: We investigated whether Stiles-Crawford (SCE) functions, a measure of photoreceptor orientation and alignment, are disturbed in patients with nasal fundus ectasia (tilted disc; Fuch's coloboma without apparent pupillary involvement). METHODS: SCE functions were obtained in three observers with nasal fundus ectasia, using psychophysical methods. RESULTS: In all cases, disruption of photoreceptor alignment can be inferred. Results include location of the SCE peaks outside the pupil in the direction of the lesion, differential alignment, and reduction of the magnitude of SCE at various retinal loci (reduced curvature or p factor). Additional results obtained with the selective adaptation technique imply that receptor disarray (splaying) may be responsible for loss of retinal directional sensitivity. CONCLUSIONS: From these results, it may be surmised that mechanical tractional forces can play a major role in defining photoreceptor orientation in the retina. Inferred anomalous photoreceptor alignment has heretofore not been specifically linked with Fuch's coloboma/tilted disc syndrome.

Adaptation, Ocular↗

PubMed1996

Vision in dementia: contrast effects.

Contrast sensitivity has been shown to be affected in Alzheimer's disease (Ad). We investigated low contrast acuity and contrast sensitivity using clinical test charts in this patient population. Additionally, we tested patients with vascular dementia (vd) and mixed dementia (md), (Alzheimer' with vascular dementia). Contrast sensitivity was assessed using the Vistech VCTS 6500 test chart. Low contrast acuity was measured using the Regan charts at four contrast levels (96%, 50%, 25% and 11%). The patient population consisted of 19 Ad patients, 9 vd patients and 10 md patients. Reduction in acuity was found with contrast level in all cases. Regression lines were fit to the data and statistical analysis was performed. We did not find a statistically significant difference between the Ad and vd or md groups. We did, however, find a difference between the vd and md groups. We did find reduction in contrast sensitivity at all spatial frequencies when compared to the elderly normal. Correspondingly, we found a significant difference in acuity when compared with normal data at the four contrast levels tested. Acuity is reduced with contrast in all patient groups. Our contrast sensitivity results are similar to those reported in the literature. This study points out the importance of using simple clinical test charts and further underscores the idea that there is a primary visual deficit in Ad.

Aged↗

PubMed1996

Ray vector fields, prentice's equation, and Fourier representation of spherocylindrical lenses.

AIM: To illustrate how the concept of ray vector fields can be used to demonstrate the elementary properties of thin lenses. METHODS: Principles of matrix algebra are used. RESULTS: Using simple geometry we give a generalization of Prentice's rule to include thick astigmatic lenses. Starting from the ray vector fields we show the connection between various representations of spherocylindrical lenses (Fourier representation, expansion in terms of the cross-cylinders). We suggest two clinical areas to which these concepts can be applied.

Eyeglasses↗

PubMed1995

H2O2 and tumor necrosis factor-alpha activate intercellular adhesion molecule 1 (ICAM-1) gene transcription through distinct cis-regulatory elements within the ICAM-1 promoter.

We investigated the mechanisms by which H2O2 increases intercellular adhesion molecule 1 (ICAM-1; CD54) expression in endothelial cells. The H2O2-induced increase in ICAM-1 mRNA was inhibited by actinomycin D, by the antioxidant N-acetylcysteine, and by 3-amino-benzamide (which blocks oxidant-induced AP-1 activity), but not by pyrrolidine dithiocarbamate (which blocks oxidant-induced NF-kappa B activity). Nuclear run-on and transient transfections of ICAM-1 promoter constructs indicated that H2O2 stimulated ICAM-1 gene transcription by activation of a distinct region of the ICAM-1 promoter. The H2O2-responsive element was localized to sequences between -981 and -769 (relative to start codon). Located within this region are two 16-base pair repeats, each containing binding sites for the transcription factors AP-1 and Ets. A similar composite AP-1/Ets element isolated from the macrophage scavenger receptor gene conferred H2O2 responsiveness to a minimal promoter. Mutation of the 16-base pair repeats within the ICAM-1 promoter prevented H2O2-induced DNA binding activity, and their deletion abrogated the H2O2-induced transcriptional activity. In contrast, TNF alpha induced ICAM-1 transcription via activation of promoter sequences between -393 and -176, a region with C/EBP and NF-kappa B binding sites. The results indicate that H2O2 activates ICAM-1 transcription through AP-1/Ets elements within the ICAM-1 promoter, which are distinct from NF-kappa B-mediated ICAM-1 expression induced by TNF alpha.

Animals↗

PubMed1995

Vernier acuity and aging.

PURPOSE/BACKGROUND: Many visual functions change with age. Hyperacuity vernier thresholds, however, seem to remain practically invariant with age. METHODS: We critically review reports on age-related changes in hyperacuity thresholds and present new data using two and three-point vernier hyperacuity thresholds. RESULTS: It appears as though the vernier (two dot or two line) alignment hyperacuity thresholds are not sensitive to age. SIGNIFICANCE: Based on these studies we propose that hyperacuity (vernier) thresholds be used as a benchmark, or a gold standard for aging studies. This measurement can serve as a valuable control and reference for other clinical studies of aging.

Adult↗

PubMed1995

Ray vector fields and representation of thin spherocylindrical lenses.

PURPOSE: To introduce the concept of the ray vector field and apply it to a problem in ophthalmic optics. METHODS: Matrix and linear algebra are used to relate ray vector fields and a representation of thin spherocylindrical lenses. RESULTS: Equations were derived relating ray vector fields and a particular coordinate system recommended previously. The method is illustrated with a simple example from ophthalmic optics, namely, addition of spherocylindrical lenses. We also illustrate the method by considering two spherocylinders separated by a distance. CONCLUSIONS: Ray vector fields are intuitively simple and can be used to solve complex ophthalmic optics problems.

Eyeglasses↗

PubMed1995

Performance on three-point vernier acuity targets as a function of age.

With certain (but not all) vernier acuity (VeA) stimulus displays observers exhibit no or slight performance decrements with aging. Because three-point VeA test displays are much more easily applied experimentally and clinically, we examined visual performance on this task as a function of age. Ages of groups tested ranged from 20 to 70+ years (some individuals were 90+ years old). Eyes were examined monocularly. We tested three- and two-point sharply defined VeA arrays and a three-point ground-glass-degraded display (simulating a 20/100 nuclear cataract). Gap or feature separations were varied. Results obtained with the three-point display showed little alteration with age. Image degradation resulted in reduction in performance when small gap separations were used between the test points, but only slight decrements for large gap separations were recorded. The finding that performance with certain VeA targets is largely unaffected by age is confirmed and is expanded.

Adult↗

PubMed1995

Incoherent spatial impulse response in variable-cross-section photoreceptors and frequency-domain analysis.

The spatial impulse response of a single variable-cross-section photoreceptor has been characterized assuming the incoming radiation to be an initial field propagating under confinement conditions inside the receptor. By application of Fourier analysis the total transfer function is determined. Both the outer and the inner segments are characterized as low-pass filters. The dependence of the transfer function on the modal parameter is analyzed.

Fourier Analysis↗

PubMed1995

The "Expected Visual Outcome" (EVO) model: methodology and clinical validation.

PROBLEM: If changes are made to the optics of the eye (e.g., intraocular lens implants, contact lenses, etc.) how will they affect performance on clinical tests of vision? METHOD: A phenomenological method is presented based on in vitro optical transfer function (OTF) and a simple model of human threshold detection. RESULTS: The model is used to predict and the results are compared with clinical data (acuity, contrast sensitivity) obtained from pseudophakic patients implanted with a multifocal intraocular lens (IOL). A good qualitative agreement is found with the clinical data. SIGNIFICANCE: This model predicts the relative change in clinical performance for a given change in the optical components of the human eye. This simple phenomenological model permits numerical prediction of clinical tests and is easily calculable.

Cataract Extraction↗

PubMed1994

Photoreceptor orientation in iris coloboma.

PURPOSE: Investigate photoreceptor orientation and alignment in an observer with a simple coloboma of the iris and no retinal involvement. METHOD: Using a psychophysical procedure, extensive measurements of the Stiles-Crawford functions of the first kind (SCE I) were obtained from this observer. RESULTS: In this observer, the usual center-of-the-exit-pupil-of-the-eye alignment tendency of photoreceptors (inferred from the peaks of the SCE I functions) is absent. The inferred orientation of photoreceptors at numerous retinal loci tested lies outside the pupil, opposite the direction of the downwardly displaced pupil center. CONCLUSIONS: These results add support to previous suggestions that nonphototropic forces such as retinal tractional forces should be considered as an integral part of the mechanism(s) subserving human photoreceptor alignment in both normal and anomalous observers.

Coloboma↗

PubMed1993

Residual aniseikonia among patients fitted with one or two intraocular lenses (pseudophakic corrections)

In the presence of one or two intraocular lenses (IOL's; pseudophakic corrections) or in the presence of naturally occurring or developmental anisometropia (due to a tumescent cataract) some induced or residual refractive aniseikonia is usually encountered. We wish to call this problem to the attention of the optometric practitioner. We provide a discussion of the resultant aniseikonia and simple rules of thumb for management of such patients with refractive aniseikonia. Aniseikonia in these patients may be less important than once had been suggested, but certainly it is more significant than it is currently being considered. Use of personal computers to calculate this aniseikonia makes appropriate correction relatively easy and readily applicable.

Aniseikonia↗

PubMed1993

Phenomenological model for interpreting the clinical significance of the in vitro optical transfer function.

We describe a methodology to predict the outcome of clinical tests caused by changes made to the optical elements of the human eye. This formalism, called the expected visual outcome model, is based on in vitro measurements of the optical transfer function and takes into account a simple model of human threshold performance. The clinical tests under consideration are high-contrast visual acuity and contrast sensitivity. Using the expected visual outcome, we describe a useful performance index called the predicted visual acuity graph, which can be measured clinically. The theoretical results are compared with visual function measured in patients with pseudophakic (multifocal and monofocal) implants.

Cataract Extraction↗