Epitope Specificity Determines Pathogenicity and Detectability of Anti-Platelet-Derived Growth Factor Receptor α Autoantibodies in Systemic Sclerosis.

Objective: To identify the epitopes recognized by autoantibodies targeting platelet-derived growth factor receptor α (PDGFRα) in systemic sclerosis (SSc) and develop novel assays for detection of serum anti-PDGFRα autoantibodies.

Methods: Epstein-Barr virus-immortalized B cells from 1 patient with SSc (designated PAM) were screened for expression of IgG binding to PDGFRα and induction of reactive oxygen species in fibroblasts. The variable regions of anti-PDGFRα IgG were cloned into an IgG expression vector to generate distinct recombinant human monoclonal autoantibodies (mAb), which were characterized by binding and functional assays.

Tear lipocalin: structure and function.

Lipocalins are a family of diverse low molecular weight proteins that act extracellularly. They use multiple recognition properties that include 1) ligand binding to small hydrophobic molecules, 2) macromolecular complexation with other soluble macromolecules, and 3) binding to specific cell surface receptors to deliver cargo. Tear lipocalin (TLC) is a major protein in tears and has a large ligand-binding cavity that allows the lipocalin to bind an extensive and diverse set of lipophilic molecules.

Inattentional blindness with the same scene at different scales.

People with severely restricted peripheral visual fields have difficulty walking confidently and safely in the physical environment. Augmented vision devices that we are developing for low-vision rehabilitation implement vision multiplexing, providing two views of the same scene at two different scales (sizes), with a cartooned minified wide view overlaying a natural see-through view. Inattentional blindness may partially limit the utility of these devices as low-vision aids.

TGF-beta and microvessel homeostasis.

Aberrant transforming growth factor-beta (TGF-beta) signaling plays a clear role in a number of pathologies, in particular, fibrotic diseases and cancer. Accumulating evidence also suggests that TGF-beta is required for vascular homeostasis, shedding light on the role of circulating TGF-beta and the expression of TGF-beta receptors in the adult vasculature, in the absence of any pathologic processes. In human pathologies such as hereditary hemorrhagic telangiectasia (HHT) and preeclampsia, TGF-beta signaling is abnormal.

Inhibition of VEGF or TGF-{beta} signaling activates endothelium and increases leukocyte rolling.

Objective: Motivated by the central roles that vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta play in the assembly and maintenance of the vasculature, we examined the impact of systemic VEGF or TGF-beta signal inhibition on endothelial activation as detected by leukocyte-endothelial interactions.

Methods And Results: VEGF or TGF-beta inhibition, accomplished using adenovirus expression of soluble Flt1 (Ad-sFlt1) or soluble endoglin (Ad-sEng), resulted in a significant increase in the number of leukocytes rolling along the mesenteric venous endothelium and a significant decrease in rolling velocity in Ad-sEng mice. Neutralization of VEGF or TGF-beta resulted in endothelial surface expression of P-selectin and impaired peripheral vasodilatation.

Arterial versus venous endothelial cells.

Vascular endothelial cells (ECs) form the inner lining of all blood vessels from the largest artery and veins, viz., the aorta and venae cavae, respectively, to the capillaries that connect the arterial and venous systems. Because these two major conducting systems of the cardiovasculature differ functionally, it is not surprising that the physical makeup of arteries and veins, including the ECs that line their lumina, are also distinct.

Efficacy of olopatadine ophthalmic solution 0.2% in reducing signs and symptoms of allergic conjunctivitis.

Olopatadine hydrochloride ophthalmic solution 0.2% (Pataday, Alcon) is a new formulation of olopatadine hydrochloride ophthalmic solution, the first topical ocular antiallergic agent indicated for once-daily dosing. The aim of this study was to evaluate the safety, efficacy, onset, and duration of action of olopatadine 0.

Quantitative analysis of mucins in mucosal secretions using indirect enzyme-linked immunosorbent assay.

Mucins are extremely large and highly O-glycosylated glycoproteins synthesized and secreted by all wet-surfaced epithelia. Within the mucosal secretion they protect the underlying epithelium by forming a selective diffusion barrier against harmful substances and microorganisms, and act as lubricants to minimize shear stress. Variation in the character and quantity of secreted mucins is important to maintain the normal function of the epithelia (e.

A low-power, LED-based, high-brightness anomaloscope.

Color matches made with a Nagel anomaloscope are used in the differentiation of color vision deficiencies. When these color matches are made over a wide range of retinal illuminances, the changes in the color match provide information about the regeneration kinetics and the absorption spectra of the middle- and long-wavelength cone photopigments. These steady-state color matches vary with a variety of conditions, and may have value in screening for eye disease.

Effects of interactions among wave aberrations on optical image quality.

Wave aberrations degrade the optical quality of the eye relative to the diffraction limit, but there are situations in which having slightly aberrated optics can provide some relative visual benefits. This fact led us to consider whether interactions among aberrations in the eye's wavefront produce an advantage for image quality relative to wavefronts with randomized combinations of aberrations with the same total RMS error. Total ocular wave aberrations from two experimental groups and corneal wave aberrations from one group were measured and expressed as Zernike polynomial expansions through the seventh-order.

Identification of steroidogenic enzyme mRNAs in the human lacrimal gland, meibomian gland, cornea, and conjunctiva.

Purpose: Sex steroids exert a significant influence on the health and well-being of the ocular surface and adnexa. These hormones affect multiple aspects of the lacrimal and meibomian glands, conjunctiva, and cornea, and have been linked to the development of many ocular surface pathologies. We hypothesize that these hormone actions, as in other tissues, occur predominantly after the local synthesis of androgens and estrogens from adrenal precursors.

Relationship between foveal birefringence and visual acuity in neovascular age-related macular degeneration.

Purpose: To investigate the relationship between visual acuity and foveal birefringence in patients with neovascular age-related macular degeneration.

Methods: In total, 40 patients with choroidal neovascularization underwent macular imaging with scanning laser polarimetry. Bowtie patterns, typically seen in birefringence images of the macula, were evaluated and classified into three categories: (1) regular bowtie present; (2) bowtie present, but disrupted; and (3) no bowtie present.

Visualization of two image variables simultaneously using cardinal directions of color vision.

Visualization of medical image information can be achieved by using color scales to enhance aspects of the data. We have used the cardinal directions of color to make a continuous and representation of phase data that wraps around every 360 deg, and added in another dimension using luminance to illustrate amplidute.

Evaluation of a prototype Minified Augmented-View device for patients with impaired night vision.

An evaluation was carried out of the first prototype (LV-3) of a new night vision device, which incorporates visual field expansion through minification (Minified Augmented-View), to provide feedback for continuing development. Six subjects with night blindness completed visual function measurements and indoor mobility assessments without a device, with the LV-3 and with a commercially available comparison device (the Multi-Vision) at light levels representative of well lit and poorly lit streets. Device performance and potential benefits in real-world situations were evaluated at four outdoor locations (well lit to very dark).

Preferred retinal locus and reading rate with four dynamic text presentation formats.

Background: Electronic display devices hold the potential to improve access to written material by people with low vision. For those with central field loss, the optimal form of electronic text presentation may vary according to the location of the preferred retinal locus, but this has never been investigated. In this study, we examined the relationship between preferred retinal locus location and reading rate for four electronic display formats (rapid serial visual presentation, horizontal scroll, vertical scroll, and page).

Won't you be my neighbor? Local induction of arteriogenesis.

Two recent papers in Cell and Developmental Cell provide evidence that VEGF directs arterial differentiation. Evidence that sensory nerves direct arteriogenesis and that the membrane-spanning Notch signaling system is downstream of VEGF emphasize the paracrine regulation of vessel formation.

Regulation of conjunctival goblet cell secretion by Ca(2+)and protein kinase C.

Conjunctival goblet cells secrete mucus in response to cholinergic (muscarinic) agonists, but the underlying signaling pathways activated in this tissue are not well understood. Cholinergic agonists usually activate phospholipase C to produce inositol 1,4,5 trisphosphate and diacylglycerol. Inositol 1,4,5 trisphosphate increases the intracellular Ca(2+)concentration ([Ca2(+)](i)) while diacylglycerol activates protein kinase C (PKC).

Factors related to subretinal proliferation in patients with primary rhegmatogenous retinal detachment.

Purpose: To evaluate factors related to subretinal proliferation in patients with primary rhegmatogenous retinal detachment (RD).

Methods: A total of 262 consecutive patients (267 eyes) with rhegmatogenous RD were evaluated retrospectively to determine factors associated with subretinal proliferation.

Results: Logistic regression analysis was used to identify the following factors associated with subretinal proliferation that caused retinal traction: number of quadrants detached (adjusted odds ratio [AOR] = 2.

Localization of gephyrin and glycine receptor subunit immunoreactivity in the rabbit retina.

Being utilized by over 40% of the amacrine cells, glycine is considered to be a major inhibitory neurotransmitter in the retinas of all vertebrate species examined. Localization of gephyrin, which is a 93-kD peripheral membrane glycine receptor-associated anchoring protein, has been used in several studies to identify the sites of glycinergic interactions in the retina and other regions of the central nervous system. Recent studies have shown that gephyrin colocalizes with GABA(A) receptors which, like those for glycine, are also inhibitory amino acid receptors usually associated with a chloride channel.

Gamma-aminobutyric acidA receptors on a bistratified amacrine cell type in the rabbit retina.

Gamma-Aminobutyric acid (GABA) is considered to be a major inhibitory neurotransmitter in the inner plexiform layer of the retinas of all vertebrate species. It is contained in and released from nearly 40% of the amacrine cells and is known to play a major role in many aspects of visual processing. By using well-characterized antibodies to several subunits of the GABA(A) receptor, we have analyzed their localization on the cell bodies and dendritic trees of two amacrine cell populations in the rabbit retina, which have been either filled intracellularly with Lucifer yellow or stained immunohistochemically.

Cloning of rat Muc5AC mucin gene: comparison of its structure and tissue distribution to that of human and mouse homologues.

The human mucin gene MUC5AC codes for a large mucin which has tandem repeat units and cysteine rich regions characteristic of several members of this class of glycoproteins. Human epithelia expressing the mucin include that of stomach, bronchus/trachea, endocervix and conjunctiva. We report here a 3.