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Biomedical subjects

William D Mathers

Publications and source records attributed to William D Mathers.

12 recordsLinked to original sources
PubMed2006

Intravital microscopy of leukocyte-endothelial dynamics using the Heidelberg confocal laser microscope in scleritis and allergic conjunctivitis.

PURPOSE: To examine leukocyte-endothelial cell rolling and arrest in human ocular vessels overlying sites of inflammation in various ocular inflammatory diseases in comparison to normal controls using the Heidelberg confocal laser microscope, which provides images with greater clarity and resolution than the tandem scanning microscope that uses white light. METHODS: Healthy controls (n=8) and patients with active anterior scleritis (n=7) or allergic eye disease (n=4) were scanned using the Heidelberg confocal laser microscope (HRT II) with the Rostock cornea module attachment for a minimum of 5 min at a depth of 45-120 microm from the conjunctival epithelial surface. RESULTS: There was a marked increase in the number of rolling leukocytes in scleritis patients (534+/-119 cells per mm2/min) versus controls (6+/-6 cells per mm2/min; p=0.0002) or allergic patients (59+/-44 cells per mm2/min; p=0.009). No statistically significant increase was seen in allergic patients compared to controls (p=0.059). A similar pattern was seen in the number of arrested leukocytes in patients with scleritis (56+/-23 cells per mm2) in comparison to either those with allergic eye disease or controls (each=0 cells per mm2; p=0.02). CONCLUSIONS: Patients with scleritis have a significantly increased number of rolling and arrested leukocytes in superficial ocular vessels in comparison to patients with mild allergic conjunctivitis and controls. The image quality with this microscope is superior to prior studies with a scanning microscope.

Adult↗
PubMed2006

Condition-specific coregulation with cis-regulatory motifs and modules in the mouse genome.

Deciphering genetic regulatory codes remains a challenge. Here, we present an effective approach to identifying in vivo condition-specific coregulation with cis-regulatory motifs and modules in the mouse genome. A resampling-based algorithm was adopted to cluster our microarray data of a stress response, which generated 35 tight clusters with unique expression patterns containing 811 genes of 5652 genes significantly altered. Database searches identified many known motifs within the 3-kb regulatory regions of 40 genes from 3 clusters and modules with six to nine motifs that were commonly shared by 60-100% of these genes. The upstream regulatory region contained the highest frequency of these common motifs. CisModule program predictions were comparable with the results from database searches and found four potentially novel motifs. This result indicates that these motifs and modules could be responsible for gene coregulation of the stress response in the lacrimal gland.

Algorithms↗
PubMed2006

Non-invasive detection of multinucleated giant cells in the conjunctiva of patients with sarcoidosis by in-vivo confocal microscopy.

AIM: To explore the use of in-vivo confocal microscopy (IVCM) as a potential non-invasive adjunctive tool for diagnosing sarcoidosis. METHODS: Conjunctivae were imaged using confocal microscopy in 10 patients with sarcoidosis and 27 control subjects. We utilized the ASL-1000 Scanning Confocal Microscope (Advanced Scanning Ltd., New Orleans, LA) and the Confoscan 3 (Nidek Co. Ltd., Gamagori, Japan). Two masked observers reviewed the in-vivo confocal images of the conjunctivae in these subjects. One masked observer was experienced in reviewing confocal images. The most striking and obvious feature seen in granulomatous inflammation on confocal microscopy is the presence of multinucleated giant cells (MGCs). RESULTS: Unmasked observation of the scans revealed MGCs in six of the 10 sarcoid patients and no MGCs in the controls. One experienced masked observer found MGCs in five of the 10 patients with sarcoidosis and had no false-positive results (Fisher's exact test, p = 0.001; specificity = 1; sensitivity = 50% for the diagnosis of sarcoidosis and 83% compared to the unmasked observer). The second less-experienced masked observer detected MGCs in three of the 10 patients and three of the 27 controls (11.1% of the controls) (p = 0.186; specificity = 0.89; sensitivity = 30% of all patients with sarcoidosis and 50% compared to the unmasked observer). CONCLUSIONS: The utilization of IVCM to visualize the basic histology and pathology in sarcoidosis of the conjunctiva is novel. Initial results indicate that trained observers can detect MGCs in granulomatous inflammation. The ASL-1000 microscope tends to have better resolution and deeper penetration of the conjunctiva compared with the Confoscan 3.

Adult↗
PubMed2005

A time course microarray study of gene expression in the mouse lacrimal gland after acute corneal trauma.

PURPOSE: To investigate the effect of corneal trauma on gene expression in the lacrimal gland and to assess how many genes and what specific genes are regulated in response to corneal trauma. METHODS: A mouse model with acute corneal trauma was created with a chemical burn to the cornea with silver nitrate. Sixty-four female BALB/c mice at 12 weeks of age were randomly divided into eight groups, eight mice per group. The corneas of four mice in each group were bilaterally cauterized with silver nitrate, and another four time-matched mice were used as the control. The total RNA of the lacrimal gland was then extracted, at eight time points--0.5, 1, 3, 8, 24, 72, 120, and 360 hours--after the corneal burn, and gene expression was examined with using cDNA microarray technology. RESULTS: Evaluation of 15,065 genes with multiple array replications showed significantly altered expression in 3,799 genes at one or more of the eight time points. Of those, 1,528 were known genes and 2,271 were unknown. The analysis of known genes showed broad and long-lasting gene suppression in most functional gene groups, including housekeeping, energy metabolism, protein degradation, DNA and protein synthesis, and apoptosis-associated genes. Heat shock genes were upregulated beginning at the 8-hour time point, indicating a stress response. CONCLUSIONS: This study demonstrates that corneal trauma has profound effects on the regulation of gene expression in the lacrimal gland and may provide genetic evidence for a cornea-to-lacrimal gland feedback mechanism in dry eye.

Acute Disease↗
PubMed2004

Cluster analysis of patients with ocular surface disease, blepharitis, and dry eye.

OBJECTIVE: To develop a classification system for blepharitis and dry eye based on a classification-tree model of a large group of subjects who were given a variety of objective physiologic tests. METHODS: We evaluated 513 subjects, some healthy and some with blepharitis and dry eye,with tests for tear volume, tear flow, and tear turnover and the Schirmer test for dry eye. Meibomian gland function was evaluated by meibomian gland lipid expression for lipid volume and lipid viscosity, evaporation, and eyelid transillumination for meibomian gland drop out. We subjected these data to cluster analysis and formulated a classification tree. MAIN OUTCOME MEASURE: The outcome measure of this study was the statistically valid groups of subjects with and without ocular surface symptoms identified by their physiologic characteristics. RESULTS: Cluster analysis most successfully grouped subjects by initially dividing them into 2 groups based on the presence or absence of gland drop out and then by lipid viscosity and volume, Schirmer test results, and evaporation. The analysis created 9 categories. This division created an objective classification system that was found to have clinical relevance. Normal subjects were distributed across several groups. CONCLUSIONS: Using a classification tree, blepharitis and dry eye can be classified with objective physiologic tests into clinically relevant groups that have common characteristics. The analysis establishes the central role of meibomian gland dysfunction in blepharitis and demonstrates the diverse characteristics of the normal population.

Adult↗
PubMed2004

In vivo confocal microscopy of keratic precipitates.

OBJECTIVE: To evaluate the heterogeneity of keratic precipitates (KP) in varying subtypes of uveitis by in vivo confocal microscopy (IVCM). METHODS: The KP were viewed with a scanning confocal microscope in patients (n = 33) who sought care at a tertiary referral uveitis service for immune-mediated and infectious forms of uveitis, including HLA-B27-associated uveitis, sarcoidosis, Vogt-Koyanagi-Harada syndrome, juvenile chronic arthritis, Fuchs heterochromic iridocyclitis, cytomegalovirus retinitis, herpes zoster ophthalmicus, ocular toxoplasmosis, and idiopathic uveitis. Images were captured and digitalized in real time. RESULTS: Forty-two eyes of 33 patients were examined in this study. Patient age ranged from 22 to 84 years, with a mean age of 49.4 years. Seventeen (52%) of the patients were women, and 16 patients (48%) were men. The KP ranged in diameter from 10 to 350 mum. We observed the following absolute and speculative outcomes: KP are markedly heterogeneous and variable as documented by IVCM; KP in individual patients are consistent throughout the cornea; the morphologic features of KP change across time; infectious vs noninfectious causes of uveitis seem to be readily distinguishable by using IVCM; and KP may have consistency for specific disease states and therefore may have diagnostic importance. CONCLUSIONS: To our knowledge, this is the first time that IVCM has been used to describe the architecture and heterogeneity of KP in uveitis. Such observations reveal a heterogeneity that could not be appreciated by conventional slitlamp microscopy and may have diagnostic relevance.

Adult↗
PubMed2004

In vivo confocal microscopy: increased conjunctival or episcleral leukocyte adhesion in patients who wear contact lenses with lower oxygen permeability (Dk) values.

PURPOSE: Contact lens wear is known to threaten the health of the ocular surface. In vivo confocal microscopy (IVCM) to visualize leukocyte rolling and extravasation in inflammation was recently described. We tested the hypothesis that contact lens wear is associated with measurable inflammation in superficial vessels. METHODS: Leukocyte rolling and sticking (hallmarks of the inflammatory process) were recorded by IVCM. IVCM was performed on conjunctival or episcleral blood vessels bilaterally on 55 contact lens wearers (15 male, 40 female) and 22 non-contact lens wearers (8 male, 14 female). Data were analyzed in 2 ways. Considering each vessel as an independent variable resulted in 132 analyzable vessel segments (13 daily disposable contact lenses, 67 traditional contact lenses, 14 rigid gas-permeable lenses, and 38 controls). Considering each subject as an independent variable resulted in analyzable data for 47 subjects (5 daily disposable contact lens wearers, 22 traditional contact lens wearers, 5 rigid contact lens wearers, and 15 control patients). Free-flowing, sticking, and rolling cells were counted in the vessels. Multiple parameters including mean flow velocity, shear rate, rolling cells/mm/min, and sticking cells/mm were calculated. RESULTS: We found no significant difference in leukocyte adhesion between control patients and patients wearing daily disposable, traditional disposable, or rigid gas-permeable lenses in both types of statistical analyses. However, the data regarding vessel segments as an independent variable show that there were more rolling cells in patients who wore contact lenses with oxygen permeability values (Dk) less than 10 as compared to those who wore contact lenses with oxygen permeability values greater than 16 (P < 0.01) or compared to controls (P < 0.01). CONCLUSION: IVCM is a novel, powerful technique to recognize a critical but subclinical component of inflammation. Although our data indicate that contact lens wear does not markedly increase rolling and sticking of leukocytes in conjunctival or episcleral vessels, there may be subclinical inflammation in association with lenses with the lowest oxygen permeability.

Adult↗