Biomedical subjects

John R Samples

Publications and source records attributed to John R Samples.

14 recordsLinked to original sources

PubMed2007

Differential expression profile prioritization of positional candidate glaucoma genes: the GLC1C locus.

OBJECTIVES: To develop and apply a model for prioritization of candidate glaucoma genes. METHODS: This Affymetrix GeneChip (Affymetrix, Santa Clara, Calif) study of gene expression in primary culture human trabecular meshwork cells uses a positional differential expression profile model for prioritization of candidate genes within the GLC1C genetic inclusion interval. RESULTS: Sixteen genes were expressed under all conditions within the GLC1C interval. TMEM22 was the only gene within the interval with differential expression in the same direction under both conditions tested. Two genes, ATP1B3 and COPB2, are of interest in the context of a protein-misfolding model for candidate selection. SLC25A36, PCCB, and FNDC6 are of lesser interest because of moderate expression and changes in expression. Transcription factor ZBTB38 emerges as an interesting candidate gene because of the overall expression level, differential expression, and function. CONCLUSIONS: Only 1 gene in the GLC1C interval fits our model for differential expression under multiple glaucoma risk conditions. The use of multiple prioritization models resulted in filtering 7 candidate genes of higher interest out of the 41 known genes in the region. CLINICAL RELEVANCE: This study identified a small subset of genes that are most likely to harbor mutations that cause glaucoma linked to GLC1C.

Adolescent↗

PubMed2006

The association of single nucleotide polymorphisms in the MMP-9 genes with susceptibility to acute primary angle closure glaucoma in Taiwanese patients.

PURPOSE: To study the relationships between single nucleotide polymorphisms (SNPs) of extracellular matrix, matrix metalloproteases (MMPs), tissue inhibitors of MMPs, and other glaucoma-associated genes and acute primary angle closure glaucoma (PACG). METHODS: We extracted DNA samples from 78 adult patients with acute PACG and 86 control subjects to study the relationships between these specific genes and acute PACG. Genotyping was performed for 35 genes by the GenomeLab SNPstream genotyping system after PCR amplification of chromosomal DNA. The association between these genetic polymorphisms and risk of primary PACG was estimated by chi2 and logistic regression. RESULTS: The genotyping success rate was 99%. Genotyping for the MMP9 site (rs2664538) was significantly different between the two groups (p=0.000001) and the odds ratio was 2.586 (95% CI: 1.715-3.898, p<0.00001). However, there were no associations of SNPs to other genes in patients with acute PACG. CONCLUSIONS: Our results reveal that SNP rs2664538, which is located at the MMP9 gene, is likely to be associated with acute PACG.

Acute Disease↗

PubMed2006

The role of the WDR36 gene on chromosome 5q22.1 in a large family with primary open-angle glaucoma mapped to this region.

OBJECTIVE: To determine whether mutations in the WD40-repeat 36 (WDR36) gene are responsible for primary open-angle glaucoma (POAG) that maps to the GLC1G locus in a family with 16 affected family members. METHODS: Ninety-two family members underwent clinical evaluation for POAG on the basis of intraocular pressures, cupping of discs, and visual fields after informed consent was obtained. All 23 exons of WDR36 were sequenced in DNA from 5 affected and 2 unaffected family members. RESULTS: Sixteen family members showed evidence of POAG. A number of sequence variations were identified in family members; most of the variations were previously described single-nucleotide polymorphisms also present in the general population. The 3 new sequence changes were all intronic; 2 were found in only 1 of the family members undergoing screening. CONCLUSIONS: Several polymorphisms, including known single-nucleotide polymorphisms, were identified; however, none of these were consistent with disease-causing mutations. A mutation in a noncoding region of WDR36 may be responsible for POAG in this family, or another gene in this region may be the actual cause of glaucoma in this family. CLINICAL RELEVANCE: The finding that the WDR36 gene is probably not the responsible gene in this family further documents the genetic heterogeneity of POAG.

Adult↗

PubMed2006

Small optic cup sizes among women using tamoxifen: assessment with scanning laser ophthalmoscopy.

PURPOSE: There is a substantial literature showing that the selective estrogen receptor modulator tamoxifen can block swelling-activated chloride channels, such as those in astrocytes. This study aimed to test the hypothesis that anatomic characteristics consistent with swelling may be measured within the optic nerve head (ONH) of tamoxifen users whose ONH appearance is considered within normal limits. METHODS: Indices of ONH topography were measured using the Heidelberg Retina Tomograph II (HRT) for two populations of women ages 40-69 years: (1) subjects using tamoxifen (20 mg/day) as adjuvant therapy after successful primary treatment for breast cancer and (2) control subjects not using any hormonal medication. All subjects had excellent visual acuity (with 20/20 or better in the test eye), and all appeared to be free of eye disease, as based on conventional photographic assessment. The study design was cross-sectional. The various ONH indices were assessed as functions of the duration of tamoxifen use. RESULTS: The optic cups of short-term tamoxifen users ( 2 years, <or=5 years) were not distinguishable from those of the control subjects. The presence of small cups among short-term users did not depend on subjects' medical histories prior to tamoxifen use. Disk margin indices were not related significantly to the duration of tamoxifen use. CONCLUSIONS: Small cup sizes consistent with localized subclinical swelling are not rare among short-term tamoxifen users. Thus, small cups are not likely to be a manifestation of a cumulative-dose toxicity. Instead, they probably result from other causes, possibly involving the action of tamoxifen on estrogen receptors. Further investigation with longitudinal and interventional methodologies is needed to definitively interpret the results.

Adult↗

PubMed2006

A large GLC1C Greek family with a myocilin T377M mutation: inheritance and phenotypic variability.

PURPOSE: POAG is a complex disease; therefore, families in which a glaucoma gene has been mapped may carry additional POAG genes. The goal of this study was to determine whether mutations in the myocilin (MYOC) gene on chromosome 1 are present in two POAG families, which have previously been mapped to the GLC1C locus on chromosome 3. METHODS: The three exons of MYOC were screened by denaturing (d)HPLC. Samples with heteroduplex peaks were sequenced. Clinical findings were compared with genotype status in all available family members over the age of 20 years. RESULTS: A T377M coding sequence change in MYOC was identified in family members of the Greek GLC1C family but not in the Oregon GLC1C family. Individuals carrying both the MYOC T377M variant and the GLC1C haplotype were more severely affected at an earlier age than individuals with just one of the POAG genes, suggesting that these two genes interact or that both contribute to the POAG phenotype in a cumulative way.

Adult↗

PubMed2006

Contrasting blue-on-yellow with white-on-white visual fields: Roles of visual adaptation for healthy peri- or postmenopausal women younger than 70 years of age.

PURPOSE: To test the hypothesis that differences between short-wavelength automated perimetry (SWAP) and white-on-white visual field sensitivities are related to between-individual variation in the visual adaptation properties of SWS cone pathways. METHODS: Twenty-six healthy amenorrheic (peri- or postmenopausal) women not using hormonal medication were tested. Subjects ranged in age from 48 to 68 years. They were tested by using foveal increment-threshold techniques and also with two types of 24-2 visual field tests: a full-threshold SWAP blue-on-yellow (B/Y) test and a white-on-white (W/W) test obtained using a Swedish Interactive Threshold Algorithm (SITA Standard). The age-corrected sensitivity differences between the two types of visual fields were compared against foveal measures of visual sensitivity and adaptation, which were obtained psychophysically using dim and bright yellow backgrounds. All measurements for each subject were made at a single testing session. The comparisons were made for the entire visual field and for separate portions of the visual field. The analyses also included pupil size data obtained during visual field testing. RESULTS: The B/Y minus W/W (B/Y - W/W) mean deviation difference was described (R = 0.80) by a multilinear model with three significant factors: (1) an adaptation factor and (2) a baseline sensitivity factor, each derived from the foveal psychophysical data for short-wavelength test stimuli, and (3) a pupil size factor, as recorded for SWAP. The total deviation differences in the periphery of the visual field (approximately 22 degrees from fixation) were described (R = 0.87) by a model with four significant factors, the fourth being an "eccentricity factor" describing the rate of change of the B/Y - W/W total deviation difference measured as a function of increasing retinal eccentricity approximately 9 degrees -17 degrees from fixation. More than 40% of the variance in the B/Y - W/W mean deviation differences was accounted for either directly or indirectly (via effects of pupil size) by variations in adaptation to the yellow background used for SWAP. CONCLUSIONS: Much of the extra variability in SWAP sensitivities for a select group of healthy women can be accounted for by differences in the degree of desensitization induced by the yellow background used for SWAP. For clinical practice, pupil status (dilated or undilated) should be altered only with caution from one SWAP testing session to another.

Adaptation, Ocular↗

PubMed2005

Hypophosphorylation of aqueous humor sCD44 and primary open-angle glaucoma.

PURPOSE: The ectodomain of CD44, the principal receptor for hyaluronic acid (HA), is shed as a 32-kDa fragment-soluble CD44 (sCD44)-which is cytotoxic to trabecular meshwork (TM) cells and retinal ganglion cells (RGCs) in culture. The purpose of this study was to characterize sCD44 further by determining the phosphorylation of aqueous humor sCD44 in normal and primary open-angle glaucoma (POAG). METHODS: Aqueous humor samples of patients were subjected to CD44 enzyme-linked immunosorbent assay (ELISA) and two-dimensional (2-D) polyacrylamide gel electrophoresis, followed by Western blot analysis with anti-CD44, anti-serine/threonine, and anti-tyrosine phosphospecific antibodies, to determine sCD44 concentration, isoelectric point (pI), and phosphorylation, respectively. The bioactivity of hypophosphorylated sCD44 was tested in cell culture and HA affinity columns. RESULTS: Two-dimensional Western blot analysis revealed that the representative pI of the 32-kDa sCD44 was 6.96 +/- 0.07 in POAG versus 6.38 +/- 0.08 in normal (P < 0.0004). Enzymatic dephosphorylation of sCD44 resulted in a basic shift in the pI. The normal aqueous humor sCD44 was positive for serine-threonine phosphorylation; however, POAG sCD44 was hypophosphorylated. Hypophosphorylated sCD44 was more toxic to TM and RGC cells than standard sCD44, and hypophosphorylated sCD44 had decreased affinity to HA, particularly with increased pressure. CONCLUSIONS: POAG aqueous is characterized by posttranslational change in the pI of sCD44 and hypophosphorylation, which clearly distinguished POAG from normal aqueous humor. The high toxicity and low HA-binding affinity of hypophosphorylated sCD44 may represent specific pathophysiologic features of the POAG disease process.

Aqueous Humor↗

PubMed2004

Hypotonus maculopathy: magnetic resonance appearance.

PURPOSE: To report the magnetic resonance appearance of hypotonus maculopathy. DESIGN: Observational case report. METHODS: A 48-year-old man with a long history of glaucoma and subsequent trabeculectomy in the right eye developed hypotonus maculopathy. Visual acuity continued to decrease in both eyes of a relatively young individual with severe primary open angle glaucoma. A magnetic resonance image was requested to look for a compressive optic neuropathy. RESULTS: Magnetic resonance imaging showed an abnormal plaquelike thickening of the macula and flattening of the posterior globe. CONCLUSION: To our knowledge, this is the first case report of the magnetic resonance appearance of hypotonus maculopathy.

Choroid Diseases↗

PubMed2004

Bartonella henselae infection associated with neuroretinitis, central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss.

PURPOSE: To report a case of Bartonella henselae infection. DESIGN: Observational case report. METHODS: Review of the clinical, laboratory, photographic, and angiographic records of a patient with cat scratch disease associated with central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss. RESULTS: A 21-year-old man had no light perception in the left eye secondary to concurrent central retinal artery and vein occlusion believed to have resulted from infection with Bartonella henselae. Forty days later, he developed neovascular glaucoma in the left eye. CONCLUSION: Ocular complications associated with Bartonella henselae infection may include central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss.

Adult↗

PubMed2003

The genetic loci of open-angle glaucoma.

As Posner stated in 1949, the bottom line "to the patient and to his family is..., whether his disease will follow a mild course or will lead to blindness". The final goal of genetic research is the identification of the causal genes in the patient, to aid the ophthalmologist in predicting the outcome, in determining diligent treatment is required, and ultimately, in providing the tools for preventing blindness.

Chromosome Mapping↗

PubMed2003

Introductory ophthalmic genetics.

Rapid progress is occurring in molecular cell biology and genetics in the understanding of basic cellular mechanisms and the potential for genetic therapy. As new methods of genetic prognosis and treatment become available, and diseases are redefined in genetic terms, it is essential that clinicians know more about genetic therapy. This article provides a basic outline of gene therapy.

Glaucoma↗

PubMed2003

High blood pressure and visual sensitivity.

The study had two main purposes: (1) to determine whether the foveal visual sensitivities of people treated for high blood pressure (vascular hypertension) differ from the sensitivities of people who have not been diagnosed with high blood pressure and (2) to understand how visual adaptation is related to standard measures of systemic cardiovascular function. Two groups of middle-aged subjects--hypertensive and normotensive--were examined with a series of test/background stimulus combinations. All subjects met rigorous inclusion criteria for excellent ocular health. Although the visual sensitivities of the two subject groups overlapped extensively, the age-related rate of sensitivity loss was, for some measures, greater for the hypertensive subjects, possibly because of adaptation differences between the two groups. Overall, the degree of steady-state sensitivity loss resulting from an increase of background illuminance (for 580-nm backgrounds) was slightly less for the hypertensive subjects. Among normotensive subjects, the ability of a bright (3.8-log-td), long-wavelength (640-nm) adapting background to selectively suppress the flicker response of long-wavelength-sensitive (LWS) cones was related inversely to the ratio of mean arterial blood pressure to heart rate. The degree of selective suppression was also related to heart rate alone, and there was evidence that short-term changes of cardiovascular response were important. The results suggest that (1) vascular hypertension, or possibly its treatment, subtly affects visual function even in the absence of eye disease and (2) changes in blood flow affect retinal light-adaptation processes involved in the selective suppression of the flicker response from LWS cones caused by bright, long-wavelength backgrounds.

Adaptation, Physiological↗

PubMed2002

Automated perimetry: a report by the American Academy of Ophthalmology.

OBJECTIVE: The purpose of this document is to summarize and evaluate the effectiveness of new automated perimetry tests and algorithms in diagnosing glaucoma and detecting disease progression. METHODS: A literature search on automated perimetry retrieved over 300 citations from 1994 to 2001, of which 71 were selected as relevant to this assessment. The quality of the evidence obtained from these studies was assessed by the methodologist. RESULTS: The four automated perimetry techniques described in this assessment are short wavelength automated perimetry (SWAP), frequency doubling technology perimetry (FDT), high-pass resolution perimetry (HPRP), and motion automated perimetry (MAP). The algorithms described are Swedish interactive threshold algorithm (SITA) and SITA fast. With the exception of SWAP, these techniques and algorithms reduce testing time and inconsistent patient performance when compared with conventional full threshold testing. CONCLUSIONS: Short wavelength automated perimetry detected visual field loss earlier than standard threshold automated perimetry, with a sensitivity and specificity of about 88% and 92% respectively. However, it is a lengthy, demanding test, is sensitive to media opacities, and has a greater magnitude of long-term fluctuation compared with standard threshold automated perimetry, which make it difficult to assess disease progression accurately. When compared to standard threshold automated perimetry, FDT perimetry showed sensitivity and specificity greater than 97% for detecting moderate and advanced glaucoma, and sensitivity of 85% and specificity of 90% for early glaucoma. As FDT perimetry has a short testing time and is resistant to blur and pupil size, it may be a useful screening tool. In a longitudinal study, high-pass resolution perimetry was more effective than standard threshold automated perimetry in monitoring progressive glaucomatous loss, detecting progression at a median of 12 months earlier in 54% of patients studied. Motion automated perimetry demonstrated usefulness in detecting early glaucomatous visual loss in a longitudinal study. Studies on SITA demonstrated greater sensitivity and reproducibility and less intertest variability when compared to standard full threshold testing and a 50% reduction in testing times. A study comparing standard full threshold, SITA, and SITA fast found a sensitivity of 95% for the first two techniques and 93% for SITA fast. Long-term follow-up studies are needed to assess the ability of these techniques to detect progression of glaucoma over time.

Algorithms↗

PubMed2002

Expression profile and genome location of cDNA clones from an infant human trabecular meshwork cell library.

PURPOSE: To delineate the profile of genes expressed in infant human trabecular meshwork and identify candidate genes for glaucoma. METHODS: Human trabecular meshwork cell cultures were established from six young donors. A cDNA library was made from the combined trabecular meshwork mRNA. The end-sequence of random clones was determined by direct sequencing. These sequences were then analyzed by a National Center for Biotechnology Information (NCBI, Bethesda, MD) database search. Nucleotide searches were performed using the BLASTN (ver. 2.1.3; against the nonredundant nucleic acid sequence) and dbEST databases (both provided by NCBI in the public domain at www.ncbi.nlm.nih.gov). RESULTS: Sequences from 1118 clones from this nonamplified trabecular meshwork cDNA library were categorized. Of these, 877 expressed sequence tags (ESTs) (78.7%) were known genes. One hundred thirty-nine ESTs (12.5%) showed close identity to EST sequences reported in the public domain database (dbEST). Thirteen ESTs (1.2%) showed no significant similarity to known genes or ESTs in the public databases and were thus defined as novel ESTs. The most abundant genes expressed by the human trabecular meshwork included ferritin H, eukaryotic translation elongation factor 1-alpha, ferritin L, fibronectin, and TIMP-1. Ferritin H was the most abundant transcript, making up more than 4% of the genes expressed by the human trabecular meshwork. Extracellular matrix proteins were also highly expressed. The chromosome location of the trabecular meshwork ESTs is reported. CONCLUSIONS: A profile of genes expressed by human trabecular meshwork is presented. Thirteen novel ESTs were identified. The combined information obtained from expression analysis and chromosomal localization of trabecular meshwork cDNAs should be valuable in identifying candidate genes for glaucoma.

Cells, Cultured↗