Biomedical subjects

Stephen Kaye

Publications and source records attributed to Stephen Kaye.

5 recordsLinked to original sources

PubMed2006

Herpes simplex keratitis.

Herpes simplex keratitis (HSK) results from an infection with the herpes simplex virus type 1 (HSV-1) also known as human herpesvirus type 1 (HHV-1). Primary infection may involve an ocular or non-ocular site, following which latency might be established principally in the trigeminal ganglion but also in the cornea. During latency, the virus appears as a circular episome associated with histones with active transcription only from the region encoding the latency-associated transcript (LAT). The LAT region is implicated in neuronal survival, anti-apoptosis, virulence, suppression of transcription, establishment of and reactivation from latency. The initial keratitis may develop after infection through the "front door route" (entry into the ocular surface from droplet spread) or "back door route" (spread to the eye from a non-ocular site, principally the mouth). The initial ocular infection may be mild. Visual morbidity results from recurrent keratitis, which leads to corneal scarring, thinning and neovascularisation. Although, recurrent disease may potentially occur through anterograde axonal spread from the trigeminal ganglion to the cornea, recent evidence suggests that HSV-1 in the cornea may be another source of recurrent disease. The pathogenesis and severity of HSK is largely determined by an interaction between viral genes encoded by the strain of HSV-1 and the make up of the host's immune system. Herpetic stromal disease is due to the immune response to virus within the cornea and the ability of the strain to cause corneal stromal disease is correlated with its ability to induce corneal vascularisation. The pathogenesis of corneal scarring and vascularisation is uncertain but appears to be a complex interaction of various cytokines, chemokines and growth factors either brought in by inflammatory cells or produced locally in response to HSV-1 infection. Evidence now suggests that HSV-1 infection disrupts the normal equilibrium between angiogenic and anti-angiogenic stimuli leading to vascularisation. Thrombospondin 1 and 2, matricellular proteins, involved in wound healing are potent anti-angiogenic factors and appear to be one of the key players. Elucidating their roles in corneal scarring and vascularisation may lead to improved therapies for HSK.

Animals↗

PubMed2005

CRYBB1 mutation associated with congenital cataract and microcornea.

PURPOSE: The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported. METHODS: Family history and clinical data were recorded. This phenotype was linked to a 7.6 cM region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified and screened for mutations on both strands using direct sequencing. RESULTS: Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1. SSCP analysis confirmed that this sequence change segregated with the disease phenotype in all available family members and was not found in 109 ethnically matched controls. CONCLUSIONS: X253R is predicted to elongate the COOH-terminal extension of the protein and would be expected to disrupt beta-crystallin interactions. This is the first documented involvement of CRYBB1 in ocular development beyond cataractogenesis.

Adolescent↗

PubMed2005

Living quarters and unmet need for personal care assistance among adults with disabilities.

OBJECTIVES: This study used a person-environment (P-E) framework to examine individual capabilities and social and physical environmental attributes for their association with unmet assistance needs in activities of daily living (ADLs). Analyses were replicated among five ADLs (bathing, dressing, transferring, toileting, eating) and test the relative risk of apartment dwellers compared to those living in houses. METHODS: Data were obtained from the National Health Interview Survey, Supplement on Disability Followback Survey. Analyses consisted of a nationally representative sample of aged and nonaged adults with one or more ADL limitations. RESULTS: Slightly less than 1 in 5 subjects with a specific ADL limitation had unmet needs for that ADL. This was true across all ADLs. The likelihood of unmet ADL assistance increased with the number of ADL limitations and other health status indicators. It was at least 50% higher among those living in apartments than in houses and higher among Hispanics. There were no differences by age or gender. DISCUSSION: The P-E framework postulates that individuals seek settings matched to their capabilities, but findings suggest that many are at risk for adaptation at any one time. Specific risk factors are identified. Selection factors like preferences, expectations, and adaptation options available have not been directly measured.

Activities of Daily Living↗

PubMed2003

Keratocyte matrix interactions and thrombospondin 2.

PURPOSE: To determine whether human keratocytes synthesize thrombospondins 2 and 3 (TSP-2, TSP-3) in a collagen matrix and the effect of addition of antibodies to TSP-2 and TSP-3 on keratocyte-populated collagen matrix contraction. METHODS: Keratocyte-populated collagen matrices were evaluated for TSP-2 and TSP-3 mRNA. Sections of matrices were stained by immunohistochemistry for TSP-2 and TSP-3. Keratocyte populated collagen matrices were treated with antibodies specific for TSP-2 and TSP-3 and these preparations were evaluated for contraction and keratocyte morphology. RESULTS: Keratocyte derived fibroblasts in collagen matrices contained TSP-2 and TSP-3 mRNA, and the cells were immunoreactive for both proteins. Compared to controls, an antibody specific to the N-terminal domain of TSP-2 significantly inhibited matrix contraction for up to 10 days at a concentration of 20 microg/ml antibody. At 2 microg/ml TSP-2 antibody concentration significant inhibition occurred up to 3 days. Removal of the antibody from the media reversed the inhibitory effect. Cultured keratocytes in TSP-2 treated collagen matrices appeared more rounded than keratocytes in control matrices. An antibody specific to TSP-3 had no effect on matrix contraction or keratocyte morphology. CONCLUSIONS: Keratocyte derived fibroblasts synthesize TSP-2 and TSP-3 when seeded in collagen matrices. Antibody specific to TSP-2 reversibly inhibits matrix contraction. TSP-2 may play a key role in keratocyte/collagen matrix interactions, as may occur during corneal stromal repair.

Cell Adhesion Molecules↗

PubMed2002

Corneal stromal cells (keratocytes) express thrombospondins 2 and 3 in wound repair phenotype.

Members of the thrombospondin (TSP) family of proteins have been implicated in wound healing. The cells of the corneal stroma (keratocytes) are capable of synthesising TSP-1 in a wound repair phenotype, but do not appear to produce the protein in the normal human adult cornea. We employed reverse-transcriptase polymerase chain reaction (RT-PCR) to determine whether human corneal stromal cells can express TSPs other than TSP-1. Cultured keratocytes contained messenger RNA (mRNA) for TSP-2 and TSP-3 (in addition to TSP-1), but not for TSP-4 or cartilage oligomeric matrix protein (COMP; TSP-5). Keratocytes in the normal cornea contained mRNA for TSP-1 but not for other TSPs. The distribution of keratocyte TSP-2 and TSP-3 immunoreactivity had some similarities to that of TSP-1 and, like TSP-1, neither protein could be detected in the cells of the normal corneal stroma. The observations suggest that keratocytes in wound repair phenotype produce TSP-2 and TSP-3 in addition to TSP-1. TSPs may play a pivotal role in corneal stromal repair and, since TSP-1 and TSP-2 have anti-angiogenic properties, may also have a function in regulating the avascularity of the central cornea.

Cells, Cultured↗