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P Hogg

Publications and source records attributed to P Hogg.

15 recordsLinked to original sources
PubMed2000

Enzymatic action of prostate-specific antigen (PSA or hK3): substrate specificity and regulation by Zn(2+), a tight-binding inhibitor.

BACKGROUND: In semen, prostate-specific antigen (PSA or hK3) digests the gel proteins semenogelin I and II, resulting in liquefaction and the release of motile spermatozoa. We characterized the substrate specificity and zinc-mediated inhibition of PSA. METHODS: The proteolysis of human semenogelin I (SgI) and II (SgII) by PSA was characterized by purification of generated SgI and SgII fragments, N-terminal sequencing, and mass spectrometry. Zn(2+)-inhibition of PSA was studied using a chromogenic substrate. RESULTS: Eighteen cleavage sites in SgI and 16 in SgII were identified. Cleavages were identified mainly as the C-terminal of certain tyrosine and glutamine residues, but also the C-terminal of histidine, aspartic acid, leucine, serine, and asparagine residues. No cleavages were identified at any arginine, lysine, phenylalanine, tryptophan, or methionine residues, indicating that the substrate specificity of PSA is distinct from that of trypsin, chymotrypsin, tissue kallkrein (hK1), and kallikrein 2 (hK2). Zn(2+) ions have a dramatic effect on PSA activity; the data indicate that Zn(2+) is a tight-binding inhibitor of PSA activity. CONCLUSIONS: The data will enable the optimized design of PSA activity assays, which may prove instrumental to uncovering the role of PSA in cancer and reproduction. The inhibition data indicate that Zn(2+) could regulate PSA activity, which may prove important in the development of efficient inhibitors of PSA activity.

Amino Acid Sequence↗
PubMed2000

Hepatocyte growth factor/scatter factor in the eye.

Hepatocyte growth factor, also known as scatter factor (HGF/SF) is a multipotential cytokine which can produce a range of responses in target cells and its influence in the eye in health and disease is just beginning to be appreciated. Usually HGF/SF is synthesised by mesenchymally derived cells and targets and signals epithelial cells in a paracrine manner via their c-Met surface receptor. However, there is growing evidence for the existence of autocrine loops in a number of cell systems prominent among which are ocular cells such as the corneal endothelium, the lens epithelium, the retinal pigment epithelium (RPE) and others. Marked cellular proliferation is stimulated when activated HGF/SF is exposed to hepatocytes, renal epithelium, melanocytes and vascular endothelial cells but it is often a poor mitogen for other cell types. In target cells the cytokine promotes other bioactions such as junctional breakdown, shape change, cell scattering, directional and nondirectional migration, cell survival, invasive behaviour and/or tubule formation. These activities seem to depend on HGF/SF linking with the c-Met receptor and pathways to stimulate the various types of cytokine/receptor response are being unravelled at the present time. In corneal wound healing, HGF/SF is produced by stromal keratocytes and targets the repairing epithelium. HGF/SF is a constituent of tears, aqueous humour and vitreous humour at levels above that found in plasma although it is not clear how much is activated. Aqueous HGF/SF may well influence lens epithelial, corneal endothelial and trabecular meshwork cell survival. Vitreous levels of HGF/SF are elevated in proliferative vitreoretinopathy (PVR), where a target cell is the RPE and in proliferative diabetic retinopathy (PDR) where HGF/SF has been shown to be a major angiogenesis factor. Finally HGF/SF may be involved in the metastatic spread of tumour cells from uveal melanomata and in the formation of vascular channels in these tumours.

Animals↗
PubMed2000

Repair in the rabbit outflow system.

An in vivo study was conducted to study repair processes in the injured rabbit outflow system. A uniform injury was produced by raising intraocular pressure (IOP) manometrically to 70 mmHg for 1 h. The recovery process, which was followed clinically for 8 weeks and morphologically for 6 weeks, led to the re-establishment of normal meshwork architecture within this period. The morphological studies included light microscopy, autoradiography and electron microscopy. The initial lesion consisted of large deficits in the meshwork with breakdown of cell-to-cell connections, loss of extracellular materials and disruption of the vessels of the aqueous plexus. There was a significant lowering of IOP in the first week of recovery, which thereafter climbed back to normal. Also in the first week the meshwork became infiltrated with inflammatory cells which cleared by 4 weeks. There was some meshwork cell death by either necrosis or apoptosis. The majority of meshwork cells became activated within the first few days and remained activated for at least the first 2 weeks. Tritiated proline incorporation was maximal between 1 and 2 weeks. Tritiated thymidine labelling was seen throughout, but only after the inflammation subsided was it clear that meshwork cells in all regions of the meshwork were proliferating. Our study provided no evidence that normal meshwork cells have a basal proliferative turnover level. Our injury model involved complete repair of the outflow tissues and that required meshwork cells to become activated, mobilise, undertake synthetic activity and proliferate. This is the first example, other than argon laser trabeculoplasty, where meshwork cells in vivo have been induced to divide. Possible therapeutic implications for glaucoma are discussed.

Animals↗
PubMed2000

Aqueous humor stimulates the migration of human trabecular meshwork cells in vitro.

PURPOSE: Depletion of trabecular meshwork cell numbers is a feature of the outflow system in aging and in primary open-angle glaucoma. It is possible that migration stimulated by factors present in aqueous humor may contribute to the cell loss. This investigation assessed the chemoattractant potential of glaucomatous and nonglaucomatous human aqueous humor and fibronectin, one of its constituents, on a range of cultured trabecular meshwork cell lines. METHODS: Migration was assessed in 48-well modified Boyden chambers. The potential migratory stimulants were soluble fibronectin and glaucomatous and nonglaucomatous aqueous humor. The glaucomatous aqueous samples were collected from patients undergoing trabeculotomy for primary open-angle glaucoma and the normal aqueous from normal bovine eyes and patients undergoing cataract surgery. The target cell types were normal human and bovine meshwork cells grown from explants and two human transformed meshwork cell lines from a normal (HTM-5) and a glaucomatous (HTM-3) source. RESULTS: Soluble fibronectin stimulated all the target cells to migrate with an optimal concentration ranging from 1 to 30 microg/ml, and Zigmond Hirsch checkerboard analysis indicated that both chemotaxis and chemokinesis took place. All the aqueous humor samples stimulated migration of the meshwork cell lines at an optimal concentration of 200 microl/ml. Glaucomatous aqueous humor stimulated a greater migratory response than nonglaucomatous aqueous for two of the four target cell types (P < or = 0.03). Neutralization of the fibronectin content of nonglaucomatous and glaucomatous aqueous by addition of excess anti-fibronectin antibody indicated that fibronectin could account for 35% to 80% of the migratory activity of the aqueous. CONCLUSIONS: Aqueous humor contains potentially powerful chemoattractants for trabecular meshwork cells. The activity of one of these constituents, fibronectin, has been accounted for by this study. Glaucomatous aqueous appears to be as good and in some cases a better migratory stimulant than nonglaucomatous aqueous in vitro. The migratory evidence points to a trend that may help to explain cell loss in the aging meshwork and possibly some of the extra loss in primary open-angle glaucoma.

Adolescent↗
PubMed1996

Non-vascular vitreoretinopathy: the cells and the cellular basis of contraction.

BACKGROUND: We consider epiretinal membrane in terms of the two repair processes of gliosis and fibrosis and look at the cellular basis of contraction. METHODS: Pathological material removed at surgery was examined by a range of morphological procedures. Cultures of fibroblasts, retinal pigment epithelium cells and retinal glia were subjected to bioassays which relate to behavioural activities in scar formation. RESULTS AND CONCLUSIONS: Our findings highlight the importance of activities such as migration and adhesion in the formation of epiretinal membranes, and also show that these activities are central to our understanding of contraction.

Animals↗
PubMed1995

Migration of cultured bovine trabecular meshwork cells to aqueous humor and constituents.

PURPOSE: To investigate the migration of cultured bovine trabecular meshwork cells to aqueous humor and some of its constituents, and to compare the migration of normally proliferating and growth-arrested cells. METHODS: Cellular migration was evaluated in 48-well microchemoattraction chambers, and the chemoattractants used were bovine aqueous humor, glycoproteins, and growth factors. RESULTS: The meshwork cells responded well to bovine aqueous humor, and antibody neutralization experiments showed that fibronectin accounted for approximately 40% of aqueous chemoattraction. The glycoproteins laminin, thrombospondin, and transferrin elicited only modest migratory activity. Platelet-derived growth factor was the most powerful chemoattractant of the growth factors tested, and the others produced moderate migratory effects. Basic fibroblast growth factor was not chemoattractive on its own but stimulated migration when combined with heparin. Growth-arrested cells showed less migration to a standardized chemoattractive stimulus than did proliferating meshwork cells. CONCLUSIONS: For the first time, aqueous humor was shown to act as a migratory stimulus for meshwork cells in vitro. The major attractant is fibronectin; the remaining active constituents must still be identified.

Animals↗
PubMed1994

Development, repair and regeneration of the retinal pigment epithelium.

An overview is presented of the retinal pigment epithelium (RPE) cell in repair and regeneration. Changes in the RPE associated with repair activities have been described as metaplasia. However, evidence is presented to show that RPE cells do not become either fibroblasts or macrophages but merely adopt the appearance of these cell types in pathological conditions. The phenotypic alterations seem to be substrate-related. The fibroblast form predominates on two-dimensional substrates rich in fibronectin and in three-dimensional collagen matrices. The macrophage form seems to be associated with insubstantial or inadequate substrates such as the vitreous, photoreceptor debris and some cell surfaces. In altered circumstances the dedifferentiated RPE can rapidly revert to an epithelioid form. However, the regeneration of an effective RPE mosaic is more difficult and dependent on many factors including the size of the initial lesion, the condition of the basement area, the status of the neuroretina and the existing pathology in the eye. The importance for the regeneration of a normal functioning RPE of the cells being out of the cell cycle, establishing effective junctioning, reorganising their cytoskeleton and having the required adhesive balance with the basement membrane is emphasised.

Cell Adhesion↗
PubMed1990

Vertebral SPET.

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Aged↗
PubMed1988

Tissue culture of retinal glial cells.

In order to be able to investigate the properties and characteristics of glia in the retina, a monotypic culture of retinal glial cells is likely to be an important research vehicle. Several techniques are now available to produce cultures of glial cells from the retina. These methods generally result in cultures of Mueller cells rather than retinal astrocytes. Publications on glial cultures involved complex procedures for the isolation of the target cell. Recent developments have resulted in simpler procedures with the advantage that large numbers of cultures can be established quickly and easily. Glial cultures have already been used in a variety of studies, simpler methods of culture, particularly if these can be adapted for culture of human glial cells, will probably result in more extensive use of cultures to unravel the properties of retinal glia.

Animals↗