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Biomedical subjects

J Rudge

Publications and source records attributed to J Rudge.

7 recordsLinked to original sources
PubMed2004

Angiopoietic factors and retinopathy in pregnancies complicated with Type 1 diabetes.

AIMS: To evaluate the role of systemic angiopoietic factors in the progression of diabetic retinopathy during pregnancy. METHODS: In a prospective study of 26 pregnant women with diabetes and eight non-diabetic pregnant women, retinopathy was graded from fundus photographs. Plasma levels of angiopoietin-1, angiopoietin-2, human vascular endothelial growth factor A (hVEGF-A), and total soluble receptor of vascular endothelial growth factor (sVEGF) receptor-1 were measured during the first and third trimester and 3 months postpartum. RESULTS: In diabetic women, levels of angiopoietin-2 were 26.5 ng/ml (12.1-47.7) (median and range) during the first trimester, 2.9 ng/ml (0.6-3.5) during the third trimester, and 0.5 ng/ml (0.3-0.7) 3 months postpartum, compared with 44.3 (38.3-61.9), 5.7 (3.1-8.4) and 0.9 (0.6-4.9) ng/ml, respectively, in non-diabetic women (P = 0.002 between groups). Levels of angiopoietin-1 and sVEGF receptor-1 did not differ between the groups. Postpartum hVEGF-A levels were lowest in women with progression of retinopathy. In logistic regression analyses, progression of retinopathy during pregnancy was not explained by the levels of the angiopoietic factors. CONCLUSIONS: The circulating levels of angiopoietic factors in pregnant diabetic women were either lower than (Ang-2) or similar to (Ang-1, hVEGF-A, VEGFR-1) those levels observed in non-diabetic pregnant women. The levels of angiopoietic factors measured here appear not to be connected with the progression of retinopathy during pregnancy.

Adult↗
PubMed2001

VEGF-initiated blood-retinal barrier breakdown in early diabetes.

PURPOSE: The objectives of this study were to (1) determine whether endogenous vascular endothelial growth factor (VEGF) triggers diabetic blood-retinal barrier breakdown, and (2) identify the site as well as phenotype of the hyperpermeable diabetic retinal vessels. METHODS: Retinal VEGF mRNA levels were quantified in 1-week diabetic rats using the RNase protection assay. VEGF bioactivity was blocked via the systemic administration of a highly specific VEGF-neutralizing soluble Flt/F(c) construct (VEGF TrapA(40)). An inactive IL6 receptor/F(c) construct (IL6R Trap) was used as an isotype control. Blood-retinal barrier breakdown was quantified using the Evans blue technique and was spatially localized with fluorescent microspheres. RESULTS: Retinal VEGF mRNA levels in 1-week diabetic animals were 3.2-fold higher than in nondiabetic controls (P < 0.0001). Similarly, retinal vascular permeability in 8-day diabetic animals was 1.8-fold higher than in normal nondiabetic controls (P < 0.05). Diabetes-induced blood-retinal barrier breakdown was dose-dependently inhibited with VEGF TrapA(40), with 25 mg/kg producing complete inhibition of the diabetes-induced increases (P < 0.05). Blood-retinal barrier breakdown in diabetic animals treated with solvent alone or IL6R Trap did not differ significantly from untreated diabetic animals (P > 0.05). Spatially, early blood-retinal barrier breakdown was localized to the retinal venules and capillaries of the superficial retinal vasculature. CONCLUSIONS: Early blood-retinal barrier breakdown in experimental diabetes is VEGF dependent and is restricted, in part, to the venules and capillaries of the superficial inner retinal vasculature. VEGF inhibition should prove a useful therapeutic approach in the treatment of early diabetic blood-retinal barrier breakdown.

Animals↗
PubMed2000

Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions.

Inflammation is a basic pathological mechanism that underlies many diseases. An important component of the inflammatory response is the passage of plasma components and leukocytes from the blood vessel into the tissues. The endothelial monolayer lining blood vessels reacts to stimuli such as thrombin or vascular endothelial growth factor by changes in cell-cell junctions, an increase in permeability, and the leakage of plasma components into tissues. Other stimuli, such as tumor necrosis factor-alpha (TNF-alpha), are responsible for stimulating the transmigration of leukocytes. Here we show that angiopoietin-1, a cytokine essential in fetal angiogenesis, not only supports the localization of proteins such as platelet endothelial cell adhesion molecule-1 (PECAM-1) into junctions between endothelial cells and decreases the phosphorylation of PECAM-1 and vascular endothelial cadherin, but it also strengthens these junctions, as evidenced by a decrease in basal permeability and inhibition of permeability responses to thrombin and vascular endothelial growth factor. Furthermore, angiopoietin-1 inhibits TNF-alpha-stimulated leukocyte transmigration. Angiopoietin-1 may thus have a major role in maintaining the integrity of endothelial monolayers.

Angiopoietin-1↗
PubMed1996

British weather: conversation topic or serious health risk?

Britain is renowned for low indoor winter temperatures and a high rate of excess winter deaths and a causal association has been drawn between the two. A lack of priority given to energy efficiency here is often justified in terms of the mild climate. However, it can be shown that British climatic features may be related to poor health as long as poor standards of construction and insulation prevail. Legislation should therefore be implemented to improve standards both for new housing and refurbishment of much existing housing stock, not only for reasons of energy conservation but also for community health.

Acclimatization↗
PubMed1986

Morphological modulation of cultured rat brain astroglial cells: antagonism by ganglioside GM1.

Secondary cultures of neonatal rat astroglial cells, maintained in a serum-free, chemically defined medium were treated with several agents thought to activate cyclic AMP-synthesizing systems. Dibutyryl cyclic AMP (dBcAMP), forskolin and cholera toxin promoted, within 2 h, the near-complete conversion of 1-day-old (D1) astroglial cells from a flat, epithelioid morphology to a stellate (star-shaped) morphology. With all 3 agents, cell susceptibility to morphological change declined with culture age, 5-day-old cultures failing to respond altogether. D1 cultures, after 48 h of treatment, had reverted to the flat morphology. Gangliosides reported to stimulate adenylate cyclase were also tested, using purified GM1 X GM1 failed to stimulate the conversion to stellate morphologies. GM1, however, did affect these astroglial cells by causing a block or reversal of their morphological response to dBcAMP, forskolin or cholera toxin. The GM1 response was specific for the intact ganglioside molecule, asialo GM1 and sialic acid having no effect. Gangliosides GD1a, GD1b and GT1b were also active, being effective at ca. 4-fold lower concentrations. The response to GM1 appeared to involve a direct interaction with the astroglial cell, rather than influencing either substratum or medium components.

Animals↗
PubMed1985

Glycoprotein composition and turnover in subcellular fractions from the cerebral cortex of normal and reeler mutant mice.

Twenty-day-old reeler and normal mice were either injected intraventricularly with radiolabelled fucose before subcellular fractionation of the cerebral cortex followed by SDS-PAGE, or gels of such fractions were overlaid with [125I]concanavalin A (ConA). While there were no differences in polypeptide profiles of normal and reeler subcellular fractions there were marked differences in the abundance of particular ConA-binding glycoproteins and in fucose incorporation into particular glycoproteins, especially in the synaptic plasma membrane (SPM) and 100,000 g soluble fractions. In addition there was a significantly lower binding (greater than 50%) of quinuclidinyl benzilate to reeler microsomal and SPM fractions as compared with normal. The differences in glycoprotein expression may be pertinent to anatomical observations of abnormal interactions between neurons and glial fibres during development of the reeler cerebrum.

Animals↗