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I Masood

Publications and source records attributed to I Masood.

10 recordsLinked to original sources
PubMed2006

The -174G/C interleukin-6 promoter polymorphism influences the development of macular oedema following uncomplicated phacoemulsification surgery.

AIM: To determine whether the functional -174 G/C interleukin-6 gene polymorphism is a risk factor for the development of cystoid macular oedema (CMO) following routine uncomplicated phacoemulsification surgery in patients with no established risk factors. METHODS: A total of 40 patients who underwent routine phacoemulsification surgery as part of a randomised controlled trial comparing the use of postoperative steroid drops against a single sub-tenon injection of triamcinolone were genotyped for the IL-6 -174G/C polymorphism. All patients underwent fluorescein angiography at 30 days and anterior chamber flare measurements pre-operatively and at day 1, 7, and 30. RESULTS: Angiographic CMO developed in 14 patients of the 40 studied. 9 out of the 14 patients carried the GG genotype (Fisher's exact test P=0.05, Hazard ratio for GG genotype; 4.05 (1.02-16.00)). There was no difference in flare measurements between the GG and Non-GG (GC/CC) group. The two groups were otherwise well matched in terms of age, sex, phacoemulsification energy used intraoperatively, and proportion of patients receiving postoperative triamcinolone or steroid drops. CONCLUSION: The -174G/C interleukin-6 promoter gene variant appears to modulate the response to phacoemulsification surgery and to influence the development of postoperative CMO. These data suggest a genetic predisposition to this complication.

Aged↗
PubMed2000

Expression of the plasminogen activator system in the human vascular wall.

In this paper we describe the expression of the tissue plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and the uPA receptor (uPAR), in normal and atheromatous human vascular tissue obtained at coronary and peripheral vascular surgery. tPA, uPA, PAI-1 and uPAR antigens were localised by immunohistochemistry. Vessel homogenates were used to quantitate tPA, uPA and PAI-1 antigens as well as uPA and PAI-1 activities using immunoassay and immunoactivity assays, respectively. Quantitative reverse transcription polymerase chain reaction assays (PAI-1 and uPA) were developed and used to quantify PAI-1 and uPA mRNA. In-situ hybridisation (tPA, uPA and PAI-1) was used to localise mRNA. In normal saphenous vein or internal mammary artery, expression of tPA, uPA and PAI expression is associated with endothelium and with intimal or medial smooth muscle cells, but expression is at a low level. uPAR protein was seen on the endothelium of normal saphenous vein or internal mammary artery but absent on the smooth muscle cells. In complex atheroma tPA, uPA, PAI and uPAR proteins were associated with the endothelium, groups of smooth muscle cells (in the intima and around vascular channels, but not with the media), infiltrating mononuclear cells, and also with acellular areas. PAI-1, tPA and uPA mRNA were demonstrated in atheroma in endothelial cells and smooth muscle cells, as well as in areas rich in macrophages. In stenosing saphenous vein grafts there was strikingly increased tPA and uPA (but not PAI-1) expression in neointimal smooth muscle cells and migrating SMC at the intima/media border. A major difference between complex atheroma and either normal vessel or saphenous vein grafts was greatly increased expression of PAI-1 mRNA associated with smooth muscle cells (SMC) in the former. In spite of the greatly increased PAI-1 mRNA expression in atheromatous lesions, the immunoactivity assay showed PAI-1 activity to be low compared to normal internal mammary artery. Our findings would be compatible with previous reports implicating the plasminogen activator/inhibitor system in the initiation and control of matrix remodelling during normal and pathological vessel growth and repair, but also emphasize the complexity of this process in human vessels.

Arteriosclerosis↗
PubMed1998

Endothelin-B receptors mediate intimal hyperplasia in an organ culture of human saphenous vein.

OBJECTIVE: Although a number of pharmacologic agents have been shown to reduce intimal hyperplasia in animal models of restenosis, to date no systemic agent has conclusively been shown to be effective in humans. Recently, considerable attention has been directed towards endothelin (ET), a potent vasoconstrictor and a powerful mitogen for vascular smooth muscle cells, as a mediator of intimal hyperplasia. Endothelin-1 has been shown to be mitogenic for human saphenous vein smooth muscle cells, and expression also is elevated in human vein graft stenosis. The aim of this study was the investigation of whether ET receptor antagonists can attenuate neointima formation in a laboratory model of vein graft intimal hyperplasia and the determination of whether the effects are mediated by a specific ET receptor subtype. METHODS: We used an organ culture of human saphenous vein, a well-validated model of vein graft intimal hyperplasia. Paired segments of human long saphenous vein were cultured with and without the following antagonists: bosentan, a nonselective ET receptor antagonist; BQ 123, a specific endothelin-A antagonist; or BQ 788, a specific endothelin-B (ETB) antagonist. After 14 days in the culture, the segments were fixed and processed and the sections were immunostained to facilitate the measurements of neointimal thickness with a computerized image analysis system. RESULTS: The nonselective antagonist bosentan and the ETB selective antagonist BQ 788 significantly reduced neointima formation by 70% (P = .001) and 50% (P = .03), respectively, but the ETA antagonist BQ 123 had no significant effect on the reduction of neointima formation (P = 1.0). CONCLUSION: The results of this study imply an important role for ET as a mediator of human vein graft intimal hyperplasia and imply further that a specific ETB antagonist may have a therapeutic potential for the prevention of vein graft stenosis.

Bosentan↗
PubMed1997

Endothelin-1 is a mediator of intimal hyperplasia in organ culture of human saphenous vein.

BACKGROUND: Endothelin-1 (ET-1) is a powerful vasoconstrictor and a potent mitogen for vascular smooth muscle cells. Excessive smooth muscle cell proliferation is a feature of intimal hyperplasia, the pathological lesion of vein graft stenosis. This study investigates the role of ET-1 in isolated human saphenous vein smooth muscle cells and also in an organ culture of the human saphenous vein. METHODS: Growth-arrested human saphenous vein smooth muscle cells were stimulated with ET-1 and proliferation quantified by [3H]thymidine uptake in these cells compared with unstimulated control cells. Organ cultures of the human saphenous vein were established with endothelium intact, with endothelium denuded, and with endothelium denuded and the culture medium supplemented with ET-1. RESULTS: ET-1 stimulated DNA synthesis in isolated smooth muscle cells in a dose-dependent manner with half-maximal stimulation at 1 nmol/l. Addition of ET-1 to denuded vein caused a significant increase in median (range) neointimal thickness, from 4 (0-19) to 20 (4-30) microns (P < 0.05). In veins cultured with ET-1 a parallel increase in median (range) neointimal proliferation index, from 21 (0-31) to 33 (23-46) per cent (P < 0.05), was also observed. CONCLUSION: These results demonstrate that ET-1 is a mediator of intimal hyperplasia in human saphenous vein in vitro. Endothelin receptor antagonists may therefore be of therapeutic value in the modulation of vein graft intimal hyperplasia.

Cell Division↗
PubMed1995

Stimulation of two vascular smooth muscle-derived cell lines by angiotensin II: differential second messenger responses leading to mitogenesis.

1. We show here that angiotensin II (AII) and endothelin-1 (ET-1) stimulate [3H]-thymidine incorporation in a smooth muscle cell line derived from aortae of spontaneously hypertensive rats (SHR), but not in cells derived from normotensive controls (WKY). We have used the differential response of the two cell lines to investigate the relationship between second messenger systems and the mitogenic response. 2. AII produced an increase in accumulation of inositol 1,4,5-triphosphate which was greater in the SHR-derived cell line than in the WKY cells. 3. AII gave an increase in cytosolic Ca2+ in each of the cell lines, with both a larger peak (15-30 s) and plateau response (2 min) in the SHR cells. ET-1 gave an enhanced response in the SHR-derived cells with respect to the peak but not the plateau of cytosolic Ca2+. 4. Phospholipase D activity was studied by monitoring the formation of [3P]-phosphatidylbutanol in 32Pi prelabelled cells. AII stimulation gave a larger phospholipase D response in the SHR-derived cells, while ET-1 gave a larger response in WKY-derived cells. 5. Stimulation of SHR-derived cells with 100 nM AII for 1 h, followed by 19 h in the absence of agonist, stimulated [3H]-thymidine incorporation over the next 4 h. When the 1 h stimulation with AII was in the presence of increasing concentrations of butanol, which diverts the product of the phospholipase D pathway, there was a loss of stimulated [3H]-thymidine incorporation which was significant at 10 mM butanol and at 30-50 mM reached a maximum loss of 40%. 6. Contrasting with this there was no apparent loss of ET-l-stimulated thymidine incorporation when butanol was present at concentrations up to 40 mM.7. These results suggest that phospholipase D is one of several pathways in the mitogenic response of SHR-derived vascular smooth muscle cells to All.

Angiotensin II↗