M J Underwood
University of Leicester
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Featured researches published by M J Underwood.
European Journal of Vascular Surgery | 1993
M J Underwood; Ranjit S. More; N. Weeresena; R.K. Firmin; D.P. de Bono
The objective of this study was to assess the effect of distension on the intrinsic fibrinolytic activity of human saphenous vein during its preparation for use as a bypass conduit prior to coronary artery surgery. Fibrinolytic activity was studied using fibrin plate techniques and Chromogenic assays for extractable tPA and uPA. Samples were obtained from patients undergoing routine coronary surgery. Fibrinolytic activity was compared in control vein (untouched) vein that had been prepared for use as a bypass conduit (surgical dissection, ligation of side branches and careful but uncontrolled manual distension) and segments of dissected vein distended in vitro to pressures of 230 or 120 mmHg. Uncontrolled distension and distension to 230 mmHg impaired fibrinolytic activity as determined by areas of lysis on fibrin plates (p < 0.05), (p < 0.005), tPA activity (p < 0.005) (p < 0.005) and uPA activity (p < 0.05), (p < 0.005). Distension to 120 mmHg had no effect on the fibrinolytic activity of human saphenous vein. Impaired fibrinolytic activity caused by uncontrolled distension of saphenous vein prior to its use as a vascular conduit may contribute to early vein graft thrombosis and can be avoided using controlled distension to < 120 mmHg.
American Heart Journal | 1994
Ranjit S. More; Guy N. Rutty; M J Underwood; Michael J. Brack; Anthony H. Gershlick
A detailed temporal assessment of cellular proliferation was carried out by means of immunostaining for proliferating cell nuclear antigen in a normolipemic rabbit model of balloon angioplasty to the iliac arteries. Assessment was made at 30 minutes, 2 hours, 1 day, 3 days, 7 days, 14 days, 1 month and 3 months after the procedure. Intimal hyperplasia was first noted at day 3; a prominent layer was formed by day 14. Cellular proliferation in the vessel media was observed as early as day 1 (percentage of positive-staining cells 0.5% +/- 0.2%), reaching a maximum by day 7 (16.9% +/- 5.1%) before returning to baseline levels by 1 month (0.2% +/- 0.02%); in the intima, cellular proliferation was first noted at day 7 (0.7% +/- 0.3%) and reached a maximum at day 14 (4.1% +/- 0.4%) before returning to baseline levels at 1 month (0.3% +/- 0.1%). Use of proliferating cell nuclear antigen expression in this model of angioplasty provided a simple and reproducible method of assessing cellular proliferation after vascular injury and may prove useful for monitoring the effects, in experimental models, of agents for reducing myointimal hyperplasia.
Journal of Vascular Research | 1993
M J Underwood; Ranjit S. More; Anthony H. Gershlick; D.P. de Bono
Increasingly, attention is focusing on the local delivery of antiplatelet and fibrinolytic therapy as a means of preventing intravascular thrombosis. A simple, reproducible model of thrombosis, based upon vascular damage is needed to test these agents in vivo. We have therefore modified a rat vena cava model of venous thrombosis based upon vascular injury and stasis. Wistar rats are anaesthetised, the inferior cava dissected free and a segment isolated by slings distally above the iliacs and proximally above the left renal vein. All other tributaries are ligated. Vascular injury is induced by externally applying soft-jaw clamps for 5 min. Agents to be tested are introduced into the isolated segment via a left renal vein cannula left in situ for 15 min and then flushed from the cava. Blood is allowed to refill the segment, all remaining slings are tied and the animal left for 30 min before being killed. The cava is then opened and thrombus removed and weighed. Scanning electron microscopy of the cava after clamping shows areas of normal endothelium interspersed with areas of denuded endothelium and exposed subendothelial connective tissue. Histological and immunohistochemical staining indicates the thrombus is composed of red cells, platelets and fibrin. The model was validated by assessing the effects of 2 different doses of locally delivered tissue-type plasminogen activator (tPA). The mean weights of thrombus were [mg (SD)]: Control (saline; n = 8) 39.0 (8.73), tPA 0.01 mg/ml (n = 6) 45.5 (10.56) and tPA 1 mg/ml (n = 8) 3.5 (3.4). Comparing 1 mg/ml tPA vs. 0.01 mg tPA vs. control, p < 0.001 (Mann-Whitney test).(ABSTRACT TRUNCATED AT 250 WORDS)
International Journal of Angiology | 1995
Ranjit S. More; M J Underwood; Michael J. Brack; S. Pringle; David de Bono; Anthony H. Gershlick
We assessed whether chemical conjugation of a monoclonal antibody (M735) against platelet glycoprotein IIb/IIIa receptors to urokinase and to a monoclonal antibody which binds to damaged endothelium (P14G11) resulted in enhanced inhibition of platelet aggregation with maintenance of localizing features (to damaged endothelium). Conjugation of M735 (an IgM monoclonal antibody) to urokinase and P14G11 (an IgG2a monoclonal antibody) was carried out using SPDP [N-Succinimidyl-3-(2-pyridyldithio)-propionate] as the cross-linking reagent. The resulting triple conjugate [ATC(3)] had fibrinolytic activity and retained platelet and damaged endothelium localizing features. Enhanced inhibition of platelet aggregation (induced by either adenosine diphosphate (ADP), collagen, or thrombin) was observed compared with both an unconjugated mixture of the three individual components and to the M735-urokinase conjugate. We conclude that it is possible to produce a bimonoclonal antibody-urokinase agent which has both potent antiplatelet aggregatory effects and additional targeting or localizing features.
The Journal of Pathology | 1994
Ranjit S. More; Guy N. Rutty; M J Underwood; Michael J. Brack; Anthony H. Gershlick
Cardiovascular Research | 1993
M J Underwood; D.P. de Bono
American Journal of Cardiology | 1994
Ranjit S. More; Michael J. Brack; M J Underwood; Anthony H. Gershlick
Cardiovascular Research | 1993
Ranjit S. More; M J Underwood; Michael J. Brack; S. Pringle; David de Bono; Anthony H. Gershlick
British Journal of Surgery | 1992
M J Underwood; S. Pringle; D.P. de Bono
Thrombosis and Haemostasis | 1994
Ranjit S. More; M J Underwood; D.P. de Bono