In memoriam: Stewart Anthony Cederholm-Williams, Ph.D. (1947-2002)

(to be published in Thrombosis and Haemostasis)

Dr. Stewart Cederholm-Williams died in a tragic accident on July 5, 2002. His death is a tremendous loss to his family, as well as numerous friends and scientific colleagues in many parts of the world.

Born in 1947, Stewart Cederholm-Williams spent his childhood and schooling years in England and Wales. Leaving school with few qualifications he began his professional career in 1964 as a laboratory assistant at the Radcliffe Infirmary, Oxford, under the tutelage of Professor R.G. MacFarlane, and maintained close links with Oxford throughout his life. Alongside his work he achieved A-levels at the Oxford Polytechnic in 1968. In that year he also married Gunnel Cederholm and they later had 2 daughters, Kerstin and Ingalill. Having obtained a B.Sc. in Biochemistry at Hatfield Polytechnic in 1972 he went on to gain a Ph.D. at Pembroke College, Oxford, in the late 70’s.

Throughout his research career Dr. Cederholm-Williams was involved in numerous studies of blood coagulation and fibrinolysis in normal and pathological states. His early research focused on plasminogen and its activators, tissue-type plasminogen activator, and streptokinase-plasminogen complex. Later he became interested in fibrin(ogen), particularly in therapeutic use of fibrin as tissue sealant. He developed a technology for preparation of fibrin I, a monomeric form of fibrin which could be converted into a clot by a simple change in pH. This technology was then used in the VivostatTM system designed for the preparation of autologous fibrin glue.

The research interests of Dr. Cederholm-Williams expanded further after he established Oxford Bioresearch, a research based company which had research programs into snake venom enzymes, clot dissolving proteins, anticancer agents, and biologically active antibodies. In addition to these new interests he continued working on further development and applications of fibrin sealants and investigation of the role of fibrin(ogen) in wound healing; he continued being a fibrinogen fan and was an active participant and contributor at the Workshops of the International Fibrinogen Research Society, attending his last one in Leiden in 2000.

Dr. Cederholm-Williams served as a Managing Director of Oxford Bioresearch for more than 10 years. After opening an International headquarters at the Magdalen Centre in Oxford in 1992, the company expanded steadily under his leadership. Being committed to high quality research, he maintained collaboration with a number of universities and academic institutes to increase the research base and potential of the company. He commenced the support of a number of Ph.D. studentships and supervised a number of Ph.D. students in different Universities in the UK. He initiated establishment of a research group in a biotechnology laboratory at Oxford Brookes University. He also maintained close scientific and business ties with his American colleagues and for several years was a consultant for Bristol-Myers Squibb Company.

In 1995 Dr. Cederholm-Williams started collaboration with the Institute of Biochemistry in Kiev, Ukraine, to draw on the long experience of former Soviet biochemistry, particularly in the area of haemostasis. This collaboration was developed into full joint venture by 1995 when Oxford Bioresearch (Kiev) was established in Ukraine. Under this collaboration a number of scientific projects were accomplished by Ukrainian scientists; a number of them visited Oxford forging scientific and cultural links between two laboratories and two countries. In recognition of his contribution to Ukrainian biomedical research, Dr. Cederholm-Williams was elected as a foreign member of the Ukrainian National Academy of Sciences in 1996.

Stewart Cederholm-Williams was an extraordinary person with a creative mind and a great sense of humour. He was sincere and generous and had a big heart. He loved people and had many friends around the world. He is and will always be remembered with a great respect and love by his family and his friends and colleagues, all of whom feel he left us too soon.

Leonid Medved, The American Red Cross Holland Laboratory, Maryland, U.S.A.
Michael Mosesson, The Blood Center of Southeastern Wisconsin, Wisconsin, U.S.A.
Ingalill Sandys, University of Bristol, U.K.
Nina Lukinova, Clearant, Inc., Maryland, U.S.A.
Martin MacPhee, Clearant, Inc., Maryland, U.S.A.
Selected Publications
  1. Cederholm-Williams SA. The binding of plasminogen (mol. wt. 84,000) and plasmin to fibrin. Throm. Res. 1977; 11:421-423.
  2. Cederholm-Williams SA. The binding of plasminogen, plasmin and streptokinase-plasminogen activator to fibrin. Biochem. Soc. Trans. 1977; 5: 1441-1443.
  3. Mishler JM, Darley JH, Cederholm-Williams S. Whole blood stored in half-strength trisodium citrate. Lancet 1977; 1(8003): 152.
  4. Uziel L, Cederholm-Williams SA. Measuring plasminogen activator. Lancet 1977; 2(8052-8053): 1368-1369.
  5. Cederholm-Williams SA, King A, Allington MJ, Gill PG, Sharp AA, Britton BJ. Coagulation and fibrinolysis during the infusion of Corynebacterium parvum in man. Br. J. Cancer. 1978; 37: 1074-1077.
  6. Cederholm-Williams SA, Swain A. The effect of fibrinogen degradation products and some lysine analogues on the dissociation of plasmin(ogen)-fibrin complexes. Thromb. Res. 1979; 16: 705-713.
  7. Cederholm-Williams SA, De Cock F, Lijnen HR, Collen D. Kinetics of the reactions between streptokinase, plasmin and a2-antiplasmin. Eur. J. Biochem. 1979;100: 125-132.
  8. Cederholm-Williams SA. The binding of plasmin-streptokinase complex to fibrin monomer-sepharose. Thromb. Res. 1980; 17: 573-576.
  9. Cederholm-Williams SA. Molecular mechanism of fibrinolysis - a system involved with malignant cells. Invasion Metastasis. 1981; 1: 85-98.
  10. Cederholm-Williams SA, Fennell SJ. Binding of plasmin(ogen) to sepharose bound fibrin(ogen) a-chain. Thromb. Res. 1981; 21: 503-506.
  11. Cederholm-Williams SA. The effect of streptokinase on the fibrin binding site of plasmin(ogen). Thromb. Res. 1981; 21: 649-654.
  12. Cederholm-Williams SA, Dornan TL, Turner RC. The metabolism of fibrinogen and plasminogen related to diabetic retinopathy in man. Eur. J. Clin. Invest. 1981; 11: 133-138.
  13. Cederholm-Williams SA. Concentration of plasminogen and antiplasmin in plasma and serum. J. Clin. Pathol. 1981; 34: 979-981.
  14. Cederholm-Williams SA, Spencer JA, Wilkinson AR. Plasma levels of selected haemostatic factors in newborn babies. Thromb. Res. 1981; 23: 555-558.
  15. Cederholm-Williams SA. Control of fibrinolysis. Br. J. Hosp. Med. 1983; 30: 107-110.
  16. Cederholm-Williams SA, Porter NW. Identification of the plasminogen activator secreted by human fibroblasts. Br. J. Dermatol. 1984; 110: 423-429.
  17. Cederholm-Williams SA, Marshall JM, Chissic H. Active site directed inhibitor used in the production of antibodies against urokinase. J. Clin. Pathol. 1984; 37: 1193-1194.
  18. Marshall JM, Rees MC, Cederholm-Williams SA. Identification of t-PA as the major active plasminogen activator in human milk. Thromb. Haemost. 1986; 55: 279-281.
  19. Williams RJ, Esnouf P, Lawrence M, Cederholm-Williams SA. The similarities and differences in structures between kringle 1 of prothrombin and kringle 4 of plasminogen. FEBS Lett. 1986; 209: 111-116.
  20. Layer GT, Burnand KG, Gaffney PJ, Cederholm-Williams SA, Mahmoud M, Houlbrook S, Pattison M. Tissue plasminogen activators in breast cancer. Thromb. Res. 1987; 45: 601-607.
  21. Booth F, Allington MJ, Cederholm-Williams SA. An in vitro model for the study of acute release of von Willebrand factor from human endothelial cells. Br. J. Haematol. 1987; 67: 71-78.
  22. Byron MA, Allington MJ, Chapel HM, Mowat AG, Cederholm-Williams SA. Indications of vascular endothelial cell dysfunction in systemic lupus erythematosus. Ann. Rheum. Dis. 1987; 46: 741-745.
  23. Cherry G, Cherry C, Jones R, Ryan T, Pickworth J, Fairbrother J, Cederholm-Williams SA. Clinical experience with duoderm in venous ulcers and clot resolution in experimental full-thickness wounds. In: Fibrinolysis and Angiogenesis in Wound Healing. 1988: 19-23.
  24. Burge SM, Ryan TJ, Cederholm-Williams SA. Darier's disease: an immunohistochemical study using antibodies to proteases. Br. J. Dermatol. 1989; 121: 613-621.
  25. Burge SM, Marshall JM, Cederholm-Williams SA. Plasminogen binding sites in normal human skin. Br. J. Dermatol. 1992; 126: 35-41.
  26. Ballance DJ, Marshall JM, Cottingham IR, Steven J, Berry SJ, Cederholm-Williams SA, Goodey AR, Courtney M. A hybrid protein of urokinase growth-factor domain and plasminogen-activator inhibitor type 2 inhibits urokinase activity and binds to the urokinase receptor. Eur.J. Biochem. 1992; 207: 77-183.
  27. Ponting CP, Holland SK, Cederholm-Williams SA, Marshall JM, Brown AJ, Spraggon G, Blake CC. The compact domain conformation of human Glu-plasminogen in solution. Biochim. Biophys. Acta. 1992; 1159: 155-161.
  28. Ponting CP, Marshall JM, Cederholm-Williams SA. Plasminogen: a structural review. Blood Coagul. Fibrinolysis 1992; 3: 605-614.
  29. Venning VA, Wojnarowska F, Cederholm-Williams S. An immunohistochemical study of the distribution of plasminogen and plasminogen activators in bullous pemphigoid. Clin. Exp. Dermatol. 1993; 18: 119-123.
  30. Elliott JM, Cross DB, Cederholm-Williams SA, White HD. Neutralizing antibodies to streptokinase four years after intravenous thrombolytic therapy. Am. J. Cardiol. 1993; 71:640-645.
  31. Cederholm-Williams SA. Fibrin glue. B.M.J. 1994; 308(6943): 1570.
  32. Cederholm-Williams SA. Autologous fibrin sealants are not yet available. Lancet 1994; 344(8918): 336-337.
  33. Parish S, Collins R, Peto R, Youngman L, Barton J, Jayne K, Clarke R, Appleby P, Lyon V, Cederholm-Williams S, et al. Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14,000 cases and 32,000 controls in the United Kingdom. The International Studies of Infarct Survival (ISIS) Collaborators. B.M.J. 1995; 311(7003): 471-477.
  34. Cederholm-Williams SA. Therapeutic use of fibrin - a new class of fibrin sealant with minimal risks. Ukr. Biochem. J. 1996; 68(4): 34-36.
  35. Cederholm-Williams SA. Therapeutic use of streptokinase. Ukr. Biochem. J. 1996; 68(4): 36-37
  36. Kjaergard HK, Fairbrother JF, Cederholm-Williams SA, Edwardson PAD, Hollingsbee DA, Holm NE. The Vivostat system for the automated preparation of autologous fibrin sealant. Cardiovasc. Eng. 1997; 2: 1-3.
  37. Cockell CS, Marshall JM, Dawson KM, Cederholm-Williams SA, Ponting CP. Evidence that the conformation of unliganded human plasminogen is maintained via an intramolecular interaction between the lysine-binding site of kringle 5 and the N-terminal peptide. Biochem. J. 1998; 333: 99-105.
  38. Quarmby J, Smith A, Collins M, Cederholm-Williams S, Burnand K. A model of in vivo human venous thrombosis that confirms changes in the release of specific soluble cell adhesion molecules in experimental venous thrombogenesis. J. Vasc. Surg. 1999; 30:139-147.
  39. Slonimskyi OY, Makogonenko EM, Cederholm-Williams SA. Features of plasminogen activation in a complex with antiplasminogen monoclonal antibody IV-1C. Ukr. Biochem. J. 1999; 71(5): 44-50.
  40. Korol'chuk VI, Makohonenko EM, Cederholm-Williams SA. Isolation and characteristics of antistreptokinase antibodies from blood serum of myocardial infarct patients treated with streptokinase. Ukr. Biochem. J. 1999; 71(6):47-55.