viously been isolated in this laboratory, and the 
gene has been localized to human chromosome 7. 
PAI-1 was shown to be a member of the serine pro- 
tease inhibitor (SERPIN) supergene family. The lab- 
oratory has now characterized the structure of the 
PAI-1 cellular gene that spans 12 kb and is inter- 
rupted by 8 introns. The intron-exon structure 
shows little similarity to that of other SERPINs, an 
observation with implications for the process of in- 
tron evolution. The promoter of the human PAI-1 
gene has also been characterized, and its function 
has been demonstrated by transfection into heter- 
ologous cells. The laboratory is continuing to study 
the regulation of PAI-1 expression in endothelial 
cells. 
Current studies of PAI-1 are centered largely on 
structure-function analysis. A system has been de- 
veloped in the laboratory for expressing PAI-1 in 
E. coli as a fusion to Staphylococcus protein A, with 
a synthetic collagen sequence inserted between the 
Staphylococcus protein A and PAI-1. With this sys- 
tem, large quantities of PAI-1 (and several other eu- 
karyotic proteins) have been expressed and puri- 
fied, with subsequent release by cleavage with the 
specific protease, coUagenase. This recombinant 
PUBLICATIONS 
PAI-1 is functionally active and will provide the 
tools for future mutagenesis studies. 
III. Biology of Bone Marrow Transplantation. 
Bone marrow transplantation (BMT) is finding 
increasing application as a treatment modality for 
human leukemias and other malignancies. This lab- 
oratory has continued its interest in the application 
of restriction fragment length polymorphism 
(RFLP) analysis to distinguish the host-versus-donor 
origin of patient blood cells after BMT. The labora- 
tory has now applied PGR to detect DNA sequence 
polymorphisms and is using this approach to inves- 
tigate the kinetics of marrow engraftment during 
the first few weeks after BMT. This laboratory is 
also using PGR to detect chronic myelogenous leu- 
kemia cells specifically and monitor their disappear- 
ance after BMT for this disorder. These observa- 
tions may have important implications for 
transplantation biology and for the continued de- 
velopment of BMT as a treatment modality. 
Dr. Ginsburg is also Assistant Professor of Inter- 
nal Medicine and of Human Genetics at the Univer- 
sity of Michigan Medical School. 
Books and Chapters of Books 
Ginsburg, D., Konkle, B.A., Gill, J.C., Montgomery, R.R., Bockenstedt, PL., Johnson, T.A., and Yang, A.Y 1989. 
Human von Willebrand's disease: analysis of platelet mRNA by PGR. In The Polymerase Chain Reaction: 
Current Communications in Molecular Biology . Cold Spring Harbor, NY: Cold Spring Harbor, pp 93-99. 
Goldberg, M.A., Ginsburg, D., Mayer, R.J., Stone, R.M., Maguire, M., Rosenthal, D.S., and Antin, J.H. 1988. Is 
heparin administration necessary during induction chemotherapy for patients with acute promyelocytic 
leukemia? In 1988 Year Book of Cancer. Houston, TX: Year Book Medical, pp 196-198. 
Articles 
Bahou, WR, Ginsburg, P. , Sikkink, R., Litwiller, R., and Pass, D.N. 1989. A monoclonal antibody to von 
Willebrand factor (vWF) inhibits factor VIII binding. Localization of its antigenic determinant to a non- 
adecapeptide at the amino terminus of the mature vWF polypeptide. J Clin Invest 84:56-61. 
Chottiner, E.G., Ginsburg, D., Tartaglia, A.P, and Mitchell, B.S. 1989. Erythrocyte adenosine deaminase over- 
production in hereditary hemolytic anemia. Blood 74:448-453. 
Ginsburg, D. , Konkle, B.A., Gill, J. C, Montgomery, R.R., Bockenstedt, PL., Johnson, T.A. , and Yang, A.Y 1989. 
Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA. Proc 
Natl Acad Sci USA 86:3723-3727. 
Gribbin, T, Chottiner, E., Ginsburg, D., and Mitchell, B. 1989. Identification of an Apa I polymorphism 
within the human adenosine deaminase (ADA) gene. Nucleic Acids Res 17:3626. 
Roth, M.S., Antin, J.H. , Bingham, E.L., and Ginsburg, D. 1989. Detection of Philadelphia chromosome-posi- 
tive cells by the polymerase chain reaction following bone marrow transplant for chronic myelogenous 
leukemia. Blood 74:882-885. 
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