Michigan). This work has demonstrated that sialyl 
Lewis x-containing oligosaccharides function as rel- 
atively potent anti-inflammatory molecules in ani- 
mal models of selectin-dependent inflammation. 
Future work will focus on defining the structural 
requirements for anti-inflammatory activity and on 
exploring the ability of these molecules to abro- 
gate selectin-dependent cell adhesion processes 
necessary for several types of acute and chronic 
inflammation. 
During the past year, experiments in Dr. Lowe's 
laboratory have defined the molecular basis for null 
alleles at the human H blood group locus, which 
corresponds to an a(l ,2)fucosyltransferase gene 
previously isolated by his group. These studies con- 
firm the hypothesis that the human genome main- 
tains other a(l,2)fucosyltransferase genes, one of 
which probably corresponds to the human Secretor 
blood group locus. Efforts are under way to isolate 
such genes, to study the biosynthesis of their en- 
zyme products, and to define their expression pat- 
terns. Work on the human a (1, 2 )fucosyl transferase 
genes will be supported by a grant from the National 
Institutes of Health. 
Also during this past year, Dr. Lowe's laboratory 
has isolated two new human a(l,3)fucosyltransfer- 
ase genes. These represent the second and third 
members of a family of structurally and functionally 
related a(l,3)fucosyltransferase genes. The en- 
zymes encoded by the most similar pair of these 
genes are nearly identical in sequence throughout 
substantial portions of their lengths. These enzymes 
nonetheless maintain a discrete and structurally di- 
verse polypeptide segment interspersed within the 
conserved sequence. These observations, together 
with the similarities and difi'erences in the catalytic 
properties of these enzymes, suggest that the struc- 
turally diverse peptide segments play pivotal roles 
in determining the efficiencies with which any one 
of several potential oligosaccharide substrates will 
be utilized by each distinct fucosyltransf erase. Ex- 
periments are in progress to test this hypothesis, as 
are studies designed to define the normal expression 
patterns of these human genes and to delineate the 
biosynthesis of their polypeptide products. The lat- 
ter studies will be supported by a grant from the 
National Institutes of Health. 
Dr. Lowe is also Associate Professor of Pathol- 
ogy at the University of Michigan Medical School. 
Articles 
Ball, G.E., O'Neill, R., Schultz, J.E., Weston, B.W., 
Lowe, J.B., Nagy, J.O., Brown, E.G., Hobbs, C, 
and Bednarski, M.D. 1992. Synthesis and struc- 
tural analysis using 2-D NMR of sialyl Lewis x 
(SLe") and Lewis x (Le") oligosaccharides: ligands 
related to ELAM-I binding. / Am Chem Soc 
114:5449-5451. 
Dumas, D.P., Ichikawa, Y , Wong, C.-H., Lowe, J.B., 
and Nair, R.P. 1991- Enzymatic synthesis of sialyl 
Le'' and derivatives based on a recombinant fuco- 
syltransferase. Bioorg Med Chem Lett 1:425- 
428. 
Lowe, J.B. 1991. Molecular cloning, expression, 
and uses of mammalian glycosyltransferases. Se- 
min Cell Biol 2:289-307. 
Lowe, J.B., Kukowska-Latallo, J.F., Nair, R.P., 
Larsen, R.D., Marks, R.M., Macher, B.A., Kelly, 
R.J., and Ernst, L.K. 1991- Molecular cloning of 
a human fucosyltransferase gene that determines 
expression of the Lewis x and VIM-2 epitopes but 
not ELAM- 1 -dependent cell adhesion. /5/o/ Chem 
266:17467-17477. 
Weston, B.W., Nair, R.P., Larsen, R.D., and Lowe, 
J.B. 1992. Isolation of a novel human a(l,3)fu- 
cosyl transferase gene and molecular comparison 
to the human Lewis blood group a(l ,3/1 ,4)fuco- 
syltransferase gene. Syntenic, homologous, nonal- 
lelic genes encoding enzymes with distinct ac- 
ceptor substrate specificities. / Biol Chem 
267:4152-4160. 
Wong, C.-H., Dumas, D.P., Ichikawa, Y., Koseki, K., 
Danishefsky, S.J., Weston, B.W., and Lowe, J.B. 
1992. Specificity, inhibition and synthetic utility 
of a recombinant human a (1,3) fucosyltransfer- 
ase. //Iw Chem Soc 114:7321-7322. 
GENETICS 227 
