Bruce S. Sachais

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Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies (autoAbs) against desmoglein 3 (Dsg3). Here, we clone anti-Dsg3 antibodies (Abs) from four PV patients and identify pathogenic VH1-46 autoAbs from all four patients. Unexpectedly, VH1-46 autoAbs had relatively few replacement mutations. We reverted antibody somatic(More)
Urokinase plasminogen activator (uPA) plays an important role in the progression of several malignancies including breast cancer. We have identified a noncompetitive antagonist of the uPA-uPAR interaction derived from a nonreceptor binding region of uPA (amino acids 136-143). This 8-mer capped peptide (A6) inhibited breast cancer cell invasion and(More)
The non-peptide substance P (SP) antagonist CP-96,345 has a 90-fold selectivity for the human neurokinin-1 (NK-1) or SP receptor over the rat NK-1 receptor, while the agonist SP shows no such selectivity. The cloned NK-1 receptors from these two species have primary protein structures that differ in only 22 of 407 residues. Wild type, chimeric, and(More)
Stably transfected Chinese hamster ovary cells expressing either the substance P receptor or neurokinin A receptor were constructed, isolated, and characterized. Equilibrium ligand binding studies performed on whole cells demonstrated that cell lines expressing either of these receptors contained a single class of high-affinity binding sites with an(More)
We examined the effect of urokinase (uPA) and its fragments on vascular smooth muscle cell contraction. Single-chain uPA inhibits phenylepherine (PE) -induced contraction of rat aortic rings, whereas two-chain uPA exerts the opposite effect. Two independent epitopes mediating these opposing activities were identified. A6, a capped peptide corresponding to(More)
WIN 51708 is a nonpeptide antagonist of the neurokinin (NK)-1 (substance P) receptor that possesses a dramatically higher affinity for the rat NK-1 receptor, compared with the human NK-1 receptor. This selectivity is the opposite of the selectivity displayed by CP-96,345 and is much greater in magnitude than the selectivity of RP 67580. The naturally(More)
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