KIAA1199 expression and hyaluronan degradation colocalize in multiple sclerosis lesions.

Modification of hyaluronan (HA) accumulation has been shown to play a key role in regulating inflammatory processes linked to the progression of multiple sclerosis (MS). The aim of this study was to characterize the enzymatic activity involved in HA degradation observed within focal demyelinating lesions in the experimental autoimmune encephalomyelitis (EAE) animal model. EAE was induced in 3-month-old female C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein 33-35 (MOG33-35) peptide.

A recombinant human hyaluronidase sustained release gel for the treatment of post-surgical edema.

Background: Edema commonly accompanies surgical procedures and when excessive, can adversely affect surgical outcomes. The skin extracellular matrix, including one of its primary components, hyaluronan (HA), is a significant barrier to effective drainage of accumulated edematous fluid. Recombinant human hyaluronidase (rHuPH20) is a human hyaluronidase that acts transiently and locally to depolymerize HA.

Mutations in the catalytic domain of human matrix metalloproteinase-1 (MMP-1) that allow for regulated activity through the use of Ca2+.

Conditionally active proteins regulated by a physiological parameter represent a potential new class of protein therapeutics. By systematically creating point mutations in the catalytic and linker domains of human MMP-1, we generated a protein library amenable to physiological parameter-based screening. Mutants screened for temperature-sensitive activity had mutations clustered at or near amino acids critical for metal binding.

An antibody to VEGF upregulates factor VIII via interleukin-1 in activated adrenal cortex-derived capillary endothelial cells.

We have previously shown in an in vitro wounding system of cultured endothelial cells (EC) that vascular endothelial growth factor (VEGF(165)) treatment upregulated the level of factor VIII (FVIII) in the cells facing an experimental wound. The FVIII upregulation induced by VEGF(165) could be abolished by rhuMab VEGF, a humanized antibody that blocks VEGF functions and inhibits tumorigenesis. Because the thrombotic system is actively involved in angiogenesis, we further investigated the effects of rhuMab VEGF on the regulation of FVIII.

Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate.

We conducted an expression analysis of prostate stem cell antigen (PSCA)in normal urogenital tissues, benign prostatic hyperplasia (n = 21), prostatic intraepithelial neoplasia (n = 33), and primary (n = 137) and metastatic (n = 42) prostate adenocarcinoma, using isotopic in situ hybridization on tissue microarrays. In normal prostate, we observe PSCA expression in the terminally differentiated, secretory epithelium; strong expression was also seen in normal urothelium. Forty-eight percent of primary and 64% of metastatic prostatic adenocarcinomas expressed PSCA RNA.