Identification of mechanisms that may modulate the role of lipoprotein(a) in thrombosis and atherogenesis.

In this report, we review recent findings concerning the identification of mechanisms that may modulate the role of lipoprotein(a), or Lp(a), in thrombosis and atherogenesis. Lp(a) binds to surface-immobilized plasmin-modified fibrin, thus providing a mechanism for incorporating Lp(a) into the vessel wall. We found that homocysteine and other sulfhydryl-containing amino acids markedly increase the binding of Lp(a) to plasmin-modified fibrin. Our results suggest that homocysteine alters the structure of Lp(a) to expose lysine-binding sites on the apolipoprotein(a) portion of the molecule, and thus provide a potential biochemical link between thrombosis and atherogenesis. We also found that transglutaminases catalyze the incorporation of primary amines into Lp(a). Studies in cell culture systems have found that Lp(a) stimulates endothelial cells to synthesize and release plasminogen activator inhibitor-1. Further, Lp(a) inhibits the activation of transforming growth factor-beta in a coculture of bovine endothelial and smooth muscle cells.     

A leg ulcer as manifestation of metastatic squamous cell vaginal carcinoma

Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg.     

Plasminogen activator inhibitor is associated with the extracellular matrix of cultured bovine smooth muscle cells.

The extracellular matrix secreted by cultured bovine smooth muscle cells (BSMC) contains an endothelial type plasminogen activator (PA) inhibitor. When PA is incubated with the matrix, a high molecular weight complex containing a truncated PA inhibitor is released into the supernatant. The inhibitor also dissociates from the matrix by treatment with glycine, pH 2.7, in its intact, functionally active, 45-kD form, whereas treatment of the matrix with thrombin results in the release of a cleaved, inactive, 41 kD PA inhibitor. Bowes melanoma cells but not smooth muscle cells cultured on BSMC matrices decrease available matrix associated PA inhibitor. PA inhibitor incorporated into the extracellular matrix may serve an important role in the regulation of plasminogen activator mediated matrix degradation.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.