In 1989, we reported the immunologic identification of a prognostic molecule in the tumor cells of breast cancer patients with a poor prognosis for recurrence and death due to their disease (1). This prognostic factor was statistically independent ofimportant clinical parameters including tumor size, lymph node involvement, and assessment of estrogen and progesterone receptors; subsequent studies also showed it to be independent of other prognostic molecules including c-erb-B2 and cathepsin D (2). Tumors marked by this prognostic molecule were nearly 4 times more likely to recur and metastasize than tumors not so marked, representing a prognostic power as strong as the presence of cancer in the axillary lymph nodes ofpatients with T1 or T2 primaries (1-3).We

Abstract. Hyperphosphatemia is thought to underlie medial vascular calcification in advanced renal failure, but calcification can occur in other conditions in the absence of hyperphosphatemia, indicating that additional factors are important. To identify these factors, a model of medial calcification in rat aorta in vitro was developed. Aortic rings from rats were incubated in serum-free medium for 9 d, and calcification was measured as incorporation of 45 Ca and confirmed by histology and x-ray diffraction. No calcification occurred in normal vessels despite elevated free Ca 2ϩ and PO 4 3Ϫ concentrations of 1.8 mM and 3.8 mM, respectively, but mechanical injury resulted in extensive calcification in the media. Co-incubation studies revealed that normal aortas produced a soluble inhibitor of calcification in injured vessels that was destroyed by alkaline phosphatase. Culture of normal aortas with alkaline phosphatase resulted in calcification of the elastic lamina identified as hydroxyapatite by x-ray diffraction. This effect of alkaline phosphatase was not due to dephosphorylation of osteopontin (OPN), and calcification was not increased in aortas from OPN-deficient mice. The inhibitor was identified as pyrophosphate on the basis of the calcification induced in aortas cultured with inorganic pyrophosphatase, the inhibition of calcification in injured aortas by pyrophosphate, and the production of inhibitory levels of pyrophosphate by normal aortas. No calcification occurred under any conditions at a normal PO 4 3Ϫ concentration. It is concluded that elevated concentrations of Ca 2ϩ and PO 4 3Ϫ are not sufficient for medial vascular calcification because of inhibition by pyrophosphate. Alkaline phosphatase can promote calcification by hydrolyzing pyrophosphate, but OPN is not an endogenous inhibitor of calcification in rat aorta.Arterial calcification is common in patients with advanced renal failure and ESRD and is thought to contribute to their increased cardiovascular mortality (1). Two distinct forms of calcification are recognized (2,3). Intimal calcification occurs in atheromatous disease and is associated with inflammatory cells (3), whereas medial calcification occurs in the matrix between smooth muscle cells in the absence of atherosclerosis and inflammatory cells (2,4). Medial calcification commonly occurs in advanced renal failure (4,5), where it is thought to result from plasma concentrations of Ca 2ϩ and PO 4 3Ϫ that exceed the solubility product for calcium phosphate. However, medial calcification is also seen in diabetes and with aging in the presence of normal serum Ca 2ϩ and PO 4 3Ϫ concentrations (6), indicating that hyperphosphatemia is not required for medial calcification.Considerable data suggest that vascular calcification is a spontaneous event, even at normal calcium and phosphate concentrations, that is prevented by inhibitory factors within the vessel wall. Several proteins have been implicated in this process. Mice deficient in matrix Gla protein (MGP) develop rapid and severe medial ...

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Cortical echogenicity is the sonographic parameter that correlates best with renal histopathology. Although size or echogenicity alone are poor predictors of chronic irreversible disease, the likelihood of treatable disease in small kidneys with increased cortical echogenicity is very low.

We conclude that steroids and intravenous cyclophosphamide reduce proliferative lesions, reduce proteinuria and stabilize renal function in patients with crescentic IgA nephropathy.