MR imaging in patients with nipple discharge: initial experience.

PURPOSE: To investigate the potential of magnetic resonance (MR) imaging in patients with nipple discharge. MATERIALS AND METHODS: Between February 1992 and December 1998, 23 patients with nipple discharge underwent contrast material-enhanced MR imaging at 1.5 T. Mammographic findings were negative in 22 of 23 patients and revealed asymmetry in one patient. Galactography was attempted in two patients, with negative findings in one patient and no success in the other. Fifteen of 23 patients underwent excisional biopsy-seven of 15 with MR imaging-guided localization, and one of 15 with mammographic localization. Eight of 23 patients were followed up clinically (range, 7-24 months; mean, 20 months). RESULTS: In 11 of the 15 (73%) patients who underwent excisional biopsy, MR imaging findings correlated with histopathologic findings. MR imaging demonstrated four of six benign papillomas and one of two fibroadenomas as circumscribed, enhancing subareolar masses. Findings of one MR imaging examination were negative, and benign tissue was found at excisional biopsy. MR imaging findings were suspicious in six of the seven patients with excisional biopsy findings of malignancy (regional enhancement [n = 2], ductal enhancement [n = 2], peripherally enhancing mass [n = 1], and spiculated mass [n = 1]). In one of the seven patients, a benign-appearing intraductal mass was identified at MR imaging; excisional biopsy revealed a benign papilloma with an adjacent focus of DCIS. CONCLUSION: MR imaging can help identify both benign and malignant causes of nipple discharge. It potentially offers a noninvasive alternative to galactography.

Steady-state kinetic analysis of human ubiquitin-activating enzyme (E1) using a fluorescently labeled ubiquitin substrate.

We report the synthesis of fluorescently labeled ubiquitin (Ub) and its use for following ubiquitin transfer to various proteins. Using Oregon green (Og) succinimidyl ester, we prepared a population of Ub mainly labeled by a single Og molecule; greater than 95% of the Og label is associated with Lys 6 of Ub. We demonstrate that Og-Ub is efficiently accepted by Ub-utilizing enzymes, such as the human ubiquitin-activating enzyme (E1). We used this fluorescent substrate to follow the steady-state kinetics of human E1-catalyzed Ub-transfer to the ubiquitin-carrier enzyme Ubc4. In this reaction, E1 uses three substrates: ATP, Ubc4, and Ub. The steady-state kinetics of Og-Ub utilization by E1 is presented. We have also used analytical ultracentrifugation methods to establish that E1 is monomeric under our assay condition (low salt) as well as under physiological condition (150 mM NaCl).

Heparin increases protein S levels in cultured endothelial cells by causing a block in degradation.

Heparin is a natural anticoagulant molecule that can alter the activity and/or levels of other molecules involved in blood coagulation. Protein S, an anticoagulant protein, is synthesized and released into the plasma by endothelial cells. Immunological assays revealed a significant increase in protein S found in the media and in the endothelial cells after heparin treatment. Time assays revealed a rapid heparin effect on protein S levels in the media. Upon treatment with chondroitin sulfate, a small increase in the amount of protein S in the conditioned medium was also detected but the change in the cell-associated protein S levels after chondroitin sulfate treatment was a decrease rather than the increase implying that heparin and chondroitin sulfate are operating through different mechanisms. Radioimmunoprecipitations and cycloheximide treatments indicated no significant difference in protein S synthesis in heparin treated cells. In experiments comparing heparin and ammonium chloride effects, heparin seems to mimic the ammonium chloride effect on the levels of protein S in the media. Together, the data indicate that heparin increases the levels of protein S found in the media of cultured endothelial cells by producing a specific block in protein S degradation.