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Objective To evaluate the clinical performance and financial costs of breast-specific gamma imaging (BSGI) as a biopsy-reducing problem-solving strategy in patients with inconclusive diagnostic imaging findings. Methods A retrospective analysis of all patients for whom BSGI was utilized for inconclusive imaging findings following complete diagnostic mammographic and sonographic evaluation between January 2013 and December 2018 was performed. Positive BSGI findings were correlated and biopsied with either US or stereotactic technique with confirmation by clip location and pathology. After a negative BSGI result, patients were followed for a minimum of 24 months or considered lost to follow-up and excluded (22 patients). Results of further imaging studies, biopsies, and pathology results were analyzed. Net savings of avoided biopsies were calculated based on average Medicare charges. Results Four hundred and forty female patients from 30 to 95 years (mean 55 years) of age were included in our study. BSGI demonstrated a negative predictive value (NPV) of 98.4% (314/319) and a positive predictive value for biopsy of 35.5% (43/121). The overall sensitivity was 89.6% (43/48), and the specificity was 80.1% (314/392). In total, 78 false positive but only 5 false negative BSGI findings were identified. Six hundred and twenty-one inconclusive imaging findings were analyzed with BSGI and a total of 309 biopsies were avoided. Estimated net financial savings from avoided biopsies were $646 897. Conclusion In the management of patients with inconclusive imaging findings on mammography or ultrasonography, BSGI is a problem-solving imaging modality with high NPV that helps avoid costs of image-guided biopsies. [ABSTRACT FROM AUTHOR]

Interhalogen fluorides were prepared from xenon difluoride or triethylamine trihydrofluoride with iodine, N-halosuccinimides or alkylhypohalites with alkenes and aromatic compounds. The above reactions were compared with techniques previously reported for the production of interhalogen fluorides. Interhalogens produced from direct action of elemental fluorine with chlorine, bromine or iodine provide a species that can react with electron-deficient alkenes or aromatics. These reagents are too reactive for electron-rich substrates.

Sphingolipids are well established effectors of signal transduction downstream of the tumor necrosis factor (TNF) receptor. In a previous study, we showed that the sphingosine kinase/sphingosine 1-phosphate (S1P) pathway couples TNF receptor to induction of the cyclooxygenase 2 gene and prostaglandin synthesis (Pettus, B. J., Bielawski, J., Porcelli, A. M., Reames, D. L., Johnson, K. R., Morrow, J., Chalfant, C. E., Obeid, L. M., and Hannun, Y. A. (2003) FASEB 1. 17, 1411- 1421). In this study, the requirement for acid sphingomyelinase and sphingomyelin metabolites in the TNFα/prostaglandin E2 (PGE2) pathway was investigated. The amphiphilic compound desipramine, a frequently employed inhibitor of acid sphingomyelinase (ASMase), blocked PGE2 production. However, the action of desipramine was independent of its action on ASMase, since neither genetic loss of ASMase (Niemann-Pick fibroblasts) nor knockdown of ASMase using RNA interference affected TNFα-induced PGE2 synthesis. Further investigations revealed that desipramine down-regulated acid ceramidase (AC), but not sphingosine kinase, at the protein level. This resulted in a time-dependent drop in sphingosine and S1P levels. Moreover, exogenous administration of either sphingosine or S1P rescued PGE2 biosynthesis after desipramine treatment. Interestingly, knockdown of endogenous AC by RNA interference attenuated cyclooxygenase 2 induction by TNFα and subsequent PGE2 biosynthesis. Taken together, these results define a novel role for AC in the TNFα/PGE2 pathway. In addition, the results of this study warrant careful reconsideration of desipramine as a specific inhibitor for ASMase. [ABSTRACT FROM AUTHOR]

Recently, we demonstrated that ceramide kinase, and its product, ceramide 1-phosphate (Cer-1-P), were mediators of arachidonic acid released in cells in response to interleukin-1β and calcium ionophore (Pettus, B. J., Bielawska, A., Spiegel, S., Roddy, P., Hannun, Y. A., and Chalfant, C. E. (2003) J. Biol. Chem. 278, 38206-38213). In this study, we demonstrate that down-regulation of cytosolic phospholipase A2 (cPLA2) using RNA interference technology abolished the ability of Cer-1-P to induce arachidonic acid release in A549 cells, demonstrating that cPLA2 is the key phospholipase A2 downstream of Cer-1-P. Treatment of A549 cells with Cer-1-P (2.5 µM) induced the translocation of full-length cPLA2 from the cytosol to the Golgi apparatus/perinuclear regions, which are known sites of translocation in response to agonists. Cer-1-P also induced the translocation of the CaLB/C2 domain of cPLA2 in the same manner, suggesting that this domain is responsive to Cer-1-P either directly or indirectly. In vitro studies were then conducted to distinguish these two possibilities. In vitro binding studies disclosed that Cer-1-P interacts directly with full-length cPLA2 and with the CaLB domain in a calcium- and lipid-specific manner with a KCa of 1.54 µM. Furthermore, Cer-1-P induced a calcium-dependent increase in cPLA2 enzymatic activity as well as lowering the EC50 of calcium for the enzyme from 191 to 31 nM. This study identifies Cer-1-P as an anionic lipid that translocates and directly activates cPLA2, demonstrating a role for this bioactive lipid in the mediation of inflammatory responses. [ABSTRACT FROM AUTHOR]

Provides information on a study that defined which specific pathway of sphingolipid metabolism may regulate the inflammatory response to tumor necrosis factor-α (TNF) and demonstrated that in murine fibroblast L929 cells and human lung adenocarcinoma A549 cells, TNF-induced cyclooxygenase-2 expression and prostaglandin E[sub2] production are dependent on activation of sphingosine kinase 1. Methodology of the study; Results and discussion on the study.

Presents a study that examined the potential role of sphingosine kinase 1 (SK1) in cyclooxygenase-2 expression during colon carcinogenesis. Down-regulation of SK1; Overexpression of SK1 in RIE-1 rat normal intestinal epithelial cells; Conclusions and significance of the study.

Describes an ordered formation of long- and very long-chain ceramide species in relation to the progression of B-cell receptor triggering induced apoptosis. Observation of an increase in long-chain ceramide species after BcR triggering; Need for the activation of the effector caspases to form very long-chain ceramide species; XIAP degradation and proteasomal activation through Bcr induced formation.