Frequency-selective non-linear blending for the computed tomography diagnosis of acute gangrenous cholecystitis: Pilot retrospective evaluation.

PURPOSE: To compare the diagnostic performance of frequency-selective non-linear blending and conventional linear blending contrast-enhanced CT for the diagnosis of acute (AC) and gangrenous (GC) cholecystitis. MATERIALS AND METHODS: Following local ethics committee approval for retrospective data analysis, a database search derived 39 patients (26 men, mean age 67.8 ±â€¯14.6 years) with clinical signs of acute cholecystitis, contrast enhanced CT (CECT) evaluation, cholecystectomy, and pathological examination of the resected specimen. The interval between CECT and surgery was 4.7 ±â€¯4.1 days. Pathological gross examination was used to categorize the cases into AC and GC. Subsequently, two radiologists categorized the CECT studies in a blinded and independent fashion into AC and GC, during two different reading sessions using linear blending and frequency-selective non-linear blending CECT. RESULTS: Histologic analysis diagnosed 31/39 (79.4%) cases of GC and 8/39 (20.6%) cases of AC. Image interpretation of linear blending CECT resulted in classification of 7/39 (17.9%) patients as GC and 32/39 (82.1%) as AC, whereas image interpretation of frequency-selective non-linear blending CECT resulted in classification of 29/39 (74.3%) patients as GC and 10/39 (25.7%) as AC. Sensitivity/specificity/PPV/NPV for detection of GC were 22.6%/100%/100%/25% with linear blending CECT and 80.6%/50%/86.2%/40% with frequency-selective non-linear blending CECT, respectively. Based on the histopathologic diagnosis frequency-selective non-linear blending had a significant improvement (p > 0.0001) in the diagnostic accuracy of gangrenous cholecystitis compared with linear blending. CONCLUSION: Frequency-selective non-linear blending post-processing increases the diagnostic accuracy of gangrenous cholecystitis owing to improved visualization of absence of focal enhancement and mural ulcerations.

Rac1 signaling protects monocytic AML cells expressing the MLL-AF9 oncogene from caspase-mediated apoptotic death.

We investigated the relevance of signaling mechanisms regulated by the Ras-homologous GTPase Rac1 for survival of acute myeloid leukemia (AML) cells harbouring the MLL-AF9 oncogene due to t(9;11)(p21;q23) translocation. Monocytic MLL-AF9 expressing cells (MM6, THP-1) were hypersensitive to both small-molecule inhibitors targeting Rac1 (EHT 1864, NSC 23766) (IC50EHT ~12.5 µM) and lipid lowering drugs (lovastatin, atorvastatin) (IC50Lova ~7.5 µM) as compared to acute myelocytic leukemia (NOMO-1, HL60) and T cell leukemia (Jurkat) cells (IC50EHT >30 µM; IC50Lova >25 µM). Hypersensitivity of monocytic cells following Rac1 inhibition resulted from caspase-driven apoptosis as shown by profound activation of caspase-8,-9,-7,-3 and substantial (~90 %) decrease in protein expression of pro-survival factors (survivin, XIAP, p-Akt). Apoptotic death was preceded by S139-posphorylation of histone H2AX (γH2AX), a prototypical surrogate marker of DNA double-strand breaks (DSBs). Taken together, abrogation of Rac1 signaling causes DSBs in acute monocytic leukemia cells harbouring the MLL-AF9 oncogene, which, together with downregulation of survivin, XIAP and p-Akt, results in massive induction of caspase-driven apoptotic death. Apparently, Rac1 signaling is required for maintaining genetic stability and maintaining survival in specific subtypes of AML. Hence, targeting of Rac1 is considered a promising novel strategy to induce lethality in MLL-AF9 expressing AML.

BSTI, a trypsin inhibitor from skin secretions of Bombina bombina related to protease inhibitors of nematodes.

From skin secretions of the European frog Bombina bombina, a new peptide has been isolated that contains 60 amino acids, including 10 cysteine residues. Its sequence was determined by automated Edman degradation and confirmed by analysis of the cDNA encoding the precursor. A search in the databanks demonstrated that the pattern of cysteine residues in this skin peptide is similar to the ones found in protease inhibitors from Ascaris and in a segment of human von Willebrand factor. The 3D structure of the trypsin inhibitor from Ascaris suum could be used as a template to build a model of the amphibian peptide. In addition, we have demonstrated that this constituent of skin secretion is indeed an inhibitor of trypsin and thrombin, with K(i) values in the range of 0.1 to 1 microM. The new peptide was thus named BSTI for Bombina skin trypsin/thrombin inhibitor.