[Show abstract][Hide abstract] ABSTRACT: A specific irreversible inhibitor of both cathepsins B and L, Fmoc-Tyr-Ala-CHN(2) (FYAD) induced apoptosis of neuroblastoma cells but not other tumor cells. Cysteine protease inhibitors that were not efficient inhibitors of both proteases did not cause death of any cell line tested. Apoptosis was preceded by accumulation of large electron dense vesicles and multivesicular bodies in the cytoplasm. Exposure of cells to the cathepsin D inhibitor, pepstatin, failed to rescue cells from FYAD-induced death. These results indicate that inhibition of cathepsins B and L may provide a unique mechanism for selectively inducing death of neuroblastoma with limited toxicity to normal cells and tissues.
Cancer letters 03/2010; 294(2):195-203. · 5.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: C3a, C4a, and C5a anaphylatoxins generated during complement activation play a key role in inflammation. C5a is the most potent of the three anaphylatoxins in eliciting biological responses. The effects of C5a are mediated by its binding to C5a receptor (C5aR, CD88). To date, C5aR has only been identified and cloned in mammalian species, and its evolutionary history remains ill-defined. To gain insights into the evolution, conserved structural domains, and functions of C5aR, we have cloned and characterized a C5aR in rainbow trout, a teleost fish. The isolated cDNA encoded a 350-aa protein that showed the highest sequence similarity to C5aR from other species. Genomic analysis revealed the presence of one continuous exon encoding the entire open reading frame. Northern blot analysis showed significant expression of the trout C5a receptor (TC5aR) message in PBLs and kidney. Flow cytometric analysis showed that two Abs generated against two different areas of the extracellular N-terminal region of TC5aR positively stained the same leukocyte populations from PBLs. B lymphocytes and granulocytes comprised the majority of cells recognized by the anti-TC5aR. More importantly, these Abs inhibited chemotaxis of PBLs toward a chemoattractant fraction purified from complement-activated trout serum. Our data suggest that the split between C5aR and C3aR from a common ancestral molecule occurred before the emergence of teleost fish. Moreover, we demonstrate that the overall structure of C5aR as well as its role in chemotaxis have remained conserved for >300 million years.
The Journal of Immunology 04/2004; 172(7):4381-90. · 5.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper illustrates how to design an appropriate input program to handle a complex file layout using data collected from pharmacy and health insurance information about individuals. Various INFILE and INPUT options are illustrated in the process, and some related functions are considered. The input file is the output of a COBOL program pulling data from a DB2 database which is then brought to the PC via FTP. Each record contains 6 types of information, called segments, for a person. The segments and the fields within are divided by unprintable hexadecimal codes, which SAS represents with notations like the hexadecimal numbers 1E (Segment separator) and 1C (Field separator) respectively. A further complication is the use of 1D which is the group separator to separate repeating segments. There are also groups of repeating fields within a segment. Since the fields do not have a fixed length and they may be missing on some records, there is no fixed record layout for the file. Although the program was written for the PC, the technique is applicable for any system. All the tools discussed are in BASE SAS ® . The typical attendee or reader will have some experience in SAS, but not a lot of experience dealing with the input of external data.