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HP Fiedler M Nega C Pfefferle I Groth C Kempter H Stephan JW Metzger 《Canadian Metallurgical Quarterly》1996,49(8):758-764
The kanchanamycins, a group of novel 36-membered polyol macrolide antibiotics were detected in the culture filtrate and mycelium of Streptomyces olivaceus Tü 4018 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. The compounds show antibacterial and antifungal activities, and are especially effective against Pseudomonas fluorescens. Besides the kanchanamycin complex, strain Tü 4018 produces the 42-membered macrolactones, oasomycin A and desertomycin A, as well as tryptophan-dehydrobutyrine diketopiperazine and daidzein. 相似文献
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The change in frequency of individual emissions in the European edible frog (Rana esculenta) when the temperature of the frog is modified, is part of a complex pattern of interaction between spontaneous otoacoustic emissions. At high temperatures (above 24 degrees C) two emissions are always detected (e.g., one near 800 Hz and one near 1200 Hz). The higher-frequency emission is lower in level and has a wider bandwidth than the lower-frequency emission. It is also often asymmetric and sometimes breaks into two emissions when an external suppressor tone is applied. When the temperature is decreased, these emissions are reduced in frequency at a rate of 0.04 octave/degree C. The higher-frequency emission becomes narrower and taller, and the lower-frequency emissions becomes broader and less intense. At approximately 18 degrees C the lowest of these emissions (now between 600 and 700 Hz) disappears and is replaced by a new emission approximately 100 Hz lower in frequency. When the temperature is carefully controlled the two emissions can exist simultaneously. The lowest-frequency emission changes 0.015 degree C/octave suggesting that the mechanisms controlling the frequency of this emission may be different than those determining the frequencies of the other emissions. All but the lowest-frequency emissions are maximal in level and have minimal bandwidth when the frequency is close to 700 Hz, which is interpreted as evidence that these emissions are filtered by a temperature-independent process. 相似文献
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C Lazure D Gauthier F Jean A Boudreault NG Seidah HP Bennett GN Hendy 《Canadian Metallurgical Quarterly》1998,273(15):8572-8580
The cleavage of parathyroid hormone (PTH) from its precursor proparathyroid hormone (pro-PTH) is accomplished efficiently by the proprotein convertase furin (Hendy, G. N., Bennett, H. P. J., Gibbs, B. F., Lazure, C., Day, R., and Seidah, N. G. (1995) J. Biol. Chem. 270, 9517-9525). We also showed that a synthetic peptide comprising the -6 to +7 sequence of human pro-PTH is appropriately cleaved by purified furin in vitro. The human pro-PTH processing site Lys-Ser-Val-Lys-Lys-Arg differs from the consensus furin site Arg-Xaa-(Lys/Arg)-Arg that is represented by Arg-Arg-Leu-Lys-Arg in the cleavage site of pro-PTH-related peptide (pro-PTHrP). An earlier study demonstrated that an internally quenched fluorogenic substrate bearing an O-aminobenzoyl fluorescent donor at the NH2 terminus and an acceptor 3-nitrotyrosine near the COOH terminus was appropriately cleaved by the convertases furin and PC1 (Jean, F., Basak, A., DiMaio, J., Seidah, N. G., and Lazure, C. (1995) Biochem. J. 307, 689-695). Here, we have synthesized a series of internally quenched fluorogenic substrates based upon the pro-PTH and pro-PTHrP sequences to determine which residues are important for furin cleavage. Purified recombinant furin and PC1 cleaved the human pro-PTH internally quenched substrate at the appropriate site in an identical manner to that observed with the nonfluorescent peptide. Several substitutions in the P6-P3 sequence were well tolerated; however, replacement of the Lys at the P6 position with Gly and replacement of the P3 Lys by an acidic residue led to markedly compromised cleavage by furin. Furin activity was very sensitive to substitution in P' positions. Replacement of Ser at P1' with Gly and Val at P2' with Ala generated substrates that were less well cleaved. Substitution at the P1' position of Val for Ser in conjunction with Ala for Val at P2', as well as a single substitution of Lys for Val at P2', generated specific inhibitors of furin cleavage. The findings of this study open the way to the rational design of inhibitors of furin with therapeutic potential. 相似文献
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M Peters P Schirmacher J Goldschmitt M Odenthal C Peschel E Fattori G Ciliberto HP Dienes KH Meyer zum Büschenfelde S Rose-John 《Canadian Metallurgical Quarterly》1997,185(4):755-766
Soluble cytokine receptors modulate the activity of their cognate ligands. Interleukin (IL)-6 in association with the soluble IL-6 receptor (sIL-6R) can activate cells expressing the gp130 signal transducer lacking the specific IL-6R. To investigate the function of the IL-6-sIL-6R complex in vivo and to discriminate the function of the IL-6-sIL-6R complex from the function of IL-6 alone, we have established a transgenic mouse model. Double-transgenic mice coexpressing IL-6 and sIL-6R were generated and compared with IL-6 and sIL-6R single-transgenic mice. The main phenotype found in IL-6-sIL-6R mice was a dramatic increase of extramedullary hematopoietic progenitor cells in liver and spleen but not in the bone marrow. In IL-6 single-transgenic mice and sIL-6R single-transgenic mice no such effects were observed. The high numbers of hematopoietic progenitor cells were reflected by a strong increase of peripheral blood cell numbers. Therefore, activators of the gp130 signal transducer like the IL-6-IL-6R complex may represent most powerful stimulators for extramedullary hematopoietic progenitor cells. gp130 activators may become important for the expansion of hematopoietic progenitor cells in vivo and in vitro. 相似文献
100.
HP Brezinschek RI Brezinschek T D?rner PE Lipsky 《Canadian Metallurgical Quarterly》1998,102(2):516-521
The variable heavy chain (V(H)) gene segment V(H)1-69/DP-10 has been shown to be over-represented in B-cell chronic lymphocytic leukaemia (CLL). Because of certain similar characteristics of their complementarity determining region 3 (CDR3), including preferential utilization of J(H)6 elements and an extended length, it has been suggested that antigenic stimulation might be involved in leukaemogenesis. Utilizing single-cell PCR to amplify and sequence genomic DNA from individual normal human peripheral blood B cells, we have obtained 7/421 productively and 1/69 nonproductively rearranged V(H) genes that used V(H)1-69/DP-10. All productive rearrangements were unmutated, used J(H)6 and had an average CDR3 length similar to that previously found in V(H)1-69/DP-10-expressing CLL cells. These results suggest that CLL may arise from B cells commonly found in the peripheral B-cell repertoire and do not represent expansion of a unique subset of specific antigen-reactive B cells. 相似文献