TY - JOUR
A1 - Schülein, Ralf
A1 - Kreft, Jürgen
A1 - Gonski, Sigrid
A1 - Goebel, Werner
T1 - Preprosubtilisin Carlsberg processing and secretion is blocked after deletion of amino acids 97-101 in the mature part of the enzyme
N2 - During an investigation into the substrate specificity and processing of subtilisin Carlsberg from Bacillus licheniformis, two major independent findings were made: (i) as has been shown previously, a stretch of five amino acids (residues 97-101 of the mature enzyme) that loops out into the binding cleft is involved in substrate binding by subtilisin Carlsberg. In order to see whether this loop element also determines substrate specificity, the coding region for these five amino acids was deleted from the cloned gene for subtilisin Carlsberg by site-directed mutagenesis. Unexpectedly the resulting mutant preproenzyme (P42c, Mr=42 kDa) was not processed to the mature form (Mr = 30 kDa) and was not released into the medium by a proteasedeficient B. subtilis host strain; rather, it accumulated in the cell membrane. This result demonstrates that the integrity of this loop element, which is very distant from the processing cleavage sites in the preproenzyme, is required for secretion of subtilisin Carlsberg. (ii) In culture supernatants from B. subtilis harbouring the cloned wild-type subtilisin Carlsberg gene the transient appearance (at 0-3 h after onset of stationary phase) of a processing intermediate (P38c, Mr = 38 kDa) oftbis protease could be demonstrated. P38c very probably represents a genuine proform of subtilisin Carlsberg.
KW - Biologie
KW - Bacillus
KW - Proenzyme
KW - Subtilisin maturation
KW - Site-directed mutagenesis
KW - Subtilisin Carlsberg
Y1 - 1991
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60577
ER -
TY - JOUR
A1 - Schoffer, Olaf
A1 - Schülein, Stefanie
A1 - Arand, Gerlinde
A1 - Arnholdt, Hans
A1 - Baaske, Dieter
A1 - Bargou, Ralf C.
A1 - Becker, Nikolaus
A1 - Beckmann, Matthias W.
A1 - Bodack, Yves
A1 - Böhme, Beatrix
A1 - Bozkurt, Tayfun
A1 - Breitsprecher, Regine
A1 - Buchali, Andre
A1 - Burger, Elke
A1 - Burger, Ulrike
A1 - Dommisch, Klaus
A1 - Elsner, Gudrun
A1 - Fernschild, Karin
A1 - Flintzer, Ulrike
A1 - Funke, Uwe
A1 - Gerken, Michael
A1 - Göbel, Hubert
A1 - Grobe, Norbert
A1 - Gumpp, Vera
A1 - Heinzerling, Lucie
A1 - Kempfer, Lana Raffaela
A1 - Kiani, Alexander
A1 - Klinkhammer-Schalke, Monika
A1 - Klöcking, Sabine
A1 - Kreibich, Ute
A1 - Knabner, Katrin
A1 - Kuhn, Peter
A1 - Lutze, Stine
A1 - Mäder, Uwe
A1 - Maisel, Tanja
A1 - Maschke, Jan
A1 - Middeke, Martin
A1 - Neubauer, Andreas
A1 - Niedostatek, Antje
A1 - Opazo-Saez, Anabelle
A1 - Peters, Christoph
A1 - Schell, Beatrice
A1 - Schenkirsch, Gerhard
A1 - Schmalenberg, Harald
A1 - Schmidt, Peter
A1 - Schneider, Constanze
A1 - Schubotz, Birgit
A1 - Seide, Anika
A1 - Strecker, Paul
A1 - Taubenheim, Sabine
A1 - Wackes, Matthias
A1 - Weiß, Steffen
A1 - Welke, Claudia
A1 - Werner, Carmen
A1 - Wittekind, Christian
A1 - Wulff, Jörg
A1 - Zettl, Heike
A1 - Klug, Stefanie J.
T1 - Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011
JF - BMC Cancer
N2 - Background
Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients.
Methods
Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival.
Results
The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%).
Conclusions
No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.
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KW - Malignant melanoma
KW - TNM staging
KW - Survival analysis
KW - Skin cancer screening
KW - Stage distribution
Y1 - 2016
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164544
VL - 16
IS - 936
ER -