@article{MalbergWesselHasartetal.2002,
  author    = {Malberg, Hagen and Wessel, Niels and Hasart, Annett and Osterziel, Karl Joseph and Voss, Andreas},
  title     = {Advanced analysis of the spontaneous baroreflex sensitivity, blood pressure and heart rate variability in patients with dilated cardiomyopathy},
  year      = {2002},
  abstract  = {Baroreflex sensitivity (BRS) is an important parameter in the classification of patients with reduced left ventricular function. This study aimed at investigating BRS in patients with dilated cardiomyopathy (DCM) and in healthy subjects (controls), as well as comparing the values of BRS parameters with parameters of heart rate variability (HRV) and blood pressure variability (BPV). ECG, continuous blood pressure and respiration curves were recorded for 30 min in 27 DCM patients and 27 control subjects. The Dual Sequence Method (DSM) includes the analysis of spontaneous fluctuations in systolic blood pressure and the corresponding beat-to-beat intervals of heart rate to estimate bradycardic, opposite tachycardic and delayed baroreflex fluctuations. The number of systolic blood pressure/beat-to- beat interval fluctuations in DCM patients was reduced in comparison with controls (DCM patients: male, 154.4+/-93.9 ms/ mmHg; female, 93.7+/-40.5 ms/mmHg; controls: male, 245.5+/-112.9 ms/mmHg; female, 150.6+/-55.8 ms/mmHg, P<0.05). The average slope in DCM patients was lower than in controls (DCM, 5.3+/-1.9 ms/mmHg; controls, 8.0+/-5.4 ms/mmHg; P<0.05). Discriminant function analysis showed that, in the synchronous range of the standard sequence method, the DCM and control groups could be discriminated to only 76\% accuracy, whereas the DSM gave an improved accuracy of 84\%. The combination of six parameters of HRV, BPV and DSM gives an accuracy of classification of 96\%, whereas six parameters of HRV and BPV could separate the two groups to only 88\% accuracy. Thus the DSM leads to an improved characterization of autonomous regulation in order to differentiate between DCM patients and healthy subjects. BRS in DCM patients is significantly reduced and apparently less effective.},
  language  = {en}
}
@article{GehmlichGeierOsterzieletal.2004,
  author    = {Gehmlich, Katja and Geier, C. and Osterziel, Karl Joseph and VanderVen, Peter F. M. and F{\"u}rst, Dieter Oswald},
  title     = {Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and alpha-actinin and their implication for hypertrophic cardiomyopathy},
  issn      = {0302-766X},
  year      = {2004},
  abstract  = {Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy. We show that MLP can form a ternary complex with two of its previously documented myofibrillar ligand proteins, N-RAP and alpha-actinin, which indicates the presence of distinct, non-overlapping binding sites. Our data also show that, in comparison to wild-type MLP, the capacity of the mutated MLP protein to bind both N-RAP and alpha-actinin is significantly decreased. In addition, this single point mutation prevents zinc coordination and proper folding of the second zinc-finger in the first LIM domain, which consequently renders the protein less stable and more susceptible to proteolysis. The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin. This assumption is supported by the previous observation that in the pathological situation accompanied by MLP down regulation, cardiomyocytes try to compensate for the decreased stability of MLP protein by increasing the expression of its ligand N-RAP, which might finally result in the development of myocyte disarray that is characteristic of this disease},
  language  = {en}
}
@article{GehmlichGeierOsterzieletal.2004,
  author    = {Gehmlich, Katja and Geier, C. and Osterziel, Karl Joseph and F{\"u}rst, Dieter Oswald},
  title     = {Mutant muscle LIM protein is associated with hypertrophic cardiomyopathy and exhibits altered binding properties in the system MLP - N-RAP - alpha-actinin},
  issn      = {0171-9335},
  year      = {2004},
  language  = {en}
}
@article{SchlagOsterzielOezceliketal.2008,
  author    = {Schlag, Peter M. and Osterziel, Karl Joseph and {\"O}zcelik, Cemil and Scherneck, Siegfried and Wenzel, Katrin and Daskalow, Katjana and Herse, Florian and Seitz, Susanne and Zacharias, Ute and Schenk, J{\"o}rg A. and Schulz, Herbert and H{\"u}bner, Norbert and Micheel, Burkhard},
  title     = {The protein phosphatase 1 inhibitor KEPI is down regulated in breast cancer cell lines and tissues and involved in the regulation of the tumour suppressor EGR1 via the MEK-ERK pathway},
  year      = {2008},
  abstract  = {KEPI is a protein kinase C-potentiated inhibitory protein for type 1 Ser/Thr protein phosphatases. We found no or reduced expression of KEPI in breast cancer cell lines, breast tumors and metastases in comparison to normal breast cell lines and tissues, respectively. KEPI protein expression and ubiquitous localization was detected with a newly generated antibody. Ectopic KEPI expression in MCF7 breast cancer cells induced differential expression of 95 genes, including the up-regulation of the tumor suppressors EGR1 (early growth response 1) and PTEN (phosphatase and tensin homolog), which is regulated by EGR1. We further show that the up-regulation of EGR1 in MCF7/KEPI cells is mediated by MEK-ERK signaling. The inhibition of this pathway by the MEK inhibitor UO126 led to a strong decrease in EGR1 expression in MCF7/KEPI cells. These results reveal a novel role for KEPI in the regulation of the tumor suppressor gene EGR1 via activation of the MEK-ERK MAPK pathway.},
  language  = {en}
}