Christoph A. Karle

Orthopädische Praxis

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Dierk Thomas

University Hospital Heidelberg

Hugo A. Katus

University Hospital Heidelberg

Edgar Zitron

Heidelberg University

Johann Kiehn

Heidelberg University

Sven Kathöfer

Heidelberg University

Eberhard P. Scholz

Heidelberg University

Wolfgang Schoels

Deutsches Herzzentrum der Charité

V. A. W. Kreye

University Hospital Heidelberg

Claudia Kiesecker

Heidelberg University

Ramona Bloehs

University Hospital Heidelberg

Cooperative Institutions

Heidelberg University

173

University Hospital Heidelberg

153

Amer Sports (United States)

122

Agruicultural Research Institute

German Centre for Cardiovascular Research

Charité - Universitätsmedizin Berlin

Heidelberg University

Inserm

Harvard University

Chirurgische Universitätsklinik Heidelberg

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Human ?3-adrenoreceptors couple to KvLQT1/MinK potassium channels in Xenopus oocytes via protein kinase C phosphorylation of the KvLQT1 protein

Naunyn-Schmiedeberg s Archives of Pharmacology (2003)

Sven Kath�fer Katja R�ckl Wei Zhang Dierk Thomas Hugo A. Katus

Gq alpha subunit

10.1007/s00210-003-0772-x

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Citations (25)

110. Operative Therapie des Diinndarmileus bei besonderer Beriicksichtigung Patienten mit fortgeschrittenem Tumorleiden

R. Bittner Meryl A. Butters W. Windmiller R. Roscher Christoph A. Karle

Summary. Between 1979 and 1984 a total of 233 patients underwent surgical treatment of small bowel obstruction. In 43 patients (18.4%) the obstruction was caused by an advanced tumor disease (peritoneal carcinosis, local recurrence). In patients with benign obstruction the operative mortality was 5.2%; in the tumor patients it was 14%. Wound infection and cardio-pulmonary disturbances were the most frequent complications. The mean survival time of the tumor patients was 159 days. In 65% of these patients the operation had a significant palliative effect.

Carcinosis

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Activation of inwardly rectifying Kir2.x potassium channels by β3-adrenoceptors is mediated via different signaling pathways with a predominant role of PKC for Kir2.1 and of PKA for Kir2.2

Naunyn-Schmiedeberg s Archives of Pharmacology (2007)

D. Scherer Claudia Kiesecker Martin Kulzer Myriam Günth Eberhard P. Scholz

10.1007/s00210-007-0167-5

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Citations (26)

Biophysical properties of zebrafish ether-à-go-go related gene potassium channels

Biochemical and Biophysical Research Communications (2009)

Eberhard P. Scholz Nora Niemer David Hassel Edgar Zitron Heinrich F. Bürgers

hERG

10.1016/j.bbrc.2009.02.042

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Citations (37)

Relativistic laser pulse compression and focusing in stratified plasma-vacuum systems

Christoph A. Karle

The compression of a laser pulse due to the relativistic mass nonlinearity inside the plasma is investigated numerically. This is done for single plasma layers as well as layered plasma-vacuum systems, where transversal focusing of the pulse is important as well. Special attention is paid to instabilities of the pulse that can arise during the compression inside the plasma.

Pulse compression

Relativistic plasma

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Bertosamil blocks HERG potassium channels in their open and inactivated states

British Journal of Pharmacology (2002)

Edgar Zitron Christoph A. Karle Gunnar Wendt‐Nordahl Sven Kathöfer Wei Zhang

1. Bertosamil is chemically related to the class-III anti-arrhythmic drug tedisamil and has been developed as a bradycardic, anti-ischemic and anti-arrhythmic drug. Its anti-arrhythmic properties might in part be attributed to its block of voltage-dependent potassium channels Kv(1.2), Kv(1.4). and Kv(1.5). However, HERG-potassium channel block as an important target for class-III drugs has not yet been investigated. 2. We investigated the effect of bertosamil on the HERG potassium channel heterologously expressed in Xenopus oocytes with the two-electrode voltage-clamp technique. 3. Bertosamil (70 microM) inhibited HERG tail currrent after a test pulse to 30 mV by 49.3+/-8.4% (n=5) and the IC(50) was 62.7 microM. Onset of block was fast, i.e. 90% of inhibition developed within 180+/-8.22 s (n=5), and block was totally reversible upon washout within 294+/-38.7 s (n=5). 4. Bertosamil-induced block of HERG potassium channels was state-dependent with block mainly to open- and inactivated channels. Half-maximal activation voltage was slightly shifted towards more negative potentials. 5. Steady-state inactivation of HERG was not influenced by bertosamil. Bertosamil block elicited voltage-but no frequency-dependent effects. 6. In summary, bertosamil blocked the HERG potassium channel. These blocking properties may contribute to the anti-arrhythmic effects of bertosamil in the treatment of atrial and particular ventricular arrhythmias.

hERG

Potassium channel blocker

Antiarrhythmic agent

Anti-Arrhythmia Agents

10.1038/sj.bjp.0704859

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Citations (23)

A multiplex PCR strategy to screen for known mutations in families with sudden cardiac death burden

Journal of Biological Methods (2017)

Giang Duong Thomas M. Helms Christoph A. Karle

Ventricular tachyarrythmia occurring in ischemic heart disease, dilated/hypertrophic cardiomyopathies or rare monogenic mutations of cardiac ion channels or associated proteins belong to the most frequent causes of sudden cardiac death (SCD). In further decades, next generation sequencing and bioinformatic analysis will become the gold standard of SCD risk stratification. At the moment, Sanger-sequencing is still obligatory in genetic diagnosis. A multiplex polymerase chain reaction (PCR) assay detecting eight SCD mutations in one reaction-tube was developed. To test the general validity of the assay, it was used with 12 patients, who had one or two of the eight mutations (LMNA, p.V256V; SCN5A, p.R1583C; RYR2, p.G1885E; MYH7, V606M; DSG2, p.T335A; KCNJ8, p.S422L; MYBPC, p.E441K; TNNT2, A38V). Thereafter, we tested the multiplex assay in a real diagnostic environment within a high risk family of several past SCD cases. This method allows efficient discrimination of multiple mutations by allele-specific PCR with standard PCR conditions. It relies on obtaining a PCR product specific to the mutation or wildtype-using primers that have the 3'end base complementary to the DNA template site, i.e. a specific primer only permits amplification to take place when its 3'terminal nucleotide matches with its target sequence. The PCR products are further analyzed by length, with Tape Station®(Agilent Technologies, Germany), a high-fidelity capillary chromatography test. The novel multiplex PCR assay strategy could be a good additional test used for SCD risk stratification. Advantages of the test are high velocity and ease of implementation, low price and flexibility of application within cardiomyopathy families for screening purposes.

Sanger sequencing

Multiplex

Primer (cosmetics)

10.14440/jbm.2017.181

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Concept of molecular prevention

The EPMA Journal (2014)

Christoph A. Karle Giang Duong Thomas M. Helms

Prior to the development of a disease, Preventive Medicine enables early detection of signs and symptoms of diseases; if logical measures are taken, an outbreak i.e the development of a disease may possibly be avoided. If the possibility of curing a disease is missed, only the treatment and relief of symptoms remains. The disease becomes incurable and chronic. Since the healing of serious illnesses is only effective as long as the patient is not yet seriously affected, the concept of healing should be redefined. Thus, the removal of a small tumor, the patient hasn’t yet noticed, could be considered to fall into the category of preventive medicine (see Figure 1). The basic principle can be illustrated particularly well by the example of a tumor, but applies to all diseases. It follows, that prevention, i.e. the early detection of disease, is the most effective method to combat disease. Since many predisposing factors for disease development are already defined during embryonic development, a lot of time is left to carry out successful prevention. Modern preventive medicine makes use of all technical means of modern diagnostics from the extensive history up to detailed genetic investigations. It examines all relevant organ systems according to the WHO (World Health Organization) defined hierarchical table of the most common life-threatening causes of diseases. Physical exams with the help of equipment allow an assessment of a patient’s condition at the time of the investigation. Sustainability, that is the period for which the test results are valid, can be estimated from the results of such studies and from the observation period of the study. Since there is no scientific advantages or postclosure plan for many diseases, routine follow-up examination are usually scheduled at set, agreed upon intervals, e.g. once a year. If a more accurate assessment of the disease risk in healthy patients is desired or the prognosis of a particular course of a known disease with known genetic factors favoring the disease is suspected, genetically predisposing factors should be checked. This is done by means of molecular genetic testing of possibly afflicted genes in the DNA of the patient. After creating an exact genetic fingerprint, worldwide comparisons of the genetic fingerprints among patients with the same or similar changes can be performed and conclusions can be drawn and predictions can be made. High quality laboratory equipment allows both targeted hotspot analysis (using the Sanger sequencing) as well as screening tests on several hundred genes (using the panel study of next-generation sequencing). For the screening tests, validated predisposing-genes are examined for the following disease groups: a.) Heart and vascular diseases b.) Tumors c.) Metabolic diseases d.) Diseases of bones and connective tissues e.) Diseases of the sense organs f.) Neurodegenerative Diseases g.) Organ and systemic diseases h.) Blood diseases The use of molecular genetic studies is subject to strict guidelines that are laid down in the so-called Gene-Diagnosis-Law. For this reason, human genetic consultations are prescribed by a specialist in human genetics before performing predictive diagnostics on healthy patients. Human genetic counseling before proceeding with the diagnostic methods may be omitted if there is the suspicion of a genetically determined disease upon physical or other examinations. The overall concept includes subtle diagnostic methods in molecular medicine, particularly translational research techniques which have not yet become standard in the medical routine examinations. Therefore, we have coined the term “molecular prevention” for it. * Correspondence: Thomas_Helms@t-online.de German Foundation for the Chronically Ill, Fuerth , Germany Full list of author information is available at the end of the article Karle et al. EPMA Journal 2014, 5(Suppl 1):A48 http://www.epmajournal.com/content/5/S1/A48

Preventive healthcare

10.1186/1878-5085-5-s1-a48

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Molekulare Grundlagen primär elektrischer Herzerkrankungen

Herzschrittmachertherapie + Elektrophysiologie (2005)

Edgar Zitron Eberhard P. Scholz Claudia Kiesecker Marion Pirot Sven Kathöfer

Risk Stratification

Clinical Practice

10.1007/s00399-005-0490-9

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Acute effects of dronedarone on both components of the cardiac delayed rectifier K⁺ current, HERG and KvLQT1/minK potassium channels

British Journal of Pharmacology (2003)

Dierk Thomas Sven Kathöfer Wei Zhang Kezhong Wu Anna‐Britt Wimmer

Dronedarone is a noniodinated benzofuran derivative that has been synthesized to overcome the limiting iodine-associated adverse effects of the potent antiarrhythmic drug amiodarone. In this study, the acute electrophysiological effects of dronedarone on repolarizing potassium channels were investigated to determine the class III antiarrhythmic action of this compound. HERG and KvLQT1/minK potassium channels conduct the delayed rectifier potassium current IK in human heart, being a primary target for class III antiarrhythmic therapy. HERG and KvLQT1/minK were expressed heterologously in Xenopus laevis oocytes, and the respective potassium currents were recorded using the two-microelectrode voltage-clamp technique. Dronedarone blocked HERG channels with an IC50 value of 9.2 microM and a maximum tail current reduction of 85.2%. HERG channels were blocked in the closed, open, and inactivated states. The half-maximal activation voltage was shifted by -6.1 mV, and HERG current block by dronedarone was voltage-dependent, but not use-dependent. Dronedarone exhibited a weaker block of KvLQT1/minK currents (33.2% at 100 microM drug concentration), without causing significant changes in the corresponding current-voltage relationships. In conclusion, these data demonstrate that dronedarone is an antagonist of cloned HERG potassium channels, with additional inhibitory effects on KvLQT1/minK currents at higher drug concentrations, providing a molecular mechanism for the class III antiarrhythmic action of the drug.

Dronedarone

hERG

Afterdepolarization

Potassium channel blocker

Cardiac action potential

10.1038/sj.bjp.0705502

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Citations (48)