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1.  The early antibiotic therapy in septic patients - milestone or sticking point? 
Critical Care  2014;18(6):671.
Sepsis is one of the oldest and most elusive syndromes in medicine. Every effort should be made to treat these patients with the best available evidence. As a milestone, empiric antimicrobial therapy is essential in order to reduce morbidity and mortality of septic patients. As a sticking point, the use of broad-spectrum antimicrobial agents may be associated with induction of resistance among common pathogens.
PMCID: PMC4331420  PMID: 25672873
2.  Homografts in aortic position: does blood group incompatibility have an impact on patient outcomes?† 
Aortic homografts are an alternative to mechanical or biological valve prostheses. Homografts are generally not transplanted ABO-compatible while this policy is still under debate. The purpose of this study was to investigate whether ABO compatibility impacts on long-term outcomes or not.
Between 1992 and 2009, 363 adult patients with a mean age of 52 years received homografts in aortic position. Donor and acceptor blood groups could be obtained for 335 patients. Sixty-three percent received blood group-compatible (n = 212) (Group iso) and 37% non-blood group-compatible allografts (n = 123) (Group non-iso).
The overall event-free survival (freedom from death or reoperation) was 55.5% (n = 186). In the iso group, the event-free survival was 84.1% at 5 years and 63.3% at 10 years. In the non-iso group, the event-free survival was 79.4% at 5 years and 51.8% at 10 years. 28.5% of patients (n = 35) with ABO-incompatible and 25.5% (n = 54) with ABO-compatible grafts required reoperation. The mean time to reoperation in the iso group was 97.3 vs 90 months in the non-iso group.
In 17 years of research, we have not yet found a statistical significant difference in blood group incompatibility regarding overall event-free survival. In our opinion, there is no need to use ABO-compatible homografts for aortic valve replacement in adults. Histological and immunohistochemical assays are mandatory to confirm our results.
PMCID: PMC3630410  PMID: 23390142
Aortic homografts; Blood group incompatibility; Reoperation
3.  Search for optimized conditions for sealing and storage of bypass vessels: influence of preservation solution and filling pressure on the degree of endothelialization 
The aim of the present study was to develop methods for the rapid assessment of intimal quality of coronary bypass segments of venous origin, and to prevent endothelial damage by improved intraoperative handling of graft segments. Particular attention was paid to the influence of the composition of the preservation solution and the intravasal filling pressure on the degree of endothelialization. Intrava-sal exposure to Alcian blue at pH<3 resulted in highly specific staining of intimal regions with functionally or structurally damaged endothelium. Standardization of preparation, staining and image acquisition of the intimal surface of graft remnants and subsequent computer-aided planimetry of these images made it possible for the first time to perform rapid serial investigations for quality control of bypass grafts. Using saline as the rinsing and intraoperative storage medium resulted in the loss of more than 50% of the endothelium at intravasal pressures of 0-100 mmHg. Increasing the pressure resulted eventually in complete de-endothelialization. In contrast, grafts incubated in a customized plasma derivative tolerated pressures of up to 200 mmHg with no significant endothelial loss; and even after exposure to 1,000 mmHg (10 times the average mean arterial pressure!) more than 70% of the endothelium were intact and vital. These findings imply strongly that the quality of aortocoronary bypass grafts of venous origin can be improved substantially by the use of a plasma derivative solution for intraoperative preservation and by monitoring and controlling the intravasal pressures reached during sealing and storage.
PMCID: PMC2848302  PMID: 20369036
Saphenous vein graft disease; endothelium; pericytes; intima; thrombosis; atherosclerosis; tissue factor; CABG; bypass operation; Alcian blue staining
4.  The Soluble NAD+-Reducing [NiFe]-Hydrogenase from Ralstonia eutropha H16 Consists of Six Subunits and Can Be Specifically Activated by NADPH 
Journal of Bacteriology  2005;187(9):3122-3132.
The soluble [NiFe]-hydrogenase (SH) of the facultative lithoautotrophic proteobacterium Ralstonia eutropha H16 has up to now been described as a heterotetrameric enzyme. The purified protein consists of two functionally distinct heterodimeric moieties. The HoxHY dimer represents the hydrogenase module, and the HoxFU dimer constitutes an NADH-dehydrogenase. In the bimodular form, the SH mediates reduction of NAD+ at the expense of H2. We have purified a new high-molecular-weight form of the SH which contains an additional subunit. This extra subunit was identified as the product of hoxI, a member of the SH gene cluster (hoxFUYHWI). Edman degradation, in combination with protein sequencing of the SH high-molecular-weight complex, established a subunit stoichiometry of HoxFUYHI2. Cross-linking experiments indicated that the two HoxI subunits are the closest neighbors. The stability of the hexameric SH depended on the pH and the ionic strength of the buffer. The tetrameric form of the SH can be instantaneously activated with small amounts of NADH but not with NADPH. The hexameric form, however, was also activated by adding small amounts of NADPH. This suggests that HoxI provides a binding domain for NADPH. A specific reaction site for NADPH adds to the list of similarities between the SH and mitochondrial NADH:ubiquinone oxidoreductase (Complex I).
PMCID: PMC1082810  PMID: 15838039
5.  Functional Expression of the Ectoine Hydroxylase Gene (thpD) from Streptomyces chrysomallus in Halomonas elongata 
The formation of hydroxyectoine in the industrial ectoine producer Halomonas elongata was improved by the heterologous expression of the ectoine hydroxylase gene, thpD, from Streptomyces chrysomallus. The efficient conversion of ectoine to hydroxyectoine was achieved by the concerted regulation of thpD by the H. elongata ectA promoter.
PMCID: PMC404422  PMID: 15128576
6.  The H2 Sensor of Ralstonia eutropha Is a Member of the Subclass of Regulatory [NiFe] Hydrogenases 
Journal of Bacteriology  2000;182(10):2716-2724.
Two energy-generating hydrogenases enable the aerobic hydrogen bacterium Ralstonia eutropha (formerly Alcaligenes eutrophus) to use molecular hydrogen as the sole energy source. The complex synthesis of the nickel-iron-containing enzymes has to be efficiently regulated in response to H2, which is available in low amounts in aerobic environments. H2 sensing in R. eutropha is achieved by a hydrogenase-like protein which controls the hydrogenase gene expression in concert with a two-component regulatory system. In this study we show that the H2 sensor of R. eutropha is a cytoplasmic protein. Although capable of H2 oxidation with redox dyes as electron acceptors, the protein did not support lithoautotrophic growth in the absence of the energy-generating hydrogenases. A specifically designed overexpression system for R. eutropha provided the basis for identifying the H2 sensor as a nickel-containing regulatory protein. The data support previous results which showed that the sensor has an active site similar to that of prototypic [NiFe] hydrogenases (A. J. Pierik, M. Schmelz, O. Lenz, B. Friedrich, and S. P. J. Albracht, FEBS Lett. 438:231–235, 1998). It is demonstrated that in addition to the enzymatic activity the regulatory function of the H2 sensor is nickel dependent. The results suggest that H2 sensing requires an active [NiFe] hydrogenase, leaving the question open whether only H2 binding or subsequent H2 oxidation and electron transfer processes are necessary for signaling. The regulatory role of the H2-sensing hydrogenase of R. eutropha, which has also been investigated in other hydrogen-oxidizing bacteria, is intimately correlated with a set of typical structural features. Thus, the family of H2 sensors represents a novel subclass of [NiFe] hydrogenases denoted as the “regulatory hydrogenases.”
PMCID: PMC101976  PMID: 10781538
7.  Ralstonia eutropha TF93 Is Blocked in Tat-Mediated Protein Export 
Journal of Bacteriology  2000;182(3):581-588.
Ralstonia eutropha (formerly Alcaligenes eutrophus) TF93 is pleiotropically affected in the translocation of redox enzymes synthesized with an N-terminal signal peptide bearing a twin arginine (S/T-R-R-X-F-L-K) motif. Immunoblot analyses showed that the catalytic subunits of the membrane-bound [NiFe] hydrogenase (MBH) and the molybdenum cofactor-binding periplasmic nitrate reductase (Nap) are mislocalized to the cytoplasm and to the inner membrane, respectively. Moreover, physiological studies showed that the copper-containing nitrous oxide reductase (NosZ) was also not translocated to the periplasm in strain TF93. The cellular localization of enzymes exported by the general secretion system was unaffected. The translocation-arrested MBH and Nap proteins were enzymatically active, suggesting that twin-arginine signal peptide-dependent redox enzymes may have their cofactors inserted prior to transmembrane export. The periplasmic destination of MBH, Nap, and NosZ was restored by heterologous expression of Azotobacter chroococcum tatA mobilized into TF93. tatA encodes a bacterial Hcf106-like protein, a component of a novel protein transport system that has been characterized in thylakoids and shown to translocate folded proteins across the membrane.
PMCID: PMC94318  PMID: 10633089

Results 1-7 (7)