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Biomedical subjects

T Rauch

Publications and source records attributed to T Rauch.

At least 19 recordsLinked to original sources
PubMed2005

Low temperature of GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of deltatigdeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C deltatigdeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of deltatigdeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/= 60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Chaperonin 10↗
PubMed2004

Low temperature or GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor and DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of DeltatigDeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C DeltatigDeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of DeltatigDeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/=60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Chaperonin 10↗
PubMed2004

Functional dissection of Escherichia coli trigger factor: unraveling the function of individual domains.

In Escherichia coli, the ribosome-associated chaperone Trigger Factor (TF) promotes the folding of newly synthesized cytosolic proteins. TF is composed of three domains: an N-terminal domain (N), which mediates ribosome binding; a central domain (P), which has peptidyl-prolyl cis/trans isomerase activity and is involved in substrate binding in vitro; and a C-terminal domain (C) with unknown function. We investigated the contributions of individual domains (N, P, and C) or domain combinations (NP, PC, and NC) to the chaperone activity of TF in vivo and in vitro. All fragments comprising the N domain (N, NP, NC) complemented the synthetic lethality of Deltatig DeltadnaK in cells lacking TF and DnaK, prevented protein aggregation in these cells, and cross-linked to nascent polypeptides in vitro. However, DeltatigDeltadnaK cells expressing the N domain alone grew more slowly and showed less viability than DeltatigDeltadnaK cells synthesizing either NP, NC, or full-length TF, indicating beneficial contributions of the P and C domains to TF's chaperone activity. In an in vitro system with purified components, none of the TF fragments assisted the refolding of denatured d-glyceraldehyde-3-phosphate dehydrogenase in a manner comparable to that of wild-type TF, suggesting that the observed chaperone activity of TF fragments in vivo is dependent on their localization at the ribosome. These results indicate that the N domain, in addition to its function to promote binding to the ribosome, has a chaperone activity per se and is sufficient to substitute for TF in vivo.

Escherichia coli↗
PubMed2004

Removal mechanisms of endocrine disrupting compounds (steroids) during soil aquifer treatment.

The objective of this study was to determine the primary removal mechanisms of endocrine disruptors such as steroidal hormones present in reclaimed water, specifically 17beta-estradiol, estriol, and testosterone, during groundwater recharge via soil aquifer treatment (SAT). Steroidal hormones were quantified using enzyme-linked immunosorbent assays. Bench-scale studies and laboratory-scale soil column experiments were employed to determine what mechanisms (i.e., adsorption, biodegradation, photolytic degradation) dominate the removal of the three compounds of interest during SAT. Findings of these studies revealed that the dominating removal mechanism for the compounds of interest during SAT is adsorption to the porous media matrix and additional attenuation to below the detection limit occurred in the presence of bioactivity. This additional removal occurred regardless of dominating redox conditions (aerobic vs. anoxic) or the type of organic carbon matrix present (hydrophobic acids, hydrophilic carbon vs. colloidal carbon).

Adsorption↗
PubMed2004

Assessing the removal potential of soil-aquifer treatment systems for bulk organic matter.

The fate of effluent organic matter (EfOM) during groundwater recharge was investigated by studying the removal behavior of four bulk organic carbon fractions isolated from a secondary effluent: Hydrophilic organic matter (HPI), hydrophobic acids (HPO-A), colloidal organic matter (OM), and soluble microbial products (SMPs). Short-term removal of the bulk organic fractions during soil infiltration was simulated in biologically active soil columns. Results revealed that the four organic fractions showed a significantly different behavior with respect to biological removal. HPI and colloidal OM were prone to biological removal during initial soil infiltration (0-30 cm) and supported soil microbial biomass growth in the infiltrative surface. Additionally, colloidal OM was partly removed by physical adsorption or filtration. HPO-A and SMPs reacted recalcitrant towards biological degradation as indicated by low soil biomass activity responses. Adsorbability assessment of the biologically refractory portions of the fractions onto powered activated carbon (PAC) indicated that physical removal is not likely to play a significantly role in further diminishing recalcitrant HPO-A, HPI and SMPs during longer travel times in the subsurface.

Adsorption↗
PubMed2003

How to find the real one (at the level of pre-mRNA splicing).

The mature mRNA always carries nucleotide sequences that faithfully mirror the protein product according to the niles of the genetic code. However, in the chromosome, the nucleotide sequence that represents a certain protein is interrupted by additional sequences. Therefore, most eukaryotic genes are longer than their final mRNA products. The human genome project revealed that only a tiny portion of sequences serves as protein-coding region and almost one quarter of the genome is occupied by non-coding intervening sequences. The elimination of these non-coding regions from the precursor RNA in a process termed splicing must be extremely precise, because even a single nucleotide mistake may cause a fatal error. At present, two types of intervening sequences have been identified in protein-coding genes. One of them, the U2-dependent or major-class is prevalent and represents 99% of known sequences. The other one, the so-called U12-dependent or minor-class of introns, occurs in much lesser amounts in the genome. The basic problem of nuclear splicing concerns i/ the molecular mechanisms, which ensure that the coding regions are correctly recognized and spliced together: ii/ the principles and mechanisms that guarantee the high fidelity of the splicing system; iii/ the differences in the excision mechanisms of the two classes of introns. We are going to present models explaining how intervening sequences are accurately removed and the coding regions correctly juxtaposed. The two splicing mechanisms will also be compared.

Exons↗
PubMed2001

Extracellular matrix gene expression correlates to left ventricular mass index after surgical induction of left ventricular hypertrophy.

The cardiac extracellular matrix (ECM) is a dynamic entity maintaining the structural and functional properties of the myocardium. Little is known about alterations in ECM regulation during controlled induction of compensated left ventricular hypertrophy (LVH) using experimental aortic stenosis. Fifteen growing sheep received supra-coronary banding at an age of 7 +/- 1 months whereas 10 age-matched sheep served as the control group (C). Explantation of the hearts was performed 8.3 +/- 1 months after banding. Gene sequences for sheep matrix metalloproteinase (MMP)-1,-2,-3,-9 and tissue inhibitors (TIMP)-1,-2,-3 were isolated and cloned. Then mRNA and protein gene expression analyses were performed. Concentric LVH with no evidence of heart failure was diagnosed at explantation. Left ventricular mass index (LVMI) was 150 +/- 33 g/m2 (LVH) versus 88 +/- 23 (C) and 82 +/- 21 (baseline) (p < 0.01 versus LVH). Parallel to LVH there was a significant increase in mRNA and protein expression for MMP-1,-2,-3, -9 and for TIMP-1,-2 whereas there was a significant decrease in TIMP-3 gene expression. A close correlation between changes in LVMI and ECM gene expression was found. Compensated LVH goes along with a significant modification of MMP and TIMP gene expression. Alterations in ECM gene expression may be part of the adaptive process during left ventricular remodeling.

Animals↗
PubMed2001

Effectiveness of two radiofrequency ablation systems in atrial tissue.

OBJECTIVE: The efficacy of the left atrial radiofrequency ablation procedure, for the curative treatment of atrial fibrillation, is dependent upon obtaining a confluent transmural line of hyperthermic cellular death. We compare the in vitro effectiveness of obtaining transmural hyperthermic cellular death (>55 degrees C) of both the Osypka single electrode and Boston Scientific Thermaline multi-electrode radiofrequency systems. METHODS: Isolated cadaver porcine hearts were used to measure epicardial temperatures either 'central' or at the 'edge' in relation to an endocardial applied radiofrequency electrode. Reference set point was 70 degrees C, and 4-6-mm thick atrial tissue was used for all applications. 'Edge' temperatures with the Boston Scientific unit were measured whilst activating both adjacent electrodes. RESULTS: Boston Scientific: Probe temperature closely approximated the set point. 'Central' epicardial temperature was lower than probe temperature until after 40 s application (P<0.05), 55 degrees C was reached at 50 s, maximal mean temperature 63.0+/-8.9 degrees C was reached at 100 s. Epicardial 'edge' temperature remained lower than probe temperature for the entire 120 s (P<0.05). Osypka: Probe temperature tended to overshoot the set point. 'Central' epicardial temperature paralleled and occasionally exceeded probe temperature reaching 55 degrees C within 10 s, maximal mean temperature 76.3+/-12.7 degrees C was reached at 10 s and exceeded the set point thereafter. 'Edge' temperature was no different to probe temperature or 'central' epicardial temperature. The mean epicardial temperatures produced with a 65 degrees C set point was no different to that with the 70 degrees C set point, except for a lower final temperature at 60 s. CONCLUSIONS: The Boston Scientific system (70 degrees C set point) requires a minimum in vitro application of 40 s to transmurally increase 4-6 mm atrial tissue temperature above 55 degrees C, and 120-s duration per application would appear to be a reasonable clinical recommendation. The Osypka system transfers thermal energy more effectively, requiring less than 10 s in vitro to achieve a similar transmural temperature, and a 30-s application can be recommended. However, a tendency to overshoot both probe and set point temperature, suggests that a lower set point of 65 degrees C might be safer and as effective.

Animals↗
PubMed2001

A new intracardiac microaxial pump: first results of a multicenter study.

As coronary artery bypass grafting (CABG) surgery in the beating heart technique is progressing, new devices have been developed to overcome hemodynamic instabilities while tilting the heart for exposure of back wall vessels. A new device for in heart biventricular intracorporeal circulation was applied in 42 patients undergoing CABG surgery (Group 1). The control group consisted of 38 patients operated on using a conventional cardiopulmonary bypass setup (Group 2). The study protocol of the prospective, randomized multicenter study was approved by the local ethics committees. Patients were included following inclusion criteria and patient informed consent. Mean age, procedure time, mean arterial pressure (MAP), and hemolysis by means of plasma free hemoglobin (fHb) were assessed preoperatively, perioperatively, on postoperative Days 1 to 3, at discharge, and at a 3 month follow-up. The mean age was 62.1 (range 59-74) years (Group 1), 62.7 (range 48-72) years (Group 2); procedure time was 112 min +/- 31.9 min (Group 1), 137.4 min +/- 36.2 min (Group 2); and 2.3 +/- 0.6 (Group 1), 2.2 +/- 0.7 (Group 2), vessels were revascularized. The flow on pump was 3.7 (2.5/4.4) L/min (Group 1), 4.9 (3.6/6.2) L/min (Group 2) which resulted in a MAP of 69.8 (4.0/143) mm Hg (Group 1), 58.3 (5.3/94) mm Hg while assessing the vessels of the back wall. Hemolysis defined by fHB was lower than 20 mg/dl at all times pre- and postoperatively. Intraoperative maximum values were up to 100 mg/dl in 4 patients (2 in Group 1 and 2 in Group 2). Body mass index was 26.4 +/- 2.6 (Group 1), 27.9 +/- 3.2. New York Heart Association Class was II to III in both groups. There were no pump related life threatening or severe adverse events. Beating heart procedures with ICC can be reliably and safely achieved. As the device is easy to use, it may deserve a more widespread use in the future.

Aged↗
PubMed2001

[Robotic surgery--surgical and anesthesiologic implications].

Because of the restricted freedom of movement inherent in endoscopic standard instruments wholly endoscopic heart surgery has not been possible up to now. The development of such techniques was especially hindered by the rib cage. Now the precision which is imperative for bypass surgery or valve reconstruction is made possible by telemanipulator systems. Preconditions for this method are cardiopulmonary bypass-techniques which allow a cardioplegic cardiac arrest with closed chest and extensive hemodynamic monitoring which enables the anesthesiologist to make exact diagnoses without having a direct view on the heart. After an extensive experimental phase a telemanipulation system is successfully in use since May 1998 in the Cardiac Center in Leipzig.

Anesthesia↗
PubMed2001

[Patient-adapted valve selection: biological vs. mechanical heart valve replacement in aortic valve diseases].

Since the first aortic valve replacement performed by Harken in 1960, the operation of aortic valve disease by replacing the native valve with a heart valve prosthesis has become one of the most frequently performed procedures in cardiac surgery. For valve replacement there are biological (xenografts and homografts) and mechanical heart valve prostheses available. When choosing the most suitable prosthesis the limited durability of a biological prosthesis and the risks of lifelong anticoagulation for a mechanical prosthesis have to be balanced. In this article the indication for operation of aortic valve stenosis and aortic regurgitation are discussed first. Based on the literature of the last 2 years the advantages and disadvantages of mechanical and biological heart valve prostheses (xenograft, homograft and ROSS procedure) are discussed. In addition rarely used techniques like aortic valve reconstruction are presented. Due to the fact that a biological prosthesis has a durability of 12-15 years and the risk of bleeding complications under anticoagulation grows with increasing age, the choice of a biological prosthesis can be recommended from the age of 65 years. Results of long-term studies at to whether this limit can be diminished by using a stentless biological prosthesis have to be awaited.

Aged↗
PubMed2000

Humoral immune response during coronary artery bypass grafting: A comparison of limited approach, "off-pump" technique, and conventional cardiopulmonary bypass.

BACKGROUND: The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory agent IL-10. This study compares the humoral immune response in patients undergoing CABG with standard, minimally invasive, and "off-pump" techniques. METHODS AND RESULTS: Thirty patients were divided into 3 operative groups: full sternotomy approach plus CPB (group A); full sternotomy approach, off pump (group B); and limited left anterior thoracotomy, off pump (group C). Plasma levels of TNF-alpha receptors p55 and p75, IL 6, IL-8, and IL-10 were taken at baseline, during CPB, and at 4, 24, and 48 hours and 6 days after surgery. A significant increased release of activated complement factors C5a and C3d, IL-8, and IL-10 was observed in patients subjected to CPB (group A) during the initial period and for a short time after perfusion (P:<0.05). TNF-alpha receptors p55 and p75 showed a prolonged elevation (up to 48 hours) in the CPB group compared with the 2 off-pump groups. IL-6 showed no different release among the 3 surgical groups throughout the entire period. There was no significant difference in any parameter measured in relation to the type of operative approach. CONCLUSIONS: There is an inflammatory, as well as an anti-inflammatory, response during CABG that is related to the general surgical trauma. The release of immune mediators is enhanced by the use of CPB during various perioperative and postoperative phases. The type of operative approach did not influence this immune response.

Aged↗
PubMed2000

Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation.

BACKGROUND: Cardiopulmonary bypass seems to be a major cause for both intraoperative microemboli and cerebral hypoperfusion. This study investigates high intensive transient signals (HITS) in transcranial Doppler ultrasound (TCD) and serum levels of the neurobiochemical marker protein S-100 in patients who underwent coronary artery bypass operation without cardiopulmonary bypass (off-pump CABG) in comparison with the conventional procedure using cardiopulmonary bypass (CPB). The results are related to the neuropsychologic outcome in both surgical groups. METHODS: Forty patients were randomized in 2 groups (20 conventional and 20 off-pump CABG). Neurocognitive status was assessed preoperatively and postoperatively. Venous serum levels of S-100 protein were measured before and after coronary operation, HITS were measured in the middle cerebral artery during the operation. RESULTS: The median value of HITS was 394.5 (0 to 2217) in the conventional versus 11 (0 to 50) in the off-pump group, p less than 0.0001. Postoperative S-100 serum levels were: 3.76 (0.13 to 11.2) microg/L (conventional) versus 0.13 (0.04 to 1.01) microg/L (off-pump), p less than 0.0001. Postoperative cognitive testing showed significantly different results with a postoperative impairment of 90% of the patients in the conventional group versus no impairment in the off-pump group. CONCLUSIONS: Cognitive impairment seems to be strongly associated to CPB and the occurrence of micro-emboli. The off-pump technique appears to be promising in order to eliminate the source of these neuropyschologic impairments following CABG operation.

Cardiopulmonary Bypass↗
PubMed2000

Endothelial function of human vena saphena magna prepared with different minimally invasive harvesting techniques.

OBJECTIVES: Minimally invasive saphenous harvesting techniques have been shown to reduce post-operative morbidity. However, when applying new techniques of vein harvesting, endothelial integrity should be preserved in order to guarantee graft quality. We investigated the impact of two different minimally invasive saphenous vein harvesting techniques on endothelial function compared with the traditional 'open' technique by inducing endothelium-dependent in vitro relaxation. METHODS: Two different minimally invasive techniques for harvesting the greater saphenous vein were used in 66 patients, either using a video-assisted dissector (ETHI, n=33) or a light coupled retractor (AUTS, n=33); other patients were treated conventionally (CONV, n=30). The physiological response was tested in vitro using an organ chamber on vein segments exposed to acetylcholine after precontraction with potassium. RESULTS: In both minimally invasive groups, two patients each had to be converted to the traditional open technique and dropped out of the study. The endothelial function of the other veins harvested by either of the minimally invasive techniques showed no significant difference compared with veins harvested conventionally. Reactivity was measured as the percentage relaxation of pharmacological contraction and was significant in all groups (P<0.05); ETHI, 49.1+/-4.2%; AUTS, 48.8+/-5.1%; and CONV, 51.7+/-6. 0%. The responder/non-responder ratio was similar in all groups: ETHI (two drop-outs), 28/3 (90.3%); AUTS (two drop-outs), 28/3 (90. 3%); and CONV, 27/3 (90.0%). CONCLUSION: Veins harvested by minimally invasive techniques have not shown an impaired reactivity of the endothelium compared with the conventional technique.

Endothelium, Vascular↗
PubMed1999

Effectiveness of different anticalcification treatments for stentless aortic bioprostheses.

BACKGROUND: New anticalcification treatments for stentless bioprostheses have not yet been compared independently. MATERIAL AND METHODS: The No-reacts (Biocor), AOA (Medtronic Freestyle), and BiLinx (SJM Toronto SPV II) methods were studied and compared with a control group. Aortic valve leaflet and aortic root tissue was subcutaneously implanted in 60 male, 21-days-old Sprague-Dawley rats. Calcium content was quantified using inductively coupled plasma spectrophotometry. RESULTS: No infections occurred. Low levels of calcium were measured in aortic valve leaflet tissue for all methods (0.4 to 1.5 mg/g dry weight) in comparison to the control group (225 mg/g), p < 0.01. Calcification of aortic root tissue was low in the Bilinx group (2.4 mg/g, p < 0.01), whereas calcium levels were high in all other groups (104 to 127 mg/g). CONCLUSIONS: Calcification of aortic valve leaflets was significantly reduced by all new anticalcification treatments, whereas aortic root calcification was only reduced by inhibition of cellular calcification (BiLinx). Maximum anticalcification properties of both leaflet and aortic root are important, as these are considered a functional unit in stentless bioprostheses.

Aluminum Chloride↗
PubMed1999

Endoscopic coronary artery bypass grafting on the beating heart using a computer enhanced telemanipulation system.

OBJECTIVE: To develop a technique for computer enhanced endoscopic arterial bypass grafting on the beating heart in an experimental canine model. METHODS: Mongrel dogs (30-35 kg) were used. After single lung ventilation of the right lung was initiated the dogs were placed to the right. The videoscope and the end-effectors of the da Vinci telemanipulation system (Intuitive Surgical, Mountain View, CA) were introduced through three ports. Surgery was performed remotely from the console (motion scaling 3:1). After harvesting of the internal thoracic artery (ITA) and preparation of its distal end, the Endostab, a newly developed endoscopic stabilizer, was introduced through an additional port. The anterior wall of the heart was stabilized and the collateral branch (RC) of the left anterior descending artery (LAD) was ligated proximally and distally. The arteriotomy was made and the ITA-graft anastomosed to the RC. The animals were sacrificed and the grafts were checked for patency using bench angiography. RESULTS: In two of five dogs total endoscopic beating heart bypass grafting, including ITA harvest, stabilization, arteriotomy and performance of the anastomosis, was successfully performed using computer enhanced technology and a new endoscopic stabilizer. In two dogs the procedure was completed with femoro-femoral cardiopulmonary bypass (CPB) support on the beating or fibrillating heart, respectively. One dog expired due to VT. Hemodynamically, endoscopic stabilization was well tolerated. All four grafts were patent despite a target vessel diameter of less than 1 mm. CONCLUSION: The endoscopic stabilizer can sufficiently immobilize the heart to enable endoscopic beating heart coronary artery bypass grafting by means of a computer controlled instrumentation system.

Animals↗
PubMed1998

Comparison of different anticalcification treatments for stentless bioprostheses.

BACKGROUND: New anticalcificant treatments have been developed because tissue calcification is a major contributing factor for bioprosthetic valve failure. METHODS: Aortic valve leaflet and aortic root tissue samples from stentless bioprostheses treated with No-React (Biocor, Belo Horizonte, Brazil), AOA (Medtronic freestyle, Minneapolis, MN), and BiLinx (St. Jude Medical, St. Paul, MN) were compared to a control group by subcutaneous implantation in 60 male weanling Sprague-Dawley rats. RESULTS: Calcium levels were in the range of 0.3 to 2.2 mg/g dry tissue at 3 and 12 weeks in all three treated aortic valve leaflet implants. The BiLinx treatment proved anticalcificant effectiveness on aortic root samples as well. There were statistically significant differences for valve leaflet tissue samples: No-React = AOA < BiLinx < < Control and for aortic root tissue samples: BiLinx < < AOA < Control = No-React. CONCLUSION: Calcification of aortic valve leaflets was significantly reduced by all new anticalcificant treatments. Inhibition of cellular calcification (BiLinx) resulted in additional reduction of aortic root calcification. Maximum anticalcificant properties upon both leaflet and aortic root is important as these are considered a functional unit in stentless bioprostheses.

Aluminum↗