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Biomedical subjects

S Thiele

Publications and source records attributed to S Thiele.

At least 19 recordsLinked to original sources

TRANSFAC: transcriptional regulation, from patterns to profiles.

The TRANSFAC database on eukaryotic transcriptional regulation, comprising data on transcription factors, their target genes and regulatory binding sites, has been extended and further developed, both in number of entries and in the scope and structure of the collected data. Structured fields for expression patterns have been introduced for transcription factors from human and mouse, using the CYTOMER database on anatomical structures and developmental stages. The functionality of Match, a tool for matrix-based search of transcription factor binding sites, has been enhanced. For instance, the program now comes along with a number of tissue-(or state-)specific profiles and new profiles can be created and modified with Match Profiler. The GENE table was extended and gained in importance, containing amongst others links to LocusLink, RefSeq and OMIM now. Further, (direct) links between factor and target gene on one hand and between gene and encoded factor on the other hand were introduced. The TRANSFAC public release is available at http://www.gene-regulation.com. For yeast an additional release including the latest data was made available separately as TRANSFAC Saccharomyces Module (TSM) at http://transfac.gbf.de. For CYTOMER free download versions are available at http://www.biobase.de:8080/index.html.

Animals↗

Interaction of 2,4,6-trinitrotoluene (TNT) and 4-amino-2,6-dinitrotoluene with humic monomers in the presence of oxidative enzymes.

Oxidative coupling of nitroaromatic compounds involving soil organic matter was examined as a means of soil remediation. Humic monomers, serving as model compounds for soil humic substances, were used as cosubstrates, applying phenoloxidases (laccase from Trametes villosa and peroxidase from horseradish) as oxidative biocatalysts. Without the addition of a cosubstrate, only 30% of 4-amino-2,6-dinitrotoluene (4ADNT) and no 2,4,6-trinitrotoluene (TNT) were transformed in the presence of the laccase. Adding various phenolic monomers produced differing effects on the enzyme-mediated transformation, which indicated that xenobiotics are preferentially bound to quinoid and phenolic moieties of soil humic substances. In the presence of the humic monomer catechol and the enzyme, up to 100% of 4ADNT and up to 80% of TNT were transformed. Enzymatic transformation of 4ADNT in the presence of catechol reached a maximum at pH 6.8. TNT transformation, however, further increased at pH values above 6.8, even in the absence of the enzyme, due to chemical polymerization of catechol. We postulate a two-step reaction mechanism. The humic monomer is initially oxidized to a semi-quinone radical by a phenoloxidase. Subsequent oxidative coupling involves reactions with additional humic monomers or anilinic products derived from TNT, forming an anilinoquinone via nucleophilic addition or a benzoquinone-imine through condensation.

Aniline Compounds↗

The TRANSFAC system on gene expression regulation.

The TRANSFAC database on transcription factors and their DNA-binding sites and profiles (http://www.gene-regulation.de/) has been quantitatively extended and supplemented by a number of modules. These modules give information about pathologically relevant mutations in regulatory regions and transcription factor genes (PathoDB), scaffold/matrix attached regions (S/MARt DB), signal transduction (TRANSPATH) and gene expression sources (CYTOMER). Altogether, these distinct database modules constitute the TRANSFAC system. They are accompanied by a number of program routines for identifying potential transcription factor binding sites or for localizing individual components in the regulatory network of a cell.

Binding Sites↗

Internet-assisted exercises in structural analysis.

In this report we describe our experience in the analytical chemistry curriculum of teaching spectrometer principles and preparing spectroscopy laboratory exercises by means of virtual instruments. The benefits of the intensified preparation of laboratory exercises by virtual instruments will be evaluated with respect to the subsequent handling of real instruments. The utilization of in-house electronic media with Internet resources for elucidation and verification of a structural assignment will also be considered.

Journal Article↗

[Establishment of an in vitro model for rheumatoid arthritis as test system for therapeutical substances].

In our Tissue Engineering group a 3D in vitro model for rheumatoid Arthritis (in vitro pannus) was established with the aim to develop a standardized drug-screening test to analyze the effects of drugs and different biological substances. The advanced model consists of chondrocyte pellet cultures interacting with rheumatoid arthritis (RA) synovial cell cultures. To establish interactive 3D co-cultures defined rheumatoid arthritis synovial cell populations were centrifuged directly on chondrocyte pellet cultures. Histochemical stainings during time of co-culture revealed obvious invasion by RA synovial cell populations into the chondrocyte matrix. Gene expression analysis showed a downregulation of collagen type II expression in chondrocytes within 2 weeks after co-culture with RA synovial cells. Those interactive co-cultures allow the study of single cell populations as well as the cellular interactions in this system under in vitro conditions. Thus, the established co-culture model may be suitable for routine screening tests, which can be useful in supplementing animal experiments in basic research and drug testing.

Animal Testing Alternatives↗

Interleukin-1, interleukin-6 and myocardial enzyme response after coronary artery bypass grafting - a prospective randomized comparison of the conventional and three minimally invasive surgical techniques.

OBJECTIVE: In order to evaluate the traumatic effects of median sternotomy and cardiopulmonary bypass (CPB) in conventional and minimally invasive coronary artery bypass grafting, inflammatory response was studied in a prospective randomized trial in patients referred to single-vessel coronary artery bypass grafting. METHODS: Four surgical techniques were compared: group 1, median sternotomy with CPB in ten patients (eight male, two female; aged 59.6+/-11.0 years (mean+/-SD)); group 2, median sternotomy and off-pump in ten patients (seven male, three female; aged 65.1+/-10.0 years); group 3, minithoracotomy with CPB in ten patients (seven male, three female, aged 61.2+/-10.4 years); group 4, minithoracotomy and off-pump in ten patients (nine male, one female, aged 62.9+/-9.8 years). All patients received a left internal mammary artery graft to the left anterior descending artery (LAD). Clinical data, perioperative values of cytokines and cardiac enzymes were monitored. RESULTS: There were no major complications. Troponin-T and creatine kinase isoenzyme MB (CK-MB) levels were significantly higher in CPB procedures (P<0.0056; multivariate general linear model). Interleukin-6 (IL-6) levels were significantly higher in minithoracotomy procedures. Interleukin-1 (IL-1) was significantly increased in all patients compared with the preoperative values. CONCLUSIONS: The use of CPB is combined with higher levels of troponin-T and CK-MB as signs of myocardial damage. Surgical access was identified as a trigger of inflammatory response, as minithoracotomy is related to higher levels of IL-6. IL-1 increased in all procedures and this occurred independently of the surgical access or the use of CPB, which points out a potential relationship between inflammatory response and anesthesia. Neither CPB nor surgical access influenced the clinical outcome in the treatment of coronary artery single-vessel bypass grafting.

Aged↗

The beneficial effects of calcium channel blockers on long-term kidney transplant survival are independent of blood-pressure reduction.

There is a growing body of evidence suggesting that calcium channel blockers (CCB) exert beneficial effects on kidney transplant survival. However, it is not completely understood if these agents act independently of blood-pressure reduction. In the present study, the 5-yr follow-up of 45 kidney transplant recipients receiving CCB during the 60-month follow-up period was compared to that of recipients with lower blood pressure and an antihypertensive treatment without CCB. During the whole follow-up, systolic (127.4 +/- 2.5 vs. 139.4 +/- 2.1 mmHg, p < 0.05) as well as diastolic blood pressure (78.8 +/- 1.1 vs. 84.8 +/- 1.8 mmHg, p < 0.05) was higher in the group receiving CCB. Moreover, in CCB-treated recipients, a significant (p < 0.05) higher increase in proteinuria was detected (from 759 +/- 120 to 1690 +/- 359 mg/24 h vs. 180 +/- 45 to 340 +/- 45 mg/24 h). Despite higher blood pressure and higher proteinuria, the increase in serum creatinine in the group of CCB-treated recipients was significantly lower (0.01 mg/dL/month) in comparison to that of the controls (0.02 mg/dL/month, p < 0.05). Moreover, the 5-yr transplant survival was significantly higher in CCB-treated recipients (62.3 vs. 31.8%, p < 0.05). The results of the present study further support the beneficial effects of CCB in kidney transplant recipients, which are independent of blood-pressure reduction.

Antihypertensive Agents↗

[When should a patient with severe acute respiratory distress syndrome (ARDS) be transferred to a specialized hospital?].

The mortality rate for the advanced adult respiratory distress syndrome is still high. Nevertheless there are recent publications showing decreasing incidence and an improving survival rate. This is due to early diagnosis as well as differentiated treatment concepts. The use of special therapy methods including extracorporal gas exchange is only possible at specialized centres. This raises the question as to the right timing of the transfer of those ARDS-patients, whose lungs cannot be cured by the therapy standards practiced locally. In a prospective study, all requests for transfer were noted over a period of 36 months (1992 to 1994) and analyzed by a hospital with a special ward for ARDS. In a total of 469 patients the most prominent predisposing diseases were community-acquired pneumonia (26.3%), followed by multiple trauma (24.4%), the postoperative conditions of systemic inflammatory response syndrome (SIRS) or sepsis (21.3%), bronchopulmonary aspiration (5.8%), and status asthmaticus (2.6%). With a mean preventilation time of 9.5 +/- 9 days and a mean ventilatory peak pressure of 39 +/- 8 cm H2O there was a mean oxygenation index (Horrowitz Index) of 95 (+/- 40) mm Hg. The mean Smith and Gordon Ventilator Score was 82.3 (+/- 12.8) and the mean PIF rate (Benzer Score) 12 (+/- 8.6), 121 out of 469 patients were transferred for further specialized therapy. 75 patients were treated on a conventional basis and 46 patients had to be treated with extracorporal lung assistance (ELA) because conventional treatment failed. The mortality rate was 22.3% altogether, in the group with the conventional treatment 16.0% and 32.6% in the group with ELA. As there are no generally accepted guidelines for the transfer of patients with ARDS to specialized centres, an indication for such a transfer must be established taking into consideration the individual patient history. Very early contact with the specialized centre of choice is recommended.

Adolescent↗

Influence of median sternotomy on the psychosomatic outcome in coronary artery single-vessel bypass grafting.

OBJECTIVES: New less invasive surgical techniques for the treatment of coronary artery single-vessel disease have been developed by either avoiding median sternotomy or cardiopulmonary bypass or both, however, until now no prospective randomized trial has been carried out to compare these techniques to the conventional approach with special respect to the psychosomatical effects. METHODS: In a prospective randomized trial four different surgical techniques were compared. Group 1: conventional technique (median sternotomy, cardiopulmonary bypass) in ten patients (eight male, two female, age 59.6 +/- 11.0 years); Group 2: off-pump coronary artery bypass with median sternotomy in nine patients (six male, three female, age 65.7 +/- 11.1 years); Group 3: lateral minithoracotomy and cardiopulmonary bypass in eight patients (five male, three female, age 62.3 +/- 9.9 years). Group 4: off-pump procedure and lateral minithoracotomy in nine patients (eight male, one female, age 63.8 +/- 11.3 years). All patients due to coronary artery single-vessel disease. The tests used for psychosomatic situation were post-traumatic stress disorders scale, pain behavior rating scale, pain visual analog scale, and 6' walking-distance. For detection of false results due to surgical technical failures 3-month follow-up was undertaken including echocardiography and coronary angiogram. RESULTS: There were no deaths or major complications. Operative time was longer in lateral minithoracotomy procedures, but intensive care unit stay and hospitalization were equal in all groups. Pain visual analog scale and pain behavior rating scale showed a peak on post-operative day 4 in median sternotomy procedures. Post-traumatic stress disorder scale revealed higher values on post-operative day 4 and equalizing with lateral minithoracotomy procedures 1 month post-operatively. Six-minutes walking distance on post-operative day 4 was longer in the group with lateral minithoracotomy. Three-month follow-up revealed patency of all grafts. CONCLUSIONS: Even if surgery is successful in all procedures, operative time is longer in lateral minithoracotomy procedures without compromising intensive care unit stay and hospital stay. More pain with multiple post-traumatic stress disorders is related to median sternotomy, and post-operative convalescence is superior for lateral minithoracotomy procedures.

Aged↗

[Polyneuropathy, diarrhea].

A 44-year-old patient with 24 kg reduction of body weight within three years due to recurrent diarrhea was admitted to the hospital. Physical findings of the patient were not remarkable, except for hypesthesia and hypalgesia of the front of the tibia and of the lower legs. Laboratory as well as endoscopic and functional examinations of the gastrointestinal tract did not reveal any remarkable finding. Infectious origins of the disease were excluded. A histological examination of a rectum specimen yielded amyloid deposits in the submucosa of the rectum. In the family history of the patient, relatives with liver and gastrointestinal diseases due to amyloidosis were detected. Amyloid deposits and the positive family history of the patient led to the diagnosis of a gastrointestinal manifestation of familial amyloidosis.

Adult↗

[Solid phase technique versus gel centrifugation for detection of erythrocyte antibodies--a prospective study comparison the 2 antibody detection tests].

AIM: To define differences of specifity and sensitivity between a solid phase- and a gel centrifugation test for detection of irregular erythrocyte antibodies. STUDY DESIGN: 3052 blood samples were screened for erythrocyte antibodies (AB) by gel centrifugation [ID-System, (ID) 37 degrees C Bromelin and indirect antiglobulin test with LISS (IAT)] and a solid phase antiglobulin test [Capture-R Ready Screen (CR)] in a prospective study. Identical test cells were used as immobilized monolayer in CR and as 1%-suspension in ID. Additionally, 42 sera with antibodies reacting in both tests were titered geometrically in both techniques. RESULTS: In 79 (2.6%) of all sera tested, irregular erythrocyte antibodies were detected. 64 (81%) of these positive sera were detected by both tests, 73 (92.3%) by ID and 70 (88.4%) by CR. 6 sera with AB (7.6%) were positive only with CR (1 Ce, 1 E, 1 Leb, 1 C, 1 D, 1 Cob) and 9 (11.4%) only with ID (4 Lea, 1 Fya, 1 C, 2 P1, 1 D). Seven AB solely detected in ID only reacted in the bromelin test, besides an anti-Fya, which was an IgM antibody. The titration of IgG antibodies showed a slightly higher sensitivity of the CR (less than one titre step). The ID showed clearly more unspecific reactions (1.1%) than the CR (0.5%). DISCUSSION: The antibody screening with the ID proved to detect more AB than the CR (mainly due to certainly irrelevant "enzyme only" AB). On the other hand, relevant IgG AB were detected more sensitive by the CR. Unspecific reactions appeared clearly more often in ID, predominantly when using the bromelin test. Missing a strong IgM anti-Fya in the CR is certainly a concern because of its assumed haemolytic activity. Therefore CR for antibody screening should always be combined with a method for crossmatching that safely detects IgM antibodies which are relevant for transfusion.

Blood Group Antigens↗

[The effect of ciprofloxacin on epinephrine and collagen induced thrombocyte aggregation in vitro on dialysis patients].

In recent investigations it was found that ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7 (1-piperazinyl)-3-fiquinoline-carboxylic acid, Ciprobay) in concentrations similar to maximal levels obtained in the serum of patients with normal renal function after application of therapeutic doses and 4- to 5fold such concentrations does not influence aggregation induced by epinephrine and collagen in platelet rich plasma of healthy subjects. Because in literature there are several reports about disturbances of platelet aggregation in patients with renal failure treated with antibiotics and because renal failure often is accompanied by defect platelet function the effect of ciprofloxacin on epinephrine and collagen induced aggregation was studied in platelet rich plasma of patients with chronic renal failure undergoing dialysis. Compared to platelets from patients with renal failure which had been incubated with saline instead of ciprofloxacin, patients platelets under the influence of ciprofloxacin did not show any significant differences. From this we conclude that the defect which may be present in platelets of patients with chronic renal failure is not further increased by ciprofloxacin.

Ciprofloxacin↗

[The effect of ciprofloxacin on epinephrine and collagen-induced thrombocyte aggregation in vitro].

Concentrations of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (ciprofloxacin; designated tradename: Ciprobay) similar to maximal levels obtained in the serum of patients with intact renal function after application of therapeutic doses and 4- to 5-fold such concentrations do not influence epinephrine- or collagen-induced aggregation. 100 micrograms/ml ciprofloxacin, corresponding to the 20 fold maximal serum level of patients with intact renal function, does not influence aggregation induced by 2 micrograms/ml collagen as regards degree and kinetics of aggregation, while aggregation induced by 0.2 micrograms/ml collagen is significantly reduce. Aggregation induced by 1, 2 and 4 mumol/l epinephrine is also reduced significantly by 100 micrograms/ml ciprofloxacin. Changes brought about by high doses of ciprofloxacin still occur within the normal range. It is therefore concluded from this study that the hemostatic function of the platelets is not influenced in a clinically relevant manner by ciprofloxacin. Regarding the effect on platelet aggregation ciprofloxacin corresponds to the structurally related pipemidic acid.

Adult↗

Investigations on the effects of heavy water (D2O) on the functional activity of human platelets.

Heavy water (D2O) is able to activate or to inhibit biological systems and thus influences metabolism and functions of tissues and organs. On the basis of results obtained in preservation experiments performed on various organs, the effects of D2O on the functions of human platelets (retraction, spreading, aggregation induced by adrenaline, ADP and collagen) have been investigated. The effects of D2O, involving changes of membrane receptor conformation, binding strength of substances to their specific receptors, pH-values or enzyme activities, resulted in a significant decrease of ADP- and collagen-induced aggregation, while adrenaline-induced aggregation was significantly increased at the same D2O concentration. Retraction in the presence of D2O was significantly inhibited in a dose-related manner, while spreading was diminished, but not fully inhibited even by highest concentrations of D2O (95%).

Adenosine Diphosphate↗