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J König

Publications and source records attributed to J König.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced expression and clinical significance of CC-chemokine MIP-3 alpha in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent visceral neoplasms worldwide. Using RT-PCR, ELISA, microdissection and immunohistochemistry, we investigated the expression profiles of CCL19, CCL20, CCL21 and CXCL12 and their receptors in tumourous and tumour neighbouring tissues from patients with HCC and in nonmalignant liver lesions, respectively. All chemokines were found to be expressed in normal liver and HCC tissues, yet CCL20 was the only chemokine showing significant upregulation in HCC tissues. Clinicopathological analysis revealed a distinct increase in CCL20 expression rates in HCC tissues of grade III tumours in comparison to HCC tissues from grade II tumours. On mRNA level, only chemokine receptor CCR6 revealed significant upregulation in HCC tissues. However, immunohistochemical studies indicated a marked CCR6 expression accumulated in a streak of normal cells along the tumour invasion front in all our HCC specimens which could provide a stimulative signal for the tumour to further expand. The present findings show significant overexpression of CCL20 in the tumour tissues and marked overexpression of the corresponding receptor CCR6 in the tumour invasion front of HCC patients in comparison to normal liver. Moreover, CCL20 expression was found to correlate with tumour grade and therefore, we suggest that the CCL20/CCR6 system may be involved in hepatocarcinogenesis.

Adult↗
PubMed2005

Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system.

Dehydroepiandrosterone 3-sulfate and other neurosteroids are synthesized in the CNS and peripheral nervous system where they may modulate neuronal excitability by interacting with ligand-gated ion channels. For this modulatory activity, neurosteroids have to be locally released from either neurons or glial cells. We here identify the integral membrane protein ABCC11 (multidrug resistance protein 8) as an ATP-dependent efflux pump for steroid sulfates, including dehydroepiandrosterone 3-sulfate, and localize it to axons of the human CNS and peripheral nervous system. ABCC11 mRNA was detected in human brain by real-time polymerase chain reaction. Antibodies raised against ABCC11 served to detect the protein in brain by immunoblotting and immunofluorescence microscopy. ABCC11 was preferentially found in the white matter of the brain and co-localized with neurofilaments indicating that it is an axonal protein. Additionally, ABCC11 was localized to axons of the peripheral nervous system. For functional studies, ABCC11 was expressed in polarized Madin-Darby canine kidney cells where it was sorted to the apical membrane. This apical sorting is in accordance with the localization of ABCC11 to the axonal membrane of neurons. Inside-out plasma membrane vesicles containing recombinant ABCC11 mediated ATP-dependent transport of dehydroepiandrosterone 3-sulfate with a Km value of 21 microM. This transport function together with the localization of the ABCC11 protein in vicinity to GABAA receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons to sites of dehydroepiandrosterone 3-sulfate-mediated receptor modulation. Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders.

ATP-Binding Cassette Transporters↗
PubMed2005

Gait analysis in patients with advanced Parkinson disease: different or additive effects on gait induced by levodopa and chronic STN stimulation.

The aim of our study was to observe the effects on gait parameters induced by STN stimulation and levodopa medication in patients with advanced Parkinson's disease in order to determine different or additive effects. Therefore we examined 12 patients with advanced Parkinson disease after bilateral implantation of DBS into the STN. We assessed the motor score of the UPDRS and quantitative gait analysis under 4 treatment conditions: with and without stimulation as well as with and without levodopa. The mean improvement of the UPDRS motor score was almost the same with levodopa and DBS. Combining both therapies we saw a further improvement of the motor score. Gait parameters of patients with PD treated either with levodopa or STN stimulation were greatly improved. A significant difference between levodopa and STN stimulation could only be shown for the parameters velocity and step length. These parameters improved more with levodopa than with stimulation. The combination of both therapeutic methods showed the best results on the UPDRS motor score and gait parameters.

Aged↗
PubMed2005

[Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)].

With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member states.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

[Clinical significance of stress reactivity for frequency of electric shock discharges in patients with implanted cardioverter-defibrillators].

BACKGROUND AND OBJECTIVE: Recent research indicates that discharges of implanted cardioverter-defibrillators (ICD) are triggered by psychosocial stress. This study examined the presence of patterns of psychophysiological stress reactivity in ICD-patients. Further more potential relationship between factors of stress reactivity and the frequency of implantable cardioverter-defibrillators discharges was investigated. PATIENTS AND METHODS: In 46 consecutive patients (38 male, 8 female; age: 26-80 years) with implantable cardioverter-defibrillators the following parameters of physiological reactivity were measured in a standardised experimental stress test: Heart rate, skin conductance, muscle tension and respiratory activity. In a standardised interview anxiety sensitivity, depression, desire for control, stress load, and attitude towards the defibrillator were evaluated and quantified. The relationship between the mentioned parameters were examined with factor analysis to reveal patterns of psychophysiological reactivity. Potential relationship between psychophysiological factors and frequency of shock delivery was verified with linear regression analysis. RESULTS: Factor analysis revealed four independent psychophysiological traits. The factors were named "Play Dead Reflex", "Heart Phobia", "Negativism" and "Irritability". Linear regression model showed significant correlation between "Play Dead Reflex" and discharge frequency. CONCLUSIONS: Results confirm the presence of specific psychophysiological stress reaction patterns in ICD-patients. The stress reaction pattern "Play Dead Reflex" could be discussed as a potential risk factor in developing life-threatening tachyarrhythmias leading to an increase in defibrillator discharges in patients with ICD. This hypothesis should be considered in prospective studies and psychosomatic treatment of concerned patients.

Adult↗
PubMed2004

A reverse genetic approach for generating gene replacement mutants in Ustilago maydis.

We describe a versatile strategy for generating gene replacement mutants in the phytopathogenic fungus Ustilago maydis. The system includes the choice of 32 different insertion cassettes for genetic engineering purposes, such as gene disruption and more sophisticated insertions of reporter genes, heterologous promoters or combinations of the two. PCR-amplified flanking sequences needed for homologous recombination are ligated to the respective insertion cassettes via SfiI sites. As proof of principle we generated two replacement mutants in which the endogenous promoter of the pheromone gene mfa1 drives expression of the Green Fluorescent Protein gene (gfp). Simultaneously, expression of the mfa1 ORF is controlled either by the carbon source-regulated crg1 promoter or the nitrogen source-regulated nar1 promoter. In both cases gfp expression was pheromone-inducible and pheromone expression was only detected when the heterologous promoters were active.

Base Sequence↗
PubMed2004

Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain.

Multidrug resistance proteins (MRPs, symbol ABCC) are membrane glycoproteins that mediate the ATP-dependent export of organic anions, including cytotoxic and antiviral drugs, from cells. To identify MRP family members possibly involved in the intrinsic resistance of human brain to cytotoxic and antiviral drugs, we analyzed the expression and localization of MRP1-MRP6 in rapidly frozen perilesional samples of several regions of adult human brain obtained during neurosurgery. Quantitative polymerase chain reaction analysis showed expression of MRP1, MRP2, MRP3, MRP4, and MRP5 mRNA, whereas MRP6 mRNA was below detectability. However, immunofluorescence microscopy of cryosections from human brain showed no reactivity for the MRP2 or MRP3 proteins. The proteins MRP1, MRP4, and MRP5 were clearly localized by confocal laser scanning microscopy to the luminal side of brain capillary endothelial cells. The MRP4 and MRP5 proteins were also detected in astrocytes of the subcortical white matter. Notably, MRP5 protein was present in pyramidal neurons. MRP proteins may, thus, contribute to the cellular efflux of endogenous anionic glutathione or glucuronate conjugates (substrates for MRP1), cyclic nucleotides (substrates for MRP4 and MRP5), or glutathione (co-substrate for MRP1 and MRP4); in addition, they may play an important role in the resistance of the brain to several cytotoxic and antiviral drugs.

ATP-Binding Cassette Transporters↗
PubMed2004

Dental nomograms for benchmarking based on the study of health in Pomerania data set.

AIM: Benchmarking is a means of setting goals or targets. On an oral health level, it denotes retaining more teeth and/or improving the quality of life. The goal of this pilot investigation was to assess whether the data generated by a population-based study (SHIP 0) can be used as a benchmark data set to characterize different practice profiles. MATERIAL AND METHODS: The data collected in the population-based study SHIP (n=4310) in eastern Germany were used to generate nomograms of tooth loss, attachment loss, and probing depth. The nomograms included twelve 5-year age strata (20-79 years) presented as quartiles, and additional percentiles of the dental parameters for each age group. Cross-sectional data from a conventional dental office (n=186) and from a periodontology unit (n=130, Greifswald) in the study region as well as longitudinal data set of a another periodontology unit (n=135, Kiel) were utilized in order to verify whether the given practice profile was accurately reflected by the nomogram. RESULTS: In terms of tooth loss, the data from the conventional dental office agree with the median from the nomogram. For attachment loss and probing depth, some age groups yielded slight but not uniform deviations from the median. Cross-sectional data from the periodontology unit Greifswald showed attachment loss higher than the median in younger but not in older age groups. The probing depth was uniformly less than the median and tended toward the 25th percentile with increasing age. The longitudinal data of the Unit of Periodontology in Kiel showed a pronounced trend towards higher percentiles of residual teeth, meaning that the patients retained more teeth. CONCLUSION: The profile of the Pomeranian dental office does not deviate noticeably from the population-based nomograms. The higher attachment loss of the Unit of Periodontology in Greifswald in younger age strata clearly reflects their selection because of periodontal disease; the combination of higher attachment loss and decreased probing depth may reflect the success of the treatment. The tendency of attachment loss towards the median with increasing age may indicate that the Unit of Periodontology in Greifswald does not fulfill its function as a special care unit in the older subjects. The longitudinal data set of the Unit of Periodontology in Kiel impressively reflects the potential of population-based data sets as a means for benchmarking. Thus, nomograms can help to determine the practice profile, potentially yielding benefits for the dentist, health insurance company, or--as in the case of the special care unit--public health research.

Adult↗
PubMed2003

Kondo effect in the presence of itinerant-electron ferromagnetism studied with the numerical renormalization group method.

The Kondo effect in quantum dots (QDs)-artificial magnetic impurities-attached to ferromagnetic leads is studied with the numerical renormalization group method. It is shown that the QD level is spin split due to the presence of ferromagnetic electrodes, leading to a suppression of the Kondo effect. We find that the Kondo effect can be restored by compensating this splitting with a magnetic field. Although the resulting Kondo resonance then has an unusual spin asymmetry with a reduced Kondo temperature, the ground state is still a locally screened state, describable by Fermi liquid theory and a generalized Friedel sum rule, and transport at zero temperature is spin independent.

Journal Article↗
PubMed2003

Terminal ileitis with sealed perforation--a rare complication of intestinal endometriosis: case report and short review of the literature.

INTRODUCTION: Perforation is a rare complication of intestinal endometriosis. We report on a 38-year-old patient with previously known rectovaginal and ileocecal endometriosis who was referred with an acute abdomen. CASE REPORT: On abdominal plain film an ileus of small intestine was diagnosed. The patient had fever, and the C-reactive protein was markedly increased. Upon emergency laparotomy an acute terminal ileitis with omentum-sealed perforation and a stenosis of the anterior wall of the rectum due to endometriosis were found. Partial resection of the ileum with end-to-end anastomosis, appendectomy, and short segmental rectum resection were performed. The postoperative course was uneventful. Histological examination corroborated the intraoperative diagnosis of fistulas, perforation and deep ulceration of the intestine consistent with transmural endometriosis. DISCUSSION: For proper care of these patients excellent cooperation between gynecologists and general surgeons is desirable. A short review of the literature concerning intestinal endometriosis is given.

Adult↗
PubMed2003

Kondo effect in quantum dots coupled to ferromagnetic leads.

We study the Kondo effect in a quantum dot coupled to ferromagnetic leads and analyze its properties as a function of the spin polarization of the leads. Based on a scaling approach, we predict that for parallel alignment of the magnetizations in the leads the strong-coupling limit of the Kondo effect is reached at a finite value of the magnetic field. Using an equation of motion technique, we study nonlinear transport through the dot. For parallel alignment, the zero-bias anomaly may be split even in the absence of an external magnetic field. For antiparallel spin alignment and symmetric coupling, the peak is split only in the presence of a magnetic field, but shows a characteristic asymmetry in amplitude and position.

Journal Article↗
PubMed2003

Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension.

BACKGROUND: The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. In healthy individuals, 40% to 50% of circulating ET-1 is removed on each passage through the lungs resulting in an arteriovenous ratio of <1, whereas many patients with pulmonary arterial hypertension (PAH) have ratios >1, indicating reduced clearance or increased release of endothelin. The influence of inhaled prostanoids on endothelin clearance is unknown. METHODS AND RESULTS: In a prospective investigation, plasma concentrations of big endothelin-1 (big ET-1, Elisa) were measured in 15 patients with pulmonary hypertension undergoing right heart catheterization with iloprost inhalation (4 m, 11 f, aged 35 to 75 years, mean pulmonary arterial pressure (PAPm) 54+/-2.3 mm Hg, pulmonary vascular resistance (PVR) 1061+/-141 dyn x sec x cm(-5)). There was a significant transpulmonary gradient for big ET-1 with 31% +/-11% higher concentrations in the radial artery than in the pulmonary artery (P<0.001). After inhalation of iloprost a significant decrease in the AV-ratio from 1.31+/-0.11 to 0.92+/-0.06 (P<0.007) was observed. The pulmonary net release of 3.10+/-0.65 pmol/min big ET-1 at baseline decreased to -1.24+/-1.32 pmol/min (P=0.013) within 15 minutes indicating a restored balance. Patients under long-term treatment with iloprost (n=7) tended to have a lower net release and AV-ratio for big ET-1 than patients without pretreatment. CONCLUSION: An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.

Administration, Inhalation↗
PubMed2003

Effects of purinergic stimulation, CFTR and osmotic stress on amiloride-sensitive Na+ transport in epithelia and Xenopus oocytes.

Both stimulation of purinergic receptors by ATP and activation of the cystic fibrosis transmembrane conductance regulator (CFTR) inhibit amiloride-sensitive Na+ transport and activate Cl- secretion. These changes in ion transport may well affect cell volume. We therefore examined whether cell shrinkage or cell swelling do affect amiloride-sensitive Na+ transport in epithelial tissues or Xenopus oocytes and whether osmotic stress interferes with regulation of Na+ transport by ATP or CFTR. Stimulation of purinergic receptors by ATP/UTP or activation of CFTR by IBMX and forskolin inhibited amiloride-sensitive transport in mouse trachea and colon, respectively, by a mechanism that was Cl- dependent. When exposed to a hypertonic but not hypotonic bath solution, amiloride-sensitive Na+ transport was inhibited in mouse trachea and colon, independent of the extracellular Cl- concentration. Both inhibition of Na+ transport by hypertonic bath solution and ATP were additive. When coexpressed in Xenopus oocytes, activation of CFTR by IBMX and forskolin inhibited the epithelial Na+ channel (ENaC) in a Cl- dependent fashion. However, both hypertonic and hypotonic bath solutions showed only minor effects on amiloride-sensitive conductance, independent of the bath Cl- concentration. Moreover, CFTR-induced inhibition of ENaC could be detected in oocytes even after exposure to hypertonic or hypotonic bath solutions. We conclude that amiloride-sensitive Na+ absorption in mouse airways and colon is inhibited by cell shrinkage by a mechanism that does not interfere with purinergic and CFTR-mediated inhibition of ENaC.

1-Methyl-3-isobutylxanthine↗
PubMed2003

Personality traits in multiple sclerosis (MS) patients with and without fatigue experience.

OBJECTIVES: To determine the impact of personality characteristics on feelings of fatigue in multiple sclerosis (MS) patients and to compare the results with the impact of bodily impairment. PATIENTS AND METHODS: Eighty patients with definite MS (mean age 38.5 +/- 9.0 years, 62 females) were surveyed using questionnaires assessing fatigue experience and personality traits (German Freiburg Personality Inventory-Revised; FPI-R) and by clinical examination assessing the Expanded Disability Status Scale. RESULTS: Increased levels of "neuroticism", and "excitability" and decreased levels of "extraversion" were found to relate independent of fatigue scores (0.21 < beta < 0.52; 0.05 < P < 0.0001). The impact of these personality traits on fatigue (partial R2 ranging up to 0.32; 0.02 < P < 0.0001) was much higher than the impact of physical impairment (partial R2 ranging up to 0.04; not significant). CONCLUSION: Our results support a psychological model of fatigue in MS. FPI-R-items over-weighted somatic sources of the fatigue syndrome in MS and may specifically relate to fatigue experience in chronical disorders.

Adult↗
PubMed2003

Learning root debridement with curettes and power-driven instruments. Part II: Clinical results following mechanical, nonsurgical therapy.

BACKGROUND, AIMS: In a manikin study we recently assessed how effectively student operators were able to learn scaling with curettes (GRA) and power-driven instruments (PP). Calculating the debrided root area effectiveness was low in both groups without systematic training or without a motivational program. After 10 weeks (20 h) of training, operators reached a high effectiveness of 84.7% (GRA) and 81.6% (PP). The purpose of the present study was to evaluate the clinical outcome of nonsurgical treatment as performed by these student operators. METHODS: In a clinical trial, 19 students trained in the use of Gracey curettes for 10 weeks (=20 h) (GRA10) and Periopolisher system for 1 week (=2 h) (PP1), and 20 students trained in the use of Gracey curettes for 1 week (GRA1) and the Periopolisher for 10 weeks (PP10) treated one patient each in a split-mouth design. At baseline and 6 months, we recorded probing depth (PD), probing attachment level (PAL) and bleeding on probing (BOP) by computer-assisted probing. Statistical analysis was carried out for moderate (category B) and deep sites (category C). Groups were compared using Student's t-tests (p<0.05). RESULTS: Category B sites showed a PD reduction of 1.2/1.0 mm (GRA10/GRA1) and 1.1 mm (PP10/PP1). PAL gain was 0.5/0.3 mm (GRA10/GRA1) and 0.4/0.2 mm (PP10/PP1). In category C sites, PD reduction was 2.1/2.3 mm (GRA10/GRA1) and 2.0 mm (PP10/PP1) with a PAL gain of 0.6/0.9 mm (GRA10/GRA1) and 0.4 mm (PP10/PP1). BOP was significantly lower in all groups. CONCLUSION: The results show that student operators who had received a systematical training on manikins and had attained different effectiveness results were able to treat periodontally diseased patients successfully using both Gracey and Periopolisher instruments.

Dental High-Speed Equipment↗
PubMed2002

Learning root debridement with curettes and power-driven instruments. Part I: a training program to increase effectivity.

BACKGROUND/AIMS: In a dummy-head trial, we assessed how effectively untrained operators were able to learn scaling with curettes and power-driven instruments. METHODS: Two untrained operator groups (n = 11 each) received six 2-h lessons during a 10-week period following a training program. Subgingival scaling was performed with curettes (GRA) and a power-driven system (PP). At 6 test days each subject had to instrument 10 test teeth. The percentage of debrided area was assessed with an image analysis program. Learning success was measured as a percentage of debrided root area and scaling time. Furthermore, the effectivity was related to difficulty in anatomical situations and access to root surfaces. Statistical analysis was carried out with SPSS. RESULTS: At baseline, effectivity was 63.1% (GRA) vs. 52.3% (PP). Between weeks 9 and 11, operators reached a plateau for group GRA at 84.7% and group PP at 81.3%. Scaling time did not differ between the two groups. Debridement of teeth with complex root shapes that were hard to access was less effective with the power-driven system. CONCLUSION: Independent of the instrument used, untrained operators were only able to debride root surfaces at low levels of efficacy. With systematical training, effective scaling with the power- driven system was as easy to learn as with hand instruments. On root surfaces with complicated shape and anatomy or difficult accessibility, the power-driven system works significantly less effectively.

Alveolar Bone Loss↗
PubMed2002

Learning root debridement with curettes and power-driven instruments in vitro: the role of operator motivation and self-assessment.

The influence of systematic dummy-head training with Periopolishe (PP, group A) and Gracey instruments (GRA, group B) on the effectiveness of root debridement was evaluated by Rühling et al., 2002 (9). Their results indicate that independent of the instrument used, untrained operators were only able to debride root surfaces at low levels of effectiveness. It was possible to increase effectiveness to a high level through systematic training in both groups. The aim of the present study was to assess the role of operator motivation and self-assessment on scaling effectiveness. Before baseline, operators were asked to answer a questionnaire rating the expectation of the instrument performance. Four groups of inexperienced operators (n = 11 each) received 10 weeks dummy-head training. In groups A (GRA) and B (PP), training was combined with a motivational programme. Groups C (GRA) and D (PP) received the same training, but no additional motivational programme. In a dummy-head, 10 test teeth were debrided and operators were asked to estimate their effectiveness of debridement at each test day. Effectiveness was calculated as percentage of debrided root area on 10 test teeth at different time points with an image analysis programme (NIH Image) and ANOVA. Two groups were compared using the Mann-Whitney U-test (unpaired) and the Wilcoxon signed ranks test (paired). Motivated groups (A and B) reached about 25% higher debridement results (p < 0.001) and were able to estimate their effectiveness more precisely compared to groups C and D. In the low motivation groups (C and D), overestimation of more than 20% was evident (p < 0.001). The questionnaires revealed underestimation of the GRA instruments and overestimation of PP instruments. Operator motivation and self-assessment greatly influence learning of effective root debridement.

Analysis of Variance↗