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Biomedical subjects

M Krause

Publications and source records attributed to M Krause.

At least 55 records · Page 3Linked to original sources
PubMed2003

Proliferation and micromilieu during fractionated irradiation of human FaDu squamous cell carcinoma in nude mice.

PURPOSE: Previous functional radiobiological experiments demonstrated a significant acceleration of repopulation after 3 weeks and reoxygenation after 12 days of radiotherapy of FaDu tumours. Owing to the temporal coincidence between repopulation and reoxygenation, it was hypothesized that the improved oxygenation status during fractionated irradiation might be the preceding stimulus for increased proliferation. The study investigated whether these changes in repopulation and re-oxygenation are reflected by histological parameters of proliferation and the tumour micromilieu. MATERIALS AND METHODS: Human FaDu squamous cell carcinomas in nude mice were irradiated with three to 18 fractions of 3 Gy daily or every second day under normal blood flow and clamp hypoxia. At different time points, tumours were excised and stained for Ki67, BrdUrd, epidermal growth factor receptor (EGFR) and markers of the micromilieu (HOECHST 33342, pimonidazole, ER-MP12). RESULTS: On average, Ki67 and BrdUrd labelling indices decreased initially and increased again at later times during the course of fractionated radiotherapy. A similar kinetic pattern was found for the staining intensity of the EGFR. The vascular density in the viable tumour area remained constant during the whole course of irradiation, while the perfused fraction of vessels decreased within the first week of irradiation and returned to baseline values after 2 weeks. There was a corresponding increase in perfusion and a decrease in cellular hypoxia. CONCLUSIONS: The histological results were in surprisingly good agreement with the kinetics of clonogen repopulation and re-oxygenation determined previously using functional assays. The results support that the kinetics of repopulation of FaDu squamous cell carcinoma in response to fractionated irradiation are determined not only by intracellular processes, but also by a complex interaction of proliferation parameters with a changing microenvironment.

Animals↗
PubMed2002

[Resistance problems in gastrointestinal infections].

A variety of world-wide resistance problems in bacterial gastrointestinal pathogens have emerged within the last decade. Particularly, antibiotics used to treat salmonella, campylobacter and Helicobacter pylori have lost their efficacy in a high proportion of isolates. Of major clinical significance is the resistance of H. pylori to metronidazole and clarithromycin, of Campylobacter spp. to fluoroquinolones and macrolides and of Salmonella spp. to fluoroquinolones and third generation cephalosporins. Of special concern is the spread of multiresistant isolates. Fortunately, in Clostridium difficile the resistance rate against metronidazole or vancomycin appears to be still low. Numerous investigations provided convincing evidence that the major source of emergence and dissemination of bacterial resistance is the use of antibiotics in food animals. This applies in particular to multiresistant strains of salmonella and campylobacter. A restricted use of antibiotics in the livestock is clearly warranted to control the unlimited development of resistance. The following recommendations should be considered in the care of infections with H. pylori, Campylobacter and Salmonella: 1) Treatment of H. pylori should be restricted to ulcer disease and gastric lymphoma. Eradication is not indicated in asymptomatic patients or patients with gastrointestinal pathologies that are not related to H. pylori. 2) Anti-H. pylori antibiotics should include metronidazole, clarithromycin, amoxicillin or tetracycline in combination of two of them. They should be used in short terms and in the recommended dosages together with proton pump inhibitors. If ulcers relapse after the first eradication, the resistance pattern should be determined. 3) In Campylobacter enterocolitis, antibiotics should be reserved for more severe cases. Resistance testing to exclude quinolone resistance is encouraged if antibiotics are considered. 4) In Salmonella gastroenteritis antibiotics do not significantly improve the course of infection. Their use should thus be restricted to patients which are at risk for disseminated disease including infants, elderly and immunosuppressed persons. 5) Since multiresistant Salmonella are common, resistance testing is highly recommended.

Aged↗
PubMed2002

[Breech presentation in obstetrics in Germany--an assessment of current status].

Nowadays, the CS seems to be the most favourite way of delivery in case of breech presentation. Our opinion is that the vaginal delivery has no disadvantage for the physical and mental development of the newborns [11, 12]. The outcome depends on the set-up and organisation of each department. The most important condition to reach a good outcome by breech presentation is a well-established practical training of the whole team, a careful risk selection and a well structured perinatal centre. In our opinion the CS is the second choice to deliver a pregnant woman with a breech presentation at term. High CS-rates as well as a increased perinatal morbidity at vaginal breech delivery are a sign for insufficient training of the staff and insufficient organisation in small departments not being perinatal centres. Not the breech presentation is the real risk factor, but the unqualified Obstetrician and the insufficient set-up in the most of OB/Gyn-departments. We have a very high ethic responsibility against young women resultating from our profession. It's our duty to decide and recommend the best way to save the wellbeing of the mother and the unborn child. It's also our duty to avoid surgical manoeuvers resulting from economic reasons. Therefore a complete, sufficient practical training concerning breech delivery technics is absolutely needed. In future the answer of the question: "Delivery of breech presentation--vaginally or through CS?" will depend on, if we will be able to change this politic and professional undesirable trend.

Breech Presentation↗
PubMed2002

High frequency stimulation of the basal ganglia for the treatment of movement disorders: current status and clinical results.

High frequency stimulation of the basal ganglia has gained much interest during the last years. Based on the reevaluation of the results of functional neurosurgery for movement disorders from Leksell's group, pallidotomy as lesional procedure was the first functional operation that underwent a renaissance for the treatment of movement disorders. The work by Benabid and Siegfried who carried out thalamic high frequency stimulation to suppress tremor, the knowledge about deep brain stimulation (DBS) for the treatment of chronic pain as well as better understanding in basal ganglia physiology and the development of reliable stimulation hardware led to an increasing number of centers worldwide who currently apply high frequency DBS for different movement disorders. In the present review the current status of DBS for movement disorders is presented and the results with high frequency stimulation targeted at different brain areas are summarized.

Animals↗
PubMed2002

Oxcarbazepine-induced hyponatremia and the regulation of serum sodium after replacing carbamazepine with oxcarbazepine in children.

While severe hyponatremia is reported to be more frequent in adults treated with oxcarbazepine (OXC) than with carbamazepine (CBZ), there is not sufficient data about the incidence of hyponatremia in childhood during treatment with OXC. We evaluated changes in serum electrolyte balance in 75 children with epilepsy before and during treatment with OXC and after replacing carbamazepine (CBZ) therapy with OXC therapy. All patients had normal sodium serum levels at the onset of OXC. During treatment with OXC we found hyponatremia (Na +< 135 mmol/l) without clinical symptoms in 26.6 % of the children (n = 20), sodium levels below 125 mmol/l were observed in 2 children (2.6 %). Clinically relevant hyponatremia occurred in one girl only (1.3 %). In a subgroup of 27 children, in whom CBZ was directly replaced with OXC, hyponatremia without symptoms was found in one child under CBZ (3.7 %) and in six children under OXC (22.2 %). Dosage of OXC, serum levels of the active metabolite of OXC, antiepileptic comedication or patients' age and gender were of no predictive value for the development of hyponatremia. Electrolytes should be measured before establishing OXC and if clinically relevant side effects occur.

Adolescent↗
PubMed2001

Dopamine and glutamate induce distinct striatal splice forms of Ania-6, an RNA polymerase II-associated cyclin.

Control of neuronal gene expression by drugs or neurotransmitters is a critical step in long-term neural plasticity. Here, we show that a gene induced in the striatum by cocaine or direct dopamine stimulation, ania-6, is a member of a novel family of cyclins with homology to cyclins K/T/H/C. Further, different types of neurotransmitter stimulation cause selective induction of distinct ania-6 isoforms, through alternative splicing. The longer Ania-6 protein colocalizes with nuclear speckles and is associated with key elements of the RNA elongation/processing complex, including the hyperphosphorylated form of RNA polymerase II, the splicing factor SC-35, and the p110 PITSLRE cyclin-dependent kinase. Distinct types of neuronal stimulation may therefore differentially modulate nuclear RNA processing, through altered transcription and splicing of ania-6.

Alternative Splicing↗
PubMed2001

Repopulation of FaDu human squamous cell carcinoma during fractionated radiotherapy correlates with reoxygenation.

PURPOSE: FaDu human squamous cell carcinoma (FaDu-hSCC) showed a clear-cut time factor during fractionated radiotherapy (RT) under ambient blood flow. It remained unclear whether this is caused solely by proliferation or if radioresistance resulting from increasing hypoxia contributed to this phenomenon. To address this question, repopulation of clonogenic FaDu cells during fractionated RT under clamp hypoxia was determined by local tumor control assays, and compared to the results after irradiation with the same regimen under ambient blood flow. METHODS AND MATERIALS: FaDu-hSCC was transplanted into the right hind leg of NMRI nu/nu mice. In the first set of experiments, irradiation was performed under clamp hypoxia. After increasing numbers of 3 Gy fractions (time intervals 24 h or 48 h), graded top-up doses were given to determine the TCD(50) (dose required to control 50% of the tumors). In the second set of experiments, all 3 Gy fractions were applied under ambient conditions, but as in the previous experiments the graded top-up doses were given under clamp hypoxia. A total of 26 TCD(50) assays were performed and analyzed using maximum likelihood techniques. RESULTS: With increasing numbers of daily fractions, the top-up TCD(50) under clamp hypoxia decreased from 39.4 Gy [95% CI 36, 42] after single dose to 19.8 Gy [15, 24] after 18 fractions in 18 days and to 37.8 Gy [31, 44] after 18 fractions in 36 days. The results were consistent with biphasic repopulation, with a switch to rapid repopulation after about 22 days [13, 30]. The clonogen doubling time (T(clon)) decreased from 9.8 days [0, 21] in the beginning of RT to 3.4 days after 22 days. Under ambient blood flow the top-up TCD(50) decreased from 37.6 Gy [34, 40] after single dose irradiation to 0 Gy [0, 1] after 18 fractions in 18 days and 22.4 Gy [18, 27] after 18 fractions in 36 days. Similar to results from irradiations under clamp hypoxia, the ambient data were consistent with a biphasic course of clonogen inactivation. Comparison of both data sets revealed significant reoxygenation after 12 fractions. CONCLUSIONS: Our data are most consistent with a biphasic course of clonogen repopulation during fractionated RT of FaDu-hSCC under clamp hypoxia with a switch in T(clon) after about 22 days of treatment ("dog-leg"). A similar biphasic course of cell repopulation was observed under ambient conditions. The temporal coincidence between repopulation and reoxygenation suggests that the latter might be the stimulus for proliferation in FaDu tumors.

Animals↗
PubMed2001

Nuclear hormone receptor CHR3 is a critical regulator of all four larval molts of the nematode Caenorhabditis elegans.

CHR3 (nhr-23, NF1F4), the homologue of Drosophila DHR3 and mammalian ROR/RZR/RevErbA nuclear hormone receptors, is important for proper epidermal development and molting in the nematode Caenorhabditis elegans. Disruption of CHR3 (nhr-23) function leads to developmental changes, including incomplete molting and a short, fat (dumpy) phenotype. Here, we studied the role of CHR3 during larval development by using expression assays and RNA-mediated interference. We show that the levels of expression of CHR3 (nhr-23) cycle during larval development and reduction of CHR3 function during each intermolt period result in defects at all subsequent molts. Assaying candidate gene expression in populations of animals treated with CHR3 (nhr-23) RNA-mediated interference has identified dpy-7 as a potential gene acting downstream of CHR3. These results define CHR3 as a critical regulator of all C. elegans molts and begin to define the molecular pathway for its function.

Animals↗
PubMed2001

Identification of androgen-regulated genes in the prostate cancer cell line LNCaP by serial analysis of gene expression and proteomic analysis.

A common therapy for nonorgan-confined prostate cancer involves androgen deprivation. To develop a better understanding of the effect of androgen on prostatic cells, we have analyzed gene expression changes induced by dihydrotestosterone (DHT) in the androgen responsive prostate cancer line LNCaP, at both RNA and protein levels. Changes at the RNA level induced by DHT were determined by means of serial analysis of gene expression (SAGE), and protein profiling was done by means of quantitative two-dimensional polyacrylamide gel electrophoresis. Among 123,371 transcripts analyzed, a total of 28,844 distinct SAGE tags were identified representing 16,570 genes. Some 351 genes were significantly affected by DHT treatment at the RNA level (p < 0.05), of which 147 were induced and 204 repressed by androgen. In two independent experiments, the integrated intensity of 32 protein spots increased and 12 decreased at least two-fold in response to androgen, out of a total of 1031 protein spots analyzed. The change in intensity for most of the affected proteins identified could not be predicted based on the level of their corresponding RNA. Our study provides a global assessment of genes regulated by DHT and suggests a need for profiling at both RNA and protein levels for a comprehensive evaluation of patterns of gene expression.

Androgens↗
PubMed2001

Central retinal vein occlusion in a patient with thrombotic thrombocytopenic purpura.

PURPOSE: To describe the occurrence of central retinal vein occlusion in a patient with thrombotic thrombocytopenic purpura. METHODS: Case report. RESULTS: A 52-year-old woman developed central retinal vein occlusion in the acute phase of thrombotic thrombocytopenic purpura, followed by iris neovascularization only 1 month after the onset of central retinal vein occlusion. Color Doppler imaging of the affected eye showed an increased resistive index of the central retinal artery and reduced blood flow velocity of the central retinal vein compared to the fellow eye. CONCLUSION: We describe a rare association between central retinal vein occlusion and thrombotic thrombocytopenic purpura with rapid evolution of iris neovascularization. Our case demonstrates that close ophthalmologic attention is important in thrombotic thrombocytopenic purpura.

Acute Disease↗
PubMed2001

Paramecium--a model system for studying cellular graviperception.

Experiments under varied gravitational accelerations as well as in density-adjusted media showed that sensation of gravity in protists may be linked to the known principles of mechanosensation. Paramecium, a ciliate with clear graviresponses (gravitaxis and gravikinesis) is an ideal model system to prove this hypothesis since the ciliary activity and thus the swimming behaviour is controlled by the membrane potential. It has also been assumed that the cytoplasmic mass causes a distinct stimulation of the bipolarly distributed mechano-sensitive K+ and Ca2+ ion channels in the plasma membrane in dependence of the spatial orientation of the cell. In order to prove this hypothesis, different channel blockers are currently under investigation. Gadolinium did not inhibit gravitaxis in Paramecium, showing that it does not specifically block gravireceptors. Further studies concentrated on the question of whether second messengers are involved in the gravity signal transduction chain. Exposure to 5 g for up to 10 min led to a significant increase in cAMP.

Animals↗
PubMed2001

Bacterial replication initiator DnaA. Rules for DnaA binding and roles of DnaA in origin unwinding and helicase loading.

We review the processes leading to the structural modifications required for the initiation of replication in Escherichia coli, the conversion of the initial complex to the open complex, loading of helicase, and the assembly of two replication forks. Rules for the binding of DnaA to its binding sites are derived, and the properties of ATP-DnaA are described. We provide new data on cooperative interaction and dimerization of DnaA proteins of E. coli, Streptomyces and Thermus thermophilus, and on the stoichiometry of DnaA-oriC complexes of E. coli.

Bacterial Proteins↗
PubMed2001

Regulating cellular actin assembly.

Cellular actin assembly is tightly regulated. The study of pathogen motility has led to the identification of several cellular factors that are critical for controlling this process. Pathogens such as Listeria require Ena/VASP and Arp2/3 proteins to translate actin polymerization into movement. Recent work has extended these observations and uncovered some similarities and surprising differences in the way cells and pathogens utilize the actin cytoskeleton.

Actin-Related Protein 2↗
PubMed2001

Cardiomyocyte-transistor-hybrids for sensor application.

An extracellular recording system has been designed for the detection of electrical cell signals using p-channel or n-channel field-effect transistor (FET) arrays with non-metallized gates. Signals from rat heart muscle cell were recorded by these devices and the results described on the basis of an equivalent circuit. This technique is sensitive enough to detect minute changes of the extracellular membrane voltage and has potential applications in drug screening. We show that known cardiac stimulants (isoproterenol, norepinephrine) and relaxants (verapamil, carbamylcholine) have characteristic effects on the heart cells in terms of the changes of beat frequencies in the absence or presence of corresponding agents.

Action Potentials↗
PubMed2001

Enzyme-catalyzed prodrug approaches for the histamine H3-receptor agonist (R)-alpha-methylhistamine.

Five novel prodrug types of the potent and selective histamine H3-receptor agonist (R)-alpha-methylhistamine (1) were prepared and pharmacologically tested in vitro as well as in vivo. In particular, an amide of fatty acid, mono- and dicarbamates, an (acyloxy)alkylcarbamate, and a diphthalidyl derivative were synthesized, all of which require initial prodrug activation through an enzyme-catalyzed reaction in contrast to formerly developed azomethine prodrugs which are cleaved by chemical hydrolysis only. Further drug liberation may ensue spontaneously in a cascade to give 1. Since they have diverse stabilities the prodrugs were investigated for drug liberation in vitro under neutral, acidic, and basic conditions at different temperatures as well as with liver homogenates. In vivo investigation of prodrugs after oral administration to mice proved that the fatty amide 2, the Nalpha-methylcarbamate 4a, and the Nalpha-(1-(acetyloxy)ethylcarbamate) 5 showed moderate to high plasma levels of 1. Compound 5 displayed even more than 2.5 times the AUC for 1 than that of the reference azomethine prodrug BP2.94 in the periphery and also displayed a detectable drug level in the central nervous system. It was shown that prodrug approaches based on an initial enzyme-catalyzed liberation step are successfully applicable to different pro-moieties for improved bioavailability and prolonged half-live. These approaches may also be used for other aminergic compounds of this class to optimize pharmacokinetic behavior.

Animals↗
PubMed2001

Regression of high-grade gastric B-cell lymphoma after eradication of Helicobacter pylori.

Regression of high-grade gastric B-cell lymphoma after eradication of Helicobacter pylori with antibiotic therapy has recently been shown in a very small number of patients. We describe here a patient with a 5-cm polypoid gastric lymphoma, who received a 7-day course of triple therapy when the histopathology was unknown. A second endoscopic examination 4 weeks later showed partial tumor regression without biopsy evidence of malignancy. Endoscopic mucosectomy was performed 8 weeks after the initial diagnosis. Again, in the histological analysis of the specimen, no evidence of B-cell lymphoma could be found. To confirm that the original biopsies were from the same patient, DNA analyses were carried out which gave identical results. This case suggests that a subgroup of primary gastric B-cell lymphomas responds to eradication of H. pylori with antibiotic therapy.

Anti-Bacterial Agents↗
PubMed2001

Zyxin is not colocalized with vasodilator-stimulated phosphoprotein (VASP) at lamellipodial tips and exhibits different dynamics to vinculin, paxillin, and VASP in focal adhesions.

Actin polymerization is accompanied by the formation of protein complexes that link extracellular signals to sites of actin assembly such as membrane ruffles and focal adhesions. One candidate recently implicated in these processes is the LIM domain protein zyxin, which can bind both Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the actin filament cross-linking protein alpha-actinin. To characterize the localization and dynamics of zyxin in detail, we generated both monoclonal antibodies and a green fluorescent protein (GFP)-fusion construct. The antibodies colocalized with ectopically expressed GFP-VASP at focal adhesions and along stress fibers, but failed to label lamellipodial and filopodial tips, which also recruit Ena/VASP proteins. Likewise, neither microinjected, fluorescently labeled zyxin antibodies nor ectopically expressed GFP-zyxin were recruited to these latter sites in live cells, whereas both probes incorporated into focal adhesions and stress fibers. Comparing the dynamics of zyxin with that of the focal adhesion protein vinculin revealed that both proteins incorporated simultaneously into newly formed adhesions. However, during spontaneous or induced focal adhesion disassembly, zyxin delocalization preceded that of either vinculin or paxillin. Together, these data identify zyxin as an early target for signals leading to adhesion disassembly, but exclude its role in recruiting Ena/VASP proteins to the tips of lamellipodia and filopodia.

Actinin↗