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Biomedical subjects

U Hansen

Publications and source records attributed to U Hansen.

At least 19 recordsLinked to original sources
PubMed2004

Effect of inertia in Rayleigh-Bénard convection.

We have investigated the influence of the Prandtl number on the dynamics of high Rayleigh number thermal convection. A numerical parameter study in a three-dimensional Rayleigh-Bénard configuration was carried out, where we varied the Prandtl number between 10(-3)< or =Pr< or =10(2). The Rayleigh number was fixed at a value of Ra=10(6). Our main focus lay on the question how the value of the Prandtl number affects the spatial structure of the flow. We investigated the functional dependence of the Nusselt number and the Reynolds number and compared our results with a recent theoretical approach of Grossmann and Lohse [J. Fluid Mech. 407, 27 (2000); Phys. Rev. Lett. 86, 3316 (2001)].

Journal Article↗
PubMed2003

[Mechanisms and prevention of windsurfing injuries].

Aim of this study was to analyse the mechanisms of windsurfing injuries. For this purpose we performed a internet based survey among 327 windsurfers in Germany. Overall 630 accidents have been registered among all 327 athletes during the 2000 season. The majority of injuries were classified as minor injury. The most common injury was the bruise. 70 participants reported fractures, 26 participants ruptured a ligament. 280 injuries required medical treatment; in 67 cases even surgical treatment was necessary. The majority of accidents happened at wind power of 5-6 Beaufort after 2 hour exercise. A technical mistake was the most frequent cause for the accident. The most dangerous manoeuvres were difficult jumps (e. g. front loop, backward loop, 70 injuries). In 46 cases the weather conditions were underestimated. Only 10 windsurfers reported about broken material as cause for the injury. One half of the injuries happened in wave conditions. The analysis of injury mechanisms allows conclusions regarding injury prevention. A longer break after 60 minutes windsurfing might help to prevent injuries due to poor physical fitness. After one hour windsurfing without a break training of difficult manoeuvres should not be performed. The use of a helmet might prevent head injuries during training of difficult jumps. "Overpower situations" should be prevented by choosing the right board and sail size.

Adult↗
PubMed2002

Elevated plasma levels of vascular endothelial growth factor and plasminogen activator inhibitor-1 decrease during improvement of psoriasis.

OBJECTIVE AND DESIGN: An evaluation of angiogenesis related molecules during open treatment of psoriasis. MATERIALS AND SUBJECTS: Plasma samples and skin biopsies from 16 patients with psoriasis and plasma samples from 13 healthy controls. TREATMENT: Ranitidine 300 mg orally twice daily for 6 months. METHODS: Vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) were determined by ELISA methods in plasma collected from the patients before treatment and after 1, 3 and 6 months. Vessel counts were performed in biopsies from affected skin areas taken before treatment and after 3 and 6 months. The results were compared to simultaneous PASI scores. RESULTS: Pre-treatment plasma levels of VEGF and PAI-1 were significantly elevated in patients compared with levels in healthy persons (p = 0.02 and p = 0.04, respectively). The plasma levels decreased significantly during treatment (p = 0.03 and p = 0.01, respectively), and the decrease in combined levels correlated with the decrease in PASI score. However, the vessel density in affected skin did not change during treatment. CONCLUSIONS: Increased pre-treatment levels of VEGF and PAI-1 and decrease during improvement of the disease suggest that the two molecules may play a role in pathogenesis of psoriasis.

Adult↗
PubMed2002

[Mechanisms and prevention of kitesurfing injuries].

Aim of this study was to analyse the mechanisms of kitesurfing injuries. For this purpose we performed a survey among 72 kitesurfers in the north of Germany. 31 accidents have been registrated among all 72 athletes during the 2001 season. 3 additional accidents occurred where a windsurfer got injured. 5 athletes had medium injuries such as fractures, all remaining athletes presented with minor injuries, that did not require medical treatment. The incidence of medium kite injuries was 1/1000 hours; the incidence of minor kite injuries was 5/1000 hours. The most common injury mechanism was a direct trauma against things such as stones and boats lying on the beach. The most common situation in which the injury occurred was the lost of control about the kite on the beach or close to the beach due to technical mistakes of the surfer, oversized kites, or the wind conditions (onshore wind, overpower). Further injuries occurred due to collisions with windsurfers or sailing boats. Kitesurfing is a new rapidly growing sport. To date the risk potential of this new sport is unclear. The analysis of the injury mechanisms allows conclusion regarding the prevention of kitesurfing injuries.

Accident Prevention↗
PubMed2001

Combination of reduced oxygen tension and intermittent hydrostatic pressure: a useful tool in articular cartilage tissue engineering.

Cartilage cells are normally studied under atmospheric pressure conditions and without loading. However, since cartilage exists in a condition of reduced oxygen and intermittent hydrostatic pressure we hypothesized lower partial oxygen pressures (PO2) and different intermittent hydrostatic pressures (IHP) would increase articular chondrocyte proliferation and matrix production and to stabilize chondrocyte phenotype in vitro. Monolayers of adult bovine articular chondrocytes were cultured under 5% or 21% PO2 in combination with IHP (0.2 MPa amplitude, frequencies 5/5s = 0.1 Hz, 30/2 or 2/30 min on/off loading). We measured proliferation (3H-thymidine incorporation) and collagen secretion (protein-binding assay, collagen type II-ELISA and immunocytochemical staining of pericellular collagen types I, II and IX). Reduced PO2 stimulated proliferation and collagen type II and IX secretion of chondrocytes in comparison to 21% PO2. Additionally, collagen type I expression was delayed by low PO2, indicating a stabilization of the cell phenotype. IHP 5/5s and 30/2 min inhibited proliferation but increased collagen secretion (pericellular collagen type IX was decreased). IHP 30/2 min delayed first expression of collagen type I. In contrast, IHP 2/30 min increased proliferation, but lowered collagen expression. All stimulating or inhibiting effects of PO2 and IHP were additive and vice versa. Reduced PO2 and different settings of IHP increased proliferation, collagen secretion, and phenotype stability of chondrocytes. The oxygen- and IHP-induced effects were additive, suggesting that a combination of these parameters might be a useful tool in cartilage tissue engineering.

Animals↗
PubMed2001

Detection of cis-element clusters in higher eukaryotic DNA.

MOTIVATION: Computational prediction and analysis of transcription regulatory regions in DNA sequences has the potential to accelerate greatly our understanding of how cellular processes are controlled. We present a hidden Markov model based method for detecting regulatory regions in DNA sequences, by searching for clusters of cis-elements. RESULTS: When applied to regulatory targets of the transcription factor LSF, this method achieves a sensitivity of 67%, while making one prediction per 33 kb of non-repetitive human genomic sequence. When applied to muscle specific regulatory regions, we obtain a sensitivity and prediction rate that compare favorably with one of the best alternative approaches. Our method, which we call Cister, can be used to predict different varieties of regulatory region by searching for clusters of cis-elements of any type chosen by the user. Cister is simple to use and is available on the web. AVAILABILITY: http://sullivan.bu.edu/~mfrith/cister.shtml. CONTACT: mfrith@bu.edu; zhiping@bu.edu.

Algorithms↗
PubMed2001

Binding of TATA binding protein to a naturally positioned nucleosome is facilitated by histone acetylation.

The TATA sequence of the human, estrogen-responsive pS2 promoter is complexed in vivo with a rotationally and translationally positioned nucleosome (NUC T). Using a chromatin immunoprecipitation assay, we demonstrate that TATA binding protein (TBP) does not detectably interact with this genomic binding site in MCF-7 cells in the absence of transcriptional stimuli. Estrogen stimulation of these cells results in hyperacetylation of both histones H3 and H4 within the pS2 chromatin encompassing NUC T and the TATA sequence. Concurrently, TBP becomes associated with the pS2 promoter region. The relationship between histone hyperacetylation and the binding of TBP was assayed in vitro using an in vivo-assembled nucleosomal array over the pS2 promoter. With chromatin in its basal state, the binding of TBP to the pS2 TATA sequence at the edge of NUC T was severely restricted, consistent with our in vivo data. Acetylation of the core histones facilitated the binding of TBP to this nucleosomal TATA sequence. Therefore, we demonstrate that one specific, functional consequence of induced histone acetylation at a native promoter is the alleviation of nucleosome-mediated repression of the binding of TBP. Our data support a fundamental role for histone acetylation at genomic promoters in transcriptional activation by nuclear receptors and provide a general mechanism for rapid and reversible transcriptional activation from a chromatin template.

Acetylation↗
PubMed2000

Inhibition of the mammalian transcription factor LSF induces S-phase-dependent apoptosis by downregulating thymidylate synthase expression.

The thymidylate synthase (TS) gene, which is induced at the G(1)-S transition in growth-stimulated cells, encodes an enzyme that is essential for DNA replication and cell survival. Here we demonstrate that LSF (LBP-1c, CP2) binds to sites within the TS promoter and intronic regions that are required for this induction. Mutation of the LSF binding sites inhibits G(1)-S induction of mRNA derived from a TS minigene. Furthermore, expression of dominant-negative LSF (LSFdn) prevents the increase in TS enzyme levels during G(1)-S, and induces apoptosis in growth- stimulated mouse and human cell lines. Such apoptosis can be prevented either by circumventing the TS requirement through addition of low concentrations of thymidine, or by coexpression of the TS gene driven by a heterologous promoter. Induction of apoptosis by LSFdn parallels the process known as thymineless death, which is induced by the TS inhibitor and chemotherapeutic drug 5-fluorodeoxyuridine. Thus, LSF is a novel regulatory factor that supports progression through S-phase by targeting a single gene that is critical for cell survival.

Amino Acid Sequence↗
PubMed2000

The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1.

Enigmatic mechanisms restore the resting state in activated lymphocytes following human immunodeficiency virus type 1 (HIV-1) infection, rarely allowing persistent nonproductive infection. We detail a mechanism whereby cellular factors could establish virological latency. The transcription factors YY1 and LSF cooperate in repression of transcription from the HIV-1 long terminal repeat (LTR). LSF recruits YY1 to the LTR via the zinc fingers of YY1. The first two zinc fingers were observed to be sufficient for this interaction in vitro. A mutant of LSF incapable of binding DNA blocked repression. Like other transcriptional repressors, YY1 can function via recruitment of histone deacetylase (HDAC). We find that HDAC1 copurifies with the LTR-binding YY1-LSF repressor complex, the domain of YY1 that interacts with HDAC1 is required to repress the HIV-1 promoter, expression of HDAC1 augments repression of the LTR by YY1, and the deacetylase inhibitor trichostatin A blocks repression mediated by YY1. This novel link between HDAC recruitment and inhibition of HIV-1 expression by YY1 and LSF, in the natural context of a viral promoter integrated into chromosomal DNA, is the first demonstration of a molecular mechanism of repression of HIV-1. YY1 and LSF may establish transcriptional and virological latency of HIV, a state that has recently been recognized in vivo and has significant implications for the long-term treatment of AIDS.

DNA, Viral↗
PubMed2000

Comparative localization of cathepsin B protein and activity in colorectal cancer.

Cathepsin B is a lysosomal cysteine proteinase that may participate in cancer progression. We compared localization of its protein and activity during progression of human colorectal cancer. In adenomas and carcinomas, protein expression and, particularly, activity were elevated compared with those in normal colorectal mucosa. In normal mucosa, cathepsin B protein expression was moderate in stroma and variable in epithelium, whereas activity was mainly present in distinct areas of stroma directly underneath the surface of the colon and in epithelium at the surface of the colon. Stroma in adenomas and carcinomas contained moderate to high protein levels but little activity except for areas of angiogenesis, inflammation, and necrosis, in which activity was high. In adenomas and the majority of well-differentiated carcinomas and moderately differentiated carcinomas, cathepsin B protein and activity were found in granular form in the epithelium, close to the basement membrane. Protein and activity levels were low and diffusely distributed in cancer cells in the remainder of the well-differentiated and moderately differentiated carcinomas and in all poorly differentiated carcinomas. Invasive fronts in most cancers contained moderate protein levels but high activity. We conclude that (a) activity localization is essential to understand the role of cathepsin B in cancer progression, and (b) cathepsin B activity in human colon is associated with invasion of cancer cells, endothelial cells, and inflammatory cells, and in cell death, both apoptotic and necrotic.

Adenomatous Polyps↗
PubMed1999

Prognostic estimation of survival of colorectal cancer patients with the quantitative histochemical assay of G6PDH activity and the multiparameter classification program CLASSIF1.

Prognosis of colorectal cancer patients that show similar histopathology may vary substantially. An attempt was made to improve prognosis by the self-learning classification program CLASSIF1, based on automated multiparameter analysis of quantitative histochemical and clinical parameters of 64 colorectal carcinomas and adjacent normal mucosae. The histochemical parameters applied were the oxygen-insensitivity assay of glucose-6-phosphate dehydrogenase (G6PDH) activity, a valid discriminator between normal and cancerous mucosae, and related parameters CuZn- and Mn-superoxide dismutase (SOD) levels, and lipid peroxidation (LPO) capacity. Data were processed on the basis of a postoperative follow-up of minimally 32 and maximally 56 months. CLASSIF1 selected the parameters oxygen insensitivity of G6PDH activity, CuZn-SOD and Mn-SOD levels, LPO capacity, lymph node metastasis, Dukes' stage, and age for the highest prognostic value. On the basis of these selected parameters, CLASSIF1 correctly predicted favorable outcome in 100% of the surviving patients and fatal outcome in 64% of the deceased patients. G6PDH activity appeared to be the major information carrier for CLASSIF1. On the basis of G6PDH activity parameters alone, 96% of the surviving patients and 55% of the deceased patients were correctly classified. In comparison, estimation of prognosis on the basis of Dukes' stage alone resulted in 71% correctly classified surviving patients and 61% of patients who died. It is concluded that the self-learning classification program CLASSIF1, on the basis of quantitative histochemical and clinical parameters, is the best prognostic estimator for colon cancer patients yet available.

Adult↗
PubMed1999

Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue.

Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours, but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification. In the present study, the prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed. Intra-operative tumour tissue samples from 584 patients undergoing elective surgery for colorectal cancer were included. None of the patients received pre- or post-operative adjuvant chemotherapy. Tissue blocks were cut from the periphery of the tumours and embedded in paraffin. All blocks included both tumour tissue and normal bowel tissue. Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used to dichotomize the cell counts with respect to survival. The median observation period was 61 (49-75) months. In a multivariate analysis including Dukes' stage, gender, age, peri-operative blood transfusion, tumour location, and counts of specific inflammatory cells, only advanced Dukes' stage ( p< 0.0001), high age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth.

Adult↗
PubMed1999

Influence of fulvic acid on the collagen secretion of bovine chondrocytes in vitro.

High concentrations of fulvic acid and selenium deficiency in drinking water are the main causative factors of Kashin-Beck disease, an endemic degenerative chronic osteoarticular disorder found in China. The influence of fulvic acid on collagen secretion was investigated in articular chondrocyte cultures from bovine interphalangeal joints. Collagen secretion in 7-day-old chondrocyte monolayers was determined by measuring [3H]-proline incorporation into collagen macromolecules after a 24-h application in cultured supernatants. Additionally, collagen secretion was measured with a collagen assay based on a dye-binding method of soluble collagens. Both methods showed a dose-dependent increase of collagen secretion after treatment with fulvic acid. The collagen was identified by immunoblotting and immunocytochemistry as type II collagen. Fulvic acid also induced H2O2 production in cartilage cells. After co-incubation with catalase and fulvic acid, the cells secreted the same amount of H2O2 or collagen as the non-treated controls, indicating an influence of H2O2 on collagen secretion. Chondrocytes were then treated directly with H2O2. This led to increased collagen secretion showing a positive correlation with the concentration of H2O2 up to 1 pM H2O2. Larger amounts of H2O2 decreased collagen secretion. Effects of reactive oxygen species, such as lipid peroxidation or lactate dehydrogenase (LDH) release from damaged cells, were not inducable by fulvic acid (<10 ppm). Our results demonstrate a fulvic-acid-induced stimulation of collagen secretion into the supernatant by articular chondrocytes via physiological amounts of H2O2.

Animals↗
PubMed1998

How powerful is the dwell-time analysis of multichannel records?

Exact algorithms for the kinetic analysis of multichannel patch-clamp records require hours to days for a single record. Thus, it may be reasonable to use a fast but less accurate method for the analysis of all data sets and to use the results for a reanalysis of some selected records with more sophisticated approaches. For the first run, the tools of single-channel analysis were used for the evaluation of the single-channel rate constants from multichannel dwell-time histograms. This could be achieved by presenting an ensemble of single channels by a "macrochannel" comprising all possible states of the ensemble of channels. Equations for the calculations of the elements of the macrochannel transition matrix and for the steady-state concentrations for individual states are given. Simulations of multichannel records with 1 to 8 channels with two closed and one open states and with 2 channels with two open and two closed states were done in order to investigate under which conditions the one-dimensional dwell-time analysis itself already provides reliable results. Distributions of the evaluated single-channel rate constants show that a bias of the estimations of the single-channel rate constants of 10 to 20% has to be accepted. The comparison of simulations with signal-to-noise ratios of SNR = 1 or SNR = 25 demonstrates that the major problem is not the convergence of the fitting routine, but failures of the level detector algorithm which creates the dwell-times distributions from noisy time series. The macrochannel presentation allows the incorporation of constraints like channel interaction. The evaluation of simulated 4-channel records in which the rate-constant of opening increased by 20% per already open channel could reveal the interaction factor.

Algorithms↗
PubMed1998

LSF and NTF-1 share a conserved DNA recognition motif yet require different oligomerization states to form a stable protein-DNA complex.

The mammalian transcription factor LSF (also known as CP2 and LBP-1c) binds as a homo-oligomer to directly repeated elements in viral and cellular promoters. LSF and the Drosophila transcription factor NTF-1 (also known as Elf-1 and Grainyhead) share a similar DNA binding region, which is unlike any established DNA binding motifs. However, we demonstrate that dimeric NTF-1 can bind an LSF half-site, whereas LSF cannot. To characterize further the DNA binding and oligomerization characteristics of LSF, truncation mutants were used to demonstrate that between 234 and 320 amino acids of LSF are required for high affinity DNA binding. Mixing of a truncation mutant with full-length LSF in a DNA binding assay established that the form of LSF that binds DNA is larger than a dimer. Unexpectedly, one C-terminal deletion derivative, partially defective in oligomerization properties, could occupy odd numbers of adjacent, tandem LSF half-sites, unlike full-length LSF. The numbers of DNA-protein complexes formed on multiple half-sites with this mutant indicated that LSF binds DNA as a tetramer, although cross-linking experiments confirmed a previous report concluding that LSF is primarily dimeric in solution. The DNA binding and oligomerization properties of LSF support models depicting novel mechanisms to prevent continual, adjacent binding by a protein that recognizes directly repeated DNA sequences.

Animals↗
PubMed1998

Studies on mast cells and histamine release in psoriasis: the effect of ranitidine.

The purpose of this study was to investigate histamine and skin mast cells in psoriasis before and during 6 months of treatment with high-dose ranitidine. Sixteen psoriasis patients, presenting a mean PASI score of 15.4, were compared with 13 age- and sex-matched healthy controls. Resting extracellular skin levels of histamine and histamine release to mast cell secretagogues, as measured by the microdialysis technique, were increased in involved psoriasis skin compared to normal skin in the controls. Plasma histamine, but not basophil histamine release, was significantly increased in the patients. Mast cells and lymphocytes were significantly increased in numbers in involved versus non-involved skin in the patients, the lymphocytes being predominantly T-lymphocytes expressing HLA-DR activation. During 6 months of ranitidine treatment, mean PASI score of 15.4 decreased to 5.8. The lymphocyte infiltration, but not mast cell numbers, was significantly reduced during treatment, and histamine release to mast cell secretagogues was normalized. These observations suggest that skin mast cells in active psoriasis are functionally hyperreactive. The biochemical findings together with the clinical effect of ranitidine indicate that histamine may be involved in the pathophysiology of psoriasis.

CD4-CD8 Ratio↗
PubMed1997

Nucleosome positioning and transcription-associated chromatin alterations on the human estrogen-responsive pS2 promoter.

The positioning of nucleosomes on a promoter is a significant determinant in its responsiveness to inducing signals. We have mapped the chromatin structure of the human, estrogen-responsive pS2 promoter at nucleotide level resolution within the context of its normal genomic location in human mammary epithelial cells. In vivo digestion by nucleases followed by ligation-mediated polymerase chain reaction analysis revealed two rotationally phased and translationally positioned nucleosomes within the promoter between nucleotide positions -450 and +7. The estrogen response elements at -400 and TATAA box at -35 are each located at the edge of a nucleosome. The two precisely positioned nucleosomes exist in both transformed and nontransformed human mammary epithelial cells, regardless of estrogen receptor status or transcriptional activity of the gene. However, two structural alterations correlate with the transcriptional potential of the promoter. In MCF-7 cells, in which the pS2 promoter is inducible, the chromatin exhibits an increased sensitivity to DNase I in a region of DNA adjacent to the TATAA box and an additional micrococcal nuclease-hypersensitive site in the linker DNA between the two positioned nucleosomes. We were also able to demonstrate that nucleotides -1100 to +10 of the pS2 promoter are sufficient to determine the positioning of these two nucleosomes. Our results establish the structural features of the chromatin covering the pS2 promoter as well as transcriptionally associated alterations, suggesting how the nucleosomal template influences transcriptional regulation by estrogen receptor.

Animals↗