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M Hansen

Publications and source records attributed to M Hansen.

At least 73 records · Page 4Linked to original sources
PubMed2000

Profiling the immune responses in patient sera with peptide and cDNA display libraries.

Peptide and cDNA phage display libraries can be used to determine the specificities of antibodies present in the whole sera of patients where information about the parental antigens is unknown. In this respect, patient serum antibody binding ligands have been identified. Such ligands would facilitate the design of diagnostic assays and therapeutic vaccines. In the case of cancer, this novel technology is expected to improve our understanding of the immune responses against tumour cells and to discriminate between autoantigen and true tumour specific antigens. Here, we review work on how peptide and cDNA phage display libraries can be used to address the specificity of the immune responses in patients with autoimmune diseases and cancer.

Animals↗
PubMed2000

Resistance of senescent keratinocytes to UV-induced apoptosis.

Irradiation with ultraviolet (UV) triggers programmed cell death (apoptosis) in keratinocytes. This process is believed to protect against skin carcinogenesis since the cells with damaged DNA are selectively removed, limiting the likelihood of the development of a malignant keratinocyte clone. The p53 protein is able to detect mutation-bearing DNA fragments and is thus indispensable for the UV-induced apoptosis in the epidermis. Since age is a risk factor for the development of skin tumors we investigated whether ultraviolet induces apoptosis and p53 activation in senescent keratinocytes. Cultured senescent keratinocytes were irradiated with broad-band ultraviolet, apoptosis was assessed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) technique and the p53 activation pattern was determined with Western blotting and immunofluorescent staining with a panel of anti-p53 antibodies recognising different conformational forms of the protein (PAb 122, PAb 240, DO-7). In senescent keratinocytes arrested in the G1 phase of cell cycle, ultraviolet irradiation (100-2000 J/m2) caused accumulation and nuclear translocation of p53. However, in contrast to young cells where UV induces apoptotic cell death in G1, apoptosis was not detected in senescent cells. There were subtle differences in the p53 activation pattern between senescent keratinocytes and known patterns in young keratinocytes and other cell types. In senescent keratinocytes a constitutional nuclear expression of p53 (conformational form recognized by PAb 240) was present and the p53 induction in response to ultraviolet radiation was rapid. Suppression of apoptosis in senescent keratinocytes may be an important mechanism responsible for enhanced skin carcinogenesis in old age.

Antibodies, Monoclonal↗
PubMed2000

Whole small fish as a rich calcium source.

The present rat balance study investigated Ca availability from the whole indigenous small fish species, mola (Amblypharyngodon mola) from Bangladesh and from skimmed milk. Four groups of six young male rats each were fed ad libitum with diets containing either small fish or milk, at 100 or 160 g crude protein/kg diet dry matter. The study was conducted for 28 d and faeces and urine samples were collected in two balance periods: day 8-14 and 22-28. The Ca and N contents of the diets, faeces and urine were analysed. Ca intake, fractional Ca absorption and Ca retention in relation to N retention were measured. Digestibility and protein utilization of the experimental diets, weight gain of the rats, femur bone weight and mineral composition as well as bone alkaline phosphatase activity were also determined. It was concluded from the values of these variables that Ca from small fish with bones was available and appeared to be a useful Ca source in rats, though perhaps not as available as Ca from milk. This study suggests that small fish with bones may be an important source of Ca in human diets. Promotion of the production and consumption of small fish in population groups with low intakes of milk and milk products should therefore be encouraged.

Absorption↗
PubMed2000

The effect of grape-skin extract on oxidative status.

Epidemiological studies indicate that moderate alcohol consumption, particularly wine, reduce the risk of CHD. The present study was designed to investigate the effect of grape-skin extract on markers of oxidative status. The study was designed as a randomised crossover. A diet with a low content of flavonoids was served with strict control of intake in two consecutive 1-week intervention periods to fifteen subjects (nine women, six men) divided randomly into two groups. During one of the weeks the subjects from either group consumed 200 ml grape-skin extract in water (1 mg extract/ml) at each of three daily meals (31.3 mg total phenolics, including 9.0 mg catechin). An increased activity of glutathione reductase and a borderline increase of glutathione peroxidase activity in erythrocytes were observed after grape-skin intervention, while the intervention had no significant effect on superoxide dismutase or catalase. Likewise, no effect was found on 2-aminoadipic semialdehyde (AAS) residues, a plasma protein oxidation product, or on malondialdehyde in plasma or in LDL, which are markers of lipoprotein oxidation. A marginal effect of grape-skin intervention was observed on plasma ascorbate levels. Intake of the experimental diet significantly reduced plasma vitamin C and plasma AAS in both groups. This effect was most pronounced in the particular week with no grape-skin extract addition. We speculate that grape-skin extract may have a sparing effect on vitamin C. The effects of the experimental diet may be partly ascribed to a low content of several fruit- and vegetable-related antioxidants like flavonoids and vitamin C and a relatively high content of carrot-derived antioxidants, such as carotenes.

2-Aminoadipic Acid↗
PubMed1999

Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying antirheumatic drug (DMARD) therapy alone (11 patients) or DMARDs in combination with oral prednisolone (15 patients), were followed up for 1 year with contrast-enhanced MRI of the dominant wrist (months 0, 3, 6, and 12), conventional radiography (months 0 and 12), and clinical and biochemical examinations. Bone erosion (by MRI and radiography) and synovial membrane volumes (by MRI) were assessed. RESULTS: Significant synovial membrane volume reductions were observed after 3 and 6 months in the DMARD + prednisolone group, and after 6 and 12 months in the DMARD-alone group (P < 0.01-0.02, by Wilcoxon-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P < 0.001), but not with baseline or AUC values of local or global clinical or biochemical parameters, or with prednisolone treatment. In none of 5 wrists with baseline volumes <5 cm3, but in 8 of 10 wrists with baseline volumes > or =10 cm3, erosive progression was found by MRI and/or radiography, indicating a predictive value of synovial membrane volumes. MRI was more sensitive than radiography for the detection of progressive bone destruction (22 versus 12 new bone erosions). CONCLUSION: MRI-determined synovial membrane volumes are closely related to the rate of progressive joint destruction. Quantitative MRI assessment of synovitis may prove valuable as a marker of joint disease activity and a predictor of progressive joint destruction in RA.

Administration, Oral↗
PubMed1999

YKL-40 in giant cells and macrophages from patients with giant cell arteritis.

OBJECTIVE: YKL-40, a mammalian member of the family 18 glycosyl hydrolases, is secreted by activated macrophages at a late stage of differentiation. Macrophages are present in inflammation of the arterial wall and are thought to participate in the pathogenesis of giant cell arteritis (GCA). The aim of this study was to evaluate whether macrophages and giant cells of patients with GCA produce YKL-40, and whether serum YKL-40 concentrations are elevated in these patients. METHODS: Serum YKL-40 was determined by radioimmunoassay in 19 patients with GCA and 8 patients with polymyalgia rheumatica (PMR) who were followed up prospectively during 1 year of treatment with prednisolone. Immunohistochemical staining for YKL-40 was performed in temporal artery biopsy samples that were obtained before treatment. RESULTS: In the arteritic vessels of patients with GCA, positive staining for the YKL-40 antigen was found in CD68+ giant cells and mononuclear cells located in the media. Macrophages located in the adventitia and intima were negative for YKL-40. At the time of diagnosis, patients with GCA had an increased median serum level of YKL-40 (256 microg/liter; P<0.01) compared with healthy age-matched controls (median 118 microg/liter), and the serum level of YKL-40 decreased to normal levels during prednisolone treatment (-38% after 1 month; P<0.001). Most patients with PMR had normal serum YKL-40 levels (median 158 microg/liter) and had no changes in the serum YKL-40 levels during prednisolone treatment. The observed changes in serum YKL-40 did not always parallel the changes in serum C-reactive protein levels and erythrocyte sedimentation rate during the 1-year study period. CONCLUSION: YKL-40 is found in CD68+ giant cells and mononuclear cells in the media of arteritic vessels of patients with GCA, and the concentration of serum YKL-40 may reflect the local activity of these cells in the inflamed artery.

Adipokines↗
PubMed1999

Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach.

In a systematic approach to the study of Saccharomyces cerevisiae genes of unknown function, 150 deletion mutants were constructed (1 double, 149 single mutants) and phenotypically analysed. Twenty percent of all genes examined were essential. The viable deletion mutants were subjected to 20 different test systems, ranging from high throughput to highly specific test systems. Phenotypes were obtained for two-thirds of the mutants tested. During the course of this investigation, mutants for 26 of the genes were described by others. For 18 of these the reported data were in accordance with our results. Surprisingly, for seven genes, additional, unexpected phenotypes were found in our tests. This suggests that the type of analysis presented here provides a more complete description of gene function.

Cell Differentiation↗
PubMed1999

Adaptive restriction rules provide functional and safe stimulation pattern for foot drop correction.

We report on our advances in sensory feedback data processing and control system design for functional electrical stimulation (FES) assisted correction of foot drop. We have applied 2 methods of signal purification on the bin integrated electroneurogram (i.e., optimized low pass filtering and wavelet denoising) before training adaptive logic networks (ALN). ALN generated stimulation control pulses, which correspond to the swing phase of the impaired leg when dorsal flexion of the foot is necessary to provide safe ground clearance. However, the obtained control signal contained sporadic stimulation spikes in the stance phase, which can collapse the subject, and infrequent broken stimulation pulses in the swing phase, which can result in unpredictable consequences. In this study, we have introduced adaptive restriction rules (ARR), which are initially used as previously reported and then dynamically adapted during the use of the system. Our results suggest that ARR provide a safer and more reliable stimulation pattern than fixed restriction rules.

Adult↗
PubMed1999

[Low-field MRI of the knee joint: results of a prospective, arthroscopically controlled study].

PURPOSE: To define the diagnostic accuracy of an open low-field MR unit (Magnetom Open, Siemens, Erlangen) in traumatic knee lesions. MATERIALS AND METHODS: The MRIs of 150 patients were prospectively evaluated by two independent readers with different experience levels. The study protocol included a proton-density weighted SE-sequence in the sagittal, a T2.-weighted Flash-2D-sequence in the coronal, and a 3D-acquisition (DESS) in the axial plane. 75 patients were treated either conservatively or operatively. RESULTS: Based on arthroscopy as the gold standard, the sensitivities, specificities, and diagnostic accuracies for lesions of the medial and lateral meniscus, the anterior cruciate ligament (ACL), the hyaline cartilage, and the posterior cruciate ligament (PCL) were 92%, 92% and 92%, 83%, 93% and 92%, 95%, 96% and 96%, 74%, 93% and 85%, and 100%, respectively, for reader 1. The values for reader 2 were 81%, 74% and 77% (medial meniscus), 61%, 86% and 80% (lateral meniscus), 79%, 95% and 91% (ACL), 48%, 91% and 73% (hyaline cartilage), and 100% each (PCL), respectively. There were no statistical differences between the two readers (Fisher's Exact Test, 95%-confidence interval). CONCLUSIONS: Using a time-consuming examination protocol, the diagnostic accuracies of the open low-field MR unit are well comparable to those obtained with mid- or high-field units. Although not statistically significant in this study, the experience level of the examiner seems to be of considerable clinical relevance.

Adult↗
PubMed1999

Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis.

The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP in the femoral artery blood was significantly higher than in the group of patients with normal liver function (median 145 microg/l, 95% CI 98-195 versus 57 microg/l, 95% CI 42-92, p<0.001). A significant decrease in the concentration of PINP between the femoral artery (median 57 microg/l, 95% CI 42-92) and the hepatic vein (median 45 microg/l, 95% CI 40-70, p<0.001) was found in patients with normal liver function. In this group we also observed a significantly higher concentration of PINP in femoral artery blood (median 60 microg/l, 95% CI 45-87) as compared with that in renal vein (median 50 microg/l, 95% CI 40-65, p<0.001). In contrast, serum-PINP did not differ between arterial and hepatic or venous venous blood in patients with alcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney. It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired/reduced in patients with alcoholic cirrhosis.

Adult↗
PubMed1999

DINAMO: interactive protein alignment and model building.

MOTIVATION: To facilitate the process of structure prediction by both comparative modeling and fold recognition, we describe DINAMO, an interactive protein alignment building and model evaluation tool that dynamically couples a multiple sequence alignment editor to a molecular graphics display. DINAMO allows the user to optimize the alignment and model to satisfy the known heuristics of protein structure by means of a set of analysis tools. The analysis tools return information to both the alignment editor and graphics model in the form of visual cues (color, shape), allowing for rapid evaluation. Several analysis tools may be employed, including residue conservation, residue properties (charge, hydrophobicity, volume), residue environmental preference, and secondary structure propensity. RESULTS: We demonstrate DINAMO by building a model for submission in the 3rd annual Critical Assessment of Techniques for Protein Structure Prediction (CASP3) contest. AVAILABILITY: DINAMO is freely available as a local application or Web-based Java applet at http://tito.ucsc.edu/dinamo

Amino Acid Sequence↗
PubMed1999

Serum YKL-40 concentrations in patients with rheumatoid arthritis: relation to disease activity.

OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA.

Adipokines↗
PubMed1999

Analysis of posterior plagiocephaly: deformational versus synostotic.

Appropriate management of posterior plagiocephaly requires differentiation of occipitoparietal flattening caused by lambdoid synostosis from that caused by deformational forces. In a 2 1/2-year prospective study of 115 infants presenting with unilateral posterior cranial flattening, only one child had synostotic posterior plagiocephaly (lambdoid synostosis), whereas 114 infants had deformational posterior plagiocephaly. Deformational occipitoparietal flattening was more common on the right (61 percent) than on the left (30 percent), and minor contralateral frontal flattening was not unusual (52 percent). The ipsilateral ear was anteriorly displaced in virtually all infants (97 percent). Some infants had ipsilateral torticollis (19 percent); a few had contralateral torticollis (8 percent). Gender ratio was 3:1, male:female. A total of 114 infants with deformational posterior plagiocephaly were treated conservatively either by head positioning in the crib (n = 63) or with a molding helmet (n = 51). Outcome was assessed by pretreatment and posttreatment anthropometry on 53 of these infants, who were either positioned (n = 17) or helmeted (n = 36). Improvement occurred in 52 of 53 patients (mean follow-up 4.6 months), i.e., the difference in length between the long and short transcranial axis diminished in 52 infants (mean 1.2 to 0.7 cm), did not progress in any child, and was unchanged in one infant. At an average age of 10 months, posterior cranial symmetry was better in infants treated with a helmet (mean difference 0.6 cm) than in those managed by positioning (mean difference 1.0 cm) (p < 0.001). Age at initiation of helmet therapy (from 2 to 9 months) was unrelated to rate of improvement. In a 10-year retrospective study, the authors identified 12 infants who had an operation for posterior plagiocephaly. All but one had confirmed premature lambdoid fusion; thus, this condition accounted for 3.4 percent of all primary operations performed for craniosynostosis during this decade (n = 323). In retrospect, the physical findings of synostotic posterior plagiocephaly were not clearly different from those of deformational posterior plagiocephaly. Plain radiography was sometimes used to confirm the clinical diagnosis. Neither sutural narrowing, deep interdigitations, nor perisutural sclerosis indicated lambdoid synostosis. Computed tomography (CT) was necessary if the physical findings were suspicious for lambdoid synostosis or if plain films did not give a definitive diagnosis. Axial CT scans (n = 7) showed a symmetric forehead in all but one patient with lambdoid synostosis. CT studies also demonstrated that auricular position was indeterminate in synostotic posterior plagiocephaly, being anterior, posterior, or symmetric, whereas the ipsilateral ear was virtually always anterior in deformational posterior plagiocephaly.

Craniosynostoses↗
PubMed1999

Continuous assessment of time-varying speech quality.

This paper addresses the question of whether subjects are able to assess the perceived time-varying quality of speech material continuously. A method is introduced which is characterized by a subjective continuous rating of the perceived speech quality by moving a slider along a graphical scale. The usability of this method is illustrated with an experiment in which different sequences of sentences were degraded in quality with a Modulated Noise Reference Unit. The modulation depth was varied with time and the subject's task was to assess the perceived quality. The results indicate that subjects can monitor speech quality variations very accurately with a delay of approximately 1 s. An objective speech quality measure based on an auditory processing model was applied to predict the subjective speech quality results. The speech quality measure qC was modified to allow for time-dependent objective measurement of the speech quality. The averaged subjective response data could be modeled by the scale transformed and low-pass filtered measure qC(t) with a high degree of accuracy.

Adult↗
PubMed1999

Counting and size classification of active soil bacteria by fluorescence in situ hybridization with an rRNA oligonucleotide probe.

A fluorescence in situ hybridization (FISH) technique based on binding of a rhodamine-labelled oligonucleotide probe to 16S rRNA was used to estimate the numbers of ribosome-rich bacteria in soil samples. Such bacteria, which have high cellular rRNA contents, were assumed to be active (and growing) in the soil. Hybridization to an rRNA probe, EUB338, for the domain Bacteria was performed with a soil slurry, and this was followed by collection of the bacteria by membrane filtration (pore size, 0.2 micrometer). A nonsense probe, NONEUB338 (which has a nucleotide sequence complementary to the nucleotide sequence of probe EUB338), was used as a control for nonspecific staining. Counting and size classification into groups of small, medium, and large bacteria were performed by fluorescence microscopy. To compensate for a difference in the relative staining intensities of the probes and for binding by the rhodamine part of the probe, control experiments in which excess unlabelled probe was added were performed. This resulted in lower counts with EUB338 but not with NONEUB338, indicating that nonspecific staining was due to binding of rhodamine to the bacteria. A value of 4.8 x 10(8) active bacteria per g of dry soil was obtained for bulk soil incubated for 2 days with 0.3% glucose. In comparison, a value of 3.8 x 10(8) active bacteria per g of dry soil was obtained for soil which had been air dried and subsequently rewetted. In both soils, the majority (68 to 77%) of actively growing bacteria were members of the smallest size class (cell width, 0.25 to 0.5 micrometer), but the active (and growing) bacteria still represented only approximately 5% of the total bacterial population determined by DAPI (4', 6-diamidino-2-phenylindole) staining. The FISH technique in which slurry hybridization is used holds great promise for use with phylogenetic probes and for automatic counting of soil bacteria.

Bacteria↗
PubMed1999

A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects.

OBJECTIVES: To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. METHODS: One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. RESULTS: The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm. CONCLUSIONS: This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the other hand the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses.

Adult↗
PubMed1999

Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism.

BACKGROUND: The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. AIMS: To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. METHODS: In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. RESULTS: Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. CONCLUSIONS: ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.

Adult↗