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Biomedical subjects

B Hansen

Publications and source records attributed to B Hansen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mitogenesis in glioblastoma multiforme cell lines: a role for NGF and its TrkA receptors.

Neurotrophins have definitive roles in the growth/maintenance of neuronal populations, but their function in malignant gliomas is unknown. The ability for nerve growth factor (NGF) to serve as a mitogenic agent was investigated in several human glioblastoma multiforme (GBM) cell lines, including U251, U87, and U373. In a serum-free medium, the addition of NGF (200 ng/ml) to these cell lines increased cell counts over controls, after 3 days in culture by 9%, 16%, and 33%, respectively. Dose-dependent increases in cell counts and [3H]thymidine uptake were found in the more rigorously investigated U373 cell line. Proteins for both the high affinity NGF-specific tyrosine kinase binding site (p140TrkA; TrkA) and the low affinity neurotrophin (p75NTR) receptor were present in all three GBM cell lines. TrkA mRNA was identified in U373 (only cell line studied). NGF-stimulated proliferation was inhibited in a dose-dependent fashion by K252a, a blocker of Trk-induced receptor kinases. NGF, measured by ELISA, was detectable in all GBM cell lines even after 7 days of growth in serum-free medium. These data suggest that GBM cell growth can be enhanced by NGF acting via Trk receptor phosphorylation. Future studies of antiproliferative therapies should consider agents directed against intracellular Trk signaling cascades.

Carbazoles↗
PubMed1999

Incidence of myocardial infarction in the Danish MONICA population 1982-1991.

BACKGROUND: Cardiovascular mortality has been declining in Denmark over the past 20 years. Trends in incidence of myocardial infarction (MI) over the period 1982-1991 are described within the framework of the World Health Organization MONICA Project. METHODS: The DAN-MONICA heart register included all cases of MI in 25-74-year-old men and women living in 11 municipalities around Glostrup County Hospital evolving over a period of 10 years. They were identified retrospectively based mainly on relevant ICD diagnoses in death certificates and hospital discharge reports. Cases meeting WHO-MONICA criteria for definite or possible MI, recurrent as well as first-ever MI, were registered. Subsequent tracing of cases through national registers on deaths and hospitalizations by means of the patient's civil registration number ensured the completeness of the registration. RESULTS: A total of 6025 cases of MI occurred in the period, 4532 among men and 1493 among women. A total of 2923 men and 1047 women had a first-ever MI in the period. The age-standardized rates show a definite decline over the registration period for men and a less distinct decline for women. CONCLUSIONS: The DAN-MONICA heart register meets the requirements for completeness and uniformity throughout the registration period. Causes and magnitude of bias are well described. Even when possible sources of bias are taken into account, the incidence of MI decreased significantly over the 10-year-period 1982-1991 by an average of 5.0% per year for men and 3.5% per year for women.

Adult↗
PubMed1999

Glucose-lowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice, diabetic fatty Zucker rats, and diabetic rhesus monkeys (Macaca mulatta).

Exendin-4 is a 39 amino acid peptide isolated from the salivary secretions of the Gila monster (Heloderma suspectum). It shows 53% sequence similarity to glucagon-like peptide (GLP)-1. Unlike GLP-1, exendin-4 has a prolonged glucose-lowering action in vivo. We compared the potency and duration of glucose-lowering effects of exendin-4 and GLP-1 in hyperglycemic db/db and ob/ob mice. Whereas reductions in plasma glucose of up to 35% vanished within 1 h with most doses of GLP-1, the same doses of exendin-4 resulted in a similar glucose-lowering effect that persisted for >4 h. Exendin-4 was 5,530-fold more potent than GLP-1 in db/db mice (effective doses, 50% [ED50s] of 0.059 microg/kg +/-0.15 log and 329 microg/kg+/-0.22 log, respectively) and was 5,480-fold more potent in ob/ob mice (ED50s of 0.136 microg/kg+/-0.10 log and 744 microg/kg+/-0.21 log, respectively) when the percentage fall in plasma glucose at 1 h was used as the indicator response. Exendin-4 dose-dependently accelerated glucose lowering in diabetic rhesus monkeys by up to 37% with an ED50 of 0.25 microg/kg +/-0.09 log. In two experiments in which diabetic fatty Zucker rats were injected subcutaneously twice daily for 5-6 weeks with doses of exendin-4 up to 100 microg x rat(-1) x day(-1) (approximately 250 microg/kg), HbA1c was reduced relative to saline-injected control rats. Exendin-4 treatment was also associated in each of these experiments with weight loss and improved insulin sensitivity, as demonstrated by increases of up to 32 and 49%, respectively, in the glucose infusion rate (GIR) in the hyperinsulinemic euglycemic clamp. ED50s for weight loss and the increase in clamp GIR were 1.0 microg/kg+/-0.15 log and 2.4 microg/kg+/-0.41 log, respectively. In conclusion, acute and chronic administration of exendin-4 has demonstrated an antidiabetic effect in several animal models of type 2 diabetes.

Animals↗
PubMed1998

Purified truncated recombinant HLA-B7 molecules abrogate cell function in alloreactive cytotoxic T lymphocytes by apoptosis induction.

BACKGROUND: Soluble MHC class I molecules are ubiquitous in human body fluids, including serum, urine, sweat, and cerebrospinal fluid. However, their biological function has remained unresolved. Membrane-derived human soluble MHC molecules (soluble human leukocyte antigen; sHLA) have been shown to induce apoptosis in alloreactive cytotoxic T lymphocytes (CTL). Here we report the efficacy of recombinant soluble HLA-B7 (rsHLA-B7) to modulate T-cell function. METHODS: Primers of HLA-B7 were designed to allow amplification of a cDNA lacking the transmembrane and cytoplasmic domains yielding a truncated gene. rsHLA-B7 molecules were expressed in the human myeloma cell line 721.221 and purified by affinity chromatography using the BB7.7 mouse monoclonal antibody. CTL were generated from peripheral blood lymphocytes derived from healthy blood donors by stimulation with irradiated Epstein Barr virus-transformed HLA-B7-positive B cells. CTL were preincubated with rsHLA-B7, and cytotoxicity and apoptosis were tested according to standard procedure. RESULTS: A total of 2 x 10(6) cells/ml secreted 10 microg/ml rsHLA-B7 as determined by a conformation-dependent ELISA, suggesting that rsHLA-B7 do not require the transmembrane and cytoplasmic regions for proper folding. After purification by affinity chromatography, rsHLA-B7 induced apoptosis in anti-HLA-B7 CTL, but not in anti-HLA-A2-specific, CTL. As a consequence, allorecognition of target cells by the CTL was significantly blocked. CONCLUSION: Recombinant sHLA are sufficient binding cues for T cells, which efficiently induce apoptosis and block allorecognition of target cells by CTL. Thus, recombinant sHLA molecules may become a valuable new modality for specific immunological therapeutic intervention.

Animals↗
PubMed1998

Migrating planets

A planet orbiting in a disk of planetesimals can experience an instability in which it migrates to smaller orbital radii. Resonant interactions between the planet and planetesimals remove angular momentum from the planetesimals, increasing their eccentricities. Subsequently, the planetesimals either collide with or are ejected by the planet, reducing the semimajor axis of the planet. If the surface density of the planetesimals exceeds a critical value, corresponding to approximately 0.03 solar mass of gas inside the orbit of Jupiter, the planet will migrate inward a large distance. This instability may explain the presence of Jupiter-mass objects in small orbits around nearby stars.

Journal Article↗
PubMed1998

The structural basis of MHC control of collagen-induced arthritis; binding of the immunodominant type II collagen 256-270 glycopeptide to H-2Aq and H-2Ap molecules.

The Aq major histocompatibility complex (MHC) class II molecule is associated with susceptibility to murine collagen-induced arthritis (CIA), whereas the closely related H-2Ap molecule is not. To understand the molecular basis for this difference, we have analyzed the ability of H-2Aq and H-2Ap molecules (referred to as Aq and Ap) to bind and present collagen type II (CII)-derived glycosylated and non-glycosylated peptides. T cell clones specific for the immunodominant CII 256-270 peptide and restricted to both Aq and Ap molecules were identified. When these clones were incubated with CII protein and either Aq- or Ap-expressing antigen-presenting cells (APC), only Aq-expressing APC were able to induce stimulation. With the use of A(beta) transgenic mice this could be shown to be solely dependent on the MHC class II molecule itself and to be independent of other MHC- or non-MHC genes. Peptide binding studies were performed using affinity-purified MHC class II molecules. The CII 256-270 peptide bound with lower affinity to the Ap molecule than to the Aq molecule. Using a set of alanine-substituted CII 256-270 peptides, MHC class II and T cell receptor (TCR) contacts were identified. Mainly the side chains of isoleucine 260 and phenylalanine 263 were used for binding both the Aq and Ap molecule, i.e. the peptide was orientated similarly in the binding clefts. The major TCR contact amino acids were lysine 264, which can be posttranslationally modified, and glutamic acid 266, which is the only amino acid in the heterologous peptide which differs from the mouse sequence. Glycosylation at positions 264 and 270 of the CII 256-270 peptide did not change the anchor positions used for binding to the Aq or Ap molecules. The autologous form of the peptide (with aspartic acid at position 266) bound with lower affinity to the Aq molecule as compared with the heterologous peptide. The variable affinity displayed by the immunodominant CII 256-270 peptide for different MHC class II molecules, the identification of MHC and TCR contacts and the significance of glycosylation of these have important implications for the understanding of the molecular basis for inherited MHC class II-associated susceptibility to CIA and in turn, for development of novel treatment strategies in this disease.

Amino Acid Sequence↗
PubMed1998

Long-term graft survival after liver transplantation in the UW era: late effects of cold ischemia and primary dysfunction. European Multicentre Study Group.

The use of University of Wisconsin (UW) solution in liver transplantation (LTX) has significantly prolonged preservation times and facilitated semielective transplant procedures. Despite this advantage potential risk factors related to the donor, recipient, or cold storage method will persist in the UW era and detrimental effects will be reflected by primary dysfunction (PDF) after LTX. Concern has been voiced about the maximum period of UW preservation in LTX and various cold ischemia times (CIT) are mentioned. To evaluate the effect of UW solution in LTX, a prospective European multicenter study was initiated in 1988 and short-term results have been reported previously. This report focuses on the long-term effects and survival of prolonged preservation with UW solution and primary function after LTX. Three hundred and fifteen LTXs were performed in 288 patients in participating European centers. Complete follow up of at least 6 years was available for 296 grafts in 277 patients. Effects of donor, preservation, and recipient risk factors on PDF including primary non-function (PNF) and initial poor function (IPF) were evaluated. Next, the effect of risk factors on graft survival (GS) was analyzed including the long-term impact of PNF and IPF using multivariate analyses and the Kaplan-Meyer method. PDF occurred in 15.2% (45/296) with PNF in 7.8% and IPF in 7.4%. Patients with IPF had a 34% lower GS at 3 months those with immediate function (IF; 58% vs 91%; P < 0.001). This difference persisted up to 6 years for patients with IPF with a 39% GS vs 72% after IF (P < 0.001). Median CIT was significantly longer in grafts with PNF compared to IPF or IF (P = 0.03). Long-term GS, however, was significantly influenced at a lower CIT threshold with a 6-year GS for CIT < or = 16 h of 67%, compared to a CIT > 16 h of 51% (P = 0.02). Other independent risk factors for the 6-year survival rate were re-LTX, ABO incompatibility, and recipient diagnosis of acute hepatic failure. In conclusion, liver patients with PNF, but not with IPF, have a significantly lower CIT. IPF is associated with a significantly lower 3 month GS compared to IF, but this difference of 34% does not further increase during a 6-year follow up. Although a short term follow up (3 months) shows that with UW solution CIT up to 18 h has no adverse effect on GS, the 6-year data clearyl suggest that CIT should be kept to less than < 16 h to avoid tetrimental effects on lang-term GS after LTX.

Adenosine↗
PubMed1998

Trends in treatment and long-term survival of thyroid cancer in southeastern Netherlands, 1960-1992.

Thyroid cancer (TC), comprising less than 1% of all cancers in the Netherlands, has a good prognosis in general. Controversy still remains on the extent of surgical treatment and the indication for additional Iodine-131 (131I) therapy in the management of differentiated TC. The aim of this study was to describe (changes in) the treatment of TC and to determine independent prognostic factors for crude and relative survival of differentiated TC diagnosed in general hospitals. This population-based, retrospective study was based on data from the Eindhoven Cancer Registry, Comprehensive Cancer Centre South (I.K.Z.), Eindhoven, the Netherlands. Data were collected on all 343 TC patients diagnosed from 1 January 1960 to 31 December 1992. All available information on treatment (initial and additional) and survival (on 1 April 1994) were recorded. Initial surgical treatment was defined as limited or extended. Multivariate analysis of crude and relative survival to determine prognostic factors for differentiated TC was performed. Mean follow-up was 7.6 years. The proportion of patients with differentiated TC increased from 60% in 1960-1972 to 84% in 1985-1992. TC patients were treated in all hospitals in the region, approximately 2-4/year. Ninety per cent of all TC patients initially underwent surgical treatment; the extended procedures increasing from 27% in 1960-1974 to 61% in 1985-1992. 131I was also administered increasingly (from 18-44%) to patients with differentiated TC. The relative 5, 10 and 20 year survival rates for all TC were 80, 75 and 75%, respectively. In the first 5 years after diagnosis the crude death ratio was higher with the rise of age and for the follicular type and after 5 years for males and advanced disease. After inclusion of surgical treatment into the model, the estimates of the other death ratios did not change. Patients treated with 131I did better only during the first 5 years. Although the prognosis for TC patients treated in general hospitals in Southeastern Netherlands was similar to that found for patients treated in referral centres, concentration of treatment should be considered.

Adult↗
PubMed1998

Isolation of a toxin B-deficient mutant strain of Clostridium difficile in a case of recurrent C. difficile-associated diarrhea.

Clostridium difficile-associated diarrhea (CDAD) recurs in approximately 15%-20% of patients after discontinuation of metronidazole or vancomycin therapy. Most recurrences are believed to be endogenous relapses due to the persistence of spores. However, there is evidence that reinfection with a different strain is a cause of recurrence. We report the case of a patient with a history of multiple episodes of C. difficile colitis. The patient, a 56-year-old female, has had 5 years of repeated recurrences, each shortly after discontinuing vancomycin therapy. During the course of these episodes, three isolates were cultured from her stools at different times. These isolates were analyzed for the presence of toxin A and B gene sequences and genotyped by means of arbitrarily primed polymerase chain reaction (AP-PCR). The original two isolates contained the toxin A and B genes, as determined by PCR, and were of the same AP-PCR type. During her last relapse, a C. difficile strain lacking at least a portion of the toxin B gene was isolated. AP-PCR analysis of this isolate showed a different DNA banding pattern from that of the previous isolates. A vancomycin susceptibility assay revealed a slight decrease in vancomycin activity as compared with that against the prior isolate. This case demonstrates two unique features: (1) recurrent infections can be due to reinfections and (2) toxin B mutants can possibly cause CDAD. This study also raises concerns about long-term vancomycin use and the development of resistance of C. difficile to vancomycin.

Bacterial Proteins↗
PubMed1998

Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039) MICs and mutations in grlA, grlB, gyrA and gyrB in 116 unrelated clinical isolates of Staphylococcus aureus.

The in-vitro activities of five fluoroquinolones were tested against 70 ciprofloxacin-resistant and 46 ciprofloxacin-susceptible unrelated isolates of Staphylococcus aureus. All 116 S. aureus isolates were studied for the presence of mutations in the grl and gyr loci. The order of efficacy of the fluoroquinolones tested, from least to most active, was: ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039), in response to all characterized mutations in grlA, grlB, gyrA and gyrB. Moxifloxacin was active against most S. aureus isolates tested (MIC90 = 1 mg/L for ciprofloxacin-resistant isolates) and was less influenced by known mutations.

Anti-Infective Agents↗
PubMed1998

Sleep in rheumatoid arthritis: a comparison with healthy subjects and studies of sleep/wake interactions.

Sleep complaints are frequent in patients with rheumatoid arthritis (RA) and sleep disturbances may contribute to pain and other daytime complaints. The aims of the current study were to compare ambulatory sleep recordings from consecutively selected patients with RA to those obtained in healthy controls, and to study the relationships between sleep structure and clinical symptoms. Sleep recordings were obtained from 41 out-patients with RA and 19 matched controls. All had clinical examinations and completed different questionnaires. Recordings were scored traditionally and, moreover, the electroencephalography (EEG) was subjected to frequency analysis. For the study of sleep-wake interactions in the patients, a graphical chain model was used. The patients had many sleep-related complaints. An increase in the number of periodic movements of the legs (PML) during sleep was seen in comparison with controls, but otherwise only minor differences were observed in classical sleep stages. Data from frequency analysis showed an increase in alpha (8-12 Hz)-EEG activity in sleep stages non-rapid eye movement (NREM) 2-4 in most sleep cycles. The statistical model demonstrated a complex but independent correlation between morning stiffness, pain and joint tenderness on the one hand, and awakenings, stage NREM2, slow-wave sleep and stage REM on the other, probably reflecting a relationship between sleep patterns and pain in RA. In conclusion, only the increase in PML and alpha-EEG activity distinguished the sleep in RA patients from that of healthy controls. However, the demonstrated interaction between daytime complaints and sleep patterns may increase the understanding and treatment of the disease. In future research, graphical chain models may improve our understanding of complex relationships between multiple variables.

Adult↗
PubMed1998

Characterization of grlA, grlB, gyrA, and gyrB mutations in 116 unrelated isolates of Staphylococcus aureus and effects of mutations on ciprofloxacin MIC.

One hundred sixteen unrelated clinical isolates of Staphylococcus aureus (70 ciprofloxacin resistant and 46 ciprofloxacin susceptible) from eight countries were studied for the presence of mutations in the grlA, grlB, gyrA, and gyrB gene loci. Two mutations within grlA (located at codons 80 and 84) and two mutations within gyrA (located at codons 84 and 88) were clearly associated with ciprofloxacin resistance, although other mutations detected within the four genes studied may also contribute to decreased susceptibility.

Anti-Infective Agents↗
PubMed1997

[Enuresis nocturna--parents' and therepists' attitudes].

In a questionnaire study concerning voiding habits among seven year-old children starting school the prevalence of enuresis nocturna was 13.4% among girls and 22.2% among boys. For 5.4% of girls and 8.2% of boys the symptom occurred at least once a week. Half of the children had secondary enuresis. Forty-six percent had consulted their doctor about the problem and 44% had received some kind of treatment. Ten percent had tried an alarm bell and 33% had tried desmopressin.

Adult↗
PubMed1997

European Union System for the Evaluation of Substances (EUSES). Principles and structure.

In the European Union, Directive 92/32/EC and EC Council Regulation (EC) 793/93 require the risk assessment of new and existing substances, respectively. Principles for this risk assessment have been laid down, supported by a detailed package of Technical Guidance Documents. Against this background the European Union System for the Evaluation of Substances (EUSES) has been developed. This software can be used to carry out tiered risk assessments of increasing complexity on the basis of increasing data requirements. The exposure assessment, effects assessment and risk characterisation are carried out for environmental populations as well as for human beings, including workers, consumers and man exposed through the environment. EUSES is the result of a co-ordinated effort of EU Member States, the European Commission and the European Chemical Industry.

Animals↗