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Biomedical subjects

B Pedersen

Publications and source records attributed to B Pedersen.

At least 37 records · Page 2Linked to original sources

[Emergency room patients and alcohol consumption].

To investigate the consumption of alcohol among emergency room patients, we included 395 patients above 18 years old entering the emergency room during a period of ten days. The patients completed a questionnaire about alcohol consumption, smoking habits and medication. In our investigation 56% of the men and 25% of the women had a daily consumption above the limits recommended by the Ministry of Health (three drinks daily for men and two for women), while 41% men and 14% women consumed at least five drinks daily or 35 per week. Trauma seen in male patients with high alcohol consumption was characterised by excessive damage to the head, trauma of the lower limb and blows from an object, person or an animal. The alcoholic women were characterised by excessive chemical injuries, incisions and stab wounds, and trauma of the upper limb. In conclusion a surprisingly large amount of emergency room patients can be defined as alcohol abusers and drinking is found to be associated with excessive damage.

Adult↗

New technology for regiospecific covalent coupling of polysaccharide antigens in ELISA for serological detection.

In this study we demonstrate a new UV irradiation technique for covalent coupling of bacterial polysaccharides derived from lipopolysaccharides to microtiter plates and the use of such plates in an enzyme linked immunosorbent assay (ELISA). Lipopolysaccharides were cleaved by mild acid hydrolysis into the lipid A part and the polysaccharide part. The polysaccharide was conjugated regiospecifically to a photochemically active compound, anthraquinone, resulting in a polysaccharide-anthraquinone conjugate. Anthraquinones forms active radicals when exposed to soft UV irradiation (350 nm) permitting the formation of stable covalent bonds to polymers e.g. microtiter plates. By this technique the polysaccharides are bound through the anthraquinone part of the polysaccharide-anthraquinone conjugates to the microtiter plates. This minimizes denaturation of O-antigen epitopes during binding to the microtiter plates and avoids cross-reactivity due to conserved domains in the lipid A. Furthermore, the covalent binding of the polysaccharide antigens are compatible with harsh assay conditions, such as extensive washing procedures and buffers with high salt concentrations with no risk of antigen leakage. Here we describe the use of this technique for the immobilization of lipopolysaccharide derived polysaccharides from Salmonella Typhimurium and Salmonella Choleraesuis lipopolysaccharides, representing the O-antigens 1, 4, 5, 6, 7, and 12. The functional polysaccharide surface gave similar ELISA results to plates coated passively with the corresponding unmodified lipopolysaccharide antigens. The plates were highly reproducible, showed very low inter- and intra-plate variation and were stable at room temperature for more than 8 months.

Animals↗

A quantitative enzyme-linked immunoassay for the detection of 2, 6-dichlorobenzamide (BAM), a degradation product of the herbicide dichlobenil.

2,6-Dichlorobenzamide (BAM) is the dominant degradation product in soil of the widely used herbicide dichlobenil. To detect BAM in water, a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) was developed. As an alternative to conventional coating of ELISA plates, the assay is based on direct covalent immobilisation. We achieved a surface which requires a short time for the immobilisation of ligand, is stable under dry storage, and which permits assays with a low CV. The performance of the assay was demonstrated by an inter-well CV that was generally less than 6%, a detection limit (DL(15)) of 0.02 microg/l and an IC(50) of 0.19 microg/l. Cross-reactivity was measured against nine analytes with structural homology to BAM. The highest degree of cross-reactivity (10.8%) was seen with 2,6-dichlorothiobenzamide (Chlorthiamid). Considering an EU-limit of 0.1 microg/l as the permissible maximum for the presence of pesticides in drinking water, this ELISA-procedure is suitable for large-scale screening of water samples suspected of being contaminated with BAM.

Animals↗

T cell receptor complementarity determining region 3 length analysis reveals the absence of a characteristic public T cell repertoire in neonatal tolerance. The response in the "tolerant" mouse within the residual repertoire is quantitatively similar but qualitatively different.

All adult BALB/c mice immunized with hen egg white lysozyme (HEL) or its dominant determinant, peptide (p)106-116, mount a T cell response using a "public" Vbeta8.2Jbeta1.5 T cell clone. Neonatal exposure to tolerance-inducing doses of antigen can drastically diminish responsiveness in the draining lymph nodes but not in the spleens of animals challenged as adults with the cognate antigen. To determine the role of T cell deletion or anergy within the mechanisms of observed neonatal "tolerance," we treated neonatal BALB/c mice with HEL and directly followed the characteristic public clone using complementarity determining region 3 length T cell repertoire analysis. Our results confirm that despite intraperitoneal injection of neonates with a high dose of HEL emulsified in incomplete Freund's adjuvant, a strong splenic proliferative response to HEL was observed upon recall. However, the adult splenic T cell response of these neonatally treated mice lacked the usual Vbeta8.2Jbeta1.5 public clone characteristic of HEL-primed BALB/c mice. After challenge with HEL-complete Freund's adjuvant as adults, immunoglobulin (Ig)G2a isotype antibody was drastically reduced, and IgG1 was found to be the predominant anti-HEL IgG isotype expressed, indicating a deviation of cytokine response toward T helper type 2. 5-wk-old mice, nasally instilled with tolerogenic doses of HEL p106-116, also showed significant inhibition of this public T cell expansion. These results demonstrate that during neonatal and adult nasal tolerance induction, deletion/anergy removes the public clone, exposing a response of similar specificity but that is characterized by the T helper type 2 phenotype and a splenic residence.

Administration, Intranasal↗

Many unbalanced translocations show duplication of a translocation participant. Clinical and cytogenetic implications in myeloid hematologic malignancies.

If a translocation is followed by loss of one of the two derivative chromosomes, the result is an unbalanced translocation, showing monosomy for the segments making up the lost derivative. We have found that in most unbalanced translocations, a third event takes place: a morphologically normal copy of one of the two translocation participants is added to the karyotype. This creates a complex abnormal karyotype with monosomy, disomy, and trisomy for different segments of the translocation participants. We have examined 82 unbalanced translocations from 77 patients, 73 of whom had a myeloid hemopoietic malignancy. Acquisition of a normal copy of a translocation participant was found in 49 translocations. Twenty-five of these showed trisomy for 1q. In 16 of the 25 1q-trisomic cases the translocation was t(1;7)(q10;p10) (trisomy for 1q and monosomy for 7q). Patients with trisomy for 1q were younger than the remaining patients. Whereas those with t(1;7))(q10;p10) showed brief survivals, those with trisomy 1q but monosomy for regions other than 7q survived longer than the remaining patients. We conclude that most unbalanced translocations involve a partial trisomy, that 1q is trisomic far more frequently than any other segment, and that partial trisomy is associated with patient age and survival.

Acute Disease↗

Risk factors among young women with endometrial cancer: a Danish case-control study.

OBJECTIVE: This study was undertaken to identify and quantify risk factors for endometrial cancer among young women. STUDY DESIGN: This case-control study included all Danish women <50 years old who had endometrial cancer diagnosed during the period 1987 to 1994. A total of 237 case patients and 538 population control subjects matched with the case patients for age and residence were included in the analysis. RESULTS: Women with a family history of endometrial cancer had an odds ratio for endometrial cancer of 2.1 (95% confidence interval, 1.1-3.8)). Completion of 1 term pregnancy implied an odds ratio of 0.6 (95% confidence interval, 0.3-1.1). The risk of endometrial cancer decreased significantly with increasing age at first birth and with the number of induced abortions. Use of oral contraceptives for 1 to 5 years decreased the risk of endometrial cancer (odds ratio, 0.2; 95% confidence interval, 0.1-0.3). The odds ratio for endometrial cancer among women who received hormone replacement therapy for 1 to 5 years was 3.1 (95% confidence interval, 1.4-7.0). Body mass index was not demonstrated to be an independent risk factor in this study. The protective impacts of the different exposures (risk factors) can be expressed as etiologic fractions, which indicate how much each exposure reduces the occurrence of endometrial cancer compared with a situation without the existence of that particular exposure. These fractions were as follows: oral contraceptive use for > or =1 year, -45%; 2 term pregnancies, -88%; age > or =30 y when giving birth for the first time, -38%; and a history of incomplete pregnancy, -16%. CONCLUSION: A number of risk factors for endometrial cancer are common to premenopausal and postmenopausal women: family history, reproductive history, hormone replacement therapy, and the use of oral contraceptives. Among young women reproductive variables imply the greatest prophylactic potential.

Abortion, Induced↗

Identification of acute myeloid leukemia patients with diminished expression of CD13 myeloid transcripts by competitive reverse transcription polymerase chain reaction (RT-PCR).

Normal myeloid cells of monocytic and granulocytic origin express the metallopeptidase cluster of differentiation 13 (CD13) on the surface just as leukemic blasts in most acute myeloid leukemias (AML). A minor percentage of AML patients, however, lack the surface expression of CD13 antigen. To study this difference in CD13 surface expression, specific CD13 mRNA from 44 individuals were quantified by competitive reverse transcription polymerase chain reaction (RT-PCR). Absolute values for CD13 transcripts were normalised against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcript levels to control for variations in sample preparation and mRNA degradation. By correlating normalised CD13 transcript levels and CD13 surface expression, a subgroup of AML patients was identified, having simultaneous diminished levels of myeloid CD13 transcripts and surface expression of the corresponding antigen. For this subgroup we suggest CD13/aminopeptidase N (APN) gene expression to be restricted primarily by limited amounts of transcripts. For the majority of AML patients determinants in addition to transcript levels must be involved in regulating CD13/APN gene expression.

Adult↗

Characterization of three hairy cell leukemia- derived cell lines (ESKOL, JOK-1, and hair-M) by multiplex-FISH, comparative genomic hybridization, FISH, PRINS, and dideoxyPRINS.

Hairy cell leukemia (HCL) is a chronic B-lymphocyte leukemia. Due to the proliferative inertia of the malignant cells, HCL-derived cell lines are an important tool for studies on this disease. We have elaborated the karyotypes of three HCL-derived cell lines, ESKOL, JOK-1, and Hair-M, by combining a range of molecular cytogenetic techniques, including multiplex (multicolor) fluorescence in situ hybridization (M-FISH), comparative genomic hybridization (CGH), conventional FISH, primed in situ labeling (PRINS), and dideoxyPRINS. We found ESKOL to be monoclonal with a single chromosome aberration, der(7)t(3;7)(q26.3;q31). JOK-1 also appeared to be monoclonal, having the karyotype 48,XY,der(4) t(1;4)(1pter-->p32::4qter-->pter), der(6)(6qter-->p22::q12--> qter), +der(7)t(7;11)(7pter-->q21::11p15-->pter),der(8)t(5;8;12) (5pter-->p14::12p11.2-->p12::8q12-->q21::8?cen-->-->24 .?2), der(14)t(8;14)(8qter-->q24.?2::14q32.3-->pter),+20. These karyotypes differ from the original descriptions of ESKOL and JOK-1. The Hair-M cells analyzed by us were found to be peritetraploid with numerous chromosomal rearrangements. The cell line was also found to be multiclonal. On this basis, we do not regard the Hair-M cell line to be suitable for HCL studies.

Aged↗

Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities.

The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg) into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 15, 17, or 21, or into rat pups on postnatal day (P) 10. The principal findings were the following: (1) BrdU exposure on E11 produces profound effects on body morphology, and animals must be fed a special diet because of chronic tooth abnormalities; (2) BrdU exposure at E17 or earlier produces a change in coat spotting pattern, the precise pattern varying with age; (3) BrdU exposure on E15 or earlier produces a reduction in both brain and body weight; (4) BrdU exposure on E17 or earlier reduces cortical thickness; (5) BrdU exposure on E11-E13 and at P10 reduces cerebellar size relative to cerebral size; (6) spatial learning is significantly affected after injections of BrdU at E11-E17, but the largest effect is on E17; (7) the deficit in spatial learning may be related in part to a reduction in visual acuity; and (8) skilled forelimb ability is most disrupted after BrdU exposure at E15 but is also impaired after injections on E13 or earlier. BrdU thus has teratological effects on body, brain, and behavior that vary with the developmental age of the fetus or infant.

Abnormalities, Drug-Induced↗

A single intramuscular injection with an adenovirus-expressing IL-12 protects BALB/c mice against Leishmania major infection, while treatment with an IL-4-expressing vector increases disease susceptibility in B10.D2 mice.

Experimental infection of the susceptible BALB/c (H-2d) mouse with the intracellular parasite Leishmania major induces a predominant Th2-type T cell response that eventually leads to death. In contrast, the resistant B10.D2 (H-2d) strain develops Th1 cells that control parasite replication and disease. In this study, we tested the ability of a recombinant adenovirus vector-expressing IL-12 to skew the immune response in a Th1 direction and prevent leishmaniasis in susceptible mice. We report that BALB/c mice treated with the Ad5IL-12 vector on the same day as parasitic challenge are significantly protected against leishmaniasis and acquired long-lasting immunity, because upon rechallenge with L. major parasites they were resistant to disease. The vector-derived IL-12 expression was transient and highly localized to the tissue after i.m. injection; it caused an increase in the number of Ag-specific IFN-gamma-secreting lymphocytes and enhanced NK cell activity in the draining popliteal node. In contrast, resistant B10.D2 mice given i.m. injections with a recombinant adenovirus-expressing IL-4 displayed greater susceptibility to disease, and severe lesions were produced in some of the infected animals. These results suggest the potential use of recombinant adenoviruses expressing cytokines as potent immunomodulatory agents for the generation of protective immune responses against intracellular pathogens.

Adenoviridae↗

Quantification of intracellular metabolic fluxes from fractional enrichment and 13C-13C coupling constraints on the isotopomer distribution in labeled biomass components.

A method for the quantification of intracellular metabolic flux distributions from steady-state mass balance constraints and from the constraints posed by the measured 13C labeling state of biomass components is presented. Two-dimensional NMR spectroscopy is used to analyze the labeling state of cell protein hydrolysate and cell wall components. No separation of the biomass hydrolysate is required to measure the degree of 13C-13C coupling and the fractional 13C enrichment in various carbon atom positions. A mixture of [1-13C]glucose and uniformly labeled [13C6]glucose is applied to make fractional 13C enrichment data and measurements of the degree of 13C-13C coupling informative with respect to the intracellular flux distribution. Simulation models that calculate the complete isotopomer distribution in biomass components on the basis of isotopomer mapping matrices are used for the estimation of intracellular fluxes by least-squares minimization. The statistical quality of the estimated intracellular flux distributions is assessed by Monte Carlo methods. Principal component analysis is performed on the outcome of the Monte Carlo procedure to identify groups of fluxes that contribute major parts to the total variance in the multiple flux estimations. The methods described are applied to a steady-state culture of a glucoamylase-producing recombinant Aspergillus niger strain.

Aspergillus niger↗

Positron emission tomography of cortical centers of tinnitus.

Tinnitus is associated with a wide variety of disorders in the auditory system. Whether generated peripherally or centrally, tinnitus is believed to be associated with activity in specific cortical regions. The present study tested the hypothesis that these cortical centers subserve the generation, perception and processing of the tinnitus stimulus and that these processes are suppressed by lidocaine and masking. Positron emission tomography was used to map the tinnitus-specific central activity. By subtracting positron emission tomography images of regional cerebral blood flow distribution obtained during suppression of the tinnitus from positron emission tomography images obtained during the habitual tinnitus sensation, we were able to identify brain areas concerned with the cerebral representation of tinnitus. Increased neuronal activity caused by tinnitus occurred predominantly in the right hemisphere with significant foci in the middle frontal and middle temporal gyri, in addition to lateral and mesial posterior sites. The results are consistent with the hypothesis that the sensation of tinnitus is associated with activity in cortical regions functionally linked to subserve attention, emotion and memory. For the first time, the functional anatomy of conditions with and without the habitual tinnitus sensation was obtained and compared in the same subjects.

Adult↗

Salmeterol reduces the need for inhaled corticosteroid in steroid-dependent asthmatics.

Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800-1600 microg day(-1)). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period (P<0.01). A 50% reduction of the MAD was achieved by more patients treated with salmeterol than placebo (P = 0.001). Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed beta2-agoinist therapy between sensitivity and treatment periods compared with placebo (P<0.05 for both). The results demonstrate, that the addition of salmeterol to corticosteroid treatment offers a clinically relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics.

Administration, Inhalation↗

Medical technology assessment photic stimulation--standardization of screening methods.

RATIONALE: In many EEG laboratories in Europe, intermittent photic stimulation (IPS) is not performed routinely, and consequently, great variation exists in the type of photo stimulator used, the methodology employed, and the interpretation of the EEG curves, thus leading to different outcomes. METHODOLOGY: It was decided to hold a consensus meeting with experts in the field of photic stimulation from various European countries. This meeting was held at the Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands. The consensus reached was presented and discussed at the 9th European Congress of Clinical Neurophysiology in Ljubjana in June 1998. RESULTS: Patients should be positioned at a distance of 30 cm from the photic stimulator (nasion to lamp) with dim surrounding lights, just enough to see the patient. Flashes should be delivered in separate trains of 10 s for each frequency, with intervals of 7 s minimum. First stimulation occurs with eyes open followed after 5 s by eye closure, while starting at 1 Hz progressing to 20 Hz, unless generalised epileptiform discharges are evoked at a lower frequency. Then, frequencies should start at 60 Hz decreasing to 25 Hz. The following frequencies should be used: 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 60, 50, 40, 30 and 25 Hz. The total duration is a maximum of 6 min (patients without a reaction to IPS). In interpreting the evoked responses, a clear distinction should be made between epileptiform responses confined to the occipital area (OSW), starting occipitally and spreading to frontal regions (OGSW), or generalised from the start (GSW). Other responses include generalised spikes (OR). CONCLUSION: This standard is safe, relatively quick, simple and reliable. Comparison of data within patients and between patients of various laboratories will also be possible. This will improve the quality of the care of the individual patient and make collaborative research possible.

Electroencephalography↗

Leukaemia cell drug resistance and prognostic factors in AML.

In 93 cases of acute myeloid leukaemia (AML) the extent to which prognostic factors mirrored the in vitro cellular chemotherapy resistance (to anthracyclines aclarubicin (Acla) and daunorubicin (Dau) as well as nucleoside analogue cytarabine (Ara-C)) was investigated using a 4-d MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. We found that age at presentation and presence of secondary AML were significantly correlated to leukaemia cell Ara-C resistance. Thus, analysis of in vitro drug resistance data revealed that age at presentation and presence of secondary leukaemia were both independently correlated to cellular drug resistance, with older age being associated with higher Ara-C resistance in vitro (p=0.02 and 0.01 in univariate and multivariate analyses, respectively) and with secondary leukaemia being associated with higher Ara-C resistance (p=0.04 and 0.059 in univariate and multivariate analysis, respectively). Median LC-50 values (Ara-C) were: 178 ng/ml in paediatric cases, 356 ng/ml in younger adult cases, and 584 ng/ml in elderly (age > or = 60 yr) cases giving a resistance ratio between these age subgroups of 1:2.0:3.3. Median LC-50 values (Ara-C) was 381 ng/ml in de novo cases as opposed to 891 ng/ml (resistance ratio 1:2.3) in secondary cases. By contrast, cytogenetic findings, presenting leucocyte count, FAB-subtype, and gender were not consistently correlated to in vitro drug resistance to any of the three drugs. We conclude that at least two major adverse prognostic factors in AML (advanced age at presentation and presence of secondary leukaemia) are associated with increased leukaemia cell Ara-C resistance. High leucocyte count is not associated with increased cellular drug resistance towards Acla, Ara-C or Dau.

Aclarubicin↗

Habitat-specific genetic effects on growth rate and morphology across pH and water-level gradients within a population of the moss Sphagnum angustifolium (Sphagnaceae).

To study genetic adaptations in bryophytes on small ecological and spatial scales and to assess the adaptive significance of morphological trait variation, genotypes of Sphagnum angustifolium originating from habitats characterized by different pH and height above water table were clonally propagated and grown along the same gradients that exist in the field. Clones from ombrotrophic habitats grew consistently better ombrotrophically than clones from minerotrophic habitats and vice versa, suggesting that the genotypes were adapted to different pH levels. Genetic variation was found in several morphological traits, but habitat-specific genetic effects were detected only in length of spreading branches. Covariation between morphology and growth was generally environmentally induced. Positive and negative cross-environment genetic correlations suggested the presence of constraints on adaptive reaction norm evolution. The indications of small-scale genetic adaptations suggest either selective establishment of genotypes adapted to specific habitats, strong selective forces operating at the later stages of the life cycle, restricted gene flow over short distances, or a combination of these. In contrast to prevailing views, these results indicate that bryophytes are likely to respond genetically to small-scale environmental gradients.

Journal Article↗

[Multidisciplinary diagnostics in acute leukemia].

Establishing the exact diagnosis of patients suspected for acute leukemia is of paramount importance not only for instituting first-line treatment, but also for prognosticating the patient and determining the status of disease, e.g. in relation to minimal residual disease. In this overview the most recent developments regarding the methods for leukaemia diagnosis (cytology, histology, immunology, cytogenetics and molecular biology) are described and their respective merits and drawbacks are discussed. Special emphasis is given to the temporal relationship for application of the methods in the course of disease in these patients.

Bone Marrow Examination↗