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Biomedical subjects

H Andersen

Publications and source records attributed to H Andersen.

At least 19 recordsLinked to original sources
PubMed2000

Expression of intracellular IFN-gamma in HSV-1-specific CD8+ T cells identifies distinct responding subpopulations during the primary response to infection.

Cutaneous infection in the footpads of C57BL/6 mice with HSV-1 results in an accumulation of activated (CD44high CD25+) CD8+ T cells within the draining popliteal lymph node (PLN). These studies were undertaken to evaluate the frequency and phenotype of the CD8+ T cell population within the PLN, recognizing the single immunodominant HSV-1 epitope derived from the viral envelope glycoprotein, glycoprotein B (gB), using an intracellular IFN-gamma-staining assay. It revealed that approximately 6% of the CD8+ T cells were specific for the gB epitope. Phenotypic analysis of the IFN-gamma-producing gB-specific CD8+ T cells generated in the PLN during the course of the acute infection expressed the CD44high CD25+ phenotype on days 3-5 postinfection. Surprisingly, IFN-gamma-producing CD8+ T cells expressed the CD44high CD25- phenotype on days 5-8 postinfection, in contrast to expectations for a CD8+ effector T cell. IFN-gamma-producing CD25- CD8+ T cells were detected in the PLN on day 21 postinfection, long after infectious virus had been cleared. Throughout the response, the spleen was found to be the major reservoir of gB-specific CD8+ T cells, even during the peak of the response. In contrast to the gB-specific CD8+ T cell population within the PLN, the entire gB-specific CD8+ T cell population within the spleen was CD25-. Collectively, these results suggest the generation of subpopulations of virus-specific CD8+ T cells, distinguished by the expression of CD25, during the acute phase of the primary response to a localized viral infection.

Animals↗
PubMed2000

Post-exercise facilitation of compound muscle action potentials evoked by transcranial magnetic stimulation in healthy subjects.

Post-exercise facilitation (PEF) of motor evoked potentials (MEPs) was studied by transcranial magnetic stimulation in 15 healthy subjects following standardized and controlled isometric contraction of the biceps brachii muscle. PEF was highly dependent on the time delay (TD) from muscle relaxation to delivery of the magnetic stimulus and only to a minor degree on the duration of the maintained muscular contraction of 2, 4, and 6 s. In addition, PEF was unaffected by the contraction levels of 25%, 50%, and 100% of maximal voluntary contraction (MVC). There was a linear relationship between the log amplitude of the post-exercise MEPs and the TD. The time point at which PEF had vanished was calculated to be 15.2 s. In order to challenge the question whether segmental and/or suprasegmental mechanisms are primarily responsible for PEF, MEPs and H-reflexes were recorded from the soleus muscle following a sustained plantar flexion at the ankle joint in three healthy subjects. PEF of MEPs was present at a TD of 1000 ms following a sustained contraction of 6 s at a level of 50% of MVC. It was accompanied by a pronounced decrease in the soleus H-reflex amplitude at a TD of 1000 ms.

Action Potentials↗
PubMed2000

Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement.

The aims of this study were to investigate myopathy in relation to vitamin D status, and to study the muscular effects of vitamin D treatment on vitamin D-deficient individuals. Further, hypovitaminosis D myopathy was investigated in relation to alkaline phosphatase (ALP), the most commonly used marker for hypovitaminosis D osteopathy. Eight patients with osteomalacia had an isokinetic dynamometer test of all major muscle groups before and after 3 months of vitamin D treatment. The most pronounced improvements in muscle power were seen in the weight-bearing antigravity muscles of the lower limbs. A cross-sectional study was performed among 55 vitamin D-deficient veiled Arab women living in Denmark and 22 Danish controls. An isometric dynamometer model was used for determination of quadriceps muscle power. Both maximal voluntary contraction (MVC) and electrically stimulated values (single twitch, maximal production rate (MPR), and maximal relaxation rate (MRR)) were determined. The women underwent high-dose vitamin D treatment and were retested after 3 and 6 months. Prior to vitamin D treatment all parameters of muscle function in the group of vitamin D-deficient Arab women were significantly reduced compared with Danish controls. MVC: 259.4 +/- 11.0 N (Newton) versus 392.6 +/- 11. 4 N (P < 10(-6)), single twitch: 47.0 +/- 1.8 N versus 74.6 +/- 2.2 N (P < 10(-5)), MPR 8.9 +/- 0.3 N/10 ms versus 14.3 +/- 0.4 N/10 ms (P < 10(-6)), MRR 4.5 +/- 0.2 N/10 ms versus 6.2 +/- 0.2 N/10 ms (P < 10(-6)). Muscle function was affected to a similar degree in women with and without bone involvement (as indicated by elevated ALP). After 3 months of vitamin D treatment all muscle-related parameters improved significantly. After 6 months only MVC was reduced compared with Danish controls (320.7 +/- 14.3 N (P < 0.02)), whereas all other measurements were normalized. Hypovitaminosis D myopathy is a prominent symptom of vitamin D deficiency, and severely impaired muscle function may be present even before biochemical signs of bone disease develop. Full normalization of hypovitaminosis D myopathy demands high-dose vitamin D treatment for 6 months or more. Our findings indicate that serum levels of ALP cannot be used in the screening for hypovitaminosis D myopathy. Assessment of s-25OHD is the only reliable test.

Alkaline Phosphatase↗
PubMed2000

The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder.

OBJECTIVE: To investigate the effect of partial bladder outlet obstruction on detrusor blood flow and oxygen tension (PdetO2) in female pigs. MATERIALS AND METHODS: Detrusor-layer oxygen tension and blood flow were measured using oxygen-sensitive electrode and radiolabelled microsphere techniques in five female Large White pigs with a partial urethral obstruction and in five sham-operated controls. The effects of chronic outlet obstruction on bladder weight, and cholinergic nerve density and distribution, are also described. RESULTS: In the obstructed bladders, blood flow and oxygen tension were, respectively, 54.9% and 74.3% of control values at low bladder volume, and 47.5% and 42.5% at cystometric capacity. Detrusor blood flow declined by 27.8% and 37.5% in the control and obstructed bladders, respectively, as a result of bladder filling, whilst PdetO2 did not decrease in the controls, but fell by 42.7% in the obstructed bladders. Bladder weight increased whilst cholinergic nerve density decreased in the obstructed animals. CONCLUSION: In pigs with chronic bladder outlet obstruction, blood flow and oxygen tension in the detrusor layer were lower than in control animals. In addition, increasing detrusor pressure during filling caused significantly greater decreases in blood flow and oxygen tension in the obstructed than in the control bladders.

Animals↗
PubMed2000

Effect of ischemia and cooling on the response to high frequency stimulation in rat tail nerves.

In normal rat tail nerves the effect of temperature and ischemia on the response to long-term high frequency stimulation (HFS) (143 Hz) was studied. The effect of temperature was studied in two consecutive tests at 14 degrees C and 35 degrees C. Prior to the HFS the peak-to-peak amplitude (PP-amp) of the compound nerve action potential was 139 +/- 20 microV (mean +/- SD) and 127 +/- 37 microV at 35 degrees C and 14 degrees C, respectively (NS). After 15 min of HFS the PP-amp was reduced to 45.3 +/- 20.5% of baseline level at 14 degrees C as compared with 80.8 +/- 10.2% at 35 degrees C (p < 0.001). Applying ischemia to the rat tail, an additional fall of the PP-amp was seen after 15-20 min of HFS at both low (20 Hz) and high (143 Hz) stimulation frequencies. In conclusion, ischemia and cooling result in an impaired ability to transmit high frequency impulses.

Action Potentials↗
PubMed1999

Protease-activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity.

The activation of human platelets by thrombin is mediated primarily by protease-activated receptors (PARs). PAR1 and PAR4 are present on human platelets and are activated by the hexapeptides SFLLRN and GYPGQV, respectively. To further characterize the involvement of PAR1 and PAR4 in platelet activation, the ability of SFLLRN or GYPGQV to generate annexin V binding to newly exposed phospholipids on the platelet surface and generate procoagulant activity has been examined. Exposure of phosphatidylserine and phosphatidylethanolamine on platelets, as determined by an increase in annexin V binding, was strongly stimulated by SFLLRN, thrombin, and collagen, but only to a minor extent by GYPGQV. In a clotting assay initiated with factor VIIa, soluble tissue factor, and calcium, the clotting time in the absence of platelets was >5 min. In the presence of unstimulated platelets, the clotting time was 200 +/- 20 sec. In the presence of platelets activated with SFLLRN or collagen, the clotting time decreased to 100 +/- 10 sec. This shortening of the clotting time is equivalent to about a 5-fold increase in coagulant activity when stimulated platelets are compared with unstimulated platelets and activated platelets are used as a reference. These results indicate that thrombin initiates a very strong response in platelets through PAR1, leading to exposure of anionic phospholipids that support blood clotting. The response mediated by PAR4, however, was limited to platelet aggregation and similar to that triggered in platelets by weaker agonists such as ADP or epinephrine.

Annexin A5↗
PubMed1999

Multivariate statistical analysis of organ weights in toxicity studies.

Toxicity studies with drugs in animals are performed to establish the toxicity profile including the no-toxic-effect-level in the animals. One of the responses used in the search for effects is organ weight. Since organ weight is related to body weight of the animal, the analysis of organ weight has to be adjusted. A traditional analysis of covariance with body weight as covariate is not always appropriate since the body weight itself can be affected by the test compound. Hence, a multivariate analysis of variance is suggested, where the correlation between organ weight and body weight is taken into account in testing an overall treatment effect. Two dimensional plots of the contour curves are used to visualize the treatment effect on organ weight and body weight simultaneously. The test procedure suggested for comparing differences between control and treated groups of animals is: start by testing hypotheses of equality of covariance matrices for the different treatment groups and then, depending on the results from the first test, test equality of the mean vectors.

Algorithms↗
PubMed1999

Single leukapheresis products collected from healthy donors after the administration of granulocyte colony-stimulating factor contain ten-fold higher numbers of long-term reconstituting hematopoietic progenitor cells than conventional bone marrow allografts.

Cytokine-mobilized peripheral blood progenitor cells (PBPCs) have been used successfully for hematopoietic reconstitution following allogeneic transplantation. The ease of harvest, the faster engraftment and the high yield of CD34+ cells have made this source of hematopoietic progenitor cells (HPCs) an attractive alternative to bone marrow (BM). In the present study we compared the engraftment potential of conventional BM allografts and single leukapheresis products (LPs) collected from healthy donors following the administration of granulocyte colony-stimulating factor (G-CSF). For this, lineage-committed and primitive HPCs were assessed by flow cytometry and by colony- and cobblestone area-forming cell (CFC, CAFC) assays. Mean numbers of CD34+ cells in LPs (n = 11) were similar to that of BM grafts (n = 12) (278+/-57 vs 227+/-34 x 10(6) CD34+ cells). The frequencies of CFCs, week 5 CAFCs and week 8 CAFCs were 1.6-, 8.4- and 10.3-fold higher in the CD34+ compartment of mobilized blood than that of marrow, resulting in significantly higher yields of clonogenic HPCs in LPs when compared to BM grafts. We conclude that G-CSF preferentially mobilizes clonogenic progenitors capable of short- and, in particular, longterm reconstitution, and that the engraftment potential of single LPs is superior to that of BM allografts. Hence, the use of PBPCs may be favorable for protocols that include graft manipulations with expected cell loss (eg T cell depletion, CD34+ selection). PBPCs may also be advantageous for gene therapy trials due to their high numbers of potential target cells (eg CAFCs).

Adolescent↗
PubMed1999

Selective loss of progenitor subsets following clinical CD34+ cell enrichment by magnetic field, magnetic beads or chromatography separation.

In this preclinical evaluation we have compared the efficacy of three clinical CD34+enrichment procedures with respect to purity, yield and recovery, as well as risk of selective loss of CD34+ lineage-specific subsets. The three devices work by different principles and have several different manipulation steps: The magnetic field separator uses paramagnetic iron-dextran particles; the magnetic microbead selection is based on the advantage of a large surface area for immobilisation of the monoclonal antibody within a very small volume; the original immunoabsorption technique is based on the use of biotinylated antibody applied to a column of avidin-coated sephadex beads. The results of this evaluation gave a median purity 96% (88-98%), 86% (62-97%), and 49% (18-85%), and median yield of 65% (54-100%), 40% (21-74%), and 30% (8-55%), respectively. Subset analysis recognised a selective loss of CD34+/61+ after enrichment, most likely due to class I-II antibodies used for the enrichment step or, alternatively, nonspecific binding of megakaryocytic progenitors. Tumour cell spiking experiments on a clinical scale documented an expected 2-4 log reduction resulting in a number of potentially malignant cells in the CD34 enriched product. Our data support four major conclusions: First, that magnetic field separation is superior to magnetic beads and chromatography selection, mainly due to the risk of cell loss and insufficient recovery with the two latter methods. Second, that late differentiated progenitors with CD34 class III epitopes present are lost during the enrichment procedures. The third major conclusion is that chromatography selection results in a selective loss of CD34bright cells, which are most likely uncommitted early progenitors. This was an unexpected finding which may be a consequence of an imbalance between the strong forces between biotin-avidin and insufficient physical manipulation for CD34+ cell release. Finally, the data document that CD34 selection alone is an inappropriate way to eliminate tumour cells due to the uncontrolled variables and the inconsistent outcome. The only products which can be expected to be purged free of tumour cells are the ones with very minimal (<10-5) contamination in the starting products, ie products documented tumour free with the most sensitive techniques for quantitation. If this is not the case, the optimal purging strategy may be a two-step procedure including CD34 selection and subsequent depletion of the tumour cells in question.

Antigens, CD34↗
PubMed1999

Circulating clonal cells in multiple myeloma do not express CD34 mRNA, as measured by single-cell and real-time RT-PCR assays.

The peripheral blood (PB) mononuclear cells in patients with multiple myeloma (MM) have been reported to include CD34-expressing cells that are clonally related to the myeloma cells. To determine whether there were elevated levels of CD34 mRNA or whether CD34+ cells in the PB include myeloma-related cells, we developed a quantitative real-time and a competitive CD34 RT-PCR assay working on single flow-sorted cells. Myeloma-specific cells were detected with allele-specific oligonucleotides (ASO) IgH PCR. PBSC products and mononuclear cell fractions in blood from normal donors, untreated and treated myeloma patients were analysed. When measured by flow cytometry, the numbers of CD34+/CD19+ cells were consistently < 0.1% of the mononuclear cells. In addition, no significant difference was found in the levels of CD34 mRNA between normal subjects and untreated MM patients (P = 0.935). In the treated group of MM patients the CD34 mRNA levels were significantly reduced (P = 0.052) because of the stem cell toxicity of melphalan. Further, no cells clonally related to the MM clone were found within the CD34 compartment, defined by a sort-gate that included all cells expressing CD34 mRNA, as no cells outside the used CD34 sort-gate had a detectable level of CD34 mRNA. We conclude that in myeloma patients, the myeloma clone is not found within the CD34 compartment.

Antigens, CD34↗
PubMed1999

Motor function in diabetic neuropathy.

In contrast to sensory and autonomic disturbances motor function has seldomly been studied in diabetic neuropathy. Recently quantitative studies of long-term type 1 diabetic patients have shown that the strength of the ankle and knee extensors and flexors are moderately impaired. The weakness is closely related to the severity of neuropathy. Applying quantitative electromyography the degree of reinnervation is related to the muscle strength in diabetic patients suggesting the reinnervation to be insufficient. Magnetic resonance imaging of the distal part of the leg has revealed substantial muscular atrophy closely related to the degree of muscle weakness. The present findings indicate that diabetic neuropathy often is a mixed sensory-motor neuropathy.

Diabetic Neuropathies↗
PubMed1999

A comparative study of CD34+ cells, CD34+ subsets, colony forming cells and cobblestone area forming cells in cord blood and bone marrow allografts.

Cord blood (CB) has become an alternative source of hematopoietic progenitor cells (HPCs) for allogeneic transplantation. We have developed a new efficient protocol for CB collection. Using this method an average of 17.7 x 10(8) [range (6.8-29.6) x 10(8), n = 13] total nucleated cells (TNCs) were harvested. Based on recent Eurocord data, which have shown safe engraftment using a threshold dose of 0.37 x 10(8) CB TNCs/kg body weight (BW), we calculated that six out of thirteen CB grafts collected by this method were sufficient to engraft adults. The CB derived CD34+ population contained two-fold higher numbers of committed HPCs (CFU-GM, BFU-E) and six-fold higher numbers of pluripotent HPCs [CD34+/CD38- cells, wk 5 and wk 8 cobblestone area forming cells (CAFCs)] than the CD34+ population of BM. Extrapolation revealed that BM grafts providing the threshold dose for allogeneic transplantation of 2 x 10(8) TNCs/kg BW contained nearly 3 times more pluripotent HPCs than CB grafts providing the Eurocord threshold dose. The assessment of CD34+/CD38(-) cell numbers in CB grafts was highly reproducible and correlated well with the in vitro performance of pluripotent HPCs, i.e. numbers of CAFCs. We conclude that CB grafts providing high numbers of TNCs have the potential to engraft adults and that the enumeration of pluripotent HPCs by flow cytometry may be a useful tool to define the ultimate threshold dose for CB transplantation.

ADP-ribosyl Cyclase↗
PubMed1999

Volume of ankle dorsiflexors and plantar flexors determined with stereological techniques.

The validity of the methods used for determination of muscle mass has not been evaluated previously. We determined muscle mass by estimating muscle volume with assumption-free stereological techniques applied to magnetic resonance imaging (MRI) in 18 healthy untrained subjects (6 women, 12 men) aged 41 yr (29-64 yr; median, range). Muscle mass was also estimated by measuring leg circumference and cross-sectional muscle areas (CSA) from MRIs at three predetermined levels. Power [peak torque (PT)] of the ankle dorsiflexors and plantar flexors was estimated by using isokinetic dynamometry. Dorsiflexor volume (r2 = 0.76, P < 5 x 10(-6)) and CSA (r2 = 0.73, P < 5 x 10(-5)) were related to PT, whereas circumference was not (r2 = 0.17, not significant). Correspondingly, a relationship to plantar PT was established for plantar flexor volume (r2 = 0.69, P < 5 x 10(-5)) and CSA (r2 = 0.46, P < 5 x 10(-3)) but not leg circumference (r2 = 0.15, not significant). SDs of the residuals were smaller for the relationship between dorsiflexor PT and volume than between PT and CSA (0.42 vs. 0.45) for plantar flexors (1.5 vs. 2.0). By using the Cavalieri method, six MRI sections and 15 min of point counting are sufficient to obtain a valid estimate of the volume of the muscles of the lower leg.

Adult↗
PubMed1998

Cloning and characterization of human protease-activated receptor 4.

Protease-activated receptors 1-3 (PAR1, PAR2, and PAR3) are members of a unique G protein-coupled receptor family. They are characterized by a tethered peptide ligand at the extracellular amino terminus that is generated by minor proteolysis. A partial cDNA sequence of a fourth member of this family (PAR4) was identified in an expressed sequence tag database, and the full-length cDNA clone has been isolated from a lymphoma Daudi cell cDNA library. The ORF codes for a seven transmembrane domain protein of 385 amino acids with 33% amino acid sequence identity with PAR1, PAR2, and PAR3. A putative protease cleavage site (Arg-47/Gly-48) was identified within the extracellular amino terminus. COS cells transiently transfected with PAR4 resulted in the formation of intracellular inositol triphosphate when treated with either thrombin or trypsin. A PAR4 mutant in which the Arg-47 was replaced with Ala did not respond to thrombin or trypsin. A hexapeptide (GYPGQV) representing the newly exposed tethered ligand from the amino terminus of PAR4 after proteolysis by thrombin activated COS cells transfected with either wild-type or the mutant PAR4. Northern blot showed that PAR4 mRNA was expressed in a number of human tissues, with high levels being present in lung, pancreas, thyroid, testis, and small intestine. By fluorescence in situ hybridization, the human PAR4 gene was mapped to chromosome 19p12.

Amino Acid Sequence↗
PubMed1998

[Frequency of admissions to neonatal care units of 1994 birth cohorts in Funen and Frederiksborg Counties].

The frequency of admission to neonatal intensive care units is higher in Denmark than in the UK. The organization of the paediatric departments varies from county to county in Denmark. To investigate possible differences due to the organization, the records for all hospitalized newborns in a one year period in two counties (FR and FU) were studied. The rate of prematurity was higher in county FU than in FR, but, surprisingly, the admission rate was lowest in county FU. For full term infants the highest admission rate was found in county FR, where more infants were treated with nasal continuous positive airway pressure compared to FU. Short admissions were more common in FR. The on-call paediatrician is a senior doctor in FU, whereas it is a junior doctor in FR, and this could be a possible explanation for the differences between the two counties.

Denmark↗
PubMed1998

Association of muscle strength and electrophysiological measures of reinnervation in diabetic neuropathy.

Motor function was assessed in 34 non-insulin-dependent and 19 insulin-dependent diabetic patients with macroelectromyography and isokinetic dynamometry. Fiber density (FD) and the amplitude of the macro motor unit potential (macro MUP) of the anterior tibial and lateral vastus muscles were obtained and maximal isokinetic strength of the ankle and knee extensors were determined. All patients underwent standardized clinical examination including a neurological disability score (NDS), quantitative sensory examination, and conventional motor nerve conduction studies. The amplitude of the macro MUP and FD of the anterior tibial muscle were increased in neuropathic patients without weakness (P < 0.05) and further increased in neuropathic patients with weakness (P < 0.05). The NDS was related to the FD and the amplitude of the macro MUP for the anterior tibial and lateral vastus muscle [r=0.55-0.75 (P < 0.005)]. Muscle strength of ankle and knee extensors correlated with the FD [r=-0.69 (P < 0.0001) and r=-0.58 (P< 0.001), respectively] and with the amplitude of the macro MUP of the two muscles [r=-0.63 (P < 0.0001) and r=-0.37 (P < 0.05), respectively]. Our findings support the hypothesis that loss of muscle strength in diabetic patients is due to incomplete reinnervation following axonal loss.

Adult↗
PubMed1998

Association of IgM type anti-GM1 antibodies and muscle strength in chronic acquired demyelinating polyneuropathy.

The pathogenetic role of anti-GM1 in chronic acquired demyelinating polyneuropathy (CADP) is uncertain. An association between antibodies and disease activity has not yet been established. In 8 patients with CADP followed longitudinally, anti-GM1 antibodies were monitored with a standardized enzyme-linked immunosorbent assay technique and muscle performance with isokinetic dynamometry. During a mean observation period of 24 months, strength improved in 6 of 8 patients by a median value of 54.5%, and anti-GM1 fell in all 6 patients; the reduction being 43%. In 2 patients, muscle performance deteriorated by 30 and 8%, whereas anti-GM1 titers increased by 10 and 9%, respectively. The relative change in anti-GM1 was inversely related to muscle performance. Clinical scoring of muscle performance according to the Medical Research Council scale failed to show an association with anti-GM1. It is concluded that anti-GM1 antibodies are closely related to disease activity, and that the close association indicates a role of anti-GM1 in the pathogenesis of CADP.

Adult↗