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Biomedical subjects

P Nielsen

Publications and source records attributed to P Nielsen.

At least 37 records · Page 2Linked to original sources

Serum ferritin iron in iron overload and liver damage: correlation to body iron stores and diagnostic relevance.

The iron content of serum ferritin has been determined in groups of patients with normal or increased iron stores by using a technique of ferritin immunoprecipitation followed by iron quantitation with atomic absorption spectroscopy. The results were correlated to individual liver iron concentrations, measured non-invasively by superconducting quantum interference device (SQUID) biomagnetometry. A close correlation between serum concentrations of ferritin protein and ferritin iron was found (r = 0.92) in all groups of patients. However, the correlation between ferritin iron concentration and individual liver iron concentration was poor in patients with hemochromatosis (r = 0.63) and patients with beta-thalassemia major (r = 0.57). The degree of ferritin iron saturation was about 5% in iron-loaded patients, which contrasts with results in two recent studies but confirms older observations. In patients with liver cell damage, the ferritin iron saturation in serum was significantly higher than that found in groups with iron overload disease, probably indicating the release of intracellular iron-rich ferritin into the blood. The monitoring of patients undergoing bone marrow transplantation indicated that the release of iron-rich and iron-poor ferritin occurred during phases of hepatocellular damage and inflammation, respectively. We find the benefits of serum ferritin iron measurement to be marginal in patients with iron overload disease.

Adult↗

Surgical outcome in malignant parotid tumours.

Of 494 parotid gland tumours treated in Copenhagen county (population 600,000 inhabitants) in the period 1986-95, 50 patients (34 males, 16 females) had tumours that were proven to be malignant, making an incidence of 0.62/100,000/year. The patients age ranged from 14 to 87 years, mean 64 years. According to the UICC classification system, 6 tumours (12%) were classified as stage I, 23 (46%) as stage II, 14 (28%) as stage III, and 7 (14%) as stage IV. The material included 41 primary parotid gland tumours, histologically the tumours were verified as mucoepidermoid carcinoma (n = 13), adenocarcinoma (n = 9), squamous cell carcinoma (n = 6), carcinoma ex pleomorph adenoma (n = 3), acinic cell carcinoma (n = 3), adenoid cystic carcinoma (n = 3) and other histological diagnoses (n = 4). Primary malignant lymphoma of the parotid gland was diagnosed in six tumours and the last three tumours were metastatic carcinoma. Four therapeutic modalities were applied: surgery only, surgery + radiation, surgery + chemotherapy, and surgery + chemotherapy + radiation. Surgical radicality was achieved in 76% and radicality was unrelated to tumour histology. Normal or nearly normal facial nerve function (HB1&2) was noted at last follow-up in 60%. Five-year crude survival for all patients was 68%. Survival was not dependent on N-classification. Patients in stage I had a better survival than did patients in stages II, III and IV. No significant difference was observed in 5-year crude survival or in the post-operative facial nerve function between the radically operated patients (n = 38) and patients with residual tumour (p = 0.27, Log-rank test), (p = 0.48, chi 2 test).

Adolescent↗

The solution structure of a DNA duplex containing a single 1-(2-O,3-C-ethylene-beta-D-arabinofuranosyl)thymidine nucleoside.

The structure of a DNA duplex containing one 1-(2-O,3-C-ethylene-beta-D-arabinofuranosyl)-thymidine nucleoside (T5) modification was investigated by use of two-dimensional 1H NMR spectroscopy at 750 MHz. The structure of the d(CCGCT5AGCG):d(CGCTAGCGG) duplex (CT5AG) containing one of this 2'-O,3'-C-linked bicycloarabino conformational restricted modification has been determined. We obtained inter-proton distance bounds from NOESY spectra by including a complete relaxation matrix analysis. These distance bounds were used as restraints in molecular dynamics (rMD) calculations. We also analyzed the fine structure of the cross peaks in a selective DQF-COSY spectra to determine the sugar conformations of the nucleotides. Forty final structures were generated for CT5AG from A-form and B-form dsDNA starting structures. The root-mean-square deviation (RMSD) of the coordinates for the forty structures of the complex was 0.92A. The structures were observed to be markedly irregular compared to canonical B-DNA, especially in terms of large variations in propeller twist and buckle. Also, lack of stacking of two bases near the modification site is observed. The sugar conformations of all the unmodified nucleotides are close to pure C2'-endo conformation. The structural feature of CT5AG was discussed in relation to the thermal stability and resistance towards exonucleolytic degradation.

Base Sequence↗

Pseudomonas frederiksbergensis sp. nov., isolated from soil at a coal gasification site.

Phenotypic and genotypic characterization indicated that a group of 29 closely related phenanthrene-degrading bacteria from a coal gasification site in Frederiksberg, Copenhagen, Denmark, belonged to the genus Pseudomonas. The strains were isolated at two sampling occasions 2 years apart. The isolates were phenotypically different from any known species of the genus Pseudomonas and were therefore subject to further identification. Colonies were smooth and pale yellowish and did not produce pigments fluorescent in UV light when grown on King's B agar. Cells were rod-shaped, approximately 0.5-0.8 x 1.5-3.0 microm, and grew at 4 and 30 degrees C, but not 37 degrees C. The bacteria were oxidase- and catalase-positive, accumulated poly-beta-hydroxybutyrate and denitrified, but did not utilize D-xylose. The mean G+C content was 59.6 mol%. Phenotypic data and 16S rDNA sequence data information for Pseudomonas amygdali and Pseudomonas corrugata, and 16S rDNA sequence data for Pseudomonas chlororaphis and Pseudomonas syringae showed close relationships to these strains. However, DNA-DNA hybridization data showed that the isolates belong to a new species, for which the name Pseudomonas frederiksbergensis sp. nov. is proposed. The type strain is JAJ28T (DSM 13022T).

Bacterial Typing Techniques↗

Diversity of Pseudomonas strains isolated with King's B and Gould's S1 agar determined by repetitive extragenic palindromic-polymerase chain reaction, 16S rDNA sequencing and Fourier transform infrared spectroscopy characterisation.

King's B and Gould's S1 agar were compared with regard to the isolation of Pseudomonas from four environmental samples. In all samples, King's B gave the highest number of colony-forming units, and in some environments, there were more fluorescent colony-forming units on King's B as well. However, almost all types grew on Gould's S1, which enabled us to isolate a greater variety of groups than with King's B, fluorescent as well as non-fluorescent members of Pseudomonas. The Pseudomonas isolates were comparatively typed by repetitive extragenic palindromic-polymerase chain reaction and Fourier transform infrared spectroscopy, not previously used for environmental Pseudomonas. The two typing methods were similar in resolution, thus Fourier transform infrared spectroscopy proved fast and reproducible and is a good method for discrimination at subspecies level. Representative strains were identified by partial 16S rDNA sequencing. Thus, we suggest Gould's S1 agar be used for isolation of Pseudomonas because the results are reproducible, specific and give the most diverse recovery and the least work.

Agar↗

Assessment of iron stores in children with transfusion siderosis by biomagnetic liver susceptometry.

To investigate the applicability of noninvasive Superconducting Quantum Interference Device (SQUID) biomagnetic liver susceptometry and its limitations in thalassemic children, 23 patients with beta-thalassemia major and other iron loading anemias (age: 4-16 years) and 16 age-related normal children were studied. Liver iron concentrations ranged from 600 to 11,000 microg/g(liver) for thalassemic patients and from 60 to 340 microg/g(liver) for normal patients. Measuring the respective organ volumes by sonography, liver and spleen iron stores, accounting for 80% of total body iron stores, were estimated. Nonliver contributions from the lung or intestine to the measured SQUID signals in the small-sized patients were not observed. Moreover, livers in thalassemia were found to be enlarged by 18% per 1,000 microg/g (r = 0.75, P < 10(-3)). Serum ferritin values correlate significantly with iron stores (r = 0.64, P < 10(-3)), but predict iron stores only within large error intervals of 4,000 microg/g(liver). Analyzing the experimental data from biomagnetometry and from related transfusion and chelation treatment data within the framework of a two-compartment model, we were able to derive additional information on total body iron elimination and chelation therapy efficacy. The exponential decline of iron stores allows forecast of steady-state conditions of the final iron load for a particular transfusion and chelation therapy regimen.

Adolescent↗

[Ultra-small superparamagnetic iron oxide particles: the signal behavior and relaxation times of the bone marrow after repeated i.v. application in the pig model at 1.5 tesla].

PURPOSE: Evaluation of the influence of an iron-containing MR contrast agent on the signal behaviour and the relaxation time of the bone marrow at 1.5 tesla after repeated doses. ANIMALS AND METHODS: 14 pigs received i.v. on days 1, 9, and 15 ultra-small (core diameter 6-8 nm) superparamagnetic iron oxide particles at doses of 20 (low dose = LD) or 200 mumol/kg body weight (high dose = HD). RESULTS: Following the first administration a dose-independent reduction in the bone-marrow signal intensity in the T2-weighted gradient-echo sequence (FFE) was observed together with a reduction in the T1 and T2 relaxation times. Following the second application there were no further signal-reductions in the HD-group; in contrast, there was a signal reduction in the LD-group, made possible by a signal recovery in the meantime. On the other hand, the relaxation times T1 and T2 were shortened after each administration of contrast medium. CONCLUSION: Nano-SIPS result at both doses in a signal reduction in the bone marrow. Only in the LD-group may repeated examinations with new contrast agent offer diagnostically sufficient images. Relaxometry shows a shortening of T1 as well as T2. This effect could be summed up after repeated doses. Almost no iron remained in the medullary space three weeks after i.v. administration of the contrast agent, which suggests mobilization and metabolization.

Animals↗

Description of Cellulophaga baltica gen. nov., sp. nov. and Cellulophaga fucicola gen. nov., sp. nov. and reclassification of [Cytophaga] lytica to Cellulophaga lytica gen. nov., comb. nov.

Phenotypic data indicate that gliding, yellow/orange-pigmented, agar-digesting bacterial strains were members of the Cytophaga-Flavobacterium-Bacteroides (CFB) group. The strains were isolated from the surface of the marine benthic macroalga Fucus serratus L. and the surrounding seawater at three localities in Danish waters. The bacteria were Gram-negative, flexirubin-negative, aerobic, catalase-positive and oxidase-negative and were psychrophilic and halophilic. All strains utilized D-fructose, L-fucose and alpha-ketobutyric acid and degraded alginic acid, carrageenan, starch and autoclaved yeast cells. Amplification with primers specific for repetitive extragenic palindromic elements by PCR divided the strains of this study into two groups. Both groups showed unique PCR amplification patterns compared to reference strains of the CFB group. Phylogenetic analysis of 16S rDNA sequences showed association of these organisms and [Cytophaga] lytica at the genus level. Hybridization of total chromosomal DNA revealed that the new strains and [Cytophaga] lytica ATCC 23178T were clearly distinct from each other and other previously described species of the CFB group. A new genus is described, Cellulophaga gen. nov. comprising two new species, Cellulophaga baltica gen. nov., sp. nov. (NN015840T = LMG 18535T) and Cellulophaga fucicola gen. nov., sp. nov. (NN015860T = LMG 18536T), as well as the emendation of [Cytophaga] lytica to Cellulophaga lytica gen. nov., comb. nov.

Bacteria↗

Caldicellulosiruptor kristjanssonii sp. nov., a cellulolytic, extremely thermophilic, anaerobic bacterium.

A cellulolytic anaerobic bacterium, strain I77R1BT, was isolated from a biomat sample of an Icelandic, slightly alkaline, hot spring (78 degrees C). Strain I77R1BT was rod-shaped, non-spore-forming, non-motile and stained Gram-negative at all stages of growth. It grew at 45-82 degrees C, with an optimum growth temperature around 78 degrees C. At 70 degrees C, growth occurred at pH 5.8-8.0, with an optimum near pH 7.0. At the optimum temperature and pH, with 2 g cellobiose l-1 as substrate, strain I77R1BT had a generation time of 2 h. During growth on Avicel, strain I77R1BT produced acetate, hydrogen and carbon dioxide as major fermentation products together with small amounts of lactic acid and ethanol. The strain fermented many substrates, including cellulose, xylan, starch and pectin, but did not grow with casein peptone, pyruvate, D-ribose or yeast extract and did not reduce thiosulfate to H2S. The G+C ratio of the cellular DNA was 35 mol%. Comparative 16S rDNA analysis placed strain I77R1BT among species of Caldicellulosiruptor. The closest relative was Caldicellulosiruptor lactoaceticus. Hybridization of total DNA showed 42% hybridization to C. lactoaceticus and 22% hybridization to Caldicellulosiruptor saccharolyticus. A new species, Caldicellulosiruptor kristjanssonii sp. nov. (I77R1BT) is proposed.

Cellulose↗

Cytokine-induced transcription of protein-tyrosine-phosphatases in human astrocytoma cells.

Interleukin-1 (IL-1) and Tumor Necrosis Factor-a (TNFalpha) are potent mediators of inflammatory reactions in the brain. Although much is known about the effects of IL-1 on expression of secretory proteins, few studies have addressed the question of a selective, IL-1-dependent expression of genes involved in neuromodulatory effects of inflammation. Protein-tyrosine-phosphatases (PTP's) have been shown to regulate signal transduction and adhesion processes in the developing nervous system. They are candidates for inflammation-induced neuromodulation. Therefore, we investigated if IL-1 regulates expression of PTP's. We applied a DNA-fingerprinting method based on the PCR-amplification of conserved domains of gene families and observed IL-1-dependent induction of two PTP's, cytoplasmic PTPvarepsilon and receptor-PTPgamma, RPTPgamma, in human U373-MG astrocytoma cells. Using Northern blot analysis, we confirmed this result and also show that in addition to IL-1, TNFalpha but not IL-6 induces the transcription of cytoplasmic PTPvarepsilon and RPTPgamma in human astrocytoma cells. Given the important role for PTP's in neuromodulatory aspects such as axonal guidance and neurite outgrowth, cytokine-induced induction of PTP's may play an important pathenogenic role in the development of chronic inflammatory diseases in the brain.

Astrocytoma↗

Liver iron and fibrosis during long-term treatment with deferiprone in Swiss thalassaemic patients.

Serum ferritin levels, hepatic histology and iron concentration were studied in a 'veteran' group of seven Swiss beta-thalassaemic patients after 93-99 months of treatment with the oral iron chelator deferiprone (L1), and another four patients who had received 54-82 months of L1 therapy. Despite continuous compliance, unexplained resurgence of serum ferritin levels occurred in 4/7 patients of the 'veteran' group after 4-5 years on L1. In three of these a concomitant increase of liver iron was also observed. Hepatic histology revealed significantly higher degrees of fibrosis in 6/11 hepatitis C (HC)-positive patients (fibrosis scores 1-5, mean 3.0) than in the HC-negative group (fibrosis score 0-2, mean 0.8). Two HC-negative patients had no detectable fibrosis after 98 and 93 months on deferiprone. Therefore the hepatic pathology in these patients cannot definitely be attributed as a side-effect of deferiprone. Chronic active hepatitis C and the accumulation of iron are the major causative factors to be considered.

Adolescent↗

Prevalence of the C282Y and H63D mutations in the HFE gene in patients with hereditary haemochromatosis and in control subjects from Northern Germany.

Mutation analysis was performed for two HFE mutations (C282Y, H63D) in unrelated patients with hereditary haemochromatosis (n = 92), family members of patients (n = 34), and unrelated controls (n = 157) from Northern Germany, 87/92 patients (94.6%) revealed the C282Y mutation in homozygous form, five were heterozygous. No H63D mutation was found in 174 chromosomes of patients homozygous for C282Y, whereas four of the heterozygote patients also carried the H63D mutation. Among the control group, 9.6% were heterozygotes for C282Y. 2/157 subjects were homozygous, 37/157 were heterozygous for the H63D mutation, but showed no signs of iron overload.

Adult↗

Bioavailability of spiramycin and lincomycin after oral administration to fed and fasted pigs.

The disposition of spiramycin and lincomycin was measured after intravenous (i.v.) and oral (p.o.) administration to pigs. Twelve healthy pigs (six for each compound) weighing 16-43 kg received a dose of 10 mg/kg intravenously, and 55 mg/kg (spiramycin) or 33 mg/kg (lincomycin) orally in both a fasted and a fed condition in a three-way cross-over design. Spiramycin was detectable in plasma up to 30 h after intravenous and oral administration to both fasted and fed pigs, whereas lincomycin was detected for only 12 h after intravenous administration and up to 15 h after oral administration. The volume of distribution was 5.6 +/- 1.5 and 1.1 +/- 0.2 L/kg body weight for spiramycin and lincomycin, respectively. For both compounds the bioavailability was strongly dependent on the presence of food in the gastrointestinal tract. For spiramycin the bioavailability was determined to be 60% and 24% in fasted and fed pigs, respectively, whereas the corresponding figures for lincomycin were 73% and 41%. The maximum plasma concentration of spiramycin (Cmax) was estimated to be 5 microg/mL in fasted pigs and 1 microg/mL only in fed pigs. It is concluded that an oral dose of 55 mg/kg body weight is not enough to give a therapeutically effective plasma concentration of spiramycin against species of Mycoplasma, Streptococcus, Staphylococcus and Pasteurella multocida. The maximum plasma concentration of lincomycin was estimated to be 8 microg/mL in fasted pigs and 5 microg/mL in fed pigs, but as the minimum inhibitory concentration for lincomycin against Actinobacillus pleuropneumoniae and P. multocida is higher than 32 microg/mL a therapeutically effective plasma concentration could not be obtained following oral administration of the drug. For Mycoplasma the MIC90 is below 1 microg/mL and a therapeutically effective plasma concentration of lincomycin was thus obtained after oral administration to both fed and fasted pigs.

Administration, Oral↗

Iron supplementation in athletes. Current recommendations.

There is still debate in the literature on whether or not endurance athletes tend to have low iron stores. In this article, we propose that endurance athletes really are at risk of becoming iron deficient due to an imbalance between absorption of dietary iron and exercise-induced iron loss. The purpose of this article is to present a critical review of the literature on iron supplementation in sport. The effect of iron deficiency on performance, its diagnosis and suggestions for treatment are also discussed. Studies of the nutritional status of athletes in various disciplines have shown that male, but not female, athletes clearly achieve the recommended dietary intake of iron (10 to 15 mg/day). This reflects the situation in the general population, with menstruating women being the main risk group for mild iron deficiency, even in developed countries. Whereas the benefit of iron supplementation in athletes with iron deficiency anaemia is well established, this is apparently not true for non-anaemic athletes who have exhausted iron stores alone (prelatent iron deficiency); most of the studies in the literature show no significant changes due to supplementation in the physical capacity of athletes with prelatent iron deficiency. However, the treatment protocols used in some of these studies do not meet the general recommendations for the optimal clinical management of iron deficiency, that is, with respect to adequate daily dosage, mode of administration and treatment period. For future studies, we recommend a prolonged treatment period (> or = 3 months) with standardised conditions of administration (use of a pharmaceutical iron preparation with known high bioavailability and a dosage of ferrous (Fe++) iron 100 mg/day, taken on an empty stomach). Currently, decisions regarding iron supplementation are best made on the basis of taking care of individual athletes. We believe that there are sufficient arguments to support controlled iron supplementation in all athletes with low serum ferritin levels. Firstly, the development of iron deficiency is prevented. Secondly, the nonspecific upregulation of intestinal metal ion absorption is reverted to normal, thus limiting the hyperabsorption of potentially toxic lead and cadmium even in individuals with mild iron deficiency.

Adult↗