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Biomedical subjects

T Andersen

Publications and source records attributed to T Andersen.

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

Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-gamma2 (PPAR-gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men.

AIMS/HYPOTHESIS: The objectives of the present investigation were to examine: 1) whether a Pro115Gln variant in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with juvenile-onset obesity among Danish Caucasianmen and 2) whether the relation of a Pro12Ala polymorphism in PPAR-gamma2 with BMI and long-term weight regulation differ between lean and obese subjects within the same cohort. METHODS: The Pro115Gln and Pro112Ala variants were examined using PCR and RFLP in a group of 752 subjects with a Body Mass Index (BMI) of 31.0 kg/m2 or more and in 869 non-obese control subjects. RESULTS: We did not find Pro115Gln in any of the 1621 male subjects we examined. Among the males with juvenile-onset obesity, the allelic frequency of the Pro12Ala polymorphism was 14% (95% confidence interval: 12-16%) compared with 16% (14-17%) among the non-obese control subjects (NS). Heterozygosity of the codon 12 variant was not associated with differences in BMI or changes in body weight regulation during follow up in lean or obese subjects. In the group of obese subjects, 21 homozygous Ala12Ala carriers had, however, a higher BMI (38.9 +/- 5.4 kg/m2 (means +/- SD) vs 35.5 +/- 5.5 kg/ m2, p = 0.008) and a higher weight gain (0.27 +/- 0.24 kg x m(-2) x year(-1) vs 0.10 +/- 0.24 kg x m(-2) x year(-1), p = 0.004), compared with wild-type carriers. Moreover, within the control group of 869 men the 14 homozygous carriers of the variant had a lower BMI (24.4 +/- 2.7 kg/m2 vs 26.2 +/- 3.7 kg/m2, p = 0.005) and a slower increase in BMI (0.11 +/- 0.11 kg x m(-2) x year(-1) vs 0.17 +/- 0.11 kg x m(-2) x year(-1), p = 0.002) compared with wild-type carriers. CONCLUSION/INTERPRETATION: The codon 12 variant of PPAR-gamma2 is not intrinsically associated with juvenile obesity. The variant may in its homozygous form interact, however, with various combinations of genetic and environmental factors in lean and obese subjects to cause divergent modulating effects on BMI and long-term body weight control.

Adult↗
PubMed1999

An untranslated insertion variant in the uncoupling protein 2 gene is not related to body mass index and changes in body weight during a 26-year follow-up in Danish Caucasian men.

AIMS: Associations between a 45 bp 3'untranslated insertion polymorphism in the uncoupling protein 2 (UCP2) gene and both body mass index (BMI) and sleeping metabolic rate have previously been reported. We investigated the impact of this polymorphism on BMI and long-term body weight changes. METHODS: The allelic frequency of the UCP2 insertion variant was determined in a cohort of 744 obese Danish Caucasian men who had a BMI of at least 31 kg/m2 at the draft-board examinations and a randomly selected control cohort consisting of 872 draftees. Follow-up measurements of BMI were done on average 26 years after the draft-board examinations. RESULTS: The prevalence of the insertion allele was 30.4% (95% confidence interval: 28.0-32.8%) among the obese and 29.6% (27.4-31.8%) in the control group (p = 0.6). In a lean group selected as the 354 subjects with a BMI less than 25 kg/m2 at 46 years of age from the control group, the frequency of insertion allele was 29.0% (27.2-30.8%) (p = 0.5 compared with the obese cohort). The BMI at the ages of 20 and 46 years did not differ between genotypes either in the obese or the control group. Similarly, the changes in BMI/year between examinations at 20 and 46 years of age did not differ between genotypes in either group. CONCLUSION/INTERPRETATION: In a large group of Danish Caucasian men we found no association between a 3'untranslated insertion polymorphism in the UCP2 gene and obesity. Neither did we identify a relation between this variant and BMI changes during adult age.

3' Untranslated Regions↗
PubMed1999

Enhanced platelet serotonin 5-HT2A receptor binding in anorexia nervosa and bulimia nervosa.

Some evidence exists to suggest that serotonin 5-HT2A receptor function is altered in anorexia nervosa and bulimia nervosa. In order to further investigate the 5-HT2A receptor in eating disorders, platelet [3H]lysergic acid diethylamide ([3H]LSD) binding was studied in ten patients with anorexia nervosa, 23 patients with bulimia nervosa and 33 healthy controls. At admission, Bmax for platelet [3H]LSD binding was significantly higher both in the anorexia nervosa group (30.6+/-4.2 fmol/mg protein; mean+/-S.D.) and in the bulimia nervosa group (30.8+/-7.6 fmol/mg protein) than in the control group (23.5+/-6.3 fmol/mg protein; p=0.01 and p=0.003, respectively). Kd was borderline significantly higher among anorexics (median 1.45 nM) and significantly higher among bulimics (median 1.66 nM) than among controls (median 0.95 nM; p=0.05 and 0.003, respectively). The Global Assessment of Functioning score and the body mass index were both significantly negatively correlated to Kd (r=-0.40; p=0.03 and r=-0.41 p=0.03, respectively), but not to Bmax. The present study indicates that patients with anorexia nervosa as well as patients with bulimia nervosa have an enhanced 5-HT2A receptor binding and provides further evidence for a serotonergic dysfunction in eating disorders.

Adolescent↗
PubMed1999

Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity.

OBJECTIVE: Mutations in the human gene encoding the polyhormone peptide proopiomelanocortin (POMC) are associated with obesity in rare cases and the gene co-localizes with a reported quantitative trait loci (QTL) for variations in circulating leptin levels and fat mass on human chromosome 2p21. In this study we have used polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) analysis, to test whether variations in the human POMC gene are associated with human obesity. DESIGN AND SUBJECTS: Primary mutational analysis was performed on the coding region of the POMC gene and 500 bp of the putative promoter region, by single strand conformational analysis and sequencing, in 56 subjects with juvenile onset obesity (body mass index (BMI) > or = 31 kg/m2 at the draft board examination). The prevalence of two polymorphisms were further studied in 156 obese and 205 control subjects, and in a population based cohort of 380 extensively characterized young healthy subjects. RESULTS: We have identified a total of six gene variants, five were silent nucleotide substitutions (No51(promoter) g-->c, No670(5'UTR)g-->a, No4512(codon6)c-->t Cys/Cys, No7726(codon116)c-->t Leu/Leu) of which one was prevalent (No8246(3'UTR)c-->t) and one variant changed an amino acid (No8086(codon236)g-->c Arg/Gln). The amino acid substitution was only seen in one subject. Comparing the prevalence of the frequent No8246 silent polymorphism, in an association study comprising 156 subjects with juvenile onset obesity and 205 randomly sampled control subjects (mean BMI 23.5+/-4.7 kg/m2), did not show any relationship to obesity. Also, comparing the prevalence of a known 9bp insertion/deletion variant in the coding region of the gene between obese and lean, showed no association to obesity. Furthermore, analyzing a population based cohort of 380 young healthy Caucasians for the prevalent 3'UTR polymorphism as well as the 9 bp insertion/deletion variant did not show any association to deviations in body fat contents or fasting serum leptin concentrations. CONCLUSION: In conclusion, it is unlikely that variations in the coding region and the putative promoter of the POMC gene are a major cause of juvenile onset human obesity.

3' Untranslated Regions↗
PubMed1999

Detrital Zircon Geochronology: New Evidence for an Old Model for Accretion of the Southwest Baltic Shield.

Disruption of the original crustal architecture as a result of tectonic events often complicates studies of the crustal evolution of Precambrian cratons. Ion-probe U-Pb dating of detrital zircons is one way to circumvent this problem. It yields a "fingerprint" of the source of the metasedimentary host that can be used to tie the host to a counterpart elsewhere. In this study, ion-probe U-Pb dating of detrital zircons from segments of the late Mesoproterozoic Southwest Scandinavian Domain (SSD) of the Baltic Shield provides new evidence for an old model of crustal evolution and tectonic development. Zircon ages for both the pebble and matrix fraction of the Seljord conglomerate, Telemark sector, Norway, show a 1.9-1.7-Ga frequency maximum, as was previously recognized for metasediments from the adjacent Bamble sector. However, the Telemark metasediments lack evidence for significant input of 1.4-1.6-Ga-old crustal material, characteristic of some of the Bamble metasediments. A maximum depositional age of ca. 1450 Ma is inferred for the Seljord conglomerate and a quartzite from the Bamble sector. Definite evidence for significant amounts of pre-1.6-Ga crust in the SSD is absent. Instead, provenance from the early Mesoproterozoic Svecofennian Domain for the 1.9-1.7-Ga crust is proposed, supported by the omnipresence of small amounts of Archean zircons and the distribution of Nd model ages of these and other SSD metasediments. It is proposed that the SSD originally formed a single, continuous belt, fringing the Baltic Shield, with the northernmost segments transported to their current position west of the Oslo rift along north-south-trending shear zones, i.e., at odds with the commonly held view of progressive westward growth of the Baltic Shield. The detrital zircon ages from the Faurefjell quartzite, Rogaland-Vest Agder sector, cluster around 1.65 Ga and reveal a maximum depositional age of 1244+/-40 Ma. Its deviating depositional setting indicates that the Rogaland sector evolved in a different setting, shielded from the crust of Svecofennian age. Instead, its ages allow for a source terrain within the Mesoproterozoic crust of South Norway.

Journal Article↗
PubMed1999

Antigen retrieval on epoxy sections based on tissue infiltration with a moderately increased amount of accelerator to detect immune complex deposits in glomerular tissue.

We wanted to examine the effect of antigen retrieval on epoxy sections where the tissue had been infiltrated by resin containing moderately increased amounts of accelerator. The concentration of accelerator DMP-30 (Tri(Dimethyl Amino Methyl) Phenol) was varied in the range of 0% to 4% in the infiltration step of the tissue processing. Some of the epoxy sections were fixed in osmium tetroxide, and for others this fixative was avoided. Immunogold labeling was performed on epoxy sections and LR-White sections of renal tissue with IgG-deposits, and the antibody used was anti-IgG. Antigen retrieval was performed by heating the sections in citrate buffer. The amount of immunogold labeling on retrieved sections increased according to the amount of accelerator the non-osmicated epoxy sections were based on in the infiltration steps. For the osmicated epoxy sections these differences were less pronounced. The immunogold labeling of retrieved epoxy sections was up to 70% of LR-White labeling. In addition to breaking fixation bond introduced by the chemical fixation, we believe that the antigen retrieval also breaks bonds between the epoxy resin and the embedded tissue. The combination of increased amount of accelerator in the tissue infiltration and antigen retrieval by heating the sections in citrate buffer is a good method for improving the immunolabeling of epoxy sections.

Animals↗
PubMed1998

Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group.

BACKGROUND: We undertook a randomised controlled trial to assess the efficacy and tolerability of orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain in obese patients over a 2-year period. METHODS: 743 patients (body-mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week, single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (three times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric) diet. FINDINGS: From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p<0.001] from randomisation to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p<0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p<0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments. INTERPRETATION: Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events.

Adult↗
PubMed1998

Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity.

Uncoupling proteins (UCPs) are mitochondrial transporters that uncouple the cellular respiration releasing stored energy as heat. Recently a third member of the UCP family was identified. Human UCP3 is different from UCP1 and UCP2 by its high and preferential expression in skeletal muscle and consequently the UCP3 gene is an attractive candidate gene for obesity. In this study we have determined the intron/exon organization of the coding region of the UCP3 gene and performed single strand conformation polymorphism (SSCP) analysis and direct sequencing of variants of the gene in 60 Caucasian subjects with juvenile-onset obesity. We detected 4 nucleotide substitutions in the intron regions and 2 silent amino acid variants. During the identification of the intron/exon structure of the gene in a normal healthy male subject with a BMI of 23.5 kg/m2, a nucleotide substitution replacing a glycine with a serine was identified at codon84. This variant was neither found among 156 subjects with juvenile-onset obesity nor among 205 control subjects. In a population based sample of 380 young healthy subjects the Gly/Ser84 variant was found in one female subject with a BMI of 25.5 kg/m2 and a fat mass of 23.7 kg. We conclude it is unlikely that variants in the coding region of the UCP3 gene contribute to the pathogenesis of juvenile-onset obesity among Danish Caucasians.

Adolescent↗
PubMed1998

Fasting gall bladder volume and lithogenicity in relation to glucose tolerance, total and intra-abdominal fat masses in obese non-diabetic subjects.

OBJECTIVE: To investigate whether total body fat mass or fat distribution and associated metabolic disturbances in glucose and lipid metabolism influence the well known gallstone pathogenetic factors in obese subjects in order to explain why some obese subjects develop gallstones and some do not. DESIGN: Cross sectional study of gallstone pathogenetic factors, body composition, fat distribution, glucose and lipid metabolism. SUBJECTS: 57 healthy overweight subjects (aged 26-64y, body mass index (BMI) 30-45 kg/m2). MEASUREMENTS: Total and intra-abdominal fat masses were measured by dual X-ray absorptiometry and abdominal CT scanning, respectively. The lithogenic index was measured in aspirated bile. The gallbladder volume was determined by ultrasound and the gallbladder ejection fraction% by dynamic cholescintigraphy. Plasma cholecystokinin (CCK) concentrations during a meal were measured with a specific radioimmunoassay. Insulin sensitivity was measured by the Minimal Model and glucose tolerance by an oral glucose tolerance test (OGTT). Serum lipid concentrations were measured by standard methods. RESULTS: The gallbladder volume in the fasting state increased with increasing intra-abdominal fat mass (P=0.006) and was increased in subjects with impaired glucose tolerance (41 vs 27 ml, P=0.001). The lithogenic index was > 1 in all subjects and correlated with total fat mass (P=0.04). CONCLUSION: Gallstone pathogenesis in obesity seems to be influenced by the total body fat mass and its regional distribution possibly via mutual association with the glucose tolerance.

Abdomen↗
PubMed1998

Procedure for clinical testing of hearing aids.

In 1996, the Danish audiological clinics and hearing aid manufacturers jointly developed a clinical procedure for testing novel hearing aids in a clinical setting. This endeavour cane about because it was being acknowledged that clinical testing of hearing aids was likely to become more prominent as a result of the more advanced signal processing schemes enabled by digital technology in particular. It was understood that future hearing aids would encompass a large variety of diverse features, and that a rigid and detailed test protocol would therefore be inappropriate. The procedure was therefore devised as a framework within which a test protocol can be developed, and constitutes the framework of good scientific and clinical practice.

Hearing Aids↗
PubMed1997

Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity.

The recently described putative lipostat system mediated in part by leptin and its hypothalamic receptor provides logical candidate genes for the molecular basis of inherited obesity in humans on the basis of the occurrence of profound obesity observed in obese and diabetic mice, in which the genes for leptin or its receptor, respectively, are mutated. In this study we tested the hypothesis that juvenile onset obesity in humans may be caused by leptin resistance mediated through genetic variations in isoforms of the hypothalamic leptin receptor. One hundred and fifty-six obese Danish men with a history of juvenile onset obesity were selected at the draft board examination with a body mass index (BMI) > or = 31 kg/m2. From the same study population a control group of 205 control subjects (mean BMI = 21,5 kg/m2) were randomly selected. Single strand conformational polymorphism scanning of genomic DNA from 56 obese subjects revealed a total of four amino acid variants located in coding exons 2, (Lys109Arg), 4 (Lys204Arg and Gln223Arg), and 12 (Lys656Asn), respectively. The codons 109, 223, and 656 variants were common, but their prevalence was not significantly different between obese and lean carriers with regard to allele or carrier frequency (p > 0.1 in each case). The codon 204 mutation was only found in one obese subject. In conclusion, it is unlikely that mutations in the coding region of the long isoform of the leptin receptor are a common cause of juvenile onset obesity.

Adolescent↗
PubMed1997

Mutational analysis of the coding region of the uncoupling protein 2 gene in obese NIDDM patients: impact of a common amino acid polymorphism on juvenile and maturity onset forms of obesity and insulin resistance.

Recently, a gene encoding a novel human uncoupling protein, designated UCP2, was discovered. The murine UCP2 was mapped to a region on mouse chromosome 7 which in several models has been shown to be linked to obesity and hyperinsulinaemia. Single strand conformation polymorphism (SSCP) analysis and direct sequencing of the coding region of the UCP2 gene in 35 obese Caucasian NIDDM patients of Danish ancestry revealed one nucleotide substitution, replacing an alanine with a valine at codon 55. The amino acid polymorphism was present in 24 of the 35 (69%) examined subjects. The allelic frequency of the A/V55 variant was 48.3% (95% CI: 42.5-54.1%) among 144 subjects with juvenile onset obesity, 45.6% (40.5-50.7%) among 182 subjects randomly selected at the draft board examination, and 45.5% (37.1-53.9%) among lean control subjects selected from the same study cohort. Within these cohorts there were no differences in BMI values at different ages among wild-type carriers and A/V55 carriers. In a population-based sample of 369 young healthy Caucasians the variant showed no association with alterations in BMI, waist-to-hip ratio, fat mass or weight gain during childhood or adolescence. The A/V55 polymorphism was not related to alterations in fasting values of serum insulin and C-peptide or to an impaired insulin sensitivity index. We conclude that genetic variability in the human UCP2 gene is not a common factor contributing to NIDDM in obese Danish Caucasian subjects and the common A/V55 amino acid polymorphism of the gene is not implicated in the pathogenesis of juvenile or maturity onset obesity or insulin resistance in Caucasians.

Adult↗
PubMed1997

Identification of two novel missense mutations in the human OB gene.

OBJECTIVE: To clone the human OB gene and to investigate if mutations in the OB gene are related to juvenile onset obesity in Caucasians. DESIGN: Case-cohort study with mutational scanning of the OB gene in an obese cohort and in a population sample of young Caucasians. SUBJECTS: An obese cohort of 156 subjects with juvenile onset obesity and a population sample of 380 healthy young Caucasians. MEASUREMENTS: Various anthropometric and biochemical measures of obesity and insulin sensitivity and single strand conformation polymorphism scanning and nucleotide sequencing. RESULTS: Analysis of the coding region of the OB gene in the 536 participants revealed that one obese subject was heterozygous for a mutation at codon Phe17Leu and one normal weight subject was heterozygous for a mutation at codon Val110Met. The phenotypes of the carriers were not different from matched non-mutation carrying subjects. CONCLUSIONS: Mutations exist in the OB gene among obese as well as lean subjects although they are rare. However, it is unlikely that mutations in the coding region of the OB gene are a common cause of juvenile onset obesity among Caucasians.

Adult↗
PubMed1997

Studies of genetic variability of the uncoupling protein 1 gene in Caucasian subjects with juvenile-onset obesity.

Our objective was to investigate whether genetic variants of the uncoupling protein 1 (UCP1) gene are associated with juvenile-onset obesity or alterations in weight gain and insulin sensitivity in young healthy Caucasians. Single-strand conformation polymorphism and heteroduplex analysis of the coding region of the UCP1 gene was performed in 56 subjects randomly selected at the draft board examination from a cohort of 156 males with juvenile-onset obesity. Association studies of amino acid variants were undertaken in the cohort of males with juvenile-onset obesity, a cohort of 205 randomly selected control males, and a subgroup of this cohort comprising 76 lean subjects. Genetic variants of the coding region as well as a previously described a-->g nucleotide polymorphism of the 5'-flanking region of the UCP1 gene were examined for associations with accelerated weight gain or reduced sensitivity to insulin in a cohort of 380 young healthy Caucasians. The mutational analysis revealed five nucleotide substitutions that changed the sequence of UCP1, Arg/Trp40, Ala/Thr64, Val/Met137, Met/Leu229, and Lys/Asn257 and two nucleotide substitutions in the nontranslated region of exon 1. Among subjects with juvenile-onset obesity, the allelic frequencies of Ala/Thr64 and Met/Leu229 were both 8.2% (95% confidence interval: 5.1-11.3%) vs. 8.8% (6.0-11.6%) and 8.1% (5.3-10.9%), respectively, in the cohort of randomly selected control subjects. Among lean control subjects, the allelic frequencies of the polymorphisms were 8.2% (3.7-12.7%) and 5.6% (1.9-9.3%), respectively. In the cohort of young healthy subjects, measurements of obesity and insulin sensitivity did not differ between carriers of the Ala/Thr64 and Met/Leu229 variants and wild-type carriers. The Val/Met137 and Lys/Asn257 mutations were each found in one subject with juvenile-onset obesity, and the Arg/Trp40 mutation was found in two obese subjects and in one control subject. The allelic frequency of the nucleotide polymorphism of the 5'-flanking region of the UCP1 gene was 25.3% (22.2-28.4%) in the cohort of 380 young Danes. There were no differences in body mass index, fat mass, waist-to-hip ratio, or weight gain during childhood or adolescence between carriers and noncarriers of this nucleotide variant. Although we cannot exclude an effect of the rare mutations in the UCP1 gene on susceptibility to juvenile-onset obesity, genetic variation of the coding region of the UCP1 gene is not a common factor contributing to obesity in Caucasian subjects of Danish ancestry.

Adolescent↗