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Biomedical subjects

U Pettersson

Publications and source records attributed to U Pettersson.

At least 19 recordsLinked to original sources
PubMed2006

Relationships between physical activity and physical capacity in adolescent females and bone mass in adulthood.

This study investigates whether physical activity and physical performance in adolescence are positively related to adult bone mineral density (BMD). In 1974, physical activity, endurance, and muscular strength were measured in 204 randomly selected female students, age 16.1 +/- 0.3 year (range 15-17 years). Twenty years later, 36 of the women volunteered to undergo a measurement of their BMD. Women who were members in a sports club in adolescence had significantly higher adult BMD (mean differences of 5% to 17% depending on site) compared with subjects who were not engaged in a sports club. Furthermore, women with persistent weight-bearing activity in adulthood had significantly higher BMD compared with women who had stopped being active or had never been active. The differences ranged between 5% and 19% with the highest difference found in trochanter BMD. Stepwise regression analyses showed that membership in a sports club at baseline was a significant independent predictor of BMD in the total body, lumbar spine, legs, trochanter, and femoral neck, explaining 17-26% of the variation in BMD. Change in body weight was a strong independent predictor of BMD of the total body and arms, explaining 8% of the variation in both sites. In addition, running performance at baseline was an independent predictor of total body BMD, whereas the two-hand lift performance significantly predicted BMD of the total body, legs and trochanter. The hanging leg-lift and handgrip were both significant predictors of arm BMD. In conclusion, membership in a sports club and site-specific physical performance in adolescence together with the change in body weight were significantly associated with adult BMD in premenopausal women.

Adolescent↗
PubMed2006

The genetic contribution to canine personality.

The domestic dog may be exceptionally well suited for behavioral genetic studies owing to its population history and the striking behavior differences among breeds. To explore to what extent and how behavioral traits are transmitted between generations, heritabilities and genetic correlations for behavioral traits were estimated in a cohort containing over 10,000 behaviorally tested German shepherd and Rottweiler dogs. In both breeds, the pattern of co-inheritance was found to be similar for the 16 examined behavioral traits. Furthermore, over 50% of the additive genetic variation of the behavioral traits could be explained by one underlying principal component, indicating a shared genetic component behind most of the examined behavioral traits. Only aggression appears to be inherited independently of the other traits. The results support a genetic basis for a broad personality trait previously named shyness-boldness dimension, and heritability was estimated to be 0.25 in the two breeds. Therefore, breeds of dogs appear to constitute a valuable resource for behavioral genetic research on the normal behavioral differences in broad personality traits.

Animals↗
PubMed2005

Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone.

BACKGROUND: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk. OBJECTIVE: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women. RESULTS: There was a significant association between a common haplotype "px", defined by the PvuII and XbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were approximately 14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p = 0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values. CONCLUSIONS: The ESR1px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD.

Alleles↗
PubMed2002

Chromosomal size variation in Trypanosoma cruzi is mainly progressive and is evolutionarily informative.

The evolutionary significance of chromosome size polymorphism was explored in a representative panel of 26 Trypanosoma cruzi stocks. We tested a progressive model (aCSDI) assuming that the larger the size difference between homologous chromosomes, the more divergent the parasites are. This was contrasted with a non-progressive model (Jaccard's distance), in which any chromosome size difference has the same weight. ACSDI-based dendrograms were very similar to those built-up from multilocus enzyme electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD) data: structuring in 2 major lineages (T. cruzi I and T. cruz II) and 5 small subdivisions within T. cruzi II was identical, and branching was very similar. Furthermore, a significant correlation (P < 0.001) was observed between aCSDI and phenetic distances calculated from MLEE and RAPD data. In contrast, analysis of chromosome size polymorphism with Jaccard's distance generated dendrograms with relatively long branches, causing most branching points to cluster close together, which generates statistically uncertain branching points. Our results thus support a model of progressive chromosome size-variation and show that despite an extensive polymorphism, chromosomal sizes constitute valuable characters for evolutionary analyses. Furthermore, our data are consistent with the clonal evolution model previously proposed for T. cruzi.

Animals↗
PubMed2001

Investigation of the functional effect of monoamine oxidase polymorphisms in human brain.

Monoamine oxidase A and monoamine oxidase B ( MAOA and MAOB) have been suggested to play a role in psychiatric disorders and/or behavioral traits. We have investigated whether different polymorphisms can account for variations in enzyme activity and/or mRNA levels in human brain. Whereas several association studies have been reported previously, this is the first study of the functional effect of MAO DNA variants in human brain. Four polymorphic changes were analyzed: a VNTR located in the MAOA promoter, a VNTR located in the first intron of the MAOA gene, and two single nucleotide polymorphisms located in exon 8 of MAOA and in intron 13 of MAOB. We studied the association of the variants and the resulting haplotypes, with expression levels and enzyme activities of both monoamine oxidases in human cortical brain autopsies. We did not find a significant association of any single MAOA polymorphism with expression levels or enzyme activity in human brain. We did, however, find an association of a particular haplotype with MAOA enzyme levels ( P=0.03). Our results suggest that a novel functional polymorphism that affects enzyme activity in human brain may exist in MAOA. For MAOB, we found a significant association ( P=0.02) between the MAOB intron 13 alleles and different levels of MAOB enzyme activity in human brain. We postulate that there may be a cis-regulatory element in linkage disequilibrium with the B-SNP13 polymorphisms that alters MAOB enzyme activity in human brain.

Autopsy↗
PubMed2001

Genetic linkage analysis of the antibody responses to myelin basic protein and myelin oligodendrocyte glycoprotein in rats immunized with rat spinal cord homogenate.

The genetic control of the antibody response to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) was analysed in F1 and F2 crosses of DA and E3 rats, immunized with rat spinal chord homogenate. The DA rats were highly susceptible to encephalomyelitis and made antibody responses to both MBP and MOG, whereas the E3 rats were disease-resistant and responded only to MOG. The anti-MBP response was mainly controlled by the disease-promoting MHC region of the DA strain together with several disease loci outside MHC. In contrast, the anti-MOG response was associated with loci not related to or actually conferring resistance to disease.

Animals↗
PubMed2001

A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees.

We have completed a genome scan of a 12-generation, 3,400-member pedigree with schizophrenia. Samples from 210 individuals were collected from the pedigree. We performed an "affecteds-only" genome-scan analysis using 43 members of the pedigree. The affected individuals included 29 patients with schizophrenia, 10 with schizoaffective disorders, and 4 with psychosis not otherwise specified. Two sets of white-European allele frequencies were used-one from a Swedish control population (46 unrelated individuals) and one from the pedigree (210 individuals). All analyses pointed to the same region: D6S264, located at 6q25.2, showed a maximum LOD score of 3.45 when allele frequencies in the Swedish control population were used, compared with a maximum LOD score of 2.59 when the pedigree's allele frequencies were used. We analyzed additional markers in the 6q25 region and found a maximum LOD score of 6.6 with marker D6S253, as well as a 6-cM haplotype (markers D6S253-D6S264) that segregated, after 12 generations, with the majority of the affected individuals. Multipoint analysis was performed with the markers in the 6q25 region, and a maximum LOD score of 7.7 was obtained. To evaluate the significance of the genome scan, we simulated the complete analysis under the assumption of no linkage. The results showed that a LOD score >2.2 should be considered as suggestive of linkage, whereas a LOD score >3.7 should be considered as significant. These results suggest that a common ancestral region was inherited by the affected individuals in this large pedigree.

Adult↗
PubMed2001

Histone genes expression during the cell cycle in Trypanosoma cruzi.

Histones, the basic proteins which compact DNA into the nucleosomal and solenoidal fibers are synthesized in correlation with DNA replication during the S-phase of the cell cycle. This behavior is controlled both at transcriptional and postranscriptional levels in higher eukaryotes and yeasts. We have found that histone synthesis in synchronized trypanosomes is controlled by fluctuations on the levels of their mRNAs. Though we cannot preclude the existence of a transcriptional regulatory mechanism, our results point to the participation of changes in the stability of histone mRNAs as a regulatory mechanism of their levels during the cell cycle in Trypanosoma. We have also found a postranscriptional regulatory mechanism which could be acting at the translational level. These results show both similarities and differences between Trypanosoma and higher eukaryotes regarding the expression of their histone genes.

Animals↗
PubMed2001

Interference with CD28, CD80, CD86 or CD152 in collagen-induced arthritis. Limited role of IFN-gamma in anti-B7-mediated suppression of disease.

We have investigated interference with co-stimulation by administering mAbs towards CD28, CD80, CD86, and CD152 in mice immunized for the development of collagen-induced arthritis (CIA). Anti-CD80 and anti-CD86 treatment inhibited disease score and incidence, whereas anti-CD28 treatment led only to a delayed disease onset. Administration of anti-CD152 had no effect. The CII-specific Ab-response was suppressed by the co-stimulatory blockade, with a stronger effect on IgG1 than on IgG2a. The CII-driven T cell proliferation, on the other hand, was not affected. Furthermore, T cells primed in the presence of either anti-B7 or anti-CD28 produced markedly increased amounts of IFN-gamma in response to CII. To investigate whether this increase in IFN-gamma was related to disease suppression, IFN-gamma-deficient mice were immunized with CII, treated with anti-B7 and followed for the development of arthritis. As in the wild-type mice, administration of anti-B7 to IFN-gamma-deficient mice led to a reduced disease incidence and severity as well as reduced anti-CII IgG titers. Collectively, these data stress the importance of co-stimulation for the delivery of B cell help rather than for production of Th1 cytokines. We also demonstrate that the enhanced production of IFN-gamma observed after B7-blockade is not accountable for the anti-B7 mediated inhibition of CIA.

Abatacept↗
PubMed2001

The geographic distribution of monoamine oxidase haplotypes supports a bottleneck during the dispersion of modern humans from Africa.

Every genetic locus mingles the information about the evolutionary history of the human species with the history of its own evolution. Therefore, to address the question of the origin of humans from a genetic point of view, evolutionary histories from many genetic loci have to be gathered and compared. We have studied two genes residing on the X chromosome encoding monoamine oxidases A and B (MAOA and MAOB). Both genes have been suggested to play a role in psychiatric and/or behavioral traits. To search for DNA variants of the MAO genes, the sequences of exonic and flanking intronic regions of these two genes were determined in a group of Swedish males. The sequence analysis revealed several novel polymorphisms in the MAO genes. Haplotypes containing high-frequency MAOA polymorphisms were constructed, and their frequencies were determined in additional samples from Caucasian, Asian, and African populations. We found two common haplotypes with similar frequencies in Caucasian and Asian populations. However, only one of them was also the most frequent haplotype in Africans, while the other haplotype was present in only one Kenyan male. This profound change in haplotype frequencies from Africans to non-Africans supports a possible bottleneck during the dispersion of modern humans from Africa.

Animals↗
PubMed2001

Arthritis induced in rats with nonimmunogenic adjuvants as models for rheumatoid arthritis.

Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.

Adjuvants, Immunologic↗
PubMed2000

The tyrosine aminotransferase from Trypanosoma rangeli: sequence and genomic characterization.

The complete sequence and genomic characterization of the tyrosine aminotransferase (TAT) gene from Trypanosoma rangeli is reported. The gene was found to be organized in a tandem multicopy gene array. A homologous mRNA species (2.5 kb) was identified in the epimastigote form of the parasite. From the deduced amino acid sequence, the gene encodes a protein of 420 amino acids with a predicted molecular mass of 46.4 kDa and a theoretical pI of 6.23. A high sequence identity was found with the Trypanosoma cruzi, human and rat enzymes. All the essential residues for TAT enzymatic activity are conserved, as well as a pyridoxal-phosphate attachment site typical of class-I aminotransferases. The recombinant enzyme was recognized by a monoclonal antibody against the T. cruzi enzyme. Additionally, the recombinant protein showed enzymatic activity when incubated with L-tyrosine and 2-oxoglutaric acid as substrates.

Amino Acid Sequence↗
PubMed2000

Evidence for common autoimmune disease genes controlling onset, severity, and chronicity based on experimental models for multiple sclerosis and rheumatoid arthritis.

The pathogenicity of multiple sclerosis is still poorly understood, but identification of susceptibility genes using the animal model experimental allergic encephalomyelitis (EAE) could provide leads. Certain genes may be shared between different autoimmune diseases, and identification of such genes is of obvious importance. To locate gene regions involved in the control of EAE and to compare the findings with the susceptibility loci recently identified in a model for rheumatoid arthritis (pristane-induced arthritis), we made crosses between the encephalomyelitis- and arthritis-susceptible rat strain DA and the resistant E3 strain. Genetic analysis of animals produced in a F2 intercross identified 11 loci associated with specific EAE-associated traits. Interestingly, five of these loci were situated at the same position as major loci controlling pristane-induced arthritis and showed similarities in inheritance pattern and subphenotype associations. Our results show that different phases of EAE are controlled by different sets of genes and that common genes are likely to be involved in different autoimmune diseases.

Animals↗
PubMed2000

Trypanosoma cruzi: a putative vacuolar ATP synthase subunit and a CAAX prenyl protease-encoding gene, as examples of gene identification in genome projects.

An international genome program has been initiated to increase the knowledge about the Trypanosoma cruzi genome and thereby find effective tools to treat Chagas' disease. We here report the molecular characterization of two novel genes found in the course of this project. Two of the open reading frames (ORF) identified in the sequencing of the third smallest chromosome of the CL Brener strain of T. cruzi were selected for further molecular characterization due to their similarity to genes with interesting functions in other organisms and their potential as targets to combat the parasite. The first ORF (402 bp) showed homology to a 14-kDa vacuolar ATP synthase subunit F from a variety of organisms, such as yeast, rat, bovine, human, and a number of prokaryotes. The second ORF (1188 bp) resembled a CAAX prenyl protease-encoding gene, identified in different organisms, including Homo sapiens, Saccharomyces cerevisiae, and Arabidopsis thaliana, as well as several prokaryotes. RT-PCR from T. cruzi total epimastigote RNA allowed us to isolate the complete transcripts of these genes. Furthermore, screening of an available normalized cDNA library derived from the same stage of the parasite confirmed that both genes are expressed at least in the epimastigote stage of T. cruzi. Comparison of the putative T. cruzi proteins to their counterparts in other organisms revealed significant protein sequence conservation over large evolutionary distances. Computer analysis revealed the presence of several motifs in both proteins, possibly related to the regulation and localization of these proteins in the parasite.

ATP Synthetase Complexes↗
PubMed2000

Bone mass in female cross-country skiers: relationship between muscle strength and different BMD sites.

In this cross-sectional study, bone mass and muscle strength of the thigh were investigated in 16 Caucasian female cross-country skiers, age 16.2 +/- 0.3 years, that had been ski-training for 6.4 +/- 1.8 years (range 3-9 years) and were now training for 6.3 +/- 2.4 hours/week (range 3-12 hours). They were compared with 16 nonactive females, age 16.4 +/- 0.7 years. The groups were matched according to age, weight, height, and pubertal status. Areal bone mineral density (BMD) was measured using dual energy X-ray absorptiometry, in the total body, head, both total humerus and humerus diaphyses, spine, and in the right femoral neck, greater trochanter, femoral diaphysis, distal femur, proximal tibia, and tibia diaphysis. Bone mineral apparent density (BMAD) was also calculated for the femoral neck and humerus diaphyses. Isokinetic muscle strength of the quadricep and hamstring muscles was measured in an isokinetic dynamometer. Compared with the controls, the cross-country skiing group had significantly higher BMD in the right whole humerus (6.9%), left whole humerus (9.2%), left humerus diaphysis (8.1%), femoral neck (8.9%), greater trochanter (9.3%), femur diaphysis (7.6%), and BMAD of the femoral neck (+19.4%). In the nonactive group there were significant side-to-side differences in BMD of the whole humeri, humerus diaphyses, and BMAD of the humerus diaphyses (3.1%, 5.4%, and 8.8% higher in the right arm, respectively). No such differences were found in the cross-country skiing group. Lean body mass was significantly higher in the cross-country skiers (21.7%), and fat mass (-25.5%) and body fat percent (-28.0%) were significantly lower compared with the nonactive group. There were, however, no significant differences in concentric peak torque of the thigh muscles between the two groups. Stepwise regression analyses revealed that BMI was the best predictor of several sites in the nonactive group. In the cross-country group, on the other hand, muscle strength was a strong predictor of BMD, both at adjacent and more distant BMD sites. In conclusion, it seems that this type of endurance training is associated with a site-specific higher bone mass that may be associated with the type and magnitude of loading during off-season and during the main sports activity, cross-country skiing.

Absorptiometry, Photon↗
PubMed2000

Effect of high impact activity on bone mass and size in adolescent females: A comparative study between two different types of sports.

The purpose of this cross-sectional study was to investigate the influence of two different types of weight-bearing activity, muscle strength, and body composition on bone mineral density (BMD), bone mineral content (BMC), and bone area in three different groups of late adolescent girls. The first group consisted of 10 females participating in competitive rope-skipping (age 17.8 +/- 0.8 years) training for 6.7 +/- 3.1 hours/week; the second group consisted of 15 soccer players (age 17.4 +/- 0.8 years) training for 6.1 +/- 2.0 hours/week; and the third group consisted of 25 controls (age 17.6 +/- 0.8 years) with physical activity of 0.9 +/- 1.1 hours/week. The groups were matched for age, height, and weight. BMD (g/cm(2)), BMC (g), and bone area (cm(2)) of the total body, lumbar spine, hip, total femur, distal femur, diaphyses of femur and tibia, proximal tibia, and humerus were measured using dual-energy X-ray absorptiometry (DXA). Bone density was also assessed in the radial forearm site of the dominant limb in the rope skippers and in 10 matched controls. The rope skippers had 22% higher BMD at the ultradistal site (P < 0.01). Both high-activity groups had significantly higher BMD (P < 0.05) at most loaded sites compared with the control group. When adjusting for differences in lean mass and starting age of sport-specific training between the activity groups, the rope-skipping group had a higher BMD of the total body, lumbar spine, and right humerus compared with the soccer group. They also had a significantly higher bone area of the total body, total femur, and the proximal femur than both other groups, and a significantly higher bone area of the tibia diaphysis, compared with the soccer group. In a multivariate analysis among all subjects (n = 50), all BMD sites, except the femur diaphysis, distal femur, and proximal tibia, were significantly related to type of physical activity (beta = 0.25-0.43, P < 0.05). The bone area values at different sites were strongly related to muscle strength and parameters related to body size [height, weight, lean mass, fat mass, and body mass index (BMI)]. In conclusion, it appears that in late adolescent women, weight-bearing activities are an important determinant for bone density, and high impact activities such as jumping also seem to be associated with a modification of the bone geometry (hence, the bone width) at the loaded sites.

Absorptiometry, Photon↗
PubMed2000

Environmental monitoring of the kafue river, located in the Copperbelt, Zambia.

Zambia is a country with an extensive mining industry with the majority of mines located in the Copperbelt province. Through this region of the country, the Kafue River drains and receives effluent water from mining activities as well as from other industrial point sources. In addition, production of agricultural products and pest control requires use of different pesticides in the area. Information on industrial and agricultural pollution has not been clearly identified in Zambia, and little attention has been paid to pollution control and possible impact of metals, pesticides, and other persistent compounds in the environment. The objective of this study was to introduce and to evaluate a few methodologies based on in situ bioassays for environmental assessment to promote sustainable and environmentally sound water resource management of the Kafue River. The results show that caged threespot tilapia exposed downstream of industrial points sources rapidly bioaccumulate several trace elements, i.e., Cd, Co, Cu, Cr, Ni. These elements also occurred in much higher concentrations in water samples downstream of the industrial area compared with a locality upstream. Furthermore, the use of a semipermeable membrane device (SPMD) for passive absorption of lipophilic pollutants in the water showed relatively high concentration of several pesticides, i.e., DDT with major metabolites, PCB, and dieldrin. The present study shows that only 2 weeks of in situ studies in waters contaminated by pollutants affects in situ exposed fish and that the correlation between water and tissue concentrations was relatively good. Both trace elements and persistent organic pollutants occurred in such high concentrations that they must be considered from ecotoxicological aspects and may affect aquatic animal health.

Animals↗