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Biomedical subjects

P Larsson

Publications and source records attributed to P Larsson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Organochlorine accumulation and stable isotope ratios in an Atlantic salmon (Salmo salar) population from the Baltic Sea.

We investigated the organochlorine accumulation (p,p'-DDE and sigmaPCB) and stable isotope ratios (N and C) in a migrating salmon (Salmo salar) population in the Baltic Sea. delta15N in the entire population ranged from 11.7 to 13.7 per thousand and delta13C ranged from -22.0 to - 19.6 per thousand. In the entire population, delta15N were weakly related to p,p'-DDE and sigmaPCB concentrations (r2 = 0.20 and 0.14, respectively). However, lipid content was a better predictor of organochlorine (OC) concentrations (r2 = 0.48 and 0.50, respectively). Lipid adjusted sigmaPCB concentrations were not related to delta15N, and lipid adjusted p,p'-DDE concentrations were only weakly related (r2 = 0.12). We divided the salmon population into three groups representing reproductive strategies: small males < 5 kg (SM); large males > 5 kg (LM); and females (F). delta15N varied between the three reproductive strategies. The mean delta15N for SM was 12.7+/-0.3 per thousand, for F was 12.9+/-0.3 per thousand, and for LM equalled 13.2+/-0.3 per thousand. Lipid adjusted OC concentrations differed between the three reproductive strategies, with the females having the highest concentrations. We conclude that the delta15N varied between reproductive strategies indicating differences in prey choice, but the lipid content was better able to predict OC concentrations than the trophic position of the salmon.

Animals↗
PubMed2001

Coupled and uncoupled proton movement by amino acid transport system N.

The system N transporter SN1 has been proposed to mediate the efflux of glutamine from cells required to sustain the urea cycle and the glutamine-glutamate cycle that regenerates glutamate and gamma-aminobutyric acid (GABA) for synaptic release. We now show that SN1 also mediates an ionic conductance activated by glutamine, and this conductance is selective for H(+). Although SN1 couples amino acid uptake to H(+) exchange, the glutamine-gated H(+) conductance is not stoichiometrically coupled to transport. Protons thus permeate SN1 both coupled to and uncoupled from amino acid flux, providing novel mechanisms to regulate the transfer of glutamine between cells.

Amino Acid Transport Systems↗
PubMed2001

p53 mutations in urinary bladder cancer.

We have screened for mutations in exons 5-8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1-G2a) and 106 (56%) were highly malignant (G2b-G4 or > or = T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant.

Cell Differentiation↗
PubMed2001

[Blockade of TNFalpha--new therapeutic principle in severe rheumatoid arthritis].

TNF-alpha is a proinflammatory cytokine. It has a key function in the inflammatory cascade both systemically and locally in the inflamed joints of patients affected by rheumatoid arthritis (RA). Treatment with two different "biological" drugs that block the proinflammatory capacity of TNF-alpha has recently been approved by the European drug authorities. This paper discusses experience gained in clinical trials and during the first year of treatment in Sweden using infliximab (anti-TNF-alpha monoclonal antibodies) and etanercept (recombinant TNF-alpha receptor fusion protein).

Arthritis, Rheumatoid↗
PubMed2001

Low interleukin-1alpha messenger RNA levels predict decreased overall survival time of patients with urinary bladder carcinoma.

Due to our inability to exactly characterize tumours, many patients with urinary bladder cancer undergo unnecessary surgery or cytostatic therapy. We have here studied the expression of the cytokine interleukin-1alpha (IL-1alpha ) in 73 human bladder carcinomas in relation to patient survival, and examined possible relationships between IL-1alpha and urokinase plasminogen activator (uPA) expression. Expression levels of IL-1alpha and uPA mRNA were determined by RT-PCR using the quantitative TaqMan technique. The levels of IL-1alpha mRNA expression did not differ significantly between tumours of different grade or stage. Calculation of the overall survival rates showed a decreased overall survival time for patients with low levels of IL-1alpha mRNA in their tumours (log rank; P = 0.0002, median follow up: 37 months). Low tumoral IL-1alpha expression predicted decreased survival of patients with poorly differentiated tumours (P< 0.005) and of patients with invasive tumours (P = 0.02). uPA expression was about 4-fold increased in poorly differentiated tumours. High levels of uPA mRNA were associated with decreased overall survival times (log rank; P = 0.032, n = 60). We conclude that IL-1alpha is important for bladder cancer biology, and that measurements of this cytokine may be useful in pre-treatment characterization of urinary bladder cancer.

Cohort Studies↗
PubMed2001

Influence of trophic status on PCB distribution in lake sediments and biota.

We investigated the relationship between trophic status and polychlorinated biphenyl (PCB) distribution in 19 Swedish lakes. We analyzed PCB in water, phytoplankton, zooplankton, fish and sediment during two sampling periods, in spring and summer. The mass of sigma PCB in the lake sediments was positively related to lake trophy, i.e. more PCBs were accumulated and buried in the sediment of eutrophic lakes than in oligotrophic lakes. In the oligotrophic lakes a greater fraction of the total PCB load was dissolved in water. We conclude that this is a result of higher sedimentation rates in eutrophic lakes and relatively lower turnover of organic carbon in the water column of the shallow, eutrophic lakes. In the stratified lakes, the amount of PCB per cubic meter in the epilimnion decreased from spring to summer. We suggest that sedimentation of plankton beneath the thermocline during stratification act as a sink process of PCBs from the epilimnion.

Animals↗
PubMed2001

Difference in exposure to airborne major rat allergen (Rat n 1) and to endotoxin in rat quarters according to tasks.

UNLABELLED: Endotoxins found in occupational settings constitute a risk factor in the severity of respiratory allergic symptoms. OBJECTIVES: To assess the airborne concentrations of major rat allergen (Rat n 1) and endotoxin under various circumstances. METHODS: We took 483 airborne samples from 12 sites: 114 individual samples for endotoxin measurements and 113 for Rat n 1, from 38 workers (nine animal technicians, nine laboratory technicians, nine scientists and 11 students); and 256 static samples in rat rooms and experimental rooms, with or without disturbance, for simultaneous endotoxin and Rat n 1 measurements. Rat n 1 was measured with a two-site monoclonal ELISA and endotoxins with the Limulus method. RESULTS: Airborne Rat n 1 and endotoxin were significantly higher in rat rooms than in experimental rooms. Animal technicians had the greatest exposure to both Rat n 1 and endotoxin. Cage cleaning and rat feeding induced the highest exposure to Rat n 1 and endotoxin. Furthermore, we observed no significant difference in endotoxin exposure between researchers with or without rat contact during the sample period. There was no correlation between the number of rats present and airborne endotoxin concentrations. CONCLUSIONS: Exposure to airborne Rat n 1 and endotoxin is higher during cleaning and feeding tasks than during any other task, we feel that a major source of both is contaminated bedding that becomes airborne during disturbance.

Air Pollutants, Occupational↗
PubMed2001

The actor-observer effect in virtual reality presentations.

The use of virtual reality (VR) presentations are becoming a more and more frequent means of communicating information and displaying data to large groups of viewers. VR presentations put heavy demands on reproduction of visual, aural, and tactile information. A common situation in VR presentations is that one actor acts in the virtual environment (VE), while a group of people observes the actors actions in the VE, often from the perspective of the actor. The current paper aims to study actors' (participants actively interacting with the VE) and observers' (participants passively observing the actors' interaction with the VE) evaluations of the VR presentation. In an experiment, 16 actors and 16 observers either acted in or observed a VE and performed ratings of the quality of the presentation. The results showed that actors experienced higher presence and realism, and enjoyed the VR experience more than observers did. Observers, on the other hand, experienced that external events distracted their attention more than actors did. Finally, actors experienced more symptoms of simulation sickness. However, no differences between actors and observers were found for ratings of audio quality.

Adult↗
PubMed2001

Cytochrome P450 expression and related metabolism in human buccal mucosa.

Constituents in food and fluids, tobacco chemicals and many drugs are candidates for oral absorption and oxidative metabolism. On this basis, the expression of cytochrome P450 isozymes (CYPs) and the conversion of CYP substrates were analysed in reference to buccal mucosa. A RT-PCR based analysis of human buccal tissue from 13 individuals demonstrated consistent expression of mRNA for the CYPs 1A1, 1A2, 2C, 2E1, 3A4/7 and 3A5. CYP 2D6 was expressed in six out of the 13 specimens, whereas all samples were negative for 2A6 and 2B6. Serum-free monolayer cultures of the Siman virus 40 large T-antigen-immortalized SVpgC2a and the carcinoma SqCC/Y1 buccal keratinocyte lines expressed the same CYPs as tissue except 3A4/7 and 3A5 (SVpgC2a), and 2C, 2D6 and 3A4/7 (SqCC/Y1). Dealkylation of ethoxyresorufin and methoxyresorufin in both normal and transformed cells indicated functional 1A1 and 1A2, respectively. SVpgC2a showed similar activity as normal keratinocytes for both substrates, whereas SqCC/Y1 showed about 2-fold lower 7-ethoxyresorufin O-deethylation and 7-methoxyresorufin O-demethylation activities. SVpgC2a showed detectable and many-fold higher activity than the other cell types towards chlorzoxazone, a substrate for 2E1. Absent or minute catalytic activity of 2C9, 2D6 and 3A4 in the various cell types was indicated by lack of detectable diclofenac, dextromethorphan and testosterone metabolism (<0.2-0.5 pmol/min/mg). Metabolic activation of the tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the mycotoxin aflatoxin B1 (AFB1) to covalently bound adducts was indicated by autoradiographic analysis of both monolayer and organotypic cultures of SVpgC2a. In contrast, SqCC/Y1 showed lower or absent metabolic activity for these substrates. Finally, measurements of various non-reactive AFB1 metabolites indicated rates of formation <0.1 pmol/min/mg in both normal and transformed cells. The results indicate presence of several CYPs of which some may contribute to significant xenobiotic metabolism in human buccal epithelium. Notably, metabolic activation of AFB1 was not previously implicated for oral mucosa. Further, the results show that CYP-dependent metabolism can be preserved or even activated in immortalized keratinocytes. Metabolic activity in SVpgC2a under both monolayer and organotypic culture conditions suggests that this cell line may be useful to pharmaco-toxicological and carcinogenesis studies.

Aflatoxin B1↗
PubMed2001

The use of dGPS and simultaneous metabolic measurements during orienteering.

PURPOSE: The Global Positioning System (GPS) is a satellite-based system for navigation. With this system, it is possible to pinpoint a subject's location on earth and to display the speed of movement. With the use of differentiation (dGPS), the accuracy of the GPS position and speed measurements can be improved. Our purpose was to investigate whether it would be possible to relate dGPS data with physiological variables in a field test and thus achieve a more controlled field test and hence improve the value of sport-specific testing. METHODS: 10 male orienteers were equipped with a portable metabolic gas analyzer and a differential Global Positioning System (dGPS). A field test was performed on a 4.3-km orienteering course. Oxygen uptake, carbon dioxide excretion, and heart rate were determined every 10 s. Speed was calculated by Doppler shift every 2 s and by differences in dGPS time and position. Validation of dGPS position, distance, and speed measurements was made on two fixed positions and on a 115-m straight asphalt road. RESULTS: The orienteers' route was visualized by the dGPS equipment. Detailed analysis of running speed in different sections of the course was made possible. Further, it was possible to relate each physiological data to the location of the subject. The correlation coefficient between speed measured by dGPS and speed measured by chronometry was r = 0.9995-0.9996. The mean errors of distance and position measurements were 0.04-0.7% and 1.94-2.13 m, respectively. CONCLUSION: dGPS was shown to be a method that could give detailed information about a subject's speed and position. It was further demonstrated that physiological variables could be related to dGPS data.

Acceleration↗
PubMed2001

Extensive allelic variation among Francisella tularensis strains in a short-sequence tandem repeat region.

Members of the genus Francisella and the species F. tularensis appear to be genetically very similar despite pronounced differences in virulence and geographic localization, and currently used typing methods do not allow discrimination of individual strains. Here we show that a number of short-sequence tandem repeat (SSTR) loci are present in F. tularensis genomes and that two of these loci, SSTR9 and SSTR16, are together highly discriminatory. Labeled PCR amplification products from the loci were identified by an automated DNA sequencer for size determination, and each allelic variant was sequenced. Simpson's index of diversity was 0.97 based on an analysis of 39 nonrelated F. tularensis isolates. The locus showing the highest discrimination, SSTR9, gave an index of diversity of 0.95. Thirty-two strains isolated from humans during five outbreaks of tularemia showed much less variation. For example, 11 of 12 strains isolated in the Ljusdal area, Sweden in 1995 and 1998 had identical allelic variants. Phenotypic variants of strains and extensively cultured replicates within strains did not differ, and, for example, the same allelic combination was present in 55 isolates of the live-vaccine strain of F. tularensis and another one was present in all 13 isolates of a strain passaged in animals. The analysis of short-sequence repeats of F. tularensis strains appears to be a powerful tool for discrimination of individual strains and may be useful for a detailed analysis of the epidemiology of this potent pathogen.

Alleles↗
PubMed2001

Monitoring of persistent organic pollutants (POPs): examples from Lake Vättern, Sweden.

Lake Vättern in southern Sweden is a large oligotrophic lake with high surface to catchment area ratio (ca. 0.4) and a water residence time of 60 years. The lake combines sensitivity to atmospheric POP-pollution with general susceptibility for effects of POPs and slow concentration decline. Time series, from the 1960s until 1996, of PCBs and DDT in fish and data on TCDD in sediment of L. Vättern are presented and compared to other large lakes. The long time dataset of POPs in Arctic char (Salvelinus salvelinus) shows a significant annual decline of about 5% for PCBs and 13% for DDT. These rates are in agreement with other studies. Nutrients as well as biological effects and factors affecting the fate of POPs in oligotrophic lakes with long residence times are discussed. We propose that oligotrophic clear lakes are important ecosystems for monitoring POPs in biota.

Animals↗
PubMed2000

Efficacy of ceftibuten in 5 versus 10 days treatment of recurrent acute otitis media in children.

OBJECTIVE: in recurrent acute otitis media (AOM) several alternative treatments are suggested, e.g. cephalosporins. Information about the optimal duration of treatment in recurrent AOM is sparse. The aim of the present study was to compare the efficacy of ceftibuten in 5 versus 10 days treatment in recurrent AOM in children. METHODS: this was a single-blind (doctor blinded), randomized, multicentre study with two parallel groups. Eleven investigators at six centres in the west of Sweden enrolled a total of 180 patients. Outpatients with a new clinical AOM within 1 month were randomized to 5 or 10 days treatment with ceftibuten, 9 mg/kg/day, as a single dose. RESULTS: the mean age of the patients was 1.2 years (range 6 months-8 years). The patients had on average had three antibiotic treatments during the preceding 12 months. The recurrence rates in the 5- and 10-day groups were 21.4 and 4.5%, respectively, at first follow-up visit day 12 (P=0.001). The total recurrence rates between the two groups during the whole follow-up period of 40 days, 35 and 30%, respectively, did not differ significantly. The rate of recurrence did not correlate to nasopharyngeal findings of Streptococcus pneumoniae or Haemophilus influenzae. Pneumococci with decreased susceptibility to penicillin were found in 5% of all pneumococci, and beta-lactamase producing H. influenzae in 8%. Adverse events were reported less frequently in the 5- compared with the 10-day treatment group. CONCLUSION: this study on young children with recurrent otitis media has shown no statistical difference between ceftibuten given once daily for 5 and 10 days as determined on day 40. The 10-day treatment was significantly better at early follow-up.

Acute Disease↗
PubMed2000

Relative systemic dose potency and tolerability of inhaled formoterol and salbutamol in healthy subjects and asthmatics.

OBJECTIVES: To compare the relative systemic dose potency and tolerability of inhaled formoterol and salbutamol and to describe elimination of formoterol, particularly any enantioselectivity. METHODS: Twelve healthy subjects, aged 18-28 years, completed three open study days, and eleven asthmatic patients, aged 20-56 years, completed four double-blind study days in randomised, placebo-controlled and crossover fashions. The healthy subjects inhaled 13.5 + 13.5 + 27 microg formoterol (Oxis) via Turbuhaler and 300 + 300 + 600 microg salbutamol (Ventoline) via a pressurised metered dose inhaler (pMDI). The asthmatics, being on formoterol 9 microg twice daily via Turbuhaler during the study, inhaled the same single doses as the healthy subjects plus 900 + 900 + 1800 microg salbutamol via pMDI. Doses were given cumulatively 30 min apart on separate study days. Placebo was a day of no treatment in the healthy subjects. Double dummies were used for the asthmatics. Cardiovascular and metabolic effects were evaluated. Elimination of formoterol was addressed in the healthy subjects. RESULTS: Formoterol was estimated to be 28-109 times as potent as salbutamol, depending on the systemic effect variable. The duration of systemic action seemed to differ marginally at approximately equieffective doses of formoterol and salbutamol. Systemic effects were well tolerated and tended to be more pronounced in the healthy subjects than in the asthmatic patients. The half-life of the pharmacologically more active (R;R)-formoterol was longer than that of (S;S)-formoterol. CONCLUSIONS: Systemically, formoterol was shown to be 28-109 times as potent as salbutamol. Equieffective doses seemed to have a similar duration of effect. Formoterol and salbutamol were well tolerated by healthy subjects up to the tested total doses of 54 microg and 1200 microg, respectively, and by asthmatic patients up to the tested total doses of 54 microg and 3600 microg, respectively. Elimination of formoterol was enantioselective.

Administration, Inhalation↗