Per-Anders Larsson
University of Gothenburg
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Featured researches published by Per-Anders Larsson.
Acta Oncologica | 1996
Per-Anders Larsson; Göran Carlsson; Bengt Gustavsson; Wilhelm Graf; Bengt Glimelius
The pharmacokinetics after 20 min intravenous infusion or a 2 min bolus (push) injection of 5-fluorouracil (500 mg/m2) were studied in 14 colorectal cancer patients. Treatment effects and toxicity related to the administration technique of 5-fluorouracil were retrospectively analysed in 198 colorectal cancer patients. The AUC after bolus injection was 6158 +/- 874 micromol/l*min compared to 3355 +/- 428 micromol/l*min after short-time infusion of 5-fluorouracil (p < 0.01). The mean peak-level after bolus injection was 341 +/- 34 microM versus 161 +/- 17 microM after a short-time infusion (p < 0.01). Patients receiving bolus injections had significantly better treatment result (32% partial remission) than patients receiving infusion (10% partial remissions, p < 0.001). Toxic side-effects were more frequently encountered after bolus injection but subjective improvement was also more frequently experienced by these patients. Bolus 5-fluorouracil push injection rather than a short-time infusion appears to be the more efficient administration technique.
Journal of Microscopy | 1989
Annica Dahlström; T. Kling-Petersen; S. Bööj; K. Lundmark; Per-Anders Larsson
This paper describes in detail a cytofluorimetric scanning technique used for studying amounts of material axonally transported in antero‐ and retrograde direction in peripheral nerves. Operating procedures, preparation of tissues and instrumental set‐up are described. The basis for quantification of material in a nerve section treated for immunofluorescence is discussed. The reliability of the method has been tested by comparing results with biochemical data. There are several advantages of the technique. (1) Many different substances can be studied in one single nerve segment, thus reducing biological variation and costs. (2) Both morphological data and quantitative figures can be obtained; following scanning the section can be photographed. (3) The method can also be used on studies in the central nervous system and on tissue cultures, since it is possible to scan on single axons or bundles of fibres.
Journal of Chromatography B: Biomedical Sciences and Applications | 1999
Elisabeth Odin; Yvonne Wettergren; Lars Larsson; Per-Anders Larsson; Bengt Gustavsson
The aim of this study was to evaluate a direct and automated post-polymerase chain reaction (PCR) detection system to simultaneously determine the relative gene expression levels of nine cancer-related human genes. Total RNA was prepared from flash-frozen biopsies derived from human colorectal tumors or normal mucosa and reverse-transcribed to cDNA which was PCR-amplified using primer pairs corresponding to the studied genes. In each reaction, the forward primer was labeled with a fluorescent dye. The PCR products were pooled and an internal size standard with a uniquely colored fluorescent dye was added. The samples were then subjected to automated capillary gel electrophoresis. Fragment analysis software was used to calculate the relative gene expression using beta-actin as the reference gene. We found that automated capillary gel electrophoresis with multicolor detection is a rapid, accurate and highly reproducible method for separation and quantification of PCR-amplified cDNA.
Cancer Investigation | 1998
Elisabeth Odin; Göran Carlsson; Frösing R; Bengt Gustavsson; Colin Paul Spears; Per-Anders Larsson
The in vitro stability and plasma pharmacokinetics of 5,10-methylenetetrahydrofolic acid (CH2FH4), tetrahydrofolic acid (FH4), 5-methyltetrahydrofolic acid (CH3FH4), and 5-formyltetrahydrofolic acid (5-CHOFH4) were studied in view of their potential usefulness in cancer chemotherapy. Analysis of reduced folates was done on a high-performance liquid chromatography (HPLC) system. The high sensitivity of FH4 and CH2FH4 to oxidation can be circumvented by use of high concentrations of the folates, addition of ascorbate, and by thorough exclusion of atmospheric O2. Intravenous injection of 200 mg FH4 or CH2FH4 resulted in average peak concentrations of 69.2 +/- 3.2 nmol/ml and 46.3 +/- 2.6 nmol/ml, respectively. The plasma concentration curves support the concept that these highly oxygen-sensitive reduced folates can be reliably administered as pharmaceuticals to cancer patients through the use of a suitable air-occlusive system for their preparation and administration.
Acta Oncologica | 1996
Per-Anders Larsson; Göran Carlsson; Bengt Gustavsson; C. Paul Spears
Knowledge of population thymidylate synthase (TS) levels in malignant tumors and normal tissues is essential for the use of TS as a predictor for 5-fluorouracil treatment. Tumor tissue TS levels in fresh frozen surgical biopsies from 136 patients with gastrointestinal or breast cancer, not previously subjected to chemotherapy, were analysed by [3H]FdUMP radioligand binding assay. TS levels were 2.4 +/- 0.31 pmol/g in liver metastases of colorectal cancer (n = 87), 4.2 +/- 1.0 pmol/g in primary colorectal cancer (n = 13), 2.7 +/- 0.93 pmol/g in gastric cancer (n = 13), 3.1 +/- 1.7 pmol/g in pancreatic cancer (n = 10), 3.4 +/- 1.4 pmol/g in breast cancer (n = 13) and 0.58 +/- 0.075 pmol/g in normal liver parenchyma (n = 24). TS levels were significantly higher in malignant tumor tissues compared to normal liver parenchyma.
Tumor Biology | 1998
Elisabeth Odin; Lars Larsson; Maddi Aram; Bengt Gustavsson; Per-Anders Larsson
A reverse transcriptase polymerase chain reaction (rt-PCR) for quantification of gene expression has been optimized for analysis of folylpolyglutamate synthase (FPGS) and thymidylate synthase (TS), using β-actin as an internal standard (house-keeping gene). Total RNA was isolated from tumor tissue, reversely transcribed to cDNA and PCR amplified with primers specific for TS, FPGS and β-actin in separate vials. PCR products were separated and quantified by high-pressure liquid chromatography (HPLC) without addition of radioactive or fluorescent markers, which minimizes labor and occupational hazards. The day-to-day variation in the HPLC analysis was 2.7% and the within sample variations for rt-PCR/HPLC analysis of TS and FPGS were 18.5% for both assays. This method provides a tool for convenient gene expression analysis in clinical biopsies.
Tumor Biology | 1996
Thomas A. Houze; Lars Larsson; Per-Anders Larsson; Goran Hansson; Alexzander Asea; Bengt Gustavsson
We describe a simplified and reliable polymerase chain reaction (PCR) method to quantify thymidylate synthase (TS) gene expression levels from clinical human tumor biopsy samples as small as 100 mg using the beta-actin housekeeping gene as a reference standard. The semiquantitative RT-PCR is carried out by the coamplification of the target template and an external competitor using primer pairs common to both templates in the same reaction vessel. Quantitative digital image analysis is performed directly after electrophoresis, thus mRNA quantification is done quickly and without the use of radioactive substances. The observed relative TS gene expression levels varied between 3- and 40-fold, but most of the values were grouped within a 10-fold range. There is an observed 89% correlation between TS mRNA expression and protein levels. These findings suggest that preliminary experiments used to determine the linear range of RT-PCR amplification in non-competitive semiquantitative PCR experiments, and the use of radioactive substances to quantify PCR products may be unnecessary.
Cell Biology International | 1996
Thomas A. Houze; Per-Anders Larsson; Kristoffer Hellstrand; Bengt Gustavsson
The secretion of interferon‐γ (IFN‐γ) by natural killer (NK) cells following in vitro stimulation with interleukin‐2 (IL‐2) is inhibited by co‐incubation with autologous monocytes at a transcriptional level by more than sixty‐fold. In this study, we investigate the nature of the inhibitory signal and particularly the role of reactive oxygen metabolites (ROMs). It was found that the inhibition of IFN‐γ was operating at a pre‐translational level, this was indicated by the inability of CD 56+‐enriched natural killer cells to accumulate IFN‐γ mRNA in the presence of elutriated monocytes. Both catalase, a scavenger of hydrogen peroxide and histamine, a biogenic amine which inhibits the generation of ROMs by monocytes, strongly abrogated the inhibition of IFN‐γ production. We thereby conclude that histamine behaves synergistically with IL‐2 at a transcriptional level to induce IFN‐γ even in an admixture of NK cells and monocytes.
Acta Oncologica | 1980
S. Bööj; Annica Dahlström; Per-Anders Larsson; K. Rosander; Bengt Rosengren
The content and intra-axonal transport of acetylcholine (ACh) and the cholinergic enzymes cholineacetyltransferase (CAT) and ACh-esterase (AChE) in sciatic nerve were investigated in rats following single dose proton irradiation of the lumbar intumescence of the spinal cord with 60 Gy or 200 Gy. One, 7 or 30 days after irradiation nerve-crush operations were performed 12 hours before killing and the levels of ACh and enzyme activities in nerve segments relative to the crushes were estimated by biologic (ACh) or chemical (enzyme) methods. The results indicate that alterations in intraneuronal dynamics of ACh and related enzymes are not a major cause for the development of neurologic symptoms of the motor system after irradiation, and that descending myelinated axons are of minor importance for the regulation of cholinergic substances in rat motor nerves.
Acta Oncologica | 2000
Per-Anders Larsson; Bengt Glimelius; Bengt Jeppsson; Per-Ebbe Jönsson; Martin Malmberg; Bengt Gustavsson; Göran Carlsson; Margit Svedberg
The present study was designed to study 5-FU pharmacokinetics after interferon. Weekly bolus 5-FU (500 mg/m2), immediately followed by leucovorin (60 mg/m2The present study was designed to study 5-FU pharmacokinetics after interferon. Weekly bolus 5-FU (500 mg/m2), immediately followed by leucovorin (60 mg/m2) was given in 14 weekly cycles to 55 gastrointestinal and breast cancer patients. Interferon-alpha was given on days 2, 4 and 6, starting from cycle 2 at a dose of 0.5 million units (MU) and stepwise increased to 12 MU in cycles 12 and 13. Five patients could not tolerate the treatment even at the lowest dose of interferon and 22 patients were unavailable for the pharmacokinetic analysis because of dose reductions of 5-FU. Five patients were able to follow the protocol to 12 MU, whereas most patients were unable to continue owing to toxicity. 5-FU pharmacokinetics was analysed every second cycle. Peak concentration and AUC were increased after 12 MU of interferon, but no other significant influence of interferon on pharmacokinetic parameters of 5-FU was observed.