| 1. |
- Johansson, A, et al.
(författare)
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Epitope specificity of monoclonal anticytokeratin antibody TS1
- 1999
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Ingår i: Cancer Res 1999;59:45-51.
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Tidskriftsartikel (refereegranskat)abstract
- Due to their abundance in epithelial cells and deposition in necrotic regions intratumorally, cytokeratins (CKs) have been established as valuable targets for both radioimmunolocalization and radioimmunotherapy. The target epitope for the monoclonal anti-CK8 antibody, TS1, used for both experimental radioimmunolocalization and radioimmunotherapy, was determined by means of synthesis of 96 overlapping peptides that covered the entire CK8 molecule. A highly conserved peptide sequence, spanning amino acids (aa) 343357 and covering the discontinuous epitope in the helical 2B domain, was identified. The epitope retains its helical structure, as shown with circular dichroism spectroscopy, although the length of the peptide (i.e., >20 aa) is crucial for maintenance of immunoreactivity. To determine which aa residues are crucial for binding to the monoclonal antibody, alanine scanning was performed on a 26-mer covering aa 340365, with the sequence RGELAIKDANAKLSELEAALQRAKQ. The 26 modified peptides were evaluated using ELISA and BIAcore technology. The uniqueness of this epitope has been established by data base sequence comparisons
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| 2. |
- Johansson, M L, et al.
(författare)
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Survival of Lactobacillus plantarum DSM 9843 (299v), and effect on the short-chain fatty acid content of faeces after ingestion of a rose-hip drink with fermented oats
- 1998
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Ingår i: International Journal of Food Microbiology. - 0168-1605. ; 42:1-2, s. 29-38
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Tidskriftsartikel (refereegranskat)abstract
- In a controlled and randomised double-blind study, 26 healthy adult volunteers consumed, for 21 d, 400 ml of a rose-hip drink containing oats (0.7 g/100ml) fermented with Lactobacillus plantarum DSM 9843 (RHL; containing 5 x 10(7) cfu ml(-1)), and 22 volunteers in a second group the same amount of a pure rose-hip drink (RH). Significant increases in the total faecal concentration of carboxylic acids (P < 0.05 after 1 week and P < 0.01 after 3 weeks of intake), acetic acid (P < 0.01 after 3 weeks of intake) and propionic acid (P < 0.01 after 3 weeks of intake and P < 0.05 eight days after intake ceased) were recorded in the RHL group, indicating increased fermentation in the colon. In both groups a significant increase was obtained in the concentration of faecal lactic acid (P < 0.001 after 1 and 3 weeks of intake). No changes were seen in the concentration of faecal butyrate. The numbers of faecal bifidobacteria and lactobacilli increased significantly in both groups after 3 weeks of intake. Sulphite-reducing clostridia rapidly decreased in the group receiving the product with Lb. plantarum DSM 9843 after 1 week of intake, and then also in the pure rose-hip group after 3 weeks of intake. No changes were seen in the numbers of total anaerobes, gram-negative anaerobes or total aerobes during administration. Lb. plantarum DSM 9843 was recovered in faeces from all volunteers in the RHL group. Median amounts were 7.0 (5.0-8.8) log10 cfu g(-1) after one week of intake, and 6.7 (5.0-8.9) log10 cfu g(-1) after 3 weeks, respectively. The strain was still recovered from faeces of five volunteers 8 d after administration ceased (> 4.8 log10 cfu g(-1)). During the period of intake the volunteers in the RHL group experienced a significant increase in stool volume, a significant decrease in flatulence and slightly softer stools. Volunteers in the RH group experienced a slight but significant decrease in stool volume.
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| 3. |
- Fjälling, M, et al.
(författare)
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Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.
- 1996
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:9, s. 1519-21
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Tidskriftsartikel (refereegranskat)abstract
- A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.
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| 4. |
- Hakansson, Sara, et al.
(författare)
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Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer
- 1997
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 60:5, s. 1068-1078
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.
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| 5. |
- Andersson, Sven, et al.
(författare)
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Physiological characterization of mBSA antigen induced arthritis in the rat. II. Joint blood flow, glucose metabolism, and cell proliferation
- 1998
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 25:9, s. 1778-1784
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Based on the hypothesis that blood flow in the inflamed joint is inadequate to maintain aerobic glycolysis, we sought to estimate the correlation between blood flow, glucose metabolism, and cellular proliferation rate in the arthritic joint. METHODS: Experiments were performed on rats with antigen induced arthritis (AIA). Regional blood flows (RBF) were measured with the microsphere technique, glucose metabolism by determination of [14C]2-deoxy-D-glucose (2-DG) uptake, and the proliferative response as the incorporation of [3H]-thymidine. RESULTS: In periarticular soft tissue of the arthritic knee the only significant change in the weight related RBF was an approximate 70% rise on Day 14 after arthritis onset. The RBF was lowest on Day 3 and the time course for the changes was inversely related to intensity of vascular inflammation. Weight related 2-DG uptake was more elevated than the RBF and peaked on Day 3. [3H]-thymidine incorporation in the soft tissue was only markedly enhanced on Day 3. Neither 2-DG nor [3H]-thymidine uptake was affected by treatment with methotrexate or indomethacin. In epiphyseal bone RBF was reduced on the first day of arthritis, but steadily increased thereafter. CONCLUSION: In AIA an intense vascular leakiness negatively affects the synovial blood. There is a marked enhancement of glucose metabolism, but only a minor part of this increase seems to be induced by increased cellular proliferation.
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| 6. |
- Andersson, Sven, et al.
(författare)
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Tissue and intracellular pH in normal periarticular soft tissue and during different phases of antigen induced arthritis in the rat
- 1999
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 26:9, s. 2018-2024
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To measure intracellular and tissue pH in periarticular soft tissue during different phases of antigen induced arthritis in the rat. METHODS: pH was calculated using the following values: (1) the distribution of [14C]-dimethyl-oxazolidinedione; (2) the total tissue water and the extracellular space water volume, which was measured as [14C]-sucrose distribution in nephrectomized rats. Experiments were performed during both maximal inflammation (Day 3) and the restorative phase (Day 14). RESULTS: In all animals both tissue (pHt) and intracellular (pHi) pH were lower in arthritic joints than in the contralateral control. Mean pHt in control joints was 7.37+/-0.03. In arthritic rats it was 7.30+/-0.05 on Day 3 after challenge and 7.27+/-0.03 on Day 14. The pHi ranges were 6.86-7.81 for controls, 6.65-7.28 for arthritis Day 3, and 5.66-6.91 for arthritis Day 14. CONCLUSION: In this model there is a reduction in pH in the periarticular tissue of arthritic joints. The magnitude is, however, relatively small and the pannus tissue is not uniquely acidic in comparison with other compartments. There does not seem to be a correlation between pH and changes in metabolic balance, pannus formation, or healing.
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| 7. |
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