| 1. |
- Gustafson, Stefan, et al.
(författare)
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Accessible hyaluronan receptors identical to ICAM-1 in mouse mast-cell tumours
- 1995
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Ingår i: Glycoconjugate Journal. - 0282-0080 .- 1573-4986. ; 12:3, s. 350-355
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Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemical studies of the hyaluronan (HA)-receptor (R), originally found on liver endothelial cells (LEC) and related to the intercellular adhesion molecule 1 (ICAM-1), showed that polyclonal antibodies against HARLEC (HA receptor on LEC) also stain structures in mouse mastocytomas, mainly vessels. To test if intravenously administered HA might target the tumour receptors in vivo, mice carrying an inoculated mastocytoma in one hind leg muscle were injected in the tail vein with 125I-tyrosine (T)-labelled HA and killed 75 min after injection when organs and tissues were checked for radioactivity. When doses exceeding the binding capacity of the liver were injected, a significant increase in radioactivity (up to five-fold) within the tumour tissue was found. The weight adjusted difference between control and tumour tissue was greater for smaller tumours, probably due to necrosis in the larger. HA-staining of tumours from animals receiving 125I-T-HA, showed HA in areas that also stained weakly for ICAM-1 using monoclonal antibodies. ICAM-1 staining was dramatically increased after hyaluronidase treatment of the sections, indicating that the HA is bound to these receptors and thereby blocks antibody recognition.
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| 2. |
- Josephson, Staffan, et al.
(författare)
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Proteinläkemedel kan nu skräddarsys
- 1997
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 94:30-31, s. 2650-2653
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Kalbro, Thomas, 1951-, et al.
(författare)
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Valuing Easements : Some Experimental Evidence
- 1999
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Ingår i: Journal of Real Estate Research. - 0896-5803. ; 18:3, s. 491-502
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Tidskriftsartikel (refereegranskat)abstract
- Trefzger and Munneke (1998) present a theoretical model, where the surplus that an easement gives rise to will be split equally between the parties. We provide experimental evidence from Sweden indicating that the split of the surplus depends on the context and what is judged to be reasonable principles of a fair distribution. The dominant estates got a significantly higher share of the surplus because they could start the bargaining with a bid that only included compensation for cost, whereas the servient estate could not find any principle that would give them the whole surplus. After these initial asymmetric bids, the parties usually met halfway.
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| 4. |
- Lind, Lars, et al.
(författare)
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Endothelium-dependent vasodilatation in treated and untreated hypertensive subjects
- 1999
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 8:3, s. 158-164
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Tidskriftsartikel (refereegranskat)abstract
- It has repeatedly been shown that endothelium-dependent vasodilatation (EDV) is impaired in patients with untreated hypertension. The effect of antihypertensive treatment on EDV has, however, not been extensively investigated. In the present study, EDV and endothelium-independent vasodilatation (EIDV) were studied in 20 untreated and 41 treated hypertensive subjects and in 26 matched, normotensive controls by means of infusion of methacholine (MCh), 2 and 4 microg/min, evaluating EDV, and nitroprusside (SNP), 5 and 10 microg/min, evaluating EIDV, in the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The vasodilatory action of MCh was impaired in untreated hypertensives compared with controls, with the response in the treated hypertensives in between the other two groups (p < 0.01 vs both of the other groups). EIDV, on the other hand, was enhanced in the treated hypertensives (p < 0.01), so that the MCh to SNP FBF ratio, an index of endothelial function, was attenuated in both treated and untreated hypertensives (0.97 +/- 0.24 and 0.96 +/- 0.15, respectively), compared with controls (1.27 +/- 0.29, p < 0.001). Both EDV and EIDV declined with increasing number of antihypertensive drugs used in the treated hypertensives (p < 0.05). In conclusion, the endothelial function index was found to be similarly depressed in both treated and untreated hypertensive subjects compared with normotensive controls. Antihypertensive therapy seems to improve the vasodilatory capacity in general rather than enhancing endothelial function.
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| 5. |
- Lind, Lars, et al.
(författare)
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Endothelium-dependent vasodilation and structural and functional changes in the cardiovascular system are dependent on age in healthy subjects
- 1999
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Ingår i: Clinical Physiology. - : Wiley. - 0144-5979 .- 1365-2281. ; 19:5, s. 400-409
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate possible associations between endothelium-dependent vasodilatation (EDV) and cardiovascular structure and function. EDV could influence peripheral resistance and be affected by atherosclerosis and might thereby influence indices of cardiovascular structure and function. In a group of 31 apparently healthy men and 25 women (age range 20-69 years), EDV was evaluated by infusion of metacholine (4 micrograms min-1), and endothelium-independent vasodilatation (EIDV) was assessed by nitroprusside infusion (SNP, 10 micrograms min-1) in the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Left ventricular (LV) geometry and function and the intima-media thickness in the carotid artery were assessed by ultrasonography. The stroke index to pulse pressure ratio was used to evaluate arterial compliance. Several indices of cardiovascular structure and function were found to be related to an index of endothelial function, the EDV to EIDV ratio. Furthermore, left ventricular mass (LVM), the atrio-ventricular plane displacement, E/A ratio, IVRT, the intima-media thickness of the carotid artery and arterial compliance were all significantly related to both EDV and EIDV in women. However, most indices of cardiovascular structure and function, as well as endothelial function, change with age and only the relation between LV diastolic function and endothelial function in men remained significant (P < 0.05) after including age in multiple regression analysis. Age was related to both cardiovascular structure and function, as well as to endothelial function. Multiple regression analysis showed that ageing generally affects cardiovascular characteristics and endothelial function in parallel in these healthy subjects.
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| 6. |
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| 7. |
- Lind, Thomas, et al.
(författare)
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cDNA cloning and expression of UDP-glucose dehydrogenase from bovine kidney
- 1999
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Ingår i: Glycobiology. - 0959-6658 .- 1460-2423. ; 9:6, s. 595-600
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Tidskriftsartikel (refereegranskat)abstract
- We have isolated a cDNA encoding UDP-glucose dehydrogenase from a bovine kidney cDNA-library, the first mammalian cDNA clone published. [After submission of the manuscript, a study appeared describing the molecular cloning and characterization of the human and mouse UDP-glucose dehydrogenase genes(Spicer et al., 1998).] The enzyme catalyzes the conversion of UDP-glucose to UDP-glucuronicacid, an essential precursor in glycosaminoglycan biosynthesis. The cDNA has an open reading frame of 1482 nucleotides coding for a 55 kDa protein. Expression of the enzyme in COS-7 cells showed a 3-fold increase inUDP-glucose dehydrogenase activity; also, the C-terminal 23 amino acidswas shown not to be necessary for enzyme activity. Northernblots from human and mouse tissues reveal high expression in liver and low in skeletal muscle. Human tissues have a majortranscript size of 3.2 kilobases and a minor of 2.6 whereas mousetissues have a single 2.6 kilobase transcript. We have also developed a sensitive and direct assay using UDP-[14C]Glc as a substrate for detection of small amounts of UDPGDH activity.
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| 8. |
- Lind, Thomas
(författare)
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Enzymes involved in heparan sulfate chain elongation : Function of a novel family of tumor suppressors?
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heparan sulfate (HS) is a glycosaminoglycan associated with many physiological functions such as regulation of growth factor action and cell adhesion. The HS polysaccharide is synthesized by alternating addition of D-glucuronic acid (GlcA) and N-acetyl-D-glucosamine (GlcNAc) units from the corresponding UDP-sugar precursors. Due to subsequent modifications including epimerization and sulfation the resultant polymer has a highly heterogeneous structure.The aims of this work were to isolate the enzymes involved in HS chain elongation and to also characterize a functionally similar bacterial enzyme, KfiC. An additional aim was to clone and express UDP-glucose dehydrogenase, i.e. the enzyme generating UDP-GlcA, one of the precursors in HS chain elongation.A single protein associated with the two glycosyltransferase activities (HS-POL) was purified from bovine serum. Cloning and expression of the protein confirmed its activities. HS-POL was identified as EXT2, a gene associated with hereditary multiple exostoses. This human skeletal disorder, characterized by multiple cartilaginous tumors, is ascribed to mutations in three putative tumor suppressor genes, denoted EXT1-3. EXT1 also showed HS-POL activities, implying that both EXT1 and EXT2 are glycosyltransferases required for HS biosynthesis.Bovine UDP-glucose dehydrogenase was cloned and expressed. Both a full length and a truncated form of the protein yielded UDP-glucose dehydrogenase activity.In the bacterial protein KfiC two aspartic acid residues suggested to be critical for the β-glycosyltransferase reaction were found. By site directed mutagenesis these residues were shown to be essential for GlcA transfer.
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| 9. |
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| 10. |
- Lind, Thomas, et al.
(författare)
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The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate
- 1998
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 273:41, s. 26265-26268
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary multiple exostoses, characterized by multiple cartilaginous tumors, is ascribed to mutations at three distinct loci, denoted EXT1-3. Here, we report the purification of a protein from bovine serum that harbored the D-glucuronyl (GlcA) and N-acetyl-D-glucosaminyl (GlcNAc) transferase activities required for biosynthesis of the glycosaminoglycan, heparan sulfate (HS). This protein was identified as EXT2. Expression of EXT2 yielded a protein with both glycosyltransferase activities. Moreover, EXT1, previously found to rescue defective HS biosynthesis (McCormick, C., Leduc, Y., Martindale, D., Mattison, K., Esford, L. E., Dyer, A. P., and Tufaro, F. (1998) Nat. Genet. 19, 158-161), was shown to elevate the low GlcA and GlcNAc transferase levels of mutant cells. Thus at least two members of the EXT family of tumor suppressors encode glycosyltransferases involved in the chain elongation step of HS biosynthesis.
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| 11. |
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| 12. |
- Tsuchida, Kazunori, et al.
(författare)
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Purification and characterization of fetal bovine serum beta-N-acetyl-D-galactosaminyltransferase and beta-D-glucuronyltransferase involved in chondroitin sulfate biosynthesis
- 1999
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 264:2, s. 461-467
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Tidskriftsartikel (refereegranskat)abstract
- beta-N-Acetylgalactosaminyltransferase II and beta-glucuronyltransferase II, involved in chondroitin sulfate biosynthesis, transfer an N-acetylgalactosamine (GalNAc) and glucuronic acid (GlcA) residue, respectively, through beta-linkages to an acceptor chondroitin oligosaccharide derived from the repeating disaccharide region of chondroitin sulfate. They were copurified from fetal bovine serum approximately 2500-fold and 850-fold, respectively, by sequential chromatographies on Red A-agarose, phenyl-Sepharose, S-Sepharose and wheat germ agglutinin-agarose. Identical and inseparable chromatographic profiles of both glycosyltransferase activities obtained through the above chromatographic steps and gel filtration suggest that the purified enzyme activities are tightly coupled, which could imply a single enzyme with dual transferase activities; beta-N-acetylgalactosaminyltransferase and beta-glucuronyltransferase, reminiscent of the heparan sulfate polymerase reaction. However, when a polymerization reaction was performed in vitro with the purified serum enzyme preparation under the polymerization conditions recently developed for the chondroitin-synthesizing system, derived from human melanoma cells, each monosaccharide transfer took place, but no polymerization occurred. These results may suggest that the purified serum enzyme preparation contains both beta-N-acetylgalactosaminyltransferase II and beta-glucuronyltransferase II activities on a single polypeptide or on the respective polypeptides forming an enzyme complex, but is different from that obtained from melanoma cells in that it transfers a single GalNAc or GlcA residue but does not polymerize chondroitin.
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