| 1. |
- Karlsson, Caroline, et al.
(författare)
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5-Hydroxytryptamine contracts human uterine artery smooth muscle predominantly via 5-HT2 receptors
- 1997
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Ingår i: Human Reproduction. - 0268-1161. ; 12:2, s. 361-367
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Tidskriftsartikel (refereegranskat)abstract
- Serotonergic receptors were classified in the isolated human uterine artery with intact endothelium, using agonists and antagonists for 5-hydroxytryptamine (5-HT) receptors. The efficacy for different agonists rated: alpha-methyl-5-HT (5-HT2) = 5-HT (non-selective) = 2-methyl-5-HT (5-HT3) >> sumatriptan (5-HT1), and the potency as: sumatriptan = 5-HT > 5-HT > alpha-methyl-5-HT > 2-methyl-5-HT. The contractile effects of 5-HT and alpha-methyl-5-HT were antagonized by the 5-HT2 receptor antagonist ketanserin and the non-selective antagonist methiothepin. The efficacy of sumatriptan was comparatively low. No interaction was encountered between 2-methyl-5-HT and MDL72222, suggesting an absence of 5-HT3 receptors. The results indicate that the contractile serotonergic receptor population in the human uterine artery mainly comprises 5-HT2 receptors, although a minor contribution of contractile 5-HT1 receptors cannot be excluded.
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| 2. |
- Karlsson, Caroline, et al.
(författare)
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Characterization of 5-hydroxytryptamine receptors mediating circular smooth muscle contraction in the human umbilical artery
- 1999
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Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 47:2, s. 102-107
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Tidskriftsartikel (refereegranskat)abstract
- The study was performed to characterize pharmacologically the contractile 5-hydroxytryptamine (5-HT) receptors in the circular smooth muscle of the isolated human umbilical artery. Effects of agonists and antagonists for different 5-HT receptor subtypes were studied in intact endothelium vessel segments. All agonists induced concentration-dependent circular smooth muscle contractions. The potency was in declining order 5-HT > alpha-methyl-5-HT > sumatriptan >/= 2-methyl-5-HT. The effects of 5-HT and alpha-methyl-5-HT were antagonized by ketanserin, as well as methiothepin. The contractile effect of sumatriptan was antagonized by methiothepin but not by ketanserin. The 5-HT3 receptor antagonist, MDL 72222, did not affect the contraction by any of the agonists, including 2-methyl-5-HT. It is concluded that the 5-HT-induced contraction in the circular smooth muscle of the human umbilical artery seems to be mediated by a mixed population of 5-HT1-like receptors and 5-HT2 receptors.
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| 3. |
- Karlsson, C, et al.
(författare)
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Endothelium-derived prostanoids reduce 5-hydroxytryptamine-induced contraction in the human uterine artery
- 1998
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Ingår i: Human Reproduction. - 0268-1161. ; 13:7, s. 1947-1951
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of endothelium-linked mechanisms to the contraction induced by 5-hydroxytryptamine (5-HT) was investigated in the isolated human uterine artery. 5-HT contracted the uterine artery concentration-dependently. Removal of the endothelium or treatment with the cyclooxygenase inhibitor indomethacin potentiated the contractile response to 5-HT. The nitric oxide synthase inhibitor L-N(G)-monomethyl-arginine (L-NMMA) did not influence the contraction induced by 5-HT. Indomethacin did not affect the response to 5-HT in endothelium-denuded vessels. The 5-HT1 receptor agonist 5-carboxyamidotryptamine (5-CT) did not relax precontracted arteries. Removal of the endothelium did not change the response to 5-HT in the presence of the 5-HT(1B/D) receptor antagonist GR127935 and the 5-HT1A and 5-HT1B receptor antagonist -pindolol. The 5-HT1B receptor antagonist SB224289 did not affect the contraction induced by 5-HT. The results indicate that the 5-HT-induced contraction in the human uterine artery is accompanied by the release of an endothelium-derived relaxing factor (EDRF). This EDRF seems to be a prostanoid, probably prostacyclin (PGI2). The endothelium-linked mechanism seems to be mediated via a 5-HT1 receptor, but it is not possible to further classify the receptor subtype by the information obtained in this study.
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| 4. |
- Oohashi, T, et al.
(författare)
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Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues
- 1999
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Ingår i: Journal of Cell Biology. - 0021-9525. ; 145:3, s. 563-577
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Tidskriftsartikel (refereegranskat)abstract
- The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.
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| 5. |
- Gärdlund, B, et al.
(författare)
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Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. The Heparin Prophylaxis Study Group.
- 1996
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Ingår i: The Lancet. - : Elsevier BV. - 0140-6736 .- 1474-547X. ; 347:9012, s. 1357-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fatal pulmonary embolism and other thromboembolic complications are common in hospital inpatients. However, there is little evidence on the routine use of pharmacological thromboprophylaxis in non-surgical patients. We assessed the efficacy and safety of low-dose heparin in the prevention of hospital-acquired, clinically relevant, fatal pulmonary embolism in patients with infectious diseases.METHODS: Our study used the postrandomisation consent design. 19,751 consecutive patients, aged 55 years or older, admitted to departments of infectious diseases in six Swedish hospitals, were screened for inclusion in the randomised, controlled, unblinded, multicentre trial. Of the eligible patients, 5776 were assigned subcutaneous standard heparin (5000 IU every 12 h) until hospital discharge or for a maximum of 3 weeks; 5917 were assigned no prophylactic treatment (control group). We sought consent only from the heparin group. Follow-up was for 3 weeks after discharge from hospital or for a maximum of 60 days from randomisation. The primary endpoint was necropsy-verified pulmonary embolism of predefined clinical relevance.FINDINGS: By intention-to-treat analysis mortality was similar in the heparin and control groups (5.3 vs 5.6%, p = 0.39) and the median time from admission to death was 16 days in both groups (IQR 8-31 vs 6-28 days). Necropsy-verified pulmonary embolism occurred in 15 heparin-treated and 16 control-group patients. There was a significant difference between heparin and control groups in median time from randomisation to fatal pulmonary embolism (28 [24-36] vs 12.5 [10-20] days, p = 0.007). This difference corresponds to the duration of heparin prophylaxis. Non-fatal thromboembolic complications occurred in more of the control than of the heparin group (116 vs 70, p = 0.0012).INTERPRETATION: Our findings do not support the routine use of heparin prophylaxis for 3 weeks or less in large groups of non-surgical patients. Further studies are needed to investigate whether heparin prophylaxis of longer duration may prevent fatal pulmonary embolism.
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| 6. |
- Lindblom, Anders, et al.
(författare)
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The intrinsic factor-vitamin B12 receptor, cubilin, is assembled into trimers via a coiled-coil alpha-helix
- 1999
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 274:10, s. 6374-6380
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Tidskriftsartikel (refereegranskat)abstract
- A large protein was purified from bovine kidney, using selective extraction with EDTA to solubilize proteins anchored by divalent cation-dependent interactions. An antiserum raised against the purified protein labeled the apical cell surface of the epithelial cells in proximal tubules and the luminal surface of small intestine. Ten peptide sequences, derived from the protein, all matched the recently published sequences for rat (Moestrup, S. K., Kozyraki, R., Kristiansen, M., Kaysen, J. H., Holm Rasmussen, H., Brault, D., Pontillon, F., Goda, F. O., Christensen, E. I., Hammond, T. G., and Verroust, P. J. (1998) J. Biol. Chem. 273, 5235-5242) and human cubilin, a receptor for intrinsic factor-vitamin B12 complexes, identifying the protein as bovine cubilin. In electron microscopy, a three-armed structure was seen, indicating an oligomerization of three identical subunits. This model was supported by the Mr values of about 1,500,000 for the intact protein and 440,000 for its subunits obtained by analytical ultracentrifugation. In a search for a potential assembly domain, we identified a region of heptad repeats in the N-terminal part of the cubilin sequence. Computer-assisted analysis supported the presence of a coiled-coil alpha-helix between amino acids 103 and 132 of the human cubilin sequence and predicted the formation of a triple coiled-coil. We therefore conclude that cubilin forms a noncovalent trimer of identical subunits connected by an N-terminal coiled-coil alpha-helix.
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| 7. |
- Olaison, Lars, 1949, et al.
(författare)
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Incidence of beta-lactam-induced delayed hypersensitivity and neutropenia during treatment of infective endocarditis.
- 1999
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Ingår i: Archives of internal medicine. - : American Medical Association (AMA). - 0003-9926. ; 159:6, s. 607-15
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Tidskriftsartikel (refereegranskat)abstract
- Long-term parenteral beta-lactam treatment is often complicated by adverse reactions that necessitate drug withdrawal.To evaluate the incidence and mechanism of beta-lactam adverse reactions during an 8-year period in all episodes of suspected infective endocarditis in patients treated at a university-affiliated institution.Patients with 215 consecutive episodes of beta-lactam treatment for 10 days or more were prospectively enrolled during 2 periods, January 1984 through December 1988 and January 1993 through December 1995, and compared with 51 episodes of vancomycin hydrochloride treatment for 10 days or more. Incidents of adverse reactions, such as fever, rash, or neutropenia, were registered. Neutrophil counts, eosinophil counts, and penicillin antibodies were studied. Patients with delayed adverse reactions to penicillin G sodium were rechallenged with penicillin v potassium.Incidence of delayed adverse reactions during treatment was 33% with beta-lactams compared with 4% with vancomycin. Rates of adverse event for beta-lactams increased continuously from treatment day 15 to day 30. A 6-fold difference in capacity to induce adverse events was found with different beta-lactams. Penicillin G induced neutropenia in 14% and any adverse event in 51% of treated episodes. Mean daily doses significantly influenced the frequency of adverse events. Occurrence of hemagglutinating penicillin antibodies was significantly related to patients whose penicillin-treated episodes were complicated with adverse events. Patients with delayed adverse reactions to penicillin G were safely rechallenged with penicillin.Incidence of delayed adverse reactions to beta-lactams increases sharply when parenteral treatment is extended beyond 2 weeks. Penicillin G is the most frequent inducer of adverse reactions among beta-lactams studied. An immunological reaction mediated by antibodies to the penicilloyl determinant may be involved in the pathogenesis, possibly enhanced by a dose-related toxic trigger mechanism. Beta-Lactam-induced neutropenia followed a uniform pattern, occurring after, on average, 21 days of treatment, and might be due to both immunologic and toxic effects of treatment. Patients with a late adverse reaction to penicillin can safely be re-treated with penicillin, although they should remain under close surveillance if treatment extends beyond 2 weeks.
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| 8. |
- Adlerberth, Ingegerd, 1959, et al.
(författare)
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Adhesins of Escherichia coli associated with extra-intestinal pathogenicity confer binding to colonic epithelial cells.
- 1995
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Ingår i: Microbial pathogenesis. - 0882-4010. ; 18:6, s. 373-85
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Tidskriftsartikel (refereegranskat)abstract
- Escherichia coli adhesins are virulence factors in intestinal and extra-intestinal infections, but their role in normal intestinal colonization has not been defined. We investigated the intestinal adherence of E. coli with Dr hemagglutinin, S fimbriae, CFA/I or CFA/II, using freshly isolated ileal or colonic enterocytes and cells from the human colonic cell line HT-29. E. coli with S-fimbrial adhesins (Sfa I or Sfa II), P or type 1 fimbriae, adhered in a non-polarized manner, and in similar numbers to colonic and ileal enterocytes. S fimbriae of the variety Sfa II (originating from a meningitis isolate), mediated a stronger binding than Sfa I (of uropathogenic origin). Strains expressing Dr hemagglutinin adhered preferentially to the brush borders, slightly better to colonic than ileal enterocytes. Strains expressing CFA/I or II adhered to colonic and ileal enterocytes, although brush border adherence was predominantly observed with ileal cells. Binding to HT-29 cells paralleled binding to colonic enterocytes for all adhesin specificities except CFA/I. The results suggest that Dr hemagglutinin, P-, type 1- and S-fimbrial adhesins mediate binding to both colonic and ileal enterocytes. These specificities may contribute to the establishment of E. coli in the intestinal microflora, which precedes their spread to extra-intestinal sites.
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| 9. |
- Friman, Vanda, 1952, et al.
(författare)
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Decreased expression of mannose-specific adhesins by Escherichia coli in the colonic microflora of immunoglobulin A-deficient individuals.
- 1996
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Ingår i: Infection and immunity. - 0019-9567. ; 64:7, s. 2794-8
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Tidskriftsartikel (refereegranskat)abstract
- Most Escherichia coli isolates can express type 1 fimbriae with mannose-specific adhesins. These adhesins bind to the oligosaccharide chains of secretory immunoglobulin A (IgA). Thus, in addition to specific antibody activity, secretory IgA possesses a broad reactivity with bacteria expressing type 1 fimbriae. The absence of secretory IgA in colonic secretions, as seen in IgA deficiency, might therefore alter the ability of type 1-fimbriated E. coli to colonize the large intestines of these individuals. In the present study, 10 E. coli isolates from each of 17 IgA-deficient and 17 age-matched control individuals were assessed for the carriage of the fim gene cluster by DNA-DNA hybridization and for the expression of type 1 fimbriae by hemagglutination of guinea pig erythrocytes. The contribution of type 1-fimbria-mediated adherence to HT-29 colonic cells was also analyzed. The proportion of fim+ E. coli isolates was lower in IgA-deficient than in control individuals (74 versus 94%, P < 0.05), as was the proportion of isolates expressing type 1 fimbriae in vitro (69% versus 85%, P < 0.05). The median mannose-sensitive adherence to HT-29 cells was lower for isolates from IgA-deficient individuals than from the controls (9 versus 26 bacteria per cell, P < 0.05). Isolates expressing type 1 fimbriae showed lower adherence to HT-29 cells when they were derived from IgA-deficient individuals than when they were derived from control individuals (15 versus 27 bacteria per cell, P < 0.05). The results suggest that the interaction of type 1 fimbriae with secretory IgA contributes to the large intestinal colonization by these bacteria.
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| 10. |
- Gunnarsson, Ronny K, 1955, et al.
(författare)
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The prevalence of beta-haemolytic streptococci in throat specimens from healthy children and adults. Implications for the clinical value of throat cultures
- 1997
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Ingår i: Scand J Prim Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 15:3, s. 149-55
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the influence of age and season of the year on the carrier rate of beta-haemolytic streptococci (BHS) in healthy individuals and patients with throat pain. DESIGN: The prevalence of BHS in throat specimens from healthy individuals was compared with that from patients with throat pain of the same age in a defined geographical area, collected during the same mid-winter and late summer periods. RESULTS: The prevalence of BHS in healthy individuals was low before the age of 3 years (1.9-7.1%) and in adults > or = 16 years (2.4-3.7%) and highest in the age group 3-15 years (5.0-21.2%). The difference in prevalence of BHS between healthy individuals and patients with throat pain was small during the late summer season and large during the mid-winter season. CONCLUSION: Prevalence of BHS varies with age and season in healthy individuals and patients with throat pain. During the summer, it is much more difficult to interpret the result of a throat culture in individuals aged < 16 years.
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