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| 2. |
- Bergh, Jonas C., et al.
(författare)
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The first clinical pilot study of roquinimex (Linomide) in cancer patients with special focus on immunological effects
- 1997
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Ingår i: Cancer Investigation. - 0735-7907 .- 1532-4192. ; 15:3, s. 204-11
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Tidskriftsartikel (refereegranskat)abstract
- Roquinimex (Linomide) has been demonstrated to suppress tumor growth in animal models. The effect is at least in part related to enhanced numbers and activity of natural killer (NK) cells. In this clinical pilot study, roquinimex was given at increasing doses (0.05 mg/kg to 0.6 mg/kg) to 13 patients (performance status 0-3) with various malignant disorders. Immunology parameters were followed and side effects were observed during the study. The plasma pharmacokinetics of roquinimex was studied at the 0.2 mg/kg dose level. The clinical side effects were dominated by musculoskeletal discomfort, nausea, and pain. No significant hematological or biochemical toxicity was observed. Pharmacokinetic analysis at the 0.2 mg/kg dose level revealed a Cmax of 4.0 mumol/L at tmax of 1.2 hr and an elimination half-life of 42 hr. Increased numbers of phenotypic NK cells, activated T (DR+CD4+) cells, and monocytes were observed after administration of roquinimex compared with pretreatment values. Roquinimex seems to be an active immunomodulator with manageable toxicity. Further exploration of therapeutic efficacy is warranted.
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| 3. |
- Dahl, Jonas, et al.
(författare)
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Against the flow: chemical detection of downstream predators in running waters
- 1998
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Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 265:1403, s. 1339-1344
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Tidskriftsartikel (refereegranskat)abstract
- In running waters, chemical cues have generally been assumed to always come from upstream locations. Here, we present ¢eld and laboratory evidence that Gammarus pulex can use chemical cues from down- stream predators to adaptively adjust drifting behaviour. In the ¢eld, signi¢cantly fewer Gammarus migrated into stream enclosures where brown trout (Salmo trutta) were present than into control enclo- sures. In a subsequent laboratory experiment, Gammarus actively avoided live trout and trout chemicals placed downstream in an arti¢cial stream, whereas no e¡ects were found in response to control or visual cues.We suggest that the mechanism explaining the ability of Gammarus to detect downstream predators is use of back£ows, which locally transport ¢sh chemicals against the main £ow. Such back£ows are both created by the Gammarus itself and by surrounding substrate heterogeneity. These results profoundly a¡ect the way in which we view the chemical environment of running waters and have important implications for empirical and theoretical work evaluating predator e¡ects in running waters, as they demonstrate that prey immigration rates can depend on downstream predator densities.
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| 7. |
- Erjefält, Jonas, et al.
(författare)
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Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo
- 1997
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 27:11, s. 1344-1355
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. OBJECTIVE: To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. METHODS: After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. RESULTS: Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. CONCLUSION: The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The distribution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.
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| 8. |
- Erjefält, Jonas, et al.
(författare)
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Prompt epithelial damage and restitution processes in allergen challenged guinea-pig trachea in vivo
- 1997
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 27:12, s. 1458-1470
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the induction and the morphology of epithelial damage, and of the ensuing epithelial restitution processes in allergic airways. OBJECTIVE: To examine epithelial damage and restitution in allergen challenged guinea-pig trachea. METHODS: Whole-mount techniques, transmission and scanning electron microscopy, cryosectioning, and histochemical staining were used. Cell proliferation was monitored by BrdU-immunohistochemistry. RESULTS: Allergen challenge produced patchy, crater-like, and leucocyte-rich epithelial damage sites. At 1, 5, and 24 h damage was associated with poorly differentiated epithelial restitution cells. Already at 1 h the epithelial craters had a floor of flattened restitution cells and the damaged areas comprised < 1% of the mucosal surface area (whole-mount preparations). In contrast, cryo sections displayed large areas (approximately 20%, 1 h) of denudation. Epithelial, and subepithelial (fibroblasts, smooth muscle) proliferation was increased 5 and 24 h after challenge (P < 0.01). CONCLUSION: Within 1 h allergen challenge has induced patchy damage sites where epithelial restitution is already advanced; although easily produced by cryosectioning frank denudation was not evident in whole-mount preparations. The present findings may explain the well maintained, functional tightness of allergic airways displaying epithelial damage, shedding, and even denudation. The present data also suggest the possibility that epithelial damage-restitution may be causative to allergic airway remodelling.
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| 9. |
- Greiff, Lennart, et al.
(författare)
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Topical nitroprusside may reduce histamine-induced plasma exudation in human nasal airways
- 1995
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 50:7, s. 593-597
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal exudation of nonsieved bulk plasma is a key feature of airway defense and inflammation. We have previously observed in guinea pig tracheobronchial airways that endogenous nitric oxide (NO) of the mucosa may tonically suppress the permeability of the subepithelial microcirculation, and that topical administration of the NO donor nitroprusside may reduce plasma exudation responses. The present study examines whether nitroprusside affects histamine-induced mucosal exudation of plasma in the human nasal airway. In a dose-finding tolerability experiment, using changes in nasal patency as response, placebo and nitroprusside (1.2 and 3.6 mg per nasal cavity) were applied on the mucosal surface with a nasal-spray device. Nasal peak expiratory flow (PEF) rates were measured before the application and thereafter every third minute for 15 min. Nitroprusside produced a dose-dependent decrease in nasal PEF rates compared to placebo. Placebo or nitroprusside (7.2 mg) was then given to the right nasal cavity, followed 3 min later by challenge with saline or histamine (600 micrograms). The drug and the challenge were both applied with a nasal-spray device. With a nasal pool-device, the same large part of the nasal mucosal surface was lavaged before and after the treatment/challenge. The lavage fluid levels of alpha 2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. The histamine-induced lavage fluid level of alpha 2-macroglobulin was significantly higher after treatment with placebo than with nitroprusside. The present data indicate that nitroprusside may have antiexudative effects in human airways. Hence, unlike other microvascular permeability active agents, this pharmacologic principle may be active in both guinea pig and human airways.
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- Gustafsson, Bertil, et al.
(författare)
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Boundary conditions and estimates for the steady Stokes equations on staggered grids
- 1999
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We consider the steady state Stokes equations, describing low speed flow and derive estimates of the solution for various types of boundary conditions. We formulate the boundary conditions in a new way, such that the boundary value problem becomes non-singular. By using a difference approximation on a staggered grid we are able to derive a non-singular approximation in a direct way. Furthermore, we derive the same type of estimates as for the continuous case. Numerical experiments confirm the theoretical results.
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