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- Kågedal, Katarina, et al.
(författare)
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Lysosomal membrane permeabilization during apoptosis : Involvement of Bax?
- 2005
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Ingår i: International journal of experimental pathology (Print). - : John Wiley & Sons. - 0959-9673 .- 1365-2613. ; 86:5, s. 309-321
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Tidskriftsartikel (refereegranskat)abstract
- Bcl-2 family members have long been known to control permeabilization of the mitochondrial membrane during apoptosis, but involvement of these proteins in lysosomal membrane permeabilization (LMP) was not considered until recently. The aim of this study was to investigate the mechanism underlying the release of lysosomal proteases to the cytosol seen during apoptosis, with special emphasis on the role of Bax. In human fibroblasts, exposed to the apoptosis-inducing drug staurosporine (STS), the release of the lysosomal protease cathepsin D to the cytosol was observed by immunocytochemistry. In response to STS treatment, there was a shift in Bax immunostaining from a diffuse to a punctate pattern. Confocal microscopy showed co-localization of Bax with both lysosomes and mitochondria in dying cells. Presence of Bax at the lysosomal membrane was confirmed by immuno-electron microscopy. Furthermore, when recombinant Bax was incubated with pure lysosomal fractions, Bax inserted into the lysosomal membrane and induced the release of lysosomal enzymes. Thus, we suggest that Bax is a mediator of LMP, possibly promoting the release of lysosomal enzymes to the cytosol during apoptosis.
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| 4. |
- Ackermann, PW
(författare)
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Neuronal regulation of tendon homoeostasis
- 2013
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Ingår i: International journal of experimental pathology. - : Wiley. - 1365-2613 .- 0959-9673. ; 94:4, s. 271-286
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Lebel, L, et al.
(författare)
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Sodium hyaluronate increases vascular ingrowth in the rabbit ear chamber.
- 1991
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Ingår i: International journal of experimental pathology (Print). - 0959-9673 .- 1365-2613. ; 72:2, s. 111-8
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Tidskriftsartikel (refereegranskat)abstract
- The rabbit ear-chamber model was used to study the effect of sodium hyaluronate (NaHe, Healon) on the rate of ingrowth of vascular structures of healing granulation tissue. The chamber area covered by granulation tissue was determined by in-vivo microscopy at regular intervals during a period of 32 days. Daily injections of 1% NaHe into the ear chamber, 50 microliters from day 0 to day 7 and 25 microliters from day 8 to day 21, significantly inhibited ingrowth as observed between days 20 and 26, compared with buffer-injected controls. There was no difference between the latter and non-injected chambers. Intermittent injections of 1% NaHe, 50 microliters on days 1 and 5 and 25 microliters on days 9, 13 and 22 significantly increased the ingrowth as observed between days 6 and 18. It was noted that wound macrophages internalized fluorescein-labelled NaHe. The inhibitory effect of daily injections on angiogenesis was probably due to physical hindrance caused by the NaHe. The stimulatory effect of intermittent administration of NaHe on angiogenesis may have several explanations, including activation of macrophages and their release of angiogenetic factors.
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| 15. |
- Yuksel, Muhammed, et al.
(författare)
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Hepatitis mouse models : from acute-to-chronic autoimmune hepatitis
- 2014
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Ingår i: International journal of experimental pathology (Print). - : Wiley. - 0959-9673 .- 1365-2613. ; 95:5, s. 309-320
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Forskningsöversikt (refereegranskat)abstract
- Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, raised plasma liver enzymes, the presence of autoantibodies and regulatory T-cell (Tregs) dysfunction. The clinical course is heterogeneous, manifested by a fulminant or indolent course. Although genetic predisposition is well accepted, the combination with currently undefined environmental factors is crucial for the development of the disease. Progress in the development of reliable animal models provides added understanding of the pathophysiology of AIH, and these will be very useful in evaluating potential therapeutics. It appears that artificially breaking tolerance in the liver is easy. However, maintaining this state of tolerance breakdown, to get chronic hepatitis, is difficult because liver immune homeostasis is strongly regulated by several immune response inhibitory mechanisms. For example, Tregs are crucial regulators in acute and chronic hepatitis, and C57BL/6 mice are most prone to experimental AIH. Immunization of C57BL/6 mice with liver (AIH) autoantigens (CYP2D6/FTCD or IL-4R) and the disturbance of liver regulatory mechanism(s), leading to experimental AIH, are likely to be most representative of human AIH pathology.
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| 17. |
- Cheng, Xiaowen, et al.
(författare)
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Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum
- 2018
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Ingår i: International Journal of Experimental Pathology. - : Wiley. - 0959-9673. ; 99:1, s. 38-45
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Tidskriftsartikel (refereegranskat)abstract
- Reduced blood flow to the brain induces cerebral ischaemia, potentially causing central injury and peripheral complications including gastrointestinal (GI) dysfunction. The pathophysiology behind GI symptoms is suspected to be neuropathy in the enteric nervous system (ENS), which is essential in regulating GI function. This study investigates if enteric neuropathy occurs after cerebral ischaemia, by analysing neuronal survival and relative numbers of vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS) expressing neurons in mouse ileum after three types of cerebral ischaemia. Focal cerebral ischaemia, modelled by permanent middle cerebral artery occlusion (pMCAO) and global cerebral ischaemia, modelled with either transient occlusion of both common carotid arteries followed by reperfusion (GCIR) or chronic cerebral hypoperfusion (CCH) was performed on C56BL/6 mice. Sham-operated mice for each ischaemia model served as control. Ileum was collected after 1–17 weeks, depending on model, and analysed using morphometry and immunocytochemistry. For each group, intestinal mucosa and muscle layer thicknesses, neuronal numbers and relative proportions of neurons immunoreactive (IR) for nNOS or VIP were estimated. No alterations in mucosa or muscle layer thicknesses were noted in any of the groups. Loss of myenteric neurons and an increased number of VIP-IR submucous neurons were found in mouse ileum 7 days after pMCAO. None of the global ischaemia models showed any alterations in neuronal survival or relative numbers of VIP- and nNOS-IR neurons. We conclude that focal cerebral ischaemia and global cerebral ischaemia influence enteric neuronal survival differently. This is suggested to reflect differences in peripheral neuro-immune responses.
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| 18. |
- Heinegård, Dick
(författare)
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From aggrecan to matrix
- 2009
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Ingår i: International Journal of Experimental Pathology. - 0959-9673. ; 90:2, s. 93-93
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Konferensbidrag (refereegranskat)
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| 19. |
- Heinegård, Dick
(författare)
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Proteoglycans and more--from molecules to biology.
- 2009
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Ingår i: International Journal of Experimental Pathology. - : Wiley. - 0959-9673. ; 90:6, s. 575-586
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Forskningsöversikt (refereegranskat)abstract
- In this article the organization and functional details of the extracellular matrix, with particular focus on cartilage, are described. All tissues contain a set of molecules that are arranged to contribute structural elements. Examples are fibril-forming collagens forming major fibrillar networks in most tissues. The assembly process is regulated by a number of proteins (thrombospondins, LRR-proteins, matrilins and other collagens) that can bind to the collagen molecule and in many cases remain bound to the formed fibre providing additional stability and enhancing networking to other structural networks. One such network is formed by collagen VI molecules assembled to beaded filaments in the matrix catalysed by interactions with small proteoglycans of the LRR-family, which remain bound to the filament providing for interactions via a linker of a matrilin to other matrix constituents like collagen fibres and the large proteoglycans, e.g. aggrecan in cartilage. Aggrecan is contributing an extreme anionic charge density to the extracellular matrix, which by osmotic effects leads to water retention and strive to swelling, resisted by the tensile properties of the collagen fibres. Aggrecan is bound via one end to hyaluronan, including such molecules retained at the cell surface, to form very large molecular entities that interact with other constituents of the matrix, e.g. fibulins that can form their own network. Other important interactions are those with cell surface receptors such as integrins, heparan sulphfate proteoglycans, hyaluronan receptors and others. Many of the molecules with an ability to interact with these receptors can also bind to molecules in the matrix and provide a bridge from the matrix to the cell and induce various responses. In pathology, there is an imbalance in matrix turnover with often excessive proteolytic breakdown. This results in the formation of protein fragments, where cleavage provides information on the active enzyme. Those fragments released can be specifically detected employing antibodies specific to the cleavage site and used to diagnose and monitor e.g. joint disease at early stages.
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| 22. |
- Ribeiro, Daniele Lisboa, et al.
(författare)
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Malignant lesions in the ventral prostate of alloxan-induced diabetic rats
- 2008
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Ingår i: International Journal of Experimental Pathology. - : Wiley. - 0959-9673. ; 89:4, s. 276-283
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the changes caused by chronic diabetes in the rat ventral prostate and to establish a correlation between diabetes and the development of prostatic lesions. Male rats received alloxan (42 mg/kg b.w.) to induce diabetes. Ninety days after diabetes diagnosis, animals were sacrificed and the ventral prostate was removed and prepared for general and immunohistochemical analyses. The total area showing different types of lesions was estimated. Diabetes led to a decrease in the body and prostatic weights, as well as in testosterone levels. The prostate morphology and stereology showed high variation in the diabetic group. Some animals had light changes; the great majority had an intense epithelial atrophy; and other rats showed premalignant and malignant lesions in the prostate. Such epithelial atrophy was, in some samples, combined with chronic inflammation, similar to proliferative inflammatory atrophy (PIA). The diabetic group also presented high incidence of prostatitis, adenocarcinoma and prostatic intra-epithelial neoplasia (PIN). Samples with adenocarcinoma had poorly differentiated acini with high levels of cellular proliferation and nuclear atypia. These lesions exhibited an invasive feature showing Bcl-2-positive cells and interruptions in the basement membrane. An association of PIA, PIN and adenocarcinoma was detected in one sample. Reduced androgen levels have a synergic effect to insulin dysfunction promoting negative effects in the rat prostate. Diabetic individuals had a high incidence of prostatitis, and this inflammation could stimulate the incidence of other forms of prostatic pathology.
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| 24. |
- Stotsky, Alexander, 1960
(författare)
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Nonlinear speed and yaw control for wind turbine powered vessels
- 2016
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Ingår i: Proceedings of the Institution of Mechanical Engineers. Part I: Journal of Systems and Control Engineering. - 2041-3041 .- 0959-6518. ; 230:3, s. 255-265
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Tidskriftsartikel (refereegranskat)abstract
- The application of conventional wind turbines on board a vessel creates a number of new challenges for turbine control systems. Thrust force is used in marine applications as an additional control variable for propulsion of the vessel.Variability of the wind speed and wind direction, together with the yaw rate and range constraints, impose strong requirements on the turbine control system. A new projection algorithm that projects the turbine thrust force on the heading direction of vessel is proposed in this paper for controlling propulsion. Variations in the wind direction and wind speed are counteracted via turbine yaw angle, making the turbine thrust force always aligned with the heading direction of the vessel. The conventional Kv2 speed controller is modified for varying yaw offset and a combined algorithm for simultaneous control of the turbine speed and thrust force is proposed. Stability of the Kw^2 speed controller for varying yaw offset is proved via the Lyapunov method. The controller also takes into account the constraints on the yaw rate and minimizes the turbine gyroscopic effects via a proper choice of the virtual upper bound of the input voltage of the yaw motor. All of the results are illustrated by simulations using measurement data acquired from the Hönö turbine.
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| 25. |
- Sandqvist, Madelene, 1974, et al.
(författare)
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Postprandial interstitial insulin concentrations in type 2 diabetes relatives
- 2006
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Ingår i: Eur J Clin Invest. - : Wiley. - 0014-2972 .- 1365-2362. ; 36:6, s. 383-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. SUBJECTS AND METHODS: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively. RESULTS: The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 +/- 3032 vs. Plac 4682 +/- 2613 pmol L(-1) min; P < 0.05, mean +/- SE]. However, the postprandial I-insulin(max)/P-insulin(max) ratio was similar on the two test days (nateglinide: 213 +/- 62 vs. 501 +/- 92 pmol L(-1), I/P-ratio: 0.38 +/- 0.06 and placebo: 159 +/- 39 vs. 410 +/- 74 pmol L(-1), I/P-ratio: 0.36 +/- 0.05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide. CONCLUSIONS: Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients.
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