| 21. |
- Mamontov, Eugen, 1955, et al.
(författare)
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The minimal, phase-transition model for the cell-number maintenance by the hyperplasia-extended homeorhesis
- 2006
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Ingår i: Acta Biotheoretica. - : Springer Science and Business Media LLC. - 0001-5342 .- 1572-8358. ; 54:2, s. 61-101
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Tidskriftsartikel (refereegranskat)abstract
- Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid) tumor. This stage is also the core of many other proliferative diseases. The present work proposes the first minimal model that combines homeorhesis with oncogenic hyperplasia where the latter is regarded as a genotoxically activated homeorhetic dysfunction. This dysfunction is specified as the transitions of the fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor state, and back. The key part of the model is a nonlinear reaction-diffusion equation (RDE) where the biochemical-reaction rate is generalized to the one in the well-known Schlögl physical theory of the non-equilibrium phase transitions. A rigorous analysis of the stability and qualitative aspects of the model, where possible, are presented in detail. This is related to the spatially homogeneous case, i.e. when the above RDE is reduced to a nonlinear ordinary differential equation. The mentioned genotoxic activation is treated as a prevention of the quiescent G0-stage of the cell cycle implemented with the threshold mechanism that employs the critical concentration of the cellular fluid and the nonquiescent-cell-duplication time. The continuous tumor morphogeny is described by a time-space-dependent cellular-fluid concentration. There are no sharp boundaries (i.e. no concentration jumps exist) between the domains of the homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor is used. To estimate a tumor in specific quantities, the model provides the time-dependent tumor locus, volume, and boundary that also points out the tumor shape and size. The above features are indispensable in the quantitative development of antiproliferative drugs or therapies and strategies to prevent oncogenic hyperplasia in cancer and other proliferative diseases. The work proposes an analytical-numerical method for solving the aforementioned RDE. A few topics for future research are suggested.
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| 22. |
- Eliason, Gabriella, et al.
(författare)
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Physical performance and muscular characteristics in different stages of COPD
- 2009
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley-Blackwell Publishing Inc.. - 0905-7188 .- 1600-0838. ; 19:6, s. 865-870
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Tidskriftsartikel (refereegranskat)abstract
- This study has examined exercise capacity and muscle morphology in patients with different severities of chronic obstructive pulmonary disease (COPD). Twenty-three patients and 12 healthy matched controls were recruited. Based on the severity of airflow obstruction, patients were divided into two subgroups. Exercise capacity was determined using a 6-min walk test. Muscle fiber composition, fiber area and number of satellite cells/muscle fiber were determined in muscle biopsies using immunohistochemistry. A progressive decline in exercise capacity was noted with ascending disease severity. Furthermore, a correlation between reduction in exercise capacity and changes in muscle fiber composition was observed in COPD. The group with severe and very severe COPD had a lower proportion of type I and a higher proportion of type IIa fibers compared with the other groups. In severe and very severe COPD, a reduction in fiber area of type IIa fibers was also seen. The number of satellite cells/muscle fiber did not differ between the groups. In conclusion, a decline in exercise capacity occurs already in mild and moderate COPD, indicating that the 6-min walk test is a reliable indicator of disease severity. Furthermore, changes in skeletal muscle morphology are associated with disease severity while muscle regenerative capacity is not altered.
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| 23. |
- Kadi, Fawzi, et al.
(författare)
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The behaviour of satellite cells in response to exercise : what have we learned from human studies?
- 2005
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Ingår i: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 451:2, s. 319-327
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation of training is associated with a gradual reduction of the previously enhanced satellite cell pool. In the elderly, training counteracts the normal decline in satellite cell number seen with ageing. When the transcriptional activity of existing myonuclei reaches its maximum, daughter cells generated by satellite cell proliferation are involved in protein synthesis by enhancing the number of nuclear domains. Clearly, delineating the events and the mechanisms behind the activation of satellite cells both under physiological and pathological conditions in human skeletal muscles remains an important challenge.
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| 24. |
- Dyverfeldt, Petter, 1980-, et al.
(författare)
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Quantification of intravoxel velocity standard deviation and turbulence intensity by generalizing phase-contrast MRI
- 2006
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 56:4, s. 850-858
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Tidskriftsartikel (refereegranskat)abstract
- Turbulent flow, characterized by velocity fluctuations, is a contributing factor to the pathogenesis of several cardiovascular diseases. A clinical noninvasive tool for assessing turbulence is lacking, however. It is well known that the occurrence of multiple spin velocities within a voxel during the influence of a magnetic gradient moment causes signal loss in phase-contrast magnetic resonance imaging (PC-MRI). In this paper a mathematical derivation of an expression for computing the standard deviation (SD) of the blood flow velocity distribution within a voxel is presented. The SD is obtained from the magnitude of PC-MRI signals acquired with different first gradient moments. By exploiting the relation between the SD and turbulence intensity (TI), this method allows for quantitative studies of turbulence. For validation, the TI in an in vitro flow phantom was quantified, and the results compared favorably with previously published laser Doppler anemometry (LDA) results. This method has the potential to become an important tool for the noninvasive assessment of turbulence in the arterial tree.
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| 25. |
- Turanli, Beste, et al.
(författare)
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Drug Repositioning for Effective Prostate Cancer Treatment
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-kappa B inhibition, Wnt/beta - Catenin pathway inhibition, DNMT1 inhibition, and GSK-3 beta inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.
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| 26. |
- Ambrosio, Fabrisia, et al.
(författare)
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The effect of muscle loading on skeletal muscle regenerative potential : an update of current research findings relating to aging and neuromuscular pathology
- 2009
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Ingår i: American Journal of Physical Medicine & Rehabilitation. - Baltimore : Lippincott Williams & Wilkins. - 0894-9115 .- 1537-7385. ; 88:2, s. 145-155
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Forskningsöversikt (refereegranskat)abstract
- Skeletal muscle is a dynamic tissue with a remarkable ability to continuously respond to environmental stimuli. Among its adaptive responses is the widely investigated ability of skeletal muscle to regenerate after loading or injury or both. Although significant basic science efforts have been dedicated to better understand the underlying mechanism controlling skeletal muscle regeneration, there has been relatively little impact in the clinical approaches used to treat skeletal muscle injuries and wasting. The purpose of this review article is to provide an overview of the basic biology of satellite cell function in response to muscle loading and to relate these findings in the context of aging and neuromuscular pathology for the rehabilitation medicine specialist.
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| 27. |
- Eliason, Gabriella, 1975-, et al.
(författare)
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Alterations in the muscle-to-capillary interface in patients with different degrees of chronic obstructive pulmonary disease
- 2010
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Ingår i: Respiratory Research. - London, United Kingdom : BioMed Central. - 1465-9921 .- 1465-993X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is hypothesized that decreased capillarization of limb skeletal muscle is implicated in the decreased exercise tolerance in COPD patients. We have recently demonstrated decreased number of capillaries per muscle fibre (CAF) but no changes in CAF in relation to fibre area (CAFA), which is based on the diffusion distance between the capillary and muscle fibre. The aim of the current study is to investigate the muscle-to-capillary interface which is an important factor involved in oxygen supply to the muscle that has previously been suggested to be a more sensitive marker for changes in the capillary bed compared to CAF and CAFA.Methods: 23 COPD patients and 12 age-matched healthy subjects participated in the study. Muscle-to-capillary interface was assessed in muscle biopsies from the tibialis anterior muscle using the following parameters:1) The capillary-to-fibre ratio (C:Fi) which is defined as the sum of the fractional contributions of all capillary contacts around the fibre2) The ratio between C:Fi and the fibre perimeter (CFPE-index)3) The ratio between length of capillary and fibre perimeter (LC/PF) which is also referred to as the index of tortuosity.Exercise capacity was determined using the 6-min walking test. Results: A positive correlation was found between CFPE-index and ascending disease severity with CFPE-index for type I fibres being significantly lower in patients with moderate and severe COPD. Furthermore, a positive correlation was observed between exercise capacity and CFPE-index for both type I and type IIa fibres.Conclusion: It can be concluded that the muscle-to-capillary interface is disturbed in the tibialis anterior muscle in patients with COPD and that interface is strongly correlated to increased disease severity and to decreased exercise capacity in this patient group.
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| 28. |
- Eliason, Gabriella, et al.
(författare)
-
Physical activity patterns in patients with different degrees of chronic obstructive pulmonary disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: It has previously been suggested that exercise capacity is decreased in COPD patients and that it is associated with degree of disease. The reduced exercise capacity may plausibly be due to low levels of physical activity in this patient group. In the present study we aimed to assess exercise capacity and physical activity in different stages of COPD and to examine the associations between exercise capacity, pulmonary function and degree of physical activity.Methods: 44 COPD patients and 17 healthy subjects participated in the study. Exercise capacity was assessed using the 6 minute walking test and physical activity was assessed using a uniaxial accelerometer worn all waking hours during seven days.Results: Mean exercise capacity was significantly lower in COPD patients compared to healthy subjects. Mean physical activity level and time spent at least moderately active were significantly lower in patients with moderate and severe COPD compared to healthy subjects while no differences in time spent sedentary were observed between the study groups. Pulmonary function, mean physical activity level and time spent at least moderately physically active were significantly associated with exercise capacity in the patients.Conclusions: Patients with moderate and severe COPD are significantly less physically active compared to healthy subjects. Furthermore, mean physical activity level as well as physical activity of at least moderate intensity are positively associated with exercise capacity in COPD patients while time spent sedentary is not which stresses an important role of physical activity on exercise capacity in this patient group.
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| 29. |
- Gilenstam, Kajsa M., 1974-, et al.
(författare)
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Physiological Correlates of Skating Performance in Women's and Men's Ice Hockey
- 2011
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Ingår i: Journal of Strength and Conditioning Research. - : National Strength and Conditioning Association. - 1064-8011 .- 1533-4287. ; 25:8, s. 2133-2142
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the current investigation was to identify relationships between physiological off-ice tests and on-ice performance in female and male ice hockey players on a comparable competitive level. Eleven women, 24 ± 3.0 years, and 10 male ice hockey players, 23 ± 2.4 years, were tested for background variables: height, body weight (BW), ice hockey history, and lean body mass (LBM) and peak torque (PT) of the thigh muscles, [latin capital V with dot above]o2peak and aerobic performance (Onset of Blood Lactate Accumulation [OBLA], respiratory exchange ratio [RER1]) during an incremental bicycle ergometer test. Four different on-ice tests were used to measure ice skating performance. For women, skating time was positively correlated (p < 0.05) to BW and negatively correlated to LBM%, PT/BW, OBLA, RER 1, and [latin capital V with dot above]o2peak (ml O2·kg-1 BW-1·min-1) in the Speed test. Acceleration test was positively correlated to BW and negatively correlated to OBLA and RER 1. For men, correlation analysis revealed only 1 significant correlation where skating time was positively correlated to [latin capital V with dot above]o2peak (L O2·min-1) in the Acceleration test. The male group had significantly higher physiological test values in all variables (absolute and relative to BW) but not in relation to LBM. Selected off-ice tests predict skating performance for women but not for men. The group of women was significantly smaller and had a lower physiological performance than the group of men and were slower in the on-ice performance tests. However, gender differences in off-ice variables were reduced or disappeared when values were related to LBM, indicating a similar capacity of producing strength and aerobic power in female and male hockey players. Skating performance in female hockey players may be improved by increasing thigh muscle strength, oxygen uptake, and relative muscle mass.
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| 30. |
- Kadi, Fawzi, et al.
(författare)
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Satellite cells and myonuclei in young and elderly women and men
- 2004
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Ingår i: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 29:1, s. 120-127
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Tidskriftsartikel (refereegranskat)abstract
- The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.
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