| 1. |
- Lammi, Mikko, 1961-
(författare)
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Current perspectives on cartilage and chondrocyte mechanobiology.
- 2004
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Ingår i: Biorheology. - : IOS Press. - 0006-355X .- 1878-5034. ; 41:3-4, s. 593-596
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Forskningsöversikt (refereegranskat)abstract
- It is well known that physiological forces are essential for the maintenance of normal composition and structure of articular cartilage. Although some of the mechanisms of mechanotransduction are known today, there are certainly many others left unrevealed. In order to understand the complicated systems present in articular cartilage, we have to bring together the data from all fields of cartilage mechanobiology. The 3rd Symposium on Mechanobiology of Cartilage and Chondrocyte was a good effort towards that goal.
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| 2. |
- Saarakkala, Simo, et al.
(författare)
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Ultrasound indentation of normal and spontaneously degenerated bovine articular cartilage.
- 2003
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Ingår i: Osteoarthritis and Cartilage. - : Saunders Elsevier. - 1063-4584 .- 1522-9653. ; 11:9, s. 697-705
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We have previously developed a handheld ultrasound indentation instrument for the diagnosis of cartilage degeneration. The instrument has been demonstrated to be capable of quantifying mechanical and acoustic properties of enzymatically degraded and normal bovine articular cartilage in vitro and in situ. The aim of this study was to investigate the sensitivity of the instrument to distinguish between normal and spontaneously degenerated (e.g., in osteoarthrosis) articular cartilage in vitro.DESIGN: Thirty articular cartilage samples were prepared from the bovine lateral patellae: 19 patellae with different degenerative stages and 11 patellae with visually normal appearance. Cartilage thickness, stiffness (dynamic modulus) and ultrasound reflection from the cartilage surface were measured with the handheld instrument. Subsequently, biomechanical, histological and biochemical reference measurements were conducted.RESULTS: Reproducibility of the measurements with the ultrasound indentation instrument was good. Standardized coefficient of variation was < or =6.1% for thickness, dynamic modulus and reflection coefficient. Linear correlation between the dynamic modulus, measured with the ultrasound indentation instrument, and the reference dynamic modulus was high (r=0.993, n=30, P<0.05). Ultrasound reflection coefficient, as determined from the cartilage surface, showed high linear correlations (typically r(2)>0.64, n=30, P<0.05) with the cartilage composition and histological or mechanical properties. The instrument was superior compared to visual evaluation in detecting tissue degeneration.CONCLUSION: This study indicates that the ultrasound indentation technique and instrument may significantly improve the early diagnosis of cartilage degeneration. The results revealed that visual evaluation is insensitive for estimating the structural and mechanical properties of articular cartilage at the initial stages of degeneration.
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| 3. |
- Sahlman, Janne, et al.
(författare)
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A human COL2A1 gene with an Arg519Cys mutation causes osteochondrodysplasia in transgenic mice.
- 2004
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Ingår i: Arthritis and Rheumatism. - : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 50:10, s. 3153-3160
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: An arginine-to-cysteine substitution at position 519 of the COL2A1 gene causes early generalized osteoarthritis with mild chondrodysplasia in humans. In this study, a human COL2A1 gene with the same mutation was introduced into a murine genome having 1 or no alleles of the murine Col2a1 gene, and the skeletal phenotypes of the transgenic mice were compared with those of control mice.METHODS: Mice with 1 allele of the normal murine Col2a1 gene and 1 allele of the mutated human COL2A1 gene (n = 10), those with no murine Col2a1 gene and 2 alleles of the mutated human COL2A1 gene (n = 13), those with no murine Col2a1 gene and only 1 allele of the mutated COL2A1 gene (n = 9), and normal control mice (n = 11) were studied for skeletal abnormalities, using radiographic imaging and light microscopic analyses of histologic sections. The collagen network of cartilage was also investigated with transmission electron microscopy.RESULTS: At 2 months of age, all transgenic mice had dysplastic changes in their long bones, flattened vertebral bodies, and osteoarthritic changes in their joints. The intervertebral discs of the transgenic animals were degenerated, and their histologic structure was disturbed. The changes were more severe in mice with no murine Col2a1 allele.CONCLUSION: The human COL2A1 gene with the Arg519Cys mutation causes osteochondrodysplasia in mice, as it does in humans.
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| 4. |
- Trulsson, M, et al.
(författare)
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Cortical responses to single mechanoreceptive afferent microstimulation revealed with fMRI
- 2001
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Ingår i: NeuroImage. - : Academic Press. - 1053-8119 .- 1095-9572. ; 13:4, s. 613-622
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Tidskriftsartikel (refereegranskat)abstract
- The technique of intraneural microneurography/microstimulation has been used extensively to study contributions of single, physiologically characterized mechanoreceptive afferents (MRAs) to properties of somatosensory experience in awake human subjects. Its power as a tool for sensory neurophysiology can be greatly enhanced, however, by combining it with functional neuroimaging techniques that permit simultaneous measurement of the associated CNS responses. Here we report its successful adaptation to the environment of a high-field MR scanner. Eight median-nerve MRAs were isolated and characterized in three subjects and microstimulated in conjunction with fMRI at 3.0 T. Hemodynamic responses were observed in every case, and these responses were robust, focal, and physiologically orderly. The combination of fMRI with microstimulation will enable more detailed studies of the representation of the body surface in human somatosensory cortex and further studies of the relationship of that organization to short-term plasticity in the human SI cortical response to natural tactile stimuli. It can also be used to study many additional topics in sensory neurophysiology, such as CNS responses to additional classes of afferents and the effects of stimulus patterning and unimodal/crossmodal attentional manipulations. Finally, it presents unique opportunities to investigate the basic physiology of the BOLD effect and to compare the operating characteristics of fMRI and EEG as human functional neuroimaging modalities in an unusually specific and well-characterized neurophysiological setting.
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| 5. |
- Töyräs, Juha, et al.
(författare)
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Speed of sound in normal and degenerated bovine articular cartilage.
- 2003
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier. - 0301-5629 .- 1879-291X. ; 29:3, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- The unknown and variable speed of sound may impair accuracy of the acoustic measurement of cartilage properties. In this study, relationships between the speed of sound and cartilage composition, mechanical properties and degenerative state were studied in bovine knee and ankle cartilage (n = 62). Further, the effect of speed variation on the determination of cartilage thickness and stiffness with ultrasound (US) indentation was numerically simulated. The speed of sound was significantly (n = 32, p < 0.05) dependent on the cartilage water content (r = -0.800), uronic acid content (per wet weight, r = 0.886) and hydroxyproline content (per wet weight, r = 0.887, n = 28), Young's modulus at equilibrium (r = 0.740), dynamic modulus (r = 0.905), and degenerative state (i.e., Mankin score) (r = -0.727). In addition to cartilage composition, mechanical and acoustic properties varied significantly between different anatomical locations. In US indentation, cartilage is indented with a US transducer. Deformation and thickness of tissue are calculated using a predefined speed of sound and used in determination of dynamic modulus. Based on the simulations, use of the mean speed of sound of 1627 m/s (whole material) induced a maximum error of 7.8% on cartilage thickness and of 6.2% on cartilage dynamic modulus, as determined with the US indentation technique (indenter diameter 3 mm). We believe that these errors are acceptable in clinical US indentation measurements.
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| 6. |
- Mäkelä, Olli, et al.
(författare)
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Effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate on adult equine cartilage.
- 2004
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 31:2, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the effect of radiosynovectomy with holmium-166 ferric hydroxide macroaggregate (166Ho-FHMA) on articular cartilage in 6 adult horses.METHODS: Arthritic changes and mechanical properties of articular cartilage were evaluated with arthroscopy and postmortem microscopic analyses. Glycosaminoglycan content was measured by safranin-O staining combined with digital densitometry, uronic acid analyses, and dimethylene blue binding assay. 35S-sulfate labeling and autoradiography were used to localize proteoglycan synthesis and to characterize proteoglycan structures using SDS-agarose gel electrophoresis. Northern hybridizations were performed to measure the mRNA levels for aggrecan and pro-a1(II) collagen in cartilage samples.RESULTS: Histological signs of degeneration were present in the articular cartilage of both control and radiosynovectomized equine joints. Radiosynovectomy did not aggravate degenerative changes or significantly alter the matrix glycosaminoglycan content. A slightly decreased size of proteoglycan monomers was observed 2 months after 166Ho-FHMA radiosynovectomy. Tissue analysis of extracted proteoglycans revealed lower 35S incorporation after radiosynovectomy, but corresponding changes could not be observed in aggrecan mRNA levels. Transient downregulation of pro-a1(II) collagen mRNA transcription was observed 5 days after 166Ho-FHMA radiosynovectomy.CONCLUSION: 166Ho-FHMA treatment did not markedly affect the composition or morphology of adult articular cartilage showing mild degeneration. However, minor degradation of proteoglycan monomers and transient downregulation of pro-a1(II) collagen mRNA were observed.
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| 7. |
- Georg, Dietmar, et al.
(författare)
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A practical method to calculate head scatter factors in wedged rectangular and irregular MLC shaped beams for external and internal wedges
- 2004
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 49:20, s. 4689-4700
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Tidskriftsartikel (refereegranskat)abstract
- Factor based methods for absorbed dose or monitor unit calculations are often based on separate data sets for open and wedged beams. The determination of basic beam parameters can be rather time consuming, unless equivalent square methods are applied. When considering irregular wedged beams shaped with a multileaf collimator, parametrization methods for dosimetric quantities, e.g. output ratios or wedge factors as a function of field size and shape, become even more important. A practical method is presented to derive wedged output ratios in air (S-c,S-w) for any rectangular field and for any irregular MLC shaped beam. This method was based on open field output ratios in air (Sc) for a field with the same collimator setting, and a relation f(w) between S-c,S-w and S-c. The relation f(w) can be determined from measured output ratios in air for a few open and wedged fields including the maximum wedged field size. The function fw and its parametrization were dependent on wedge angle and treatment head design, i.e. they were different for internal and external wedges. The proposed method was tested for rectangular wedged fields on three accelerators with internal wedges (GE, Elekta, BBC) and two accelerators with external wedges (Varian). For symmetric regular beams the average deviation between calculated and measured S-c,S-w/S-c ratios was 0.3% for external wedges and about 0.6% for internal wedges. Maximum deviations of 1.8% were obtained for elongated rectangular fields on the GE and ELEKTA linacs with an internal wedge. The same accuracy was achieved for irregular MLC shaped wedged beams on the accelerators with MLC and internal wedges (GE and Elekta), with an average deviation < 1 % for the fields tested. The proposed method to determine output ratios in air for wedged beams from output ratios of open beams, combined with equivalent square approaches, can be easily integrated in empirical or semi-empirical methods for monitor unit calculations.
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| 8. |
- Lenfeldt, Niklas, et al.
(författare)
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Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves
- 2004
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 101:6, s. 944-950
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Tidskriftsartikel (refereegranskat)abstract
- Object. The appearance of numerous B waves during intracranial pressure (ICP) registration in patients with idiopathic adult hydrocephalus syndrome (IAHS) is considered to predict good outcome after shunt surgery. The aim of this study was to describe which physical parameters of the cerebrospinal fluid (CSF) system B-waves reflect and to find a method that could replace long-term B-wave analysis.Methods. Ten patients with IAHS were subjected to long-term registration of ICP and a lumbar constant-pressure infusion test. The B-wave presence, CSF outflow resistance (Rout), and relative pulse pressure coefficient (RPPC) were assessed using computerized analysis. The RPPC was introduced as a parameter reflecting the joint effect of elastance and pulsatory volume changes on ICP and was determined by relating ICP pulse amplitudes to mean ICP.Conclusions. The B-wave presence on ICP registration correlates strongly with RPPC (r = 0.91, p < 0.001, 10 patients) but not with CSF Rout. This correlation indicates that B waves—like RPPC—primarily reflect the ability of the CSF system to reallocate and store liquid rather than absorb it. The RPPC-assessing lumbar short-term CSF pulse pressure method could replace the intracranial long-term B-wave analysis.
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| 9. |
- Ljungkvist, Anna, 1971-
(författare)
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Imaging the tumor microenvironment : the dynamics and modification of hypoxia
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The tumor vasculature is poor and heterogeneous which may result in inadequate oxygenation and changed energy status. In addition the balance between cell proliferation and the rate of cell death is disturbed, which results in tumor growth. The aims of this study were 1) to gain more insight into the relation between tumor vascularity, hypoxia, and proliferation in solid tumors, and 2) to study the changes and dynamics of tumor oxygenation in relation to the vascular architecture within individual tumors. For this purpose a double hypoxic marker method was developed, which was subsequently used to 3) determine the turnover rate of hypoxic cells in three different tumor models and 4) to study the effect of cytotoxic drugs on tumor hypoxia and cell death.Solid tumor models grown in mice were used. The tumor microenvironment was investigated with exogenous cell markers for hypoxia (pimonidazole and CCI-103F), cell proliferation (BrdUrd) and blood perfusion (Hoechst 33342). The vasculature and the exogenous cell markers were visualized with immunohistochemical techniques. The tumor sections were scanned and quantified with an image analysis systemconsisting of a fluorescence microscope, CCD camera and image analysis software.The spatial organization of hypoxia, proliferation, and tumor vasculature was analyzed in several xenograft lines. The study revealed two main hypoxic patterns that seemed to be the consequence of complex relations between vasculature, oxygen delivery, proliferation, and cell loss. The novel double hypoxic cell marker method, with sequential injection of two hypoxic markers, was developed to study dynamic changes of the tumor oxygenation. Based on varying injection intervals between the markers the hypoxic cell half-life was determined in three tumor lines, and ranged from 17 to 49 hours. Intra-tumoral changes in oxygenation status upon oxygen modifying treatments were measured with the double hypoxic marker method. Both decreased levels of tumor hypoxia after carbogen breathing (95%O2 and 5% CO2) and increased levels of tumor hypoxia, as a result of reduced tumor perfusion after hydralazine treatment was detected. Finally the double hypoxic marker assay was used to analyze the effects of the hypoxic cytotoxin tirapazamine in relation to the hypoxic cell population, which caused a reversible decrease of the hypoxic fraction.The results presented in this thesis now form the basis for further studies to identify subpopulations of cells that represent specific targets for therapy, and to investigate the effects of different treatment modalities.
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| 10. |
- Toma-Dasu, Iuliana, 1972-
(författare)
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Theoretical modelling of tumour oxygenation and influences on treatment outcome
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One of the main problems in curing cancer resides in the different microenvironment existing in tumours compared to the normal tissues. The mechanisms of failure are different for radiotherapy and chemotherapy, but they all relate to the poor blood supply known to exist in tumours. It is therefore very important to know the tumour microenvironmental conditions in order to devise techniques that will overcome the problems and will therefore improve the result of the treatment.The aims of the thesis were the modelling of tumour oxygenation and the simulation of polarographic oxygen measurements in order to assess and possibly to improve the accuracy of the electrode in measuring tumour oxygenation. It also aimed to evaluate the implications of tumour microenvironment for the radiotherapy outcome.The project used theoretical modelling as the main tool. The processes of oxygen diffusion and consumption were described mathematically for different conditions, the result being very accurate distributions of oxygen in tissues. A first simple model of tissue oxygenation was based on the oxygen diffusion around a single blood vessel. A more complex model built from the basic physical processes and measurable parameters allowed the simulation of realistical tissues with heterogeneous vasculature. This model also allowed the modelling of the two types of hypoxia known to appear in tumours and their influence on the tumour microenvironment. The computer simulation of tissues was also used for assessing the accuracy of the polarographic technique for measuring tumour oxygenation.The results of this study have shown that it is possible to model theoretically the tissue oxygenation starting from the basic physical processes. The particular application of our theoretical simulation to the polarographic oxygen electrode has shown that this experimental method does not give the oxygen values in individual cells. Because the electrode measures the average oxygenation in a relatively large tissue volume, the resulting oxygen distributions are different from the real ones and the extreme high and low values are not detected. It has further been found that the polarographic electrode cannot make distinction between various types of hypoxia existing in tumours, the geometrical distribution of the hypoxic cells influencing mostly the accuracy of the measurement.It was also shown that because of the averaging implied by the measurement process, electrode results should not be used directly to predict the response to radiation. Thus, the differences between the predictions in clinical tumour control obtained from the real or the measured oxygenations are of the order of tens of percents in absolute value. A method to improve the accuracy of the electrode, i.e. to improve the correlation between the results of the measurements and the actual tissue oxygenation, was proposed.In conclusion, theoretical modelling has been shown to be a very powerful tool for predicting the outcome of radiotherapy and it has the advantage of describing the tumour oxygenation in the least invasive manner. Furthermore it allows the investigation of the invasiveness and the accuracy of various experimental methods.
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