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S Faber

Publications and source records attributed to S Faber.

At least 19 recordsLinked to original sources
PubMed2006

Anti-TNF effects on destructive fibroblasts depend on mechanical stress.

Joint destruction in rheumatoid arthritis (RA) starts typically at sites of mechanically stressed inserts of the synovial membrane near the cartilage/bone border. In the therapy of RA, tumour necrosis factor (TNF) antagonists have rapidly emerged as a valuable class of anti-rheumatic agents that reduce joint destruction. The aim of this study was to investigate and profile genes involved in the interaction between articular movement and anti-TNF therapy in an in vitro model. Murine LS48 cells, an established substitute for invasive RA synovial fibroblasts, were cultured, stretched and/or treated with anti-TNF-alpha antibody for 24 h. RNA was isolated and gene transcript levels were determined using U74Av2 Affymetrix GeneChips to identify transcriptional events. Positive findings were verified by polymerase chain reaction (PCR). We identified 170 differentially regulated genes, including 44 of particular interest. Gene expression fell into different functional groups that can be explained by RA pathogenesis and experimental conditions. For 21 genes of the 44 of particular interest, regulation could be confirmed by real-time PCR. Remarkably, we found structural as well as functional genes differently regulated between stretched cells, anti-TNF-treated cells, and stretched cells treated with anti-TNF antibody. Additionally, we also found a large number of genes that are apparently not related to the experimental conditions. Mechanical exertion modulates gene expression and subsequently cellular response to anti-TNF therapy. Results in exerted cells correspond to current knowledge regarding RA pathogenesis and underline the relevance of our experimental approach. Finally, the central function of the interleukin-18 system in joint destruction could be confirmed by our findings.

Animals↗
PubMed2004

Expression of COX-2 and HER-2/neu and estrogen and progesterone receptor in primary squamous cell carcinomas of the endometrium.

PURPOSE: Primary endometrial squamous cell carcinoma (ESCC) are rare but aggressive malignancies. To evaluate therapeutically relevant molecules, ESCC were investigated immunohistochemically. MATERIAL AND METHODS: Eight ESCC were stained with antibodies against estrogen and progesterone receptors, HER-2/neu, and COX-2 followed by semiquantitative evaluation of the staining results. RESULTS: Seven out of eight ESCC were negative for estrogen receptor as well as for HER-2/neu. Four tumors showed positivity for progesterone receptor. All ESCC displayed COX-2 overexpression. CONCLUSIONS: Primary ESCC are probably not under hormonal control of estrogens and lack HER-2/neu expression. Thus, anti-hormonal or antibody therapy with herceptine is not indicated. The use of COX-2 inhibitors might be a therapeutic alternative in ESCC that requires further investigation.

Adult↗
PubMed2002

Functional adaptation of human joints to mechanical stimuli.

OBJECTIVE: This study tests the hypothesis that functional adaptation occurs in human joints, and that substantial differences in joint 'loading history' explain the phenotypic variability observed in human cartilage morphology. METHOD: We examined 18 triathletes (nine men and nine women) who had been physically active throughout life (training for >10 h per week for the last 3 years), and 18 volunteers that had never been physically active on a regular basis. The right knee joints were imaged with a previously validated fat-suppressed gradient-echo MR sequence. Cartilage volume, thickness, joint surface areas, and normalized cartilage signal intensity were determined with post-processing software, specifically designed for these applications. RESULTS: The knee joint cartilage thickness, and signal intensity were not significantly different between athletes and inactive volunteers, but male athletes displayed significantly larger knee joint surfaces (P< 0.01; +8.8%). Female athletes displayed a significantly larger medial tibia (P< 0.05; +18.9%), the difference in the total knee surface area reaching borderline significance (P=0.08; +7.0%). CONCLUSIONS: The results suggest that joint size can be modulated during growth, but that (opposite to muscle and bone) the thickness of the cartilage does not adapt to mechanical stimulation. This finding may reveal a general principle in the development and functional adaptation of diarthrodial joints, elucidating an important mechanism for reducing mechanical stress in biphasic cartilage layers.

Adaptation, Physiological↗
PubMed2001

Optimization and validation of a rapid high-resolution T1-w 3D FLASH water excitation MRI sequence for the quantitative assessment of articular cartilage volume and thickness.

In view of follow up, survey and development of therapeutic strategies for osteoarthritis where cartilage deterioration plays an important role, a non invasive, reliable and quantitative assessment of the articular cartilage is desirable. The currently available high resolution T(1)-weighted (T1-w) 3D FLASH pulse sequences with frequency selective fat suppression are very time consuming. We have 1) optimized a high resolution T1-w 3D FLASH water excitation (WE) sequence for short acquisition time and cartilage visualization, and 2) validated this sequence for cartilage volume and thickness quantification. The spectral fat presaturation was replaced by selective water excitation. The flip angle of the WE sequence was optimized for the contrast to noise (C/N(cart)) ratio of cartilage. Sagittal datasets (voxel size: 0.31 x 0.31 x 2 mm(3)) of the knees of nine healthy volunteers were acquired both, with the 3D FLASH WE (17.2/6.6/30 degrees ) sequence (WE) and a previously validated 3D FLASH fat saturated (42/11/30 degrees ) sequence (FS). For validation of the WE sequence, cartilage volume, mean and maximal cartilage thickness of the two sequences were compared. Reproducibility was assessed by calculating the coefficient of variation (COV %) of 4 consecutive WE data sets in the volunteers. The acquisition time was reduced from 16'30" (FS) down to 7'14" for the WE sequence. Image contrast and visualization of the cartilage was very similar, but delineation of the basal layer of the cartilage was slightly improved with the WE sequence. A flip angle of 30 degrees provided the best C/N(cart) ratios (WE). Reproducibility (COV) was between 1.9 and 5.9%. Cartilage volume and thickness agreed within 4% between FS and WE sequence. The WE sequence allows for rapid, valid and reproducible quantification of articular cartilage volume and thickness, prerequisites for follow-up examinations. The reduced acquisition time (50% of FS) enables routine clinical application and thus may contribute to a broader assessment of osteoarthritis.

Adult↗
PubMed2000

Precision of tibial cartilage morphometry with a coronal water-excitation MR sequence.

The aim of this study was to analyze the precision of tibial cartilage morphometry, by using a fast, coronal water-excitation sequence with high spatial resolution, to compare the reproducibility of 3D thickness vs volume estimates, and to test the technique in patients with severe osteoarthritis. The tibiae of 8 healthy volunteers and 3 patients selected for total knee arthroplasty were imaged repeatedly with a water-excitation sequence (image time 6 h 19 min, resolution 1.2 x 0.31 x 0.31 mm(3)), with the knee being repositioned between each replicate acquisition. After 3D reconstruction, the cartilage volume, the mean, and the maximal tibial cartilage thickness were determined by 3D Euclidean distance transformation. In the volunteers, the precision of the volume measurements was 2.3 % (CV%) in the medial and 2.6 % in the lateral tibia. The reproducibility of the mean cartilage thickness was similar (2.6 and 2.5 %, respectively), and that of the maximal thickness lower (6.5 and 4.4 %). The patients showed a considerable reduction in volume and thickness, the precision being comparable with that in the volunteers. We find that, using a new imaging protocol and computational algorithm, it is possible to determine tibial cartilage morphometry with high precision in healthy individuals as well as in patients with osteoarthritis.

Adult↗
PubMed2000

A technique for 3D in vivo quantification of proton density and magnetization transfer coefficients of knee joint cartilage.

OBJECTIVE: To develop an MR-based method for the in vivo evaluation of the structural composition of articular cartilage. DESIGN: Five sagittal magnetic resonance imaging (MRI) protocols were acquired throughout the knee joint of 15 healthy volunteers and the boundaries of the cartilage segmented from a previously validated sequence with high contrast between cartilage and surrounding tissue. The other sequences were matched to these data, using a 3D least-squares fit algorithm to exclude motion artefacts. In this way secondary images were computed that included information about the proton density (interstitial water content) and the magnetization transfer coefficient (macromolecules, collagen). The average signal intensities of the 3D cartilage plates were extracted from these data sets and related to a phantom. RESULTS: The signal intensity data showed a high interindividual variability for the proton density (patella 31%, lateral tibia 36%, medial tibia 29%); the patella displaying higher values than the tibia (P< 0.001). There were high correlations between the three plates. The magnetization transfer coefficient also showed high variability (patella 25%, lateral tibia 32%, medial tibia 30%) with the lowest values in the medial tibia (P< 0.01) and lower correlations between the plates. The slice-to-slice variation (medial to lateral) ranged from 9% to 24%. CONCLUSION: An MR-based method has been developed for evaluating the proton density and magnetization transfer of articular cartilage in vivo and observing systematic differences between knee joint cartilage plates. The technique has the potential to supply information about the water content and collagen of articular cartilage, in particular at the early state of osteoarthritic degeneration.

Adult↗
PubMed2000

[Precision MRI-based joint surface and cartilage density analysis of the knee joint using rapid water-excitation sequence and semi-automatic segmentation algorithm].

The aim of this study was to analyse the precision of three-dimensional joint surface and cartilage thickness measurements in the knee, using a fast, high-resolution water-excitation sequence and a semiautomated segmentation algorithm. The knee joint of 8 healthy volunteers, aged 22 to 29 years, were examined at a resolution of 1.5 mm x 0.31 mm x 0.31 mm, with four sagittal data sets being acquired after repositioning the joint. After semiautomated segmentation with a B-spline Snake algorithm and 3D reconstruction of the patellar, femoral and tibial cartilages, the joint surface areas (triangulation), cartilage volume, and mean and maximum thickness (Euclidean distance transformation) were analysed, independently of the orientation of the sections. The precision (CV%) for the surface areas was 2.1 to 6.6%. The mean cartilage thickness and cartilage volume showed coefficients of 1.9 to 3.5% (except for the femoral condyles), the value for the medial femoral condyle being 9.1%, and for the lateral condyle 6.5%. For maximum thickness, coefficients of between 2.6 and 5.9% were found. In the present study we investigate for the first time the precision of MRI-based joint surface area measurements in the knee, and of cartilage thickness analyses in the femur. Using a selective water-excitation sequence, the acquisition time can be reduced by more than 50%. The poorer precision in the femoral condyles can be attributed to partial volume effects that occur at the edges of the joint surfaces with a sagittal image protocol. Since MRI is non-invasive, it is highly suitable for examination of healthy subjects (generation of individual finite element models, analysis of functional adaptation to mechanical stimulation, measurement of cartilage deformation in vivo) and as a diagnostic tool for follow-up, indication for therapy, and objective evaluation of new therapeutic agents in osteoarthritis.

Adult↗
PubMed1999

Functional analysis of articular cartilage deformation, recovery, and fluid flow following dynamic exercise in vivo.

The function of articular cartilage depends on the interaction between the tissue matrix and the interstitial fluid bound to the proteoglycan molecules. Mechanical loading has been shown to be involved in both the metabolic regulation of chondrocytes and in matrix degeneration. The purpose of the present study was therefore to analyze the deformation, recovery, and fluid flow in human articular cartilage after dynamic loading in vivo. The patellae of 7 volunteers were imaged at physical rest and after performing knee bends, with a specifically optimized fat-suppressed FLASH-3D magnetic resonance (MR) sequence. To measure cartilage deformation, the total volume of the patellar cartilage was determined, employing 3D digital image analysis. Patellar cartilage deformation ranged from 2.4 to 8.6% after 50 knee bends, and from 2.4% to 8.5% after 100 knee bends. Repeated sets of dynamic exercise at intervals of 15 min did not cause further deformation. After 100 knee bends, the cartilage required more than 90 min to recover from loading. The rate of fluid flow during relaxation ranged from 1.1 to 3.5 mm(3)/min (0.08 to 0.22 mm(3)/min per square centimeter of the articular surface) and was highly correlated with the individual degree of deformation after knee bends. The data provide the first quantification of articular cartilage recovery and of the rate of fluid flow between the cartilage matrix and surrounding tissue in intact joints in vivo. Measurement in the living opens the possibility of relating interindividual variations of mechanical cartilage properties to the susceptibility of developing joint failure, to assess the load-partitioning between the fluid phase and solid cartilage matrix during load transfer, and to determine the role of mechanically induced fluid flow in the regulation of the metabolic activity of chondrocytes.

Adult↗
PubMed1999

In situ measurement of articular cartilage deformation in intact femoropatellar joints under static loading.

The deformational behavior of articular cartilage has been investigated in confined and unconfined compression experiments and indentation tests, but to date there exist no reliable data on the in situ deformation of the cartilage during static loading. The objective of the current study was to perform a systematic study into cartilage compression of intact human femoro-patellar joints under short- and long-term static loading with MR imaging. A non-metallic pneumatic pressure device was used to apply loads of 150% body weight to six joints within the extremity coil of an MRI scanner. The cartilage was delineated during the compression experiment with previously validated 2D and 3D fat-suppressed gradient echo sequences. We observed a mean (maximal) in situ deformation of 44% (57%) in patellar cartilage after 32 h of loading (mean contact pressure 3.6 MPa), the femoral cartilage showing a smaller amount of deformation than the patella. However, only around 7% of the final deformation (3% absolute deformation) occurred during the first minute of loading. A 43% fluid loss from the interstitial patellar matrix was recorded, the initial fluid flux being 0.217 +/- 0.083 microm/s, and a high inter-individual variability of the deformational behavior (coefficients of variation 11-38%). In conjunction with finite-element analyses, these data may be used to compute the load partitioning between the solid matrix and fluid phase, and to elucidate the etiologic factors relevant in mechanically induced osteoarthritis. They can also provide direct estimates of the mechanical strain to be encountered by cartilage transplants.

Adolescent↗
PubMed1999

Epithelial-mesenchymal interaction and insulin-like growth factors in hyperoxic lung injury.

To investigate the role of epithelial-mesenchymal interaction on oxygen-induced lung injury, we used a coculture model with lung fibroblasts (FB) embedded between 2 layers of collagen gel with and without human tracheobronchial epithelial cells (HTBE), and studied the effect of hyperoxia on the directed migration of FB towards epithelial cells and proliferation of fetal lung FB. The expression of insulin-like growth factor (IGF)-I, -II, and -IIR mRNAs and proteins was studied in FB and HTBE cells cultured separately in 95% oxygen and 5% CO2 for 48 hours. There was a significant increase in directional migration of FB in coculture with epithelial cells when exposed to 95% oxygen and 5% CO2 (P = .04 compared to cocultures without oxygen exposure). Hyperoxia stimulated the proliferation of fibroblasts cocultured with HTBE cells (0.75 +/- 0.05 x 10(6) cells per well) as compared to control (0.47 +/- 0.03 x 10(6) cells per well; P = .01). This was inhibited by anti-IGF-I antibody (69 +/- 2% of hyperoxia alone; P = .002). Western blot showed a significant increase in IGF-I protein in epithelial cells (P = .02). IGF-I mRNA was increased in HTBE cells after hyperoxia (P = .003). In conclusion, HTBE cells modulate lung FB migration and proliferation in response to hyperoxia exposure. This is mediated in part by IGF-I produced by epithelial cells.

Cell Communication↗
PubMed1999

Coagulative interstitial laser-induced thermotherapy of benign prostatic hyperplasia: online imaging with a T2-weighted fast spin-echo MR sequence--experience in six patients.

PURPOSE: To determine if hypointense lesions clearly outline on T2-weighted fast spin-echo (SE) magnetic resonance (MR) images obtained during coagulative interstitial laser-induced thermotherapy (LITT) of a prostate with benign hyperplasia. MATERIALS AND METHODS: In six patients with benign prostatic hyperplasia (BPH), 12 LITT treatments were followed online with repetitive axial T2-weighted fast SE imaging (repetition time, 3,700 msec; echo time, 138 msec; acquisition time, 19 seconds). Development, time course, correlation with interstitial tissue temperature, and diameters of hypointense lesions around the laser diffusor tip were investigated. Lesion diameters on T2-weighted images acquired during LITT were compared with diameters of final lesions on T2-weighted images and unperfused lesions on enhanced T1-weighted SE images obtained at the end of therapy. RESULTS: Hypointense lesions developed within 20-40 seconds of LITT. Average correlation coefficients between interstitial temperature development and signal intensity development were 0.92 during LITT and 0.90 after LITT. Regression slopes were significantly steeper during LITT (0.67% signal intensity change per degree Celsius) than after LITT (0.47% per degree Celsius; P = .038). Lesions remained visible after LITT for all procedures. Average maximum diameters of lesions were 1-3 mm larger during LITT than after LITT (P = .0006-.019). CONCLUSION: Repetitive T2-weighted fast SE MR imaging during interstitial coagulative LITT of BPH demonstrates the development of permanent hypointense prostate lesions. However, posttherapeutic lesion diameters tend to be overestimated during LITT.

Aged↗
PubMed1998

An MR-based technique for quantifying the deformation of articular cartilage during mechanical loading in an intact cadaver joint.

The objective of this study was to develop an MR-based technique for quantifying the deformation of articular cartilage during mechanical loading in an intact cadaver joint at high spatial and temporal resolution. A nonmetallic pressure device was constructed for applying loads of >1000 N to a femoro-patellar articulation within an extremity coil of a clinical 1.5 T MRI scanner. Digital image processing methods were used to determine the location- and time-dependent cartilage deformation in consecutive 2D fat-suppressed FLASH images. Additionally, three-dimensional reconstruction of the cartilage was performed from 3D fat-suppressed FLASH image data. During the first 10 min of static compression, thickness changes between 10 and 30% were observed. Thickness changes greater than 50% and volume changes of 20% were recorded after 3 h. The technique permits analysis of the load and time-dependent mechanical behavior of articular cartilage in its natural environment.

Adult↗
PubMed1998

[MRI of the small intestine with rapid MRI sequences in Crohn disease after enteroclysis with oral iron particles].

PURPOSE: To evaluate the efficacy of breathhold MRI following enteroclysis with addition of oral magnetic particles to study the extension, detection of stenoses and extraluminal manifestations in Crohn's disease. MATERIAL AND METHODS: 18 patients with Crohn's disease and potential of surgical intervention were studied with enteroclysis with addition of oral magnetic particles. T1-/T2-weighted breathhold MRI w/o spectral fat suppression w/o i.v. Gd-DTPA was applied. RESULTS: Typical findings were marked bowel wall thickening with strong contrast enhancement. 95.8% of affected small bowel segments and 94.7% of stenoses were correctly detected by MRI. All four fistulas were detected and important extraluminal findings were seen in 6/18 patients. Additionally, one ileoileal and two ileosigmoidal adhesions, two extraluminal abscesses and affection of the right ureter were delineated. CONCLUSION: MRI in Crohn's disease offers the potential to avoid radiation exposure in this relatively young patient group. Important additional findings relevant to indication of surgery are seen in approximately one third of cases. The replacement of transduodenal intubation by oral contrast application remains to be further studied.

Administration, Oral↗
PubMed1998

A method for quantifying time dependent changes in MR signal intensity of articular cartilage as a function of tissue deformation in intact joints.

A method is proposed to determine accurately the signal intensity changes of the articular cartilage from sectional MR images and its related cartilage deformation under compression in an intact joint. Image processing methods are developed to delineate and register the cartilage boundaries in consecutive MR images in order to track corresponding tissue sectors during the loading experiment. Regions of interest can then be defined and traced during the compression, making a spatial and temporal analysis of signal intensity changes possible. In addition, the cartilage deformation is calculated in the respective tissue sectors and is related to the MR signal changes. Using a fat-suppressed FLASH 3D sequence, the preliminary results showed location-dependent slight changes of the signal intensity varying from individual to individual. The quantitative analysis of the signal intensity changes as a function of cartilage deformation with magnetic resonance imaging (MRI) aims to characterize microstructural properties of the articular cartilage that may lead to a better understanding of degenerative joint disease.

Adult↗
PubMed1998

Intracellular pH regulation in bovine aortic endothelial cells: evidence of both Na+/H+ exchange and Na+-dependent Cl-/HCO3- exchange.

Regulation of intracellular pH (pHi) was studied in cultured bovine aortic endothelial cells, an important cell system for cardiovascular research. Suspended cells were acidified by the NH4Cl prepulse technique as well as by exposure to CO2/HCO3-. Subsequent rates of pHi recovery were monitored using the fluorescent dye 2',7'-bis(2-carboxyethyl)-5-(6)-carboxyfluorescein (BCECF). In HCO3(-)-free solutions, an EIPA-sensitive, Na+-dependent mechanism fully accounted for realkalinization, namely the Na+/H+ exchanger (NHE). In the presence of HCO3-, an additional acid efflux mechanism was found. This one was dependent on Na+ and intracellular Cl-, EIPA-insensitive but DIDS-sensitive, and therefore represented a Na+-dependent Cl-/HCO3- exchanger (NCBE). In summary, two acid-extruding mechanisms were identified in bovine aortic endothelial cells: NHE and NCBE.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

[Relevance of susceptibility-induced geometrical distortion for validity of MRI-based cartilage volume and density measurements of the knee joint].

The aim of the present study was to analyze the relevance of susceptibility-induced geometrical distortion to the accuracy of MR-based cartilage volume and thickness measurement in the human knee joint. Nine cadaveric knee joints were imaged in the sagittal plane with MRI at a resolution of 2 x 0.31 x 0.31 mm3, using a fat-suppressed gradient echo sequence, with a normal gradient orientation and also with the frequency- and phase-encoding directions changed. CT arthrographic data sets were then obtained. On the basis of 3-D constructions, we determined the cartilage volume and, with a 3-D minimal distance algorithm, the thickness distribution, of the patella, femur and tibia. Irrespective of the gradient orientation, good agreement was observed between MRI and CT arthrography in terms of cartilage volumes and maximum cartilage thickness. With a normal gradient orientation the volume was overestimated by 2.5% in MRI, and 2.3% when the gradients were changed. The maximum cartilage thickness was underestimated by 0.24 intervals (interval = 0.5 mm) with a normal gradient orientation, and by 0.22 intervals when the gradient orientation was changed. In none of the joint surfaces was a relevant difference between the two methods observed. It can be shown that, using high-resolution, fat-suppressed gradient-echo sequences--susceptibility-induced geometrical distortion has no significant effect on the accuracy of MR-based cartilage volume and thickness measurements. MRI would therefore appear suitable for the design of patient-specific finite element models with the aim of analysing load transmission in diarthrodial joints and planning surgical interventions.

Adult↗
PubMed1998

In vivo reproducibility of three-dimensional cartilage volume and thickness measurements with MR imaging.

OBJECTIVE: Previous studies suggest that MR imaging is capable of providing accurate data on knee joint cartilage volume and thickness in vitro, but the reproducibility of these data in living subjects has not been analyzed rigorously. Our aim was therefore to determine the in vivo reproducibility of volume and thickness measurements from replicated data sets, applying three-dimensional (3D) postprocessing methods. SUBJECTS AND METHODS: Eight healthy volunteers were imaged six times at a resolution of 2 x 0.31 x 0.31 mm with a fat-suppressed fast low-angle shot 3D sequence, the knee being repositioned in between replicated examinations. Three-dimensional reconstructions of the articular cartilage surfaces were obtained from sagittal data sets, and the cartilage volumes were calculated. The thickness distribution was analyzed throughout the joint surfaces independent of the section orientation, using a previously validated 3D minimal-distance algorithm. RESULTS: In the volunteers, the coefficient of variation for replicated volume measurements ranged from 1.3% (patella) to 3.4% (lateral tibia), and the standard deviation of the individual cartilage volumes ranged from +/- 16% (lateral tibia) to +/- 22% (femur). The intraclass correlation coefficient ranged from .959 (lateral tibia) to .995 (patella). The interobserver evaluation was similar to the interscan reproducibility. The mean interscan deviation of the maximal cartilage thickness interval ranged from 0.1 to 0.3 cartilage thickness intervals (of 0.5 mm); only in rare cases did we record deviations greater than one thickness interval. CONCLUSION: MR imaging can be used to determine cartilage volume and thickness in the knee joints of living subjects with high precision, provided that a fat-suppressed gradient-echo sequence with adequate resolution and 3D digital image processing are used.

Adult↗