Search PubMed⌕ Search

Biomedical subjects

B Koller

Publications and source records attributed to B Koller.

At least 19 recordsLinked to original sources
PubMed2005

Stereological measures of trabecular bone structure: comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies.

Stereology applied on histological sections is the 'gold standard' for obtaining quantitative information on cancellous bone structure. Recent advances in micro computed tomography (microCT) have made it possible to acquire three-dimensional (3D) data non-destructively. However, before the 3D methods can be used as a substitute for the current 'gold standard' they have to be verified against the existing standard. The aim of this study was to compare bone structural measures obtained from 3D microCT data sets with those obtained by stereology performed on conventional histological sections using human tibial bone biopsies. Furthermore, this study forms the first step in introducing the proximal tibia as a potential bone examination location by peripheral quantitative CT and CT. Twenty-nine trabecular bone biopsies were obtained from autopsy material at the medial side of the proximal tibial metaphysis. The biopsies were embedded in methylmetacrylate before microCT scanning in a Scanco microCT 40 scanner at a resolution of 20 x 20 x 20 microm3, and the 3D data sets were analysed with a computer program. After microCT scanning, 16 sections were cut from the central 2 mm of each biopsy and analysed with a computerized method. Trabecular bone volume (BV/TV) and connectivity density (CD) were estimated in both modalities, whereas trabecular bone pattern factor (TBPf) was estimated on the histological sections only. Trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), and structure model index (SMI) were estimated with the microCT method only. Excellent correlations were found between the two techniques for BV/TV (r = 0.95) and CD (r = 0.95). Additionally, an excellent relationship (r = 0.95) was ascertained between TBPf and SMI. The study revealed high correlations between measures of bone structure obtained from conventional 2D sections and 3D microCT data. This indicates that 3D microCT data sets can be used as a substitute for conventional histological sections for bone structural evaluations.

Aged↗
PubMed2005

Accelerated telomere shortening and telomere abnormalities in radiosensitive cell lines.

We examined telomere maintenance in cells of 11 primary fibroblast cell lines with differing genetic defects that confer sensitivity to ionizing radiation. These included cell lines derived from patients with ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, defective Artemis, DNA ligase I and DNA ligase IV, an immunodeficient patient with a defect in DNA double-strand break repair, and a patient diagnosed with xeroderma pigmentosum who, in addition, showed severe clinical sensitivity to ionizing radiation. Our results, based on Southern blot, flow-FISH and Q-FISH (quantitative FISH) measurements, revealed an accelerated rate of telomere shortening in most cell lines derived from the above patients compared to cell lines from normal individuals or a cell line isolated from a heterozygotic parent of one radiosensitive patient. This accelerated telomere shortening was accompanied by the formation of chromatin bridges in anaphase cells, indicative of the early loss of telomere capping function and in some cases low levels of chromosome abnormalities in metaphase cells. We also analyzed telomere maintenance in mouse embryonic stem cells deficient in Brca1, another defect that confers radiosensitivity. Similarly, these cells showed accelerated telomere shortening and mild telomere dysfunction in comparison to control cells. Our results suggest that mechanisms that confer sensitivity to ionizing radiation may be linked with mechanisms that cause telomere dysfunction.

Animals↗
PubMed2004

Vr2: a new apple scab resistance gene.

Reports from several European countries of the breakdown of the Vf resistance, the most frequently used source of resistance in breeding programs against apple scab, emphasize the urgency of diversifying the basis of apple scab resistance and pyramiding different apple scab resistances with the use of their associated molecular markers. GMAL 2473 is an apple scab resistant selection thought to carry the resistance gene Vr. We report the identification by BSA of three AFLP markers and one RAPD marker associated with the GMAL 2473 resistance gene. SSRs associated with the resistance gene were found by (1) identifying the linkage group carrying the apple scab resistance and (2) testing the SSRs previously mapped in the same region. One such SSR, CH02c02a, mapped on linkage group 2, co-segregates with the resistance gene. GAML 2473 was tested with molecular markers associated with other apple scab resistance genes, and accessions carrying known apple scab resistance genes were tested with the SSR linked to the resistance gene found in GMAL 2473. The results indicate that GMAL 2473 does not carry Vr, and that a new apple scab resistance gene, named Vr2, has been identified.

Ascomycota↗
PubMed2003

Creating a saturated reference map for the apple (Malus x domestica Borkh.) genome.

The availability of a high quality linkage map is essential for the detection and the analysis of quantitative traits. Such a map should cover a significant part of the genome, should be densely populated with markers, and in order to gain the maximum advantage should be transferable to populations or cultivars other than the ones on which it has been constructed. An apple genetic linkage map has been constructed on the basis of a segregating population of the cross between the cultivars Fiesta and Discovery. A total of 840 molecular markers, 475 AFLPs, 235 RAPDs, 129 SSRs and 1 SCAR, were used for the two parental maps constructed with JoinMap and spanning 1,140 cM and 1,450 cM, respectively. Large numbers of codominant markers, like SSRs, enable a rapid transfer of the map to other populations or cultivars, allowing the investigation of any chosen trait in another genetic background. This map is currently the most advanced linkage map in apple with regard to genome coverage and marker density. It represents an ideal starting point for future mapping projects in Malus since the stable and transferable SSR frame of the map can be saturated quickly with dominant AFLP markers.

Automation↗
PubMed2002

Body composition, bone mass and microstructural analysis in GH-transgenic mice reveals that skeletal changes are specific to bone compartment and gender.

Experimental and clinical studies suggest that high serum levels of growth hormone (GH) increase cortical but not trabecular bone. We studied body composition and bone structure in transgenic mice (MT-bGH) with systemic overexpression of GH. Body composition was examined with dual-energy X-ray absorptiometry (DXA), ashing, and chemical analysis, and the femora with DXA and micro computerized tomography. The absolute fat and bone tissue contents were significantly higher in GH transgenic mice vs controls (P < or = 0.05), but no significant difference was noted when normalizing the values to body weight. Male transgenics displayed no change in apparent (volumetric) femoral bone density, relative cortical area and trabecular bone volume fraction. Female transgenic mice demonstrated an increase in apparent femoral density and in trabecular bone volume fraction (+130%; P < or = 0.01). The mineralized tissue matrix density was decreased in male and female transgenic mice (P < or = 0.05). The results show that chronic GH excess affects trabecular bone in a gender-specific manner and that bone changes depend on the compartment investigated.

Animals↗
PubMed2000

A biomechanical enigma: why are tibial fractures not more frequent in the elderly?

Epidemiology revealed that diaphyseal fractures of the tibia affect young people, particularly young men; no increase was noticed for the elderly. This indicates that osteoporosis does not lead to increased bone fragility. Obviously, this is a biomechanical enigma. Torque measurements were carried out on human cadaveric tibiae and revealed a great correlation between the polar moment of inertia of the cortical bone at the tibial isthmus and the ultimate torque at failure (r = 0.83) and a lesser correlation between the cross-sectional density at the isthmus and the torque at failure (r = 0.57). Therefore, the size is more important than the degree of osteoporosis. We can speculate that endosteal resorption due to osteoporosis is compensated for by periosteal apposition and therefore does not lead to bone weakness.

Age Factors↗
PubMed1998

Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice. Insights into perinatal adaptation and pseudohypoaldosteronism.

Genetic evidence supports a critical role for the epithelial sodium channel (ENaC) in both clearance of fetal lung liquid at birth and total body electrolyte homeostasis. Evidence from heterologous expression systems suggests that expression of the alphaENaC subunit is essential for channel function, whereas residual channel function can be measured in the absence of beta or gamma subunits. We generated mice without gammaENaC (gammaENaC -/-) to test the role of this subunit in neonatal lung liquid clearance and total body electrolyte balance. Relative to controls, gammaENaC (-/-) pups showed low urinary [K+] and high urinary [Na+] and died between 24 and 36 h, probably from hyperkalemia (gammaENaC -/- 18.3 mEq/l, control littermates 9.7 mEq/l). Newborn gammaENaC (-/-) mice cleared lung liquid more slowly than control littermates, but lung water at 12 h (wet/dry = 5.5) was nearly normal (wet/dry = 5.3). This study suggests that gammaENaC facilitates neonatal lung liquid clearance and is critical for renal Na+ and K+ transport, and that low level Na+ transport may be sufficient for perinatal lung liquid absorption but insufficient to maintain electrolyte balance by the distal nephron. The gammaENaC (-/-) newborn exhibits a phenotype that resembles the clinical manifestations of human neonatal PHA1.

Adaptation, Physiological↗
PubMed1998

Applications of micro-CT and MR microscopy to study pre-clinical models of osteoporosis and osteoarthritis.

There is a tremendous unmet therapeutic need for the treatment of osteoporosis and osteoarthritis. The ovariectomized rat and the guinea pig are widely used animal models for the evaluation of new therapeutics for osteoporosis and osteoarthritis, respectively. We have utilized X-ray micro-CT techniques to quantitatively evaluate the differences in trabecular bone in the rat proximal tibia following ovariectomy and treatment with estrogen (17-B-estradiol). Results demonstrate a loss of trabecular bone and architecture following ovariectomy (p < 0.001), and a marked inhibition of trabecular bone loss in the estrogen treated group (p < 0.001). A similar change in architecture can be visualized in images obtained by high resolution MR microscopy. In addition, a good correlation was observed between the values of trabecular bone fraction (BV/TV) in the rat tibiae as obtained from 3-dimensional micro-CT data and 2-dimensional static histomorphometry (r = 0.89, 0.73, 0.79 for sham, OVX, and treated groups, respectively). Micro-CT images were also obtained from a set of lumbar vertebrae from sham operated and ovariectomized rats. Significant bone loss can be measured as early as 8 weeks following ovariectomy (p < 0.005). Micro-CT and MR images were also obtained to study age related changes in the stifle joint of the guinea pig. Significant boney changes can be seen in the tibia and femur from the animals at various ages. Changes in cartilage and joint space can also be visualized in the images. The utility of micro-CT imaging in evaluating the mouse skeletal system is illustrated by obtaining morphological and architectural details from high resolution images of the mouse hind limb and proximal tibia, respectively. The results demonstrate the advantages that multi-dimensional imaging techniques can offer in evaluating bone and joint related changes in animal models of osteoporosis and osteoarthritis.

Animals↗
PubMed1996

A microtomographic system for the nondestructive evaluation of bone architecture.

Microtomography (micro-computed-tomography, mu-CT) is a method to image and quantify trabecular bone. It has the capability to address the role of trabecular architecture on the mechanical properties of bone and to study trabecular bone remodeling. The system described in this work is based on a compact fan-beam type tomograph that can work in spiral scanning or multislice mode. An X-ray tube with a microfocus is used as a source, a CCD-array as a detector. Samples with diameters from a few millimeters to a maximum of 14 mm can be measured, typically, bone biopsies with a diameter of 8 mm and a length of approximately 10 mm are measured. Spatial resolution is 28 microns. Usually the volume of interest contains 4 x 4 x 4 mm3 and is represented in 14 x 14 x 14 microns3 voxels. 3D stereological indices are extracted according to the standard definitions used in histomorphometry. Triangular surface representation is effected with an extended marching cube algorithm and forms a convenient basis for finite element analysis. Microtomographic measurements may be employed to "calibrate" lower-dose, lower-resolution images in vivo as well as to nondestructively assess unprocessed surgical bone biopsy specimens. These specimens remain intact for mechanical or histological testing.

Bone and Bones↗
PubMed1996

[Not Available].

To the bougeoisie in the last quarter of the 19th century, the housing problem seemed to be the key problem regarding the "social issue" (Soziale Frage). This was the background on which a number of Swiss cities undertook extensive surveys of the living conditions towards the end of the century. These surveys, which were methodologically based on the quantifying and therefore objective instruments of statistics, also attracted attention in other European states. Scientific hygiene supplied its values as the seemingly objective material criteria for the surveys. These values consisted among others of the limiting value "Luftkubus" (air volume), the natural human need for air expressed in exact numbers, as well as the rules for social behaviour in connection with this value. Together they justified "sanitary living", which a closer examination reveals as being a scientifically constructed bourgeois reality. This reality was guarded by sanitary officials, who were under the municipal sanitary authorities' supervision. These officials disposed of the means of criminal law in their struggle against "unsanitary living". The obligation to maintain health mandated by the public authorities ultimately aimed at integrating the workers into the Swiss bourgeois state and ensuring and increasing national power in modern industrial society.

Austria↗
PubMed1996

Resolution dependency of microstructural properties of cancellous bone based on three-dimensional mu-tomography.

Micro-computed tomography (microCT) is an emerging technique for the non-destructive assessment and analysis of the three-dimensional cancellous bone architecture. However, the procedures the procedures and applications used to quantify bone structures are not yet standardized. The aim of this study was to provide more insight in the resolution-dependency of microstructural properties of three-dimensional trabecular bone. Ten iliac crest bone biopsies were measured using a newly devised microCT system providing a nominal isotropic resolution of 14 microns. To study the resolution dependency the measured data were reconstructed on reduced image arrays with reduction factors ranging from 2 to 20. To assess the structural properties, morphometric parameters were computed based on a truly three-dimensional approach. The results showed a strong resolution dependency of the structural properties and that, if very precise results are needed, only the highest resolution will predict the correct values. Nevertheless, since the properties either decrease or increase monotonously up to a nominal resolution of about 175 microns, the values appear to be restorable using a suitable calibration procedure.

Bone Matrix↗
PubMed1995

Inhibition of natural killer cell-mediated bone marrow graft rejection by allogeneic major histocompatibility complex class I, but not class II molecules.

The role of major histocompatibility complex (MHC) class I and class II molecules in natural killer (NK) cell-mediated rejection of allogeneic, semisyngeneic and MHC-matched bone marrow grafts was investigated. The use of beta 2-microglobulin (beta 2m) -/- and beta 2m +/- mice as bone marrow donors to MHC-mismatched recipients allowed an analysis of whether the presence of semi-syngeneic and allogeneic MHC class I gene products would be triggering, protective or neutral, in relation to NK cell-mediated rejection. Loss of beta 2m did not allow H-2b bone marrow cells to escape from NK cell-mediated rejection in allogeneic (BALB/c) or semi-allogeneic (H-2Dd transgenic C57BL/6) mice. On the contrary, it led to stronger rejection, as reflected by the inability of a larger bone marrow cell inoculum to overcome rejection by the H-2-mismatched recipients. In H-2-matched recipients, loss of beta 2m in the graft led to a switch from engraftment to rejection. At the recipient level, loss of beta 2m led to loss of the capability to reject H-2-matched beta 2m-deficient as well as allogeneic grafts. When MHC class II-deficient mice were used as donors, the response was the same as that against donors of normal MHC phenotype: allogeneic and semi-syngeneic grafts were rejected by NK cells, while syngeneic grafts were accepted. These data suggest a model in which allogeneic class I molecules on the target cell offer partial protection, while certain syngeneic class I molecules give full protection from NK cell-mediated rejection of bone marrow cells. There was no evidence for a role of MHC class II molecules in this system.

Animals↗
PubMed1995

Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule.

CD19-deficient mice were generated to examine the role of CD19 in B cell growth regulation in vivo. Deletion of CD19 had no deleterious effects on the generation of B cells in the bone marrow, but there was a significant reduction in the number of B cells in peripheral lymphoid tissues. B cells from CD19-deficient mice exhibited markedly decreased proliferative responses to mitogens, and serum immunoglobulin levels were also significantly decreased. In contrast, mice that overexpressed CD19 had significant defects in early B cell development in the bone marrow, augmented mitogenic responses, and increased serum immunoglobulin levels. These experiments indicate that CD19 functions to define signaling thresholds for cell surface receptors that regulate B lymphocyte selection, activation, and differentiation.

Animals↗
PubMed1994

DNA markers linked to Malus floribunda 821 scab resistance.

Breeding resistant apple plants is an alternative way to control fungal pathogens reducing the environmental impact due to the use of pesticides. The breeding of apple cultivars resistant to Venturia inaequalis could be much improved by marker-assisted selection. A molecular marker closely linked to the resistance locus called Vf could replace selection based on infection studies. To find such molecular markers, DNA of progenies from crossings of a resistant and a susceptible apple tree was subject to bulked segregant analysis. Two markers were found with a genetic distance of 10.6% and 19.7% recombination frequency to the Vf locus.

DNA Primers↗
PubMed1994

New classification of moricizine and propafenone based on electrophysiologic and electrocardiographic data from isolated rabbit heart.

Because the classification of propafenone and moricizine is not clear, we measured in 20 specifically equipped isolated rabbit hearts QRS duration, QT interval, action potential duration at 90% of repolarization (APD90), effective refractory period (ERP), conduction time (CT), and rise velocity (Rv) of the monophasic action potentials (AP) during exposure to moricizine and propafenone in comparison with procainamide. Propafenone and procainamide prolonged APD90 and JT. All drugs increased ERP. Propafenone demonstrated marked tonic sodium channel block. Onset of use-dependent kinetics (tau on), defined as change in Rv as fraction per beat at 300 ms cycle length (CL), were 0.047 +/- 0.004/beat for procainamide, 0.050 +/- 0.004/beat for propafenone, and 0.022 +/- 0.003/beat for miricizine. Recovery kinetics, defined as recovery of Rv after cessation of pacing, had a time constant of 5.3 +/- 0.7 s for procainamide, 6.3 +/- 0.8 s for propafenone, and 25.0 +/- 1.3 s for moricizine. Based on these data, moricizine must be classified as a Ic agent, whereas propafenone demonstrates pronounced tonic sodium channel block, in addition to its phasic block, which is similar to class Ia kinetics.

Action Potentials↗
PubMed1993

Improved renal function in mouse kidney allografts lacking MHC class I antigens.

The immunological responses that lead to rejection of organ and tissue transplants are triggered by the recognition of proteins encoded within the MHC. The relative contributions of responses directed toward MHC class I compared with class II in the loss of functional integrity of vascularized organ grafts have been difficult to define. The recent development of technologies which allow the generation of mice in which specific genes have been altered by gene targeting offers a new approach to addressing this question. We examine here the rejection of kidney allografts from mice lacking native MHC class I Ag. These mice were obtained from embryonic stem cells in which the beta 2 microglobulin (beta 2m) gene had been disrupted by homologous recombination. We found a significant improvement in function of renal allografts from MHC class I-deficient donors compared with allografts from donors with normal MHC class I expression. Surprisingly, the improved function of the MHC class I-deficient grafts was not associated with differences in mononuclear inflammatory cell infiltration of these grafts nor in differences in alloreactive proliferative or cytotoxic T cell responses. However, we did find differences in alloantibody response between the groups. Recipients of control allografts produced antibodies against both donor MHC class I and II, whereas recipients of MHC class I-deficient grafts formed alloantibodies primarily against donor MHC class II Ag. These studies confirm that immune responses directed toward donor MHC class I alloantigens contribute to kidney transplant dysfunction in this model. Also, these findings suggest that, at least for renal transplants, genetic manipulations which reduce MHC class I expression may be effective in overcoming some of the effects of MHC incompatibility.

Animals↗