PubMed Health⌕ Search

Biomedical subjects

Thomas Köhler

Publications and source records attributed to Thomas Köhler.

At least 19 recordsLinked to original sources
PubMed2006

Circular CT in combination with a helical segment.

The combination of circular CT with a helical trajectory segment results in a mathematically complete data set. We present a reconstruction algorithm which is mathematically exact and of the filtered back-projection type. The algorithm ensures that only Radon planes which are not covered along the circle are taken into account, when data from the helical segment are back-projected. Therefore, the helical segment contributes only to low-frequency parts of trans-axial slices. Data along the helix can be obtained with a very low acquisition dose.

Algorithms↗
PubMed2006

BMPs restrict the position of premuscle masses in the limb buds by influencing Tcf4 expression.

Previous studies have shown the distally retreating source of Scatter factor/Hepatocyte growth factor (SF/HGF) can account for the distal migration of myogenic precursor cells in the limb bud mesenchyme. However, the normal expression pattern of Sf/Hgf alone does not explain the distribution of muscle precursor cells. Hence, the position of the dorsal and ventral premuscle masses suggests the presence of additional patterning factors. We present evidence that BMP2 and 4 can act as such factors by inhibiting the expression of Tcf4, a downstream element of the canonical Wnt pathway. The normal position of muscle cells depends on the correct distribution of BMP and SF/HGF throughout the limb bud mesenchyme. Removal or inhibition of the BMP signals within the limb margins leads to a shift in position resulting in the fusion of the dorsal and ventral premuscle masses towards the manipulated areas. In the absence of BMPs, mispositioning requires the presence of SF/HGF. Consequently, ectopic application of exogenous SF/HGF in the presence of BMP signals does not change muscle positioning. We conclude that correct positioning of the premuscle masses in the limb buds is controlled by the combined influence of SF/HGF signals--guiding cells mainly in the proximo-distal axis--and BMP signals that restrict the positioning to the dorsal and ventral central portions of the limb buds.

Animals↗
PubMed2006

The radon-split method for helical cone-beam CT and its application to nongated reconstruction.

The mathematical analysis of exact filtered back-projection algorithms is strictly related to Radon inversion. We show how filter-lines can be defined for the helical trajectory, which serve for the extraction of contributions of particular kinds of Radon-planes. Due to the Fourier-slice theorem, Radon-planes with few intersections with the helix are associated with low-frequency contributions to transversal slices. This insight leads to different applications of the new method. The application presented here enables the incorporation of an arbitrary amount of redundant data in an approximate way. This means that the back-projection is not restricted to an n-Pi interval. A detailed mathematical analysis, in which we demonstrate how the defined filter-lines work, concludes this paper.

Algorithms↗
PubMed2006

CEnPiT: helical cardiac CT reconstruction.

Computer tomography (CT) scanners with an increasing number of detector rows offer the potential of shorter scanning times. Nevertheless, the reconstruction problem becomes more challenging, since cone beam artifacts are likely to enter. Here, we consider helical cardiac CT. We analyze how a relationship can be established between exact reconstruction algorithms and the demand to perform a cardiac gating. Utilizing the redundancies requires the consideration of all kinds of Radon planes. For the reconstruction algorithm proposed here, we separate the data into two parts. The first part contains contributions of Radon planes, which are measured with a large number of redundancies. The second part contains the remaining contributions. As it turns out, the second part contributes rather to the low-frequency contents of trans-axial slices. Therefore, we propose to perform a gated back-projection only for the first part, while the second part is back-projected in an ungated way. Data from the complete source trajectory are employed in the reconstruction process in contrary to conventional helical cardiac reconstruction methods. Moreover, all different types of Radon planes are taken into account in the reconstruction, though an ECG-dependent cardiac gating is applied. The reconstruction results, which we present for clinical and simulated data, demonstrate the high potential of CEnPiT for helical cardiac CT with large cone angle systems.

Algorithms↗
PubMed2005

Reconstruction of blood propagation in three-dimensional rotational X-ray angiography (3D-RA).

This paper presents a framework of non-interactive algorithms for the mapping of blood flow information to vessels in 3D-RA images. With the presented method, mapping of flow information to 3D-RA images is done automatically without user interaction. So far, radiologists had to perform this task by extensive image comparisons and did not obtain visualizations of the results. In our approach, flow information is reconstructed by forward projection of vessel pieces in a 3D-RA image to a two-dimensional projection series capturing the propagation of a short additional contrast agent bolus. For accurate 2D-3D image registration, an efficient patient motion compensation technique is introduced. As an exemplary flow-related quantity, bolus arrival times are reconstructed for the vessel pieces by matching of intensity-time curves. A plausibility check framework was developed which handles projection ambiguities and corrects for noisy flow reconstruction results. It is based on a linear programming approach to model the feeding structure of the vessel. The flow reconstruction method was applied to 12 cases of cerebral stenoses, AVMs and aneurysms, and it proved to be feasible in the clinical environment. The propagation of the injected contrast agent was reconstructed and visualized in three-dimensional images. The flow reconstruction method was able to visualize different types of useful information. In cases of stenosis of the middle cerebral artery (MCA), flow reconstruction can reveal impeded blood flow depending on the severeness of the stenosis. With cases of AVMs, flow reconstruction can clarify the feeding structure. The presented methods handle the problems imposed by clinical demands such as non-interactive algorithms, patient motion compensation, short reconstruction times, and technical requirements such as correction of noisy bolus arrival times and handling of overlapping vessel pieces. Problems occurred mainly in the reconstruction and segmentation of 3D-RA images in cases of complex AVMs. The concentration of injected contrast agent was often not sufficient to provide highly contrasted vessels in 3D-RA images. Another segmentation-related problem is known as 'kissing vessels' [19]. Kissing vessel artifacts introduce artificial vessel junctions and thereby distort the feeding structure of the vessel. This may finally cause implausible flow reconstruction results and inverse flow directions in vessel segments. We are currently planning to validate our reconstruction results using particle imaging velocimetry (PIV). PIV experiments with phantoms, for which the true flow parameters are known, will allow for the assessment of the accuracy of our contrast agent based method. In the context of computational fluid dynamics techniques, the potential of the presented flow reconstruction method is high. Flow reconstruction results based on the presented method could be used both as boundary conditions for simulations and as a reference for the validation of simulation results. Computational fluid dynamics provide useful information such as arterial wall shear stress and complex flow patterns in aneurysms.

Algorithms↗
PubMed2005

Elevated expression of survivin-splice variants predicts a poor outcome for soft-tissue sarcomas patients.

The aim of this study was to investigate the level and the prognostic value of the expression of different survivin transcript variants--survivin, survivin-DeltaEx3 and survivin-2B--in tumours of 76 soft tissue sarcoma (STS) patients. The expression of survivin transcript variants in STS tissue samples and in 12 nonmalignant control tissues was analysed by quantitative RT-PCRs. Expression levels of all survivin transcript variants were strongly elevated in STS compared to normal tissues. A positive correlation between expression of splice variants and tumour stage was found (P=0.02; chi2 test). The multivariate Cox's proportional hazards regression model revealed a 7.3-fold increased risk of tumour-related death for patients with survivin-DeltaEx3 overexpressing tumours (P=0.007). The effect of surivivin (wildtype variant) and survivin-2B was less pronounced but still significant (2.2- and 1.9-fold, resp., P<0.05 each). Our results show for the first time that mRNA expression of survivin-variants is significantly correlated to a poor prognosis for STS patients, and we suggest expression of survivin splice variants together with tumour stage as independent predictor of survival.

Biomarkers, Tumor↗
PubMed2005

Electronic structure, spectra, and magnetic circular dichroism of cyclohexa-, cyclohepta-, and cyclooctapyrrole.

Three recently obtained expanded porphyrins represent nice examples of compounds for which the electronic and spectral properties can be predicted from symmetry considerations alone. Perimeter-model-based theoretical analysis of the electronic structure of doubly protonated cyclo[6], cyclo[7], and cyclo[8]pyrrole leads to the anticipation of qualitatively the same electronic absorption and magnetic circular dichroism patterns for all three compounds. These predictions are fully confirmed by experiments, as well as DFT and INDO/S calculations. Due to a characteristic pattern of frontier molecular orbitals, a degenerate HOMO and a strongly split LUMO pair, the three cyclopyrroles show comparable absorption intensity in the Q and Soret regions. Magnetic circular dichroism spectra reveal both A and B Faraday terms, of which the signs and magnitudes are in remarkably good agreement with theoretical expectations. The values of the magnetic moments of the two lowest degenerate excited states have also been obtained.

Circular Dichroism↗
PubMed2005

Facile syntheses of quater-, penta-, and sexipyrroles.

alpha,alpha-Linked oligopyrroles are attractive precursors for both expanded porphyrin and conducting polymer chemistry. We demonstrate facile methods for synthesizing quater-, penta-, and sexipyrroles from more readily available bi- and terpyrrole intermediates. These products demonstrate stability in their brightly colored oxidized forms, while reduction using borohydride reagents gives the corresponding all-pyrrole oligomers, which oxidize readily in air. The oxidized quater- and sexipyrroles were characterized by single-crystal X-ray diffraction analysis.

Journal Article↗
PubMed2005

pH-dependent photoisomerization of retinal in proteorhodopsin.

The early steps in the photocycle of the bacterial proton pump proteorhodopsin (PR) were analyzed by ultrafast pump/probe spectroscopy to compare the rate of retinal isomerization at alkaline and acidic pH values. At pH 9, the functionally important primary proton acceptor (Asp97, pK(a) = 7.7) is negatively charged; consequently, a reaction cycle analogous to the archaeal bacteriorhodopsin (BR) is observed. The excited electronic state of PR displays a pronounced biphasic decay with time constants of 400 fs and 8 ps. At pH 6 where Asp97 is protonated a similar biphasic decay is observed, although it is significantly slower (700 fs and 15 ps). The results indicate, in agreement to similar findings in other retinal proteins, that also in PR the charge distribution within the chromophore binding pocket is a major determinant for the rate and the efficiency of the primary reaction.

Archaeal Proteins↗
PubMed2005

EnPiT: filtered back-projection algorithm for helical CT using an n-Pi acquisition.

In this paper, we formulate a reconstruction algorithm for an n-Pi acquisition, where n can be any positive odd integer. The algorithm is a generalization of the method presented in (Bontus et al. 2003). It is based on the results obtained by Katsevich (2004). For the algorithm, different sets of filter-lines have to be defined. We describe the variation of these lines along the detector in some detail, before we discuss, how the method gives all Radon-plane contributions the correct weighting. The different sets of filter-lines are all contained within the n-Pi window, such that a practical realization is possible. Reconstruction results, which we present in the final section, show convincing image quality.

Algorithms↗
PubMed2004

PCNA in situ hybridization: a novel and reliable tool for detection of dynamic changes in proliferative activity.

In order to investigate developmental processes, several methods have been established that allow the visualization of local proliferation zones and to follow their dynamics during morphogenesis. In this study we present a detailed description of transitory and continuous proliferation zones in the developing chick embryo. By tracing the S-phase marker proliferating cell nuclear antigen (PCNA) at the mRNA level we were able to identify the initiation and termination of proliferation programs. This approach provides additional information in comparison to the well-known BrdU incorporation or the PCNA immunostaining, which exclusively labels cells that contain PCNA protein. By means of PCNA in situ hybridization we analyzed the normal expression pattern in the 2- to 5-day-old chick embryo. We furthermore monitored the effects on PCNA expression after various manipulations such as removal of the apical ectodermal ridge (AER), the zone of polarizing activity (ZPA), and the surface ectoderm. In addition, we applied morphogens, such as fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), and retinoic acid (RA), and subsequently analyzed changes in the pattern of PCNA expression. While ablation of ZPA, AER, or ectoderm are known to reduce cell proliferation and were paralleled by loss of PCNA expression, neither BMP-2 nor BMP-4 affected PCNA expression. Upregulation of PCNA expression could be achieved by application of RA or FGFs, factors known to induce cell proliferation during limb bud outgrowth. The PCNA in situ hybridization data presented here clearly show that this method offers a novel, very sensitive tool for tracing cell proliferation and for visualizing the dynamic patterns arising due to the initiation and termination of the proliferation program.

Amino Acid Sequence↗
PubMed2004

Octaethylporphyrin and expanded porphyrin complexes containing coordinated BF2 groups.

In contrast to octaethylporphyrin, which forms a very labile bis-BF(2) complex, treatment of the hexa- and octapyrrolic expanded porphyrins amethyrin and [32]octaphyrin with BF(3).Et(2) under standard reaction and work-up conditions gives rise to stable, non-labile mono- and bis-BF(2) complexes; these were readily characterised by, inter alia, X-ray diffraction analyses.

Boron Compounds↗
PubMed2004

Quantitative reverse transcription polymerase chain reaction should not replace conventional cytogenetics for monitoring patients with chronic myeloid leukemia during early phase of imatinib therapy.

BACKGROUND AND OBJECTIVES: Imatinib is the new standard drug treatment for patients with chronic myelogenous leukemia (CML). Quantitative reverse transcription-polymerase chain reaction (qPCR) for detection of BCR-ABL transcripts is frequently used for monitoring patients in addition to or instead of conventional cytogenetics, although its place in the overall diagnostic framework is not yet clear. In this study, we compared qPCR and conventional cytogenetics for monitoring of patients during the early phases of imatinib therapy. DESIGN AND METHODS: One hundred and seventeen patients treated with imatinib for CML in chronic or accelerated phase were prospectively followed with qPCR and karyotyping. Comparisons were made between both methods and between qPCR results from bone marrow and peripheral blood. To determine the prognostic impact of qPCR and cytogenetics during the early phase of imatinib treatment on subsequent cytogenetic response and progression-free survival (PFS), a multivariate model was generated that included established prognostic baseline variables. RESULTS: We found a significant correlation between the proportion of Philadelphia (Ph) chromosome-positive metaphases and qPCR in the bone marrow and peripheral blood. Low qPCR values after 3 months of therapy were correlated with major cytogenetic response (MCyR) at 6 months and PFS at 2 years. However, in multivariate analysis, the cytogenetic response at 3 months emerged as the only independent parameter predictive of MCyR at 6 months and PFS at 2 years. INTERPRETATION AND CONCLUSIONS: Our data suggest that conventional karyotyping should remain the standard method for following patients on imatinib during the early phases of therapy.

Adult↗
PubMed2003

Formation and properties of cyclo[6]pyrrole and cyclo[7]pyrrole.

Oxidative coupling of a tetraalkylbipyrrole under FeIII-mediated coupling conditions in the presence of HCl results in a mixture of cyclo[6]- and cyclo[7]pyrroles, as well as the known cyclo[8]pyrrole. This "matched set" of heteroannulenes was analyzed by spectroscopic, electrochemical, and X-ray diffraction methods.

Journal Article↗
PubMed2003

A quasiexact reconstruction algorithm for helical CT using a 3-Pi acquisition.

Recently, an exact reconstruction method for helical CT was published by A. Katsevich. The algorithm is of the filtered backprojection type and is, therefore, computationally efficient. Moreover, during backprojection, only data are used which correspond to an illumination interval of 180 degrees as seen from the object-point. We propose a new reconstruction method, which is applicable to data obtained with a 3-Pi acquisition [IEEE Trans. Med. Imaging 19, 848-863 (2000)]. The method uses the same filter types as the Katsevich algorithm, but the directions and the number of the filter lines are chosen differently. For the derivation of the new algorithm, we analyze the relationship of the Katsevich method and radon inversion. A certain radon plane can intersect with the backprojection interval related to a 3-Pi acquisition either once, three, or five times. In analogy to the definition of quasiexactness introduced by Kudo et al. for a 1-Pi acquisition, we use the term quasiexactness for algorithms on a 3-Pi acquisition, if radon planes with one or three intersections within the backprojection interval are treated correctly. Using the results on the relationship with radon inversion, we can prove that our algorithm is quasiexact in this sense. We use simulation results in order to demonstrate that the algorithm yields excellent image quality.

Algorithms↗
PubMed2003

Mechanism of cell death of rat cardiac fibroblasts induced by serum depletion.

Serum starvation has recently been shown to cause cell death of cardiac fibroblasts and increased synthesis of extracellular matrix proteins in the surviving cells. In the present study, events occurring in the dying cells were investigated. Cultured adult rat cardiac fibroblasts were exposed to serum-free medium. Cell number was measured using a Coulter Counter Channelyzer. The activity of the extracellular signal-regulated or mitogen-activated protein kinases (ERK1/2, p42/p44(MAPK)), the p38 kinase (p38(MAPK)), the c-Jun N-terminal kinases (p46/p54(JNK)), and Akt kinase was assessed by Western blotting and phospho-specific antibodies. Caspase 7-cleavage was investigated by Western blotting and specific antibodies. Caspase 3 activity was measured by detection of its cleaved substrate. The appearance of necrosis was studied by inclusion of trypan blue. Apoptosis was assessed by DNA ladder formation. The mRNA expression of Bax and Bcl-2 was investigated by quantitative real-time PCR. Serum withdrawal led to the death of 26% of cultured isolated cardiac fibroblasts during the first 5 h. The activity of the p42/ p44(MAPK) as well as of Akt kinase was partially reduced. For p46/p54(JNK) and p38(MAPK), elevated phosphorylation was measured. Inhibition of p46/p54(JNK) and p38(MAPK) activity by SB202190 did not affect the decrease in cell number. Cleavage of caspase 7 was detected after 90 min. However, no activation of caspase 3 was measured. DNA fragmentation was not found after serum depletion. Trypan blue staining, however, was observed in 16% of the cells after 5 h. The mRNA levels of both Bax and Bcl-2 were increased after 30 min. These results indicate the appearance of necrosis during serum starvation in cardiac fibroblasts. However, some processes typical of apoptosis were also detected.

Animals↗
PubMed2002

High levels of BAX, low levels of MRP-1, and high platelets are independent predictors of response to imatinib in myeloid blast crisis of CML.

Imatinib induces remissions in approximately 30% of patients with chronic myeloid leukemia (CML) in myeloid blast crisis (M-BC). Because most patients eventually relapse, allogeneic stem cell transplantation (SCT) in remission offers the best chance for cure. Remission induction with imatinib alone would seem ideal because it is less toxic than conventional chemotherapy. Conversely, patients unlikely to respond may benefit from combination therapy up front. To identify prognostic factors, we studied the mRNA expression of genes related to drug resistance and apoptosis in leukemic cells from patients with M-BC and their in vitro sensitivity to imatinib, and analyzed the results with other baseline factors for their impact on response. We show that high levels of BAX, low levels of MRP-1, and a high platelet count are independently predictive of response to imatinib. Combined into a score, these parameters may be clinically useful for risk-adapted patient stratification.

Adult↗