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Biomedical subjects

G Schütz

Publications and source records attributed to G Schütz.

At least 19 recordsLinked to original sources

Magnetic vortex core reversal by excitation with short bursts of an alternating field.

The vortex state, characterized by a curling magnetization, is one of the equilibrium configurations of soft magnetic materials and occurs in thin ferromagnetic square and disk-shaped elements of micrometre size and below. The interplay between the magnetostatic and the exchange energy favours an in-plane, closed flux domain structure. This curling magnetization turns out of the plane at the centre of the vortex structure, in an area with a radius of about 10 nanometres--the vortex core. The vortex state has a specific excitation mode: the in-plane gyration of the vortex structure about its equilibrium position. The sense of gyration is determined by the vortex core polarization. Here we report on the controlled manipulation of the vortex core polarization by excitation with small bursts of an alternating magnetic field. The vortex motion was imaged by time-resolved scanning transmission X-ray microscopy. We demonstrate that the sense of gyration of the vortex structure can be reversed by applying short bursts of the sinusoidal excitation field with amplitude of about 1.5 mT. This reversal unambiguously indicates a switching of the out-of-plane core polarization. The observed switching mechanism, which can be understood in the framework of micromagnetic theory, gives insights into basic magnetization dynamics and their possible application in data storage.

Journal Article↗

Survival of DA neurons is independent of CREM upregulation in absence of CREB.

cAMP response element binding protein (CREB) and the related factors CREM (cAMP response element modulator) and ATF1 (activation transcription factor 1) are bZIP-domain-containing transcription factors activated through cAMP and other signaling pathways. The disruption of CREB function in developing and mature neurons affects their development and survival when associated with loss of CREM. Since dopaminergic (DA) neurons are affected in several neurological diseases, we generated CREB conditional mutants in DA neurons by using a newly generated transgenic Cre line targeting the dopaminergic system (DATCre). Here we report the generation and analysis of mutant mice lacking CREB in DA neurons (CREB(DATCre) mutants). During adulthood, lack of CREB leads to a partial loss of DA neurons. Since CREM is upregulated in absence of CREB, we have introduced this mutation in a CREM-/- genetic background to assess a compensatory role of CREM. Additional inactivation of CREM does not lead to a more severe phenotype.

Animals↗

On the imaging of the flux-line lattice of a type-II superconductor by soft X-ray absorption microscopy.

A new method is proposed for the imaging of the flux-line lattice of a type-II superconductor by soft X-ray absorption microscopy. It is shown that the method is very demanding but probably realisable in the foreseeable future. The new method has the potential to image in real space static and dynamical properties of the flux-line lattice at arbitrary external fields and with single-flux-line resolution.

Journal Article↗

Genetic dissection of corticosteroid receptor function in mice.

Functional genomic technologies, including artificial chromosome-based transgenesis and conditional gene targeting, allowed us to generate mouse models harboring genes with loss-of-function mutations, gain-of-function mutations, spatially and/or temporally restricted mutations, tissue-specific mutations, and function-selective mutations. This kind of "allelic series" for corticosteroid receptors in mouse models provides a very useful resource for the molecular understanding of corticosteroid function in vivo. These models will also support the identification of steroid receptor target genes in order to define a steroid signaling cascade in molecular terms. They provide opportunities for the identification of compounds that regulate steroid receptors in a tissue-specific and function-selective manner. For example, selective glucocorticoid receptor modulators preventing receptor dimerization and DNA binding can be expected to reduce osteoporotic and/or diabetogenic side effects, but to display partial or full anti-inflammatory potential. Thus, these mouse models will help to evaluate distinct steroid receptor functions for therapeutic intervention.

Animals↗

Surgical approach to kinking and coiling of the internal carotid artery.

AIM: Whether kinking or coiling of the internal carotid artery (ICA) simply represents a morphological variation without clinical relevance still remains an object of debate. While most patients are incidentally diagnosed in an asymptomatic state due to the broad use of non-invasive investigations (like colour coded Doppler sonography), associated neurological deficits are often unspecific and might be related to coexisting proximal stenotic lesions. Its etiology is unclear. Beside artherosclerotic genesis, a persistent embryological condition or underlying fibromuscular dysplasia is discussed. Moreover, in contrast to precise recommendations concerning the indication for endarteriectomy in carotid artery stenosis, general guidelines for surgical intervention in case of kinking or coiling are not yet established. METHODS: The characteristics of 16 patients who underwent a total of 21 reconstructive operations for isolated kinking or coiling of the ICA during 5 years of observation were retrospectively analyzed. RESULTS: In 10 out of 14 kinkings and 5 out of 7 coilings central nervous symptoms were noted including unspecific vertigo, syncope, tinnitus synchronous to pulse, transient ischemic attacks and manifest cerebral infarction. All these individual complaints disappeared postoperatively. In 1 patient presenting with an ICA coiling histological examination revealed signs of fibromuscular dysplasia. The other specimens showed typical changes of artherosclerotic disease. CONCLUSION: By precluding significant proximal stenosis and effective elimination of symptoms after surgical correction, a causal connection between cerebral dysfunction and severe ICA kinking or coiling can be supposed. An actual abnormality of the arterial wall structure only exists in exceptional cases. Rather, a sequential development from kinking to coiling was noticed.

Aged↗

Strong anisotropy of projected 3d moments in epitaxial CrO2 films.

Soft x-ray magnetic circular dichroism (XMCD) spectra have been investigated for different crystallographic projections of CrO2. Strong anisotropic orbital Cr 3d contributions and a change of sign of the XMCD signal is observed and attributed to t(2g) majority states near the Fermi level. Additionally, moment analysis exhibits anisotropic behavior in the projected spin contributions of CrO2 assigned to a strong magnetic dipole term T(z), consistent with an intrinsic magnetic easy axis behavior along the CrO2 [001] axis. A reduced projected isotropic Cr 3d spin moment has been interpreted in terms of hybridization with oxygen.

Journal Article↗

Glucocorticoid hormones inhibit food-induced phase-shifting of peripheral circadian oscillators.

The circadian timing system in mammals is composed of a master pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus and slave clocks in most peripheral cell types. The phase of peripheral clocks can be completely uncoupled from the SCN pacemaker by restricted feeding. Thus, feeding time, while not affecting the phase of the SCN pacemaker, is a dominant Zeitgeber for peripheral circadian oscillators. Here we show that the phase resetting in peripheral clocks of nocturnal mice is slow when feeding time is changed from night to day and rapid when switched back from day to night. Unexpectedly, the inertia in daytime feeding-induced phase resetting of circadian gene expression in liver and kidney is not an intrinsic property of peripheral oscillators, but is caused by glucocorticoid signaling. Thus, glucocorticoid hormones inhibit the uncoupling of peripheral and central circadian oscillators by altered feeding time.

Adrenalectomy↗

Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor.

The glucocorticoid receptor (GR) acts both as a transcription factor itself on genes carrying GR response elements (GREs) and as a modulator of other transcription factors. Using mice with a mutation in the GR, which cannot activate GRE promoters, we examine whether the important anti-inflammatory and immune suppressive functions of glucocorticoids (GCs) can be established in this in vivo animal model. We find that most actions are indeed exerted in the absence of the DNA-binding ability of the GR: inhibition of the inflammatory response of locally irritated skin and of the systemic response to lipopolysaccharides. GCs repress the expression and release of numerous cytokines both in vivo and in isolated primary macrophages, thymocytes and CD4(+) splenocytes. A transgenic reporter gene controlled by NF-kappa B exclusively is also repressed, suggesting that protein- protein interaction with other transcription factors such as NF-kappa B forms the basis of the anti-inflammatory activity of GR. The only defect of immune suppression detected so far concerns the induced apoptosis of thymocytes and T lymphocytes.

Animals↗

Altered emotional behavior in PACAP-type-I-receptor-deficient mice.

PAC1 (pituitary adenylate cyclase activating polypeptide type I receptor) is a G-protein-coupled receptor that binds the strongly conserved neuropeptide PACAP (pituitary adenylate cyclase activating polypeptide) with a thousandfold higher affinity than the related peptide VIP (vasoactive intestinal peptide). PAC1 shows strong expression in brain areas which have been implicated in the emotional control of behavior, such as the amygdala, the hypothalamus, the locus coeruleus and the periaqueductal gray. To assess whether PAC1-mediated signaling has an impact on emotional behavior, we analysed two different mutant mouse lines with an ubiquitous or a forebrain-specific inactivation of PAC1 in several testing paradigms modelling general locomotor activity and anxiety-related behavior. We clearly demonstrate that mice with a ubiquitous but not with a forebrain-specific deletion of PAC1 exhibit elevated locomotor activity and strongly reduced anxiety-like behavior. We could not observe any gross alteration in circadian rhythmicity nor any enhanced sensitivity towards ethanol in the mutant mice. We previously demonstrated that PAC1 plays a crucial role in contextual fear conditioning. Therefore the finding that PAC1-deficient mice exhibit reduced anxiety is quite exciting, since the receptor and hence its ligand PACAP seem to be important for both, innate and learned fear.

Animals↗

Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient mice.

The pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor (PAC1) is a G-protein-coupled receptor binding the strongly conserved neuropeptide PACAP with 1000-fold higher affinity than the related peptide vasoactive intestinal peptide. PAC1-mediated signaling has been implicated in neuronal differentiation and synaptic plasticity. To gain further insight into the biological significance of PAC1-mediated signaling in vivo, we generated two different mutant mouse strains, harboring either a complete or a forebrain-specific inactivation of PAC1. Mutants from both strains show a deficit in contextual fear conditioning, a hippocampus-dependent associative learning paradigm. In sharp contrast, amygdala-dependent cued fear conditioning remains intact. Interestingly, no deficits in other hippocampus-dependent tasks modeling declarative learning such as the Morris water maze or the social transmission of food preference are observed. At the cellular level, the deficit in hippocampus-dependent associative learning is accompanied by an impairment of mossy fiber long-term potentiation (LTP). Because the hippocampal expression of PAC1 is restricted to mossy fiber terminals, we conclude that presynaptic PAC1-mediated signaling at the mossy fiber synapse is involved in both LTP and hippocampus-dependent associative learning.

Animals↗

Magnetic domains in nanostructured media studied with M-TXM.

Combining X-ray magnetic circular dichroism (X-MCD) with a transmission X-ray microscope (TXM) allows to image element-specifically magnetic domain structures with 25nm lateral resolution. Both in-plane and out-of-plane systems can be studied in applied magnetic fields. Thus field-dependent parameters, as individual nucleation fields in magnetic nanostructures can be deduced and related to morphology. Images of thermomagnetically written bits in magneto-optical TbFeCo media proof the reliability of the writing process and the importance of an exact thermal design of the systems. Domains observed at corresponding Co L edges proof the chemical sensitivity of M-TXM and its potential to image few monolayer systems.

Journal Article↗

XMCD study of the Ruddlesden-Popper Phase La1.2Nd0.2Sr1.6Mn2O7.

X-ray Magnetic Circular Dichroism (XMCD) measurements of the Ruddlesden-Popper Phase La1,2Nd0,2Sr1.6Mn2O7 are reported. The Mn K. La and Nd L2,L3 edges have been measured on a powder sample at two different magnetic fields at low temperature. The analysis of the spectra at B = 1T indicates a large orbital moment of the Nd 5d-states and a significant spin-polarization of the La 5d-band. Furthermore at the Mn K-edge a XMCD-signal is observed, showing a polarization of the Mn 4p-band. At lower field (0.2T) all XMCD-signals are about two times smaller corresponding to the lower total magnetization. The signal at the Nd L2 edge vanishes completely at 0.2T.

Journal Article↗

HoFe - Garnet soft XMCD measurements below and above the compensation temperature.

We have investigated the magnetism of Holmium-Iron-Garnet (Ho3Fe5O12) at the Ho M4,5 - the Fe L2,3 - and the O K - edges. As expected switching of the sub-lattice magnetization is observed at the compensation temperature. We will give detailed analysis ofthe Ho and Fe XMCD signals, using sum rules. Fe dichroism is analyzed in terms of 3d ground state moments and compared to Gadolinium-Iron-Garnet (Gd3Fe5O12). Contributions of octahedral and tetrahedral Fe sites could be separated and analyzed quantitatively. At the oxygen K edge two different structures are observable. Those structures show different temperature dependencies. Therefore we address these features separately to Fe and Rare Earth contributions.

Journal Article↗

Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts.

The glycosylphosphatidylinositol-anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcgamma-receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co-clustering with Toll-like receptor 4, Fcgamma-RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand-specific cellular responses initiated by CD14.

Antigens, CD↗

A CamKIIalpha iCre BAC allows brain-specific gene inactivation.

We describe the generation of transgenic mouse lines expressing the Cre recombinase enzyme in brain under control of the CamKIIalpha gene present in a BAC expression vector. The CamKIIalpha BAC transgene gave a faithful expression pattern resembling the pattern of the endogenous CamKIIalpha gene. Specifically, high levels of CamKIIalpha Cre were detected in hippocampus, cortex, and amygdala, and lower levels were detected in striatum, thalamus, and hypothalamus. As expected, no expression was detected in the cerebellum or outside of the brain. The expression level of the BAC CamKIIalpha driven Cre was shown to be copy number dependent. To test the activity of the Cre recombinase, the transgenic mice were crossed with mice harbouring the CREB (cAMP response element binding protein) allele with the 10th exon flanked by two loxP sites, and recombination was monitored by the disappearance of the CREB protein. Finally, evaluation of the developmental postnatal expression of the CamKIIalpha Cre BAC revealed the expression of the Cre recombinase as early as P3.

Animals↗

Costs and efficiency of a tumor follow-up program for the detection of colorectal liver metastases.

From January 1987 until July 1999 we admitted 1003 patients with colorectal cancer and 31 with resected colorectal liver metastases to our tumor follow-up program. After R0 resection of the primary tumor 60 patients developed liver metastases during the postoperative follow-up. R0 resection of the metastases was performed in 16 of these cases without lethality and low morbidity. In the further course of the follow-up 8 of these patients again developed liver metastases, two of whom underwent reoperation. The overall 5-year survival rate after R0 resection of liver metastases was 20%. In 726 patients we performed 3719 follow-up examinations. Following the German regulations on physicians' fees for follow-up-examinations we calculated the cost of detecting a liver metastasis to be DM 16,500 per patient. Mean costs were DM 62,000 in patients in whom the metastases were successfully resected. The results of this study show that although the costs are very high for patients who benefit from the follow-up program, 26.7% of those with liver metastases are detected in such an early stage, and that an R0 resection can be performed. This study shows that the high costs of tumor follow-up programs for detecting liver metastases in patients with resected colorectal cancer can be justified by the good outcome of patients in whom an early diagnosis of recurrent disease is made.

Adenocarcinoma↗