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Biomedical subjects

H W Müller

Publications and source records attributed to H W Müller.

At least 19 recordsLinked to original sources
PubMed2006

Physical and biological performance of a novel block copolymer nerve guide.

Although the ability to regenerate is evident in the nervous system, lesioned neurites are unable to cross gaps in neuronal pathways. In order to bridge gaps, guiding cues are essential to direct neurite regrowth. To overcome many of the shortcomings of polymer-based nerve guides, we developed a bioresorbable nerve guide composed of a novel trimethylene carbonate-caprolacton block copolymer (TMC-CL). Pore formation was controlled by using special solvent/precipitation media compositions in combination with the pore forming agent poly ethylene glycol (PEG). NMR spectroscopy, shear force-, compression-, and permeation assays were used for conduit characterization. The polymer conduit has a semipermeable wall with submicron pores to allow free metabolite/drug exchange. In order to investigate the principle of temporally controlled expression of therapeutic proteins in nerve guides, Neuro-2a cells were genetically engineered to express the reporter gene product green fluorescent protein (GFP) under the control of the Tet-On system. When these transduced cells were encapsulated in nerve guides, GFP expression could be induced for days by adding the antibiotic tetracycline derivative doxycycline to the nerve guide environment. Furthermore, encapsulated dorsal root ganglia (DRG) produced long neurites in vitro. In subsequent in vivo experiments, nerve guides filled with Schwann cells (SC) were implanted into lesioned spinal cords of adult rats. Regeneration of spinal cord axons into nerve guides was promoted by co-implanted Schwann cells. The data suggest that the novel TMC-CL nerve guides provide a promising tool for neuroregeneration.

Absorbable Implants↗
PubMed2006

High-resolution multipinhole single-photon-emission computed tomography in experimental and human arthritis.

OBJECTIVE: To image inflammatory arthritic lesions in experimental arthritis and in patients with arthritis, using a newly developed high-resolution multipinhole single-photon-emission computed tomography (MPH-SPECT) technique. METHODS: Six interleukin-1 receptor antagonist-deficient mice with arthritis of the front and back paws and 2 control BALB/c mice were imaged with MPH-SPECT and scored macroscopically for arthritis. SPECT imaging was performed with a conventional gamma camera upgraded with a pyramidal lead collimator affixed with MPH apertures. All images were reconstructed, and uptake in the paws was quantified in counts/weight and injected activity. To transfer the imaging technique to humans we examined the clinically dominant hand of 6 individuals (3 with established rheumatoid arthritis [RA], 1 with early RA, 1 with osteoarthritis, and 1 healthy control). RESULTS: MPH-SPECT images were high-resolution 3-dimensional tomographic images, which allowed exact localization and quantifiable observation of increased bone metabolism. MPH-SPECT counts of inflamed joints in mice correlated with macroscopic scoring and histologic joint analysis postmortem. In humans, MPH-SPECT images depicted a detailed visualization of tracer accumulation in bony structures of hand and finger joints, and were also capable of imaging increased bone metabolism that had appeared normal with other imaging modalities, e.g., magnetic resonance imaging. CONCLUSION: The MPH-SPECT technique represents a new diagnostic tool in the detection of bone pathology in small-animal arthritis research. Compared with macroscopic scoring, this new method provides a more objective and higher-precision quantifiable measurement of bone reaction, allowing visualization of inflammatory processes of the whole skeleton in vivo. These results suggest that MPH-SPECT may be useful as a diagnostic instrument for monitoring experimental arthritis, with further potential for use in human studies of RA.

Aged↗
PubMed2003

Hydrodynamic instabilities in ferronematics.

In the hydrodynamic description of ferronematics there are various dynamic magnetic-field effects, linear in the field strength, that are negligible in usual nematics, but can play a role in ferronematics. Here, we investigate theoretically the influence of these new terms on the thermal convection (Rayleigh-Bénard) and the viscous fingering (Saffman-Taylor) instability in ferronematics in the presence of a strong magnetic field. We find that the instabilities are qualitatively changed due to the occurrence of a finite vorticity component--a feature that is known from simple liquids in the case of a superimposed mechanical rotation. We suggest to use the additional effects (cross-flow within convection rolls, oblique rolls, rotating fingers) for measuring the phenomenological coefficients involved.

Journal Article↗
PubMed2002

Proteins of peripheral myelin are associated with glycosphingolipid/cholesterol-enriched membranes.

A characteristic feature of the vertebrate nervous system is the ensheathment of axons by myelin, a multilamellar membrane specialization produced by polarized glial cells. Although the main protein and lipid components of the myelin sheath are well characterized, relatively little is known about the mechanisms of their intracellular distribution to the respective sites of assembly within the myelin sheath. To analyze whether peripheral myelin protein trafficking is mediated by glycosphingolipid/cholesterol-enriched membranes (GEMs), we studied the association of established myelin proteins, peripheral myelin protein 22 (PMP22), protein zero (P0), plasmolipin, and myelin basic protein (MBP), with these membrane microdomains. To examine the association of the selected peripheral myelin proteins with detergent-insoluble GEMs, purified myelin from sciatic nerve of adult rat was extracted with Triton X-100 at 4 degrees C and 37 degrees C and, in additional experiments, was pretreated with the cholesterol chelator methyl-beta-cyclodextrin. The material was then centrifuged to equilibrium in sucrose gradients, and fractions were analyzed by Western blotting. Here we demonstrate for the first time that PMP22, P0, and plasmolipin prepared from purified peripheral myelin are associated with GEMs. To characterize whether the association of these proteins is a specialized feature of myelinating Schwann cells, we studied the distribution of PMP22, P0, and plasmolipin in transiently transfected HeLa cells. These experiments confirm the specific association of these proteins with GEMs in both neural and nonneural cell types.

Animals↗
PubMed2002

Phase relaxation of Faraday surface waves.

Surface waves on a liquid-air interface excited by a vertical vibration of a fluid layer (Faraday waves) are employed to investigate the phase relaxation of ideally ordered patterns. By means of a combined frequency-amplitude modulation of the excitation signal a periodic expansion and dilatation of a square wave pattern is generated, the dynamics of which is well described by a Debye relaxator. By comparison with the results of a linear theory, it is shown that the measured relaxation time allows a precise evaluation of the phase diffusion constant.

Journal Article↗
PubMed2002

Transduction of wild-type merlin into human schwannoma cells decreases schwannoma cell growth and induces apoptosis.

Mutations in both alleles of the tumour suppressor gene coding for merlin/schwannomin, an ERM family protein, cause the hereditary disease neurofibromatosis type 2 (NF2). NF2 is characterized by the development of multiple nervous system tumours especially vestibular schwannomas. Efficient oncoretrovirus-mediated gene transfer of different merlin constructs was used to stably re-express wild-type merlin in primary cells derived from human schwannomas. Using two-parameter FACS analysis we show that expression of wild-type merlin in NF2 cells led to significant reduction of proliferation and G0/G1 arrest in transduced schwannoma cells. In addition, we show increased apoptosis of schwannoma cells transduced with wild-type merlin. Our findings in primary schwannoma cells from NF2 patients strongly support the hypothesis of merlin acting as a tumour suppressor and may help in understanding development of human schwannomas in NF2.

Apoptosis↗
PubMed2002

Facilitation of learning and modulation of frontal cortex acetylcholine by ventral pallidal injection of heparin glucosaminoglycan.

We examined the effects of heparin on learning and frontal cortex acetylcholine parameters following injection of the glucosaminoglycan into the ventral pallidum. In Experiment 1, possible mnemoactive effects of intrapallidal heparin injection were assessed. Rats with chronically implanted cannulae were administered heparin (0.1, 1.0, 10 ng) or vehicle (0.5 microl) and were tested on a one-trial step-through avoidance task. Two retention tests were carried out in each animal, one at 1.5 h after training to measure short-term memory and another at 24 h to measure long-term memory. Post-trial intrapallidal injection of 1.0 ng heparin improved both short- and long-term retention of the task, whereas the lower and the higher dose of the glucosaminoglycan had no effect. When the effective dose of heparin was injected 5 h, rather than immediately after training, it no longer facilitated long-term retention of the conditioned avoidance response. In Experiment 2, the effects of ventral pallidal heparin injection on frontal cortex acetylcholine and choline concentrations were investigated with in vivo microdialysis in anaesthetized rats. Heparin, administered in the dose of 1.0 ng, which was effective in facilitating avoidance performance, produced a delayed increase in cortical acetylcholine levels ipsi- and contralaterally to the side of intrabasalis injection, resembling the known neurochemical effects obtained for another glycosaminoglycan, chondroitin sulfate, which recently was shown to facilitate inhibitory avoidance learning and to increase frontal cortex acetylcholine. The present findings indicate that heparin, like other extracellular matrix proteoglycans, can exert beneficial effects on memory and strengthen the presumptive relationship between such promnestic effects of proteoglycans and basal forebrain cholinergic mechanisms. The data are discussed with respect to the presumed roles of matrix molecules in extrasynaptic volume transmission and in the 'cross-talk' between synapses.

Acetylcholine↗
PubMed2001

Structure of ferrofluid dynamics.

The complete magnetodissipative structure of ferrofluid dynamics is derived from general principles, without reference to the angular momentum of the ferromagnetic grains. The results are independent of most microscopic details, and easily interpret two previous experiments. Both the Debye theory and the effective-field theory by Shliomis are shown to be special cases of the new set of equations.

Journal Article↗
PubMed2001

A reliable method to reduce collagen scar formation in the lesioned rat spinal cord.

Following traumatic injury, the formation of a glial scar and deposition of extracellular matrix (ECM) contributes to the regeneration failure in the adult mammalian central nervous system (CNS). Using a postcommissural fornix transection as a brain lesion model in rat, we have previously shown that the collagenous basement membrane (BM) at the lesion site is a major impediment for axon regeneration. Deposition of BM in this lesion model can be delayed by administration of the iron chelator 2,2'-bipyridine (BPY), an inhibitor of prolyl 4-hydroxylase (PH), a key enzyme of collagen biosynthesis. To examine whether this potential therapeutic approach is transferable to other CNS regions, we have chosen the mechanically lesioned rat spinal cord to investigate the effects of BPY administration on BM formation. Due to the close proximity of the lesion zone to meningeal fibroblasts, a cell-type secreting large amounts of collagen IV, BM deposition was much more extensive in the spinal cord than in the brain lesion. Neither immediate injections nor continuous application of BPY resulted in a detectable reduction of BM formation in the spinal cord. Only a combination of anti-scarring treatments including (i) injection of the more potent PH inhibitor [2,2'-bipyridine]-5,5'-dicarboxylic acid (BPY-DCA), (ii) selective inhibition of fibroblast proliferation and ECM production by 8-Br-cAMP, and (iii) continuous application of BPY-DCA, reduced the lesion-induced BM significantly. The present results clearly demonstrate, that the exclusive application of BPY according to a protocol designed for treatment of brain lesions is not sufficient to reduce BM formation in the lesioned adult rat spinal cord.

2,2'-Dipyridyl↗
PubMed2001

Towards micro electrode implants: in vitro guidance of rat spinal cord neurites through polyimide sieves by Schwann cells.

Our goal is to develop biohybrid neural microprobe implants with sieve electrodes for external stimulation of co-implanted neurons whose axons penetrate through the holes of electrodes and innervate host targets such as denervated muscle fibers. For evaluation of implants, potential scar formation was imitated in fibroblast-spinal cord co-cultures. In vitro neurite extension through flexible 10-microm thick polyimide sieves was inhibited by co-cultured fibroblasts. In contrast, the neurite penetration of sieves could be greatly stimulated by oriented exposure to Schwann cells. To our knowledge this is the first direct proof that Schwann cells display a guidance effect on spinal cord neurons in vitro. The results pave the way for novel biohybrid neuro-implants and provide means to circumvent the obstacle of inhibitory scar formation.

Animals↗
PubMed2001

Amplitude measurements of Faraday waves.

A light reflection technique is used to measure quantitatively the surface elevation of Faraday waves. The performed measurements cover a wide parameter range of driving frequencies and sample viscosities. In the capillary wave regime the bifurcation diagrams exhibit a frequency independent scaling proportional to the wavelength. We also provide numerical simulations of the full Navier-Stokes equations, which are in quantitative agreement up to supercritical drive amplitudes of epsilon approximately equal 20%. The validity of an existing perturbation analysis is found to be limited to epsilon<2.5%.

Journal Article↗
PubMed2001

Plasmolipin: genomic structure, chromosomal localization, protein expression pattern, and putative association with Bardet-Biedl syndrome.

Plasmolipin is a membrane protein and belongs to the tetraspan molecule (4TM) family, an expanding group of myelin proteins many of which could be linked to human hereditary demyelinating neuropathies. We have cloned and sequenced the mouse plasmolipin gene, revealing the common organization of the 4TM gene group with four exons and a large first intron. Western blot analysis with an antibody raised against the C-terminal intracellular part of the protein showed that plasmolipin is expressed not only in the nervous system and kidney, but also in a number of other tissues such as thymus, testis, lung, and thyroid gland. By means of radiation hybrid mapping and FISH analysis, we could localize the human plasmolipin gene to Chromosome 16q13 within the putative region of the Bardet-Biedl syndrome type 2 (BBS2) gene locus. BBS2 is a clinically and genetically heterogeneous group of disorders resulting in rod-cone dystrophy, obesity, postaxial polydactyly, renal dysfunction, and mental retardation, which were very recently associated with a novel gene designated BBS2. With respect to intrafamiliar variations in the manifestation of BBS, we suggest that plasmolipin might be either another candidate gene or a modifier of the BBS2 phenotype.

Animals↗
PubMed2001

Identification of osmosensitive and ammonia-regulated genes in rat astrocytes by Northern blotting and differential display reverse transcriptase-polymerase chain reaction.

BACKGROUND/AIMS: The hepatic encephalopathy (HE) is in part the result of astrocyte swelling with alterations of glial function. Detoxification of ammonia may be one mechanism by which astrocyte swelling is triggered in HE. METHODS: The differential display polymerase chain reaction (DDRT-PCR) and Northern blot analysis were used for study the functional consequence of cell volume changes and ammonia on gene expression in primary rat astrocytes. RESULTS: Differentially expressed cDNA products were identified with about 92% homology to genes coding for mouse proline rich protein expressed in brain (PRTB), rat clusterin, elongin, and human Kelch motif containing protein. As shown by Northern blot analysis, PRTB and clusterin mRNA levels were upregulated by 19-64% after 4-8 h by both ammonia and hypoosmolarity. Elongin mRNA expression increased by 97% in response to ammonia but slightly by hypoosmolarity. Further, hypoosmotic exposure for 1-24 hours but not ammonia led to an increase of 80% in KMCP mRNA levels. CONCLUSIONS: The identification of these genes offers the opportunity to identify unrecognized molecular mechanisms of HE. The finding that several genes are induced by both, hypoosmolarity and ammonia, supports the view that astrocyte swelling is a major, but not the only pathogenetic event in HE.

Ammonia↗
PubMed2001

Molecular mechanisms of cellular interactions in peripheral nerve regeneration.

The peripheral nervous system, as opposed to the central nervous system, has the intrinsic capacity to regenerate. It was recognized long ago that this can be achieved only after an extensive clean-up procedure, the so-called Wallerian degeneration, in which myelin debris is removed and a suitable environment for growing axons is generated. Wallerian degeneration and the regeneration process itself both depend on direct cellular interactions as well as on long-range signals between all participating cell types. Elucidating the nature and functional consequences of these signals is a main goal in understanding peripheral nerve repair.

Animals↗
PubMed2001

Gene expression profiling and molecular aspects in peripheral nerve regeneration.

Regeneration of the peripheral nervous system after injury depends on a complex sequence of histopathological reactions that comprise a highly reproducible sequence of degenerative reactions, termed Wallerian degeneration. During this period a remodelling of the distal nerve stump prepares a microenvironment that permits successful regrowth of nerve fibers from the proximal nerve fragment. This stereotypical sequence of reactions is reflected by a differential and coordinate expression of genes with specific functions in the process of regeneration. This review will summarize cellular and molecular reactions that contribute to peripheral nerve regeneration including data of a pilot study in which membrane based cDNA array expression technology was applied. We examined the expression of 588 annotated genes in response to a crush lesion of rat sciatic nerves. Approximately 40 % of the genes spotted onto the array filters showed expression significantly above background and 55 of these detected genes represented differential expression profiles after nerve lesion. This approach revealed to be suitable for systematic screening of regeneration associated genes.

Animals↗
PubMed2001

The collagenous lesion scar--an obstacle for axonal regeneration in brain and spinal cord injury.

After CNS trauma a sheet-like, collagen type IV (Coll IV) immunopositive basement membrane (BM) develops in the lesion zone as well as at newly formed blood vessels. The basic scaffold of this BM is composed of Coll IV, laminin and nidogen but numerous other proteins some of which are discussed to be inhibitory for axonal regeneration, i.e. chondroitin- and heparansufate-proteoglycans, are associated with BM. This review will focus on the collagenous wound healing scar, discuss its composition and summarize the experimental results that demonstrate its role in the failure of axonal regeneration in the injured mammalian CNS.

Animals↗
PubMed2000

Long-term culture and characterization of human neurofibroma-derived Schwann cells.

Neurofibromas are benign tumors arising from the peripheral nerve sheath and are a typical finding in neurofibromatosis type 1 (NF1). Schwann cells are the predominant cell type in neurofibromas and thus are supposed to play a major role in the pathogenesis of these tumors. It is not known, however, if NF1 mutations in Schwann cells result in an altered phenotype that subsequently leads to tumor formation. To characterize the biological properties of neurofibroma-derived Schwann cells we developed cell culture techniques that enabled us to isolate Schwann cells from neurofibromas and grow them in vitro for several weeks without significant fibroblast contamination. Neurofibroma-derived Schwann cells were characterized by altered morphology, heterogeneous growth behavior, and increased expression of the P0 antigen while several other features of normal human Schwann cells were retained. We conclude that neurofibroma-derived Schwann cells exhibit a distinct phenotype in vitro but that the observed abnormalities by themselves are insufficient to explain neurofibroma formation. Application of our improved culture conditions makes neurofibroma-derived Schwann cells readily available for further studies to define their role in tumorigenesis in neurofibromatosis type 1.

Adolescent↗