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J Götz

Publications and source records attributed to J Götz.

At least 19 recordsLinked to original sources
PubMed2006

[Ultrasound evaluation of the acromioclavicular joint--a correlation of anatomical and sonographical findings].

AIM: To compare ultrasound imaging to the anatomy of the acromioclavicular joint. METHODS: 13 cadaveric acromioclavicular joints were examined by ultrasound (11 MHz linear array transducer) to determine the limits of the joint capsule and the width of the joint space. The results were compared to macroscopic sections. RESULTS: Anatomical variations were observed. The joint space of one specimen was completely filled by fibrous tissue, leaving 12 specimens for a complete study. A hypoechoic meniscoid disc was attached to the superior joint capsule, resulting in a convex curvature of the cranial part. The mean sonographic width of the joint space was 3.9 mm +/- 1.7 mm standard deviation (SD). The mean distance of the joint capsule from the articular bone rim of the clavicle, the acromion, and from the middle of the joint space was 1.1 +/- 1.0 mm, 1.3 +/- 0.7 mm, and 2.1 +/- 0.9 mm, respectively. The distance from the joint space to the capsular insertion on the clavicle and on the acromion was 4.4 +/- 1.4 mm and 5.3 +/- 2 mm, respectively. The mean difference between ultrasound and anatomical measurements in the vertical (cranio-caudal) plane was 0.5 +/- 0.5 mm (SD), whereas the mean difference between measurements in the horinzontal (medio-lateral) plane was 1.3 +/- 1.1 mm (SD). CONCLUSION: Due to low cost, safety and wide availability, sonography is suited for the evaluation of the acromioclavicular joint. However, when interpreting the results, errors in measuring, limitations in resolution of the system used, and the anatomy of the acromioclavicular joint and its anatomical variants have to be taken into consideration.

Acromioclavicular Joint↗
PubMed2006

Impaired spatial reference memory and increased exploratory behavior in P301L tau transgenic mice.

The neuropathological hallmark shared between Alzheimer's disease (AD) and familial frontotemporal dementia (FTDP-17) are neurofibrillary tangles (NFT) which are composed of filamentous aggregates of the microtubule-associated protein tau. Their formation has been reproduced in transgenic mice, which express the FTDP-17-associated mutation P301L of tau. In these mice, tau aggregates are found in many brain areas including the hippocampus and the amygdala, both of which are characterized by NFT formation in AD. Previous studies using an amygdala-specific test battery revealed an increase in exploratory behavior and an accelerated extinction of conditioned taste aversion in these mice. Here, we assessed P301L mice in behavioral tests known to depend on an intact hippocampus. Morris water maze and Y-maze revealed intact spatial working memory but impairment in spatial reference memory at 6 and 11 months of age. In addition, a modest disinhibition of exploratory behavior at 6 months of age was confirmed in the open field and the elevated O-maze and was more pronounced during aging.

Aging↗
PubMed2005

Enhanced vascular responses to adrenomedullin in mice overexpressing receptor-activity-modifying protein 2.

Adrenomedullin (AM) levels are elevated in cardiovascular disease, but little is known of the role of specific receptor components. AM acts via the calcitonin receptor-like receptor (CLR) interacting with a receptor-activity-modifying protein (RAMP). The AM1 receptor is composed of CLR and RAMP2, and the calcitonin gene-related peptide (CGRP) receptor of CLR and RAMP1, as determined by molecular and cell-based analysis. This study examines the relevance of RAMP2 in vivo. Transgenic (TG) mice that overexpress RAMP2 in smooth muscle were generated. The role of RAMP2 in the regulation of blood pressure and in vascular function was investigated. Basal blood pressure, acute angiotensin II-raised blood pressure, and cardiovascular properties were similar in wild-type (WT) and TG mice. However, the hypotensive effect of IV AM, unlike CGRP, was enhanced in TG mice (P<0.05), whereas a negative inotropic action was excluded by left-ventricular pressure-volume analysis. In aorta relaxation studies, TG vessels responded in a more sensitive manner to AM (EC50, 8.0+/-1.5 nmol/L) than WT (EC50, 17.9+/-3.6 nmol/L). These responses were attenuated by the AM receptor antagonist, AM(22-52), such that residual responses were identical in all mice. Remaining relaxations were further inhibited by CGRP receptor antagonists, although neither affected AM responses when given alone. Mesenteric and cutaneous resistance vessels were also more sensitive to AM in TG than WT mice. Thus RAMP2 plays a key role in the sensitivity and potency of AM-induced hypotensive responses via the AM1 receptor, providing evidence that this receptor is a selective target for novel therapeutic approaches.

Adrenomedullin↗
PubMed2005

[Necrosis of the carpal scaphoid after chemotherapy. Case report].

Preiser's disease--first described by Preiser in 1910--presents the rare avascular necrosis of the carpal scaphoid. There is no consensus with regard to cause and therapeutic procedure to this day. The initially postulated idiopathic origin of the disease is controversial and rare. It is mainly caused by trauma or repetitive microtrauma, but can also occur as a complication of drug therapy. The rare occurrence of necrosis of the carpal scaphoid following chemotherapy is presented. The treatment was resection of the scaphoid and mediocarpal arthrodesis. Clinical appearance, diagnostic work-up, and therapy of the disease are discussed.

Antineoplastic Agents↗
PubMed2005

[Ultrasound evaluation of the acromioclavicular joint. A comparison with magnetic resonance imaging].

INTRODUCTION: Ultrasound is useful in detecting acromioclavicular pathologies in cases of trauma, inflammations and degenerative changes in sports medicine. Many studies compare joint space and capsular dimensions of symptomatic and asymptomatic patients. However, no study has examined the reproducibility and reliability of these measurements. The aim of this study was to evaluate the reliability of ultrasonographic measurements in assessing the acromioclavicular joint. MATERIALS AND METHODS: 27 acromioclavicular joints of 15 healthy subjects were examined by T1 weighted magnetic resonance imaging (MRI) to determine the normal limits of joint space (a) and joint capsule (b). These measurements were compared to standardised ultrasonographic (11 Mhz) measurements, which were repeated three times. RESULTS: The mean difference between MRI and ultrasound measurements was 1.5 +/- 1.3 mm and 1.3 +/- 1.2 mm for distance a and b, respectively. Reproducibility of ultrasonographic measurements was high with a mean standard deviation of 0.3 +/- 0.2 mm and 0.4 +/- 0.3 mm for distance a and b, respectively. CONCLUSION: Due to low costs, safety and wide availability ultrasonography is suited for the evaluation of the acromiocalvicular joint. However, when interpreting the results measurement errors, limitations in resolution of the system used, and the anatomy of the acromioclavicular joint and its anatomic variants have to be taken into consideration.

Acromioclavicular Joint↗
PubMed2004

Transgenic animal models of Alzheimer's disease and related disorders: histopathology, behavior and therapy.

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as beta-amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. Beta-amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In beta-amyloid-producing transgenic mice, memory impairment was associated with increased levels of beta-amyloid. Active and passive beta-amyloid-directed immunization caused the removal of beta-amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.

Alzheimer Disease↗
PubMed2003

Saitohin gene is not associated with Alzheimer's disease.

BACKGROUND: The deposition of tau protein in neurofibrillary tangles constitutes an important feature of many neurodegenerative disorders, including Alzheimer's disease. A polymorphic gene, saitohin (STH), nested within the tau gene (microtubule associated protein tau, MAPT), was recently identified and an association of a non-synonymous polymorphism in STH with increased risk for Alzheimer's disease was suggested. OBJECTIVE AND METHODS: To test the above hypothesis in a case-control association study of two independent white populations within Switzerland and Greece, comparing genotype and allele frequencies from 225 Alzheimer's disease patients and 144 healthy control subjects. RESULTS: No differences in allelic or genotypic distributions between Alzheimer's disease patients and controls was found in the individual samples (Swiss/Greek) or in the combined sample. Stratification for the presence of apolipoprotein E (APOE) epsilon 4 allele, sex, or age did not show significant effects in the populations studied, nor was there an effect on the age of onset. CONCLUSIONS: No evidence was found for an association of the non-synonymous polymorphism (Q7R) in STH and Alzheimer's disease. This finding is in line with earlier studies showing no association between MAPT and Alzheimer's disease.

Aged↗
PubMed2001

Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils.

beta-Amyloid plaques and neurofibrillary tangles (NFTs) are the defining neuropathological hallmarks of Alzheimer's disease, but their pathophysiological relation is unclear. Injection of beta-amyloid Abeta42 fibrils into the brains of P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs in cell bodies within the amygdala from where neurons project to the injection sites. Gallyas silver impregnation identified NFTs that contained tau phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after Abeta42 injections. Our data support the hypothesis that Abeta42 fibrils can accelerate NFT formation in vivo.

Aged↗
PubMed2001

Compartmentalized tau hyperphosphorylation and increased levels of kinases in transgenic mice.

The formation of neurofibrillary tangles in Alzheimer's disease is preceded by a pretangle stage of hyperphosphorylated tau. To characterize pretangle tau in vivo, we correlated, in human tau transgenic mice, levels of kinases known to phosphorylate tau in vitro with the phosphorylation of tau at specific epitopes. Levels of cyclin-dependent kinase-5 were increased in axons of CA1 pyramidal neurons, where tau was phosphorylated specifically at the AD2 epitope Ser396/Ser404. The 12E8 epitope serine262/serine356 and the AT180 epitope threonine231/serine235 were phosphorylated in dendrites, and colocalized with increased levels of glycogen synthase kinase-3. CA1 neurons phosphorylated tau at more epitopes than dentate gyrus neurons, suggesting that tau phosphorylation is cell type-specific, a possible explanation for the spatial distribution of neurofibrillary tangles.

Age Factors↗
PubMed2001

Tau filament formation in transgenic mice expressing P301L tau.

Mutations in the microtubule-associated protein tau, including P301L, are genetically coupled to hereditary frontotemporal dementia with parkinsonism linked to chromosome 17. To determine whether P301L is associated with fibril formation in mice, we expressed the longest human tau isoform, human tau40, with this mutation in transgenic mice by using the neuron-specific mouse Thy1.2 promoter. We obtained mice with high expression of human P301L tau in cortical and hippocampal neurons. Accumulated tau was hyperphosphorylated and translocated from axonal to somatodendritic compartments and was accompanied by astrocytosis and neuronal apoptosis indicated by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end-labeling staining. Moreover, P301L tau formed abnormal filaments. Electron microscopy of sarcosyl-insoluble protein extracts established that the filaments had a straight or twisted structure of variable length and were approximately 15 nm wide. Immunoelcecton microscopy showed that the tau filaments were phosphorylated at the TG3, AT100, AT8, and AD199 epitopes in vivo. In cortex, brain stem, and spinal cord, neurofibrillary tangles were also identified by thioflavin-S fluorescent microscopy and Gallyas silver stains. Together, our results show that expression of the P301L mutation in mice causes neuronal lesions that are similar to those seen in human tauopathies.

Actin Cytoskeleton↗
PubMed2001

Tau and transgenic animal models.

Advances in genetics and transgenic approaches have a continuous impact on our understanding of Alzheimer's disease (AD) and related disorders, especially as aspects of the histopathology and neurodegeneration can be reproduced in animal models. AD is characterized by extracellular Abeta peptide-containing plaques and neurofibrillary aggregates of hyperphosphorylated isoforms of microtubule-associated protein tau. A causal link between Abeta production, neurodegeneration and dementia has been established with the identification of familial forms of AD which are linked to mutations in the amyloid precursor protein APP, from which the Abeta peptide is derived by proteolysis. No mutations have been identified in the tau gene in AD until today. Tau filament formation, in the absence of Abeta production, is also a feature of several additional neurodegenerative diseases including progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The identification of mutations in the tau gene which are linked to FTDP-17 established that dysfunction of tau can, as well as Abeta formation, lead to neurodegeneration and dementia. In this review, newly recognized cellular functions of tau, and the neuropathology and clinical syndrome of FTDP-17 will be presented, as well as recent advances that have been achieved in studies of transgenic mice expressing tau and AD-related kinases and phosphatases. These models link neurofibrillary lesion formation to neuronal loss, provide an in vivo model in which therapies can be assessed, and may contribute to determine the relationship between Abeta production and tau pathology.

Alzheimer Disease↗
PubMed2001

Oligodendroglial tau filament formation in transgenic mice expressing G272V tau.

Genetic evidence indicates that several mutations in tau, including G272V, are linked to frontotemporal dementia with parkinsonism. We expressed this mutation in mouse brains by combining a prion protein promoter-driven expression system with an autoregulatory transactivator loop that resulted in high expression of human G272V tau in neurons and in oligodendrocytes. We show that G272V tau can form filaments in murine oligodendrocytes. Electron microscopy established that the filaments were either straight or had a twisted structure; these were 17-20 nm wide and had a periodicity of approximately 75 nm. Filament formation was associated with tau phosphorylation at distinct sites, including the AT8 epitope 202/205 in vivo. Immunogold electron microscopy of sarcosyl-extracted spinal cords from G272V transgenic mice using phosphorylation-dependent antibodies AT8 or AT100 identified several sparsely gold-labelled 6-nm filaments. In the spinal cord, fibrillary inclusions were also identified by thioflavin-S fluorescent microscopy in oligodendrocytes and motor neurons. These results establish that expression of the G272V mutation in mice causes oligodendroglial fibrillary lesions that are similar to those seen in human tauopathies.

Animals↗
PubMed2000

Immature human NT2 cells grafted into mouse brain differentiate into neuronal and glial cell types.

NT2 cells are a transfectable human embryonal carcinoma cell line, that can be differentiated into postmitotic neuron-like cells (NT2N cells), and transplanted into rodent brains. Differentiation requires a 5-week-long treatment with retinoic acid prior to transplantation. Here, we show that this step can be omitted, and that undifferentiated NT2 cells migrate over long distances and differentiate into both neuron- and oligodendrocyte-like cell types upon grafting into brains of immunocompetent newborn mice. Grafted cells can be traced by fluorogold, with no evidence for tumor formation. Our approach provides an experimental model system which allows the immunohistological and biochemical study of neuronal and glial differentiation of human cells in vivo, and which may be suitable as an in vivo model for pharmacological studies.

Animals↗
PubMed2000

Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein.

Coding region and intronic mutations in the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17. Some of these mutations lead to an overproduction of tau isoforms with four microtubule-binding repeats. Here we have expressed the longest four-repeat human brain tau isoform in transgenic mice under the control of the murine Thy1 promoter. Transgenic mice aged 3 weeks to 25 months overexpressed human tau protein in nerve cells of brain and spinal cord. Numerous abnormal, tau-immunoreactive nerve cell bodies and dendrites were seen. In addition, large numbers of pathologically enlarged axons containing neurofilament- and tau-immunoreactive spheroids were present, especially in spinal cord. Signs of Wallerian degeneration and neurogenic muscle atrophy were observed. When motor function was tested, transgenic mice showed signs of muscle weakness. Taken together, these findings demonstrate that overexpression of human four-repeat tau leads to a central and peripheral axonopathy that results in nerve cell dysfunction and amyotrophy.

Animals↗
PubMed2000

Distinct role of protein phosphatase 2A subunit Calpha in the regulation of E-cadherin and beta-catenin during development.

Protein phosphatase 2A (PP2A) plays central roles in development, cell growth and transformation. Inactivation of the gene encoding the PP2A catalytic subunit Calpha by gene targeting generates a lethal embryonic phenotype. No mesoderm is formed in Calpha(-/-) embryos. Here, we found that during normal early embryonic development Calpha was predominantly present at the plasma membrane whereas the highly homologous isoform Cbeta was localized to the cytoplasm and nuclei, suggesting the inability of Cbeta to compensate for vital functions of Calpha in Calpha(-/-) embryos. In addition, PP2A was found in a complex containing the PP2A substrates E-cadherin and beta-catenin. In Calpha(-/-) embryos, E-cadherin and beta-catenin were redistributed from the plasma membrane to the cytosol. Cytosolic concentrations of beta-catenin were low. Our results suggest that Calpha is required for stabilization of E-cadherin/beta-catenin complexes at the plasma membrane.

Animals↗
PubMed2000

In vivo analysis of wild-type and FTDP-17 tau transgenic mice.

Mutations in the coding and intronic regions of the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Some of these mutations lead to an overproduction of tau isoforms with four microtubule-binding repeats, followed by the development of fibrillary lesions and selective cell death. In order to analyze the development of these neurofibrillary lesions in transgenic mice, the longest four-repeat human brain tau isoform was expressed under control of two different neuron-specific promoters. In a first model, utilizing the human Thy1 promoter, transgenic tau was hyperphosphorylated and abnormally localized to cell bodies and dendrites. In a second model, which made use of a human Thy1.2 expression vector, transgenic expression levels were much higher, and an additional phenotype was observed: Large numbers of pathologically enlarged axons containing neurofilament- and tau-immunoreactive spheroids were present, especially in spinal cord. Signs of Wallerian degeneration and neurogenic muscle atrophy were observed. Behaviorally, transgenic mice showed signs of muscle weakness. Our data show that overexpression of human four-repeat tau in itself is sufficient to lead to nerve cell dysfunction and amyotrophy. We have now extended our initial studies by introducing exonic mutations including G2t 2V and PS01L into the tau gene in order to achieve a more advanced FTDP-17 associated phenotype.

Animals↗