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F Stögbauer

Publications and source records attributed to F Stögbauer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Thirty-seven CAG repeats in the androgen receptor gene in two healthy individuals.

X-linked recessive spinobulbar muscular atrophy (SBMA) is an adult-onset X-linked neurodegenerative disease, characterised by muscular atrophy, bulbar symptoms and endocrinological disturbances. SBMA is caused by the expansion of a CAG repeat in the androgen receptor gene. The maximum number of CAG repeats found in a healthy person is 35 while the minimum number of repeats found in SBMA patients is 38. We have identified a 46-year-old man from an SBMA family with 37 CAG repeats who until now is clinically unaffected. Interestingly, his 85-year-old mother who has the genotype 37/51 CAG repeats is clinically unaffected as well. These results suggest an exactly defined border between normal and disease alleles.

Aged↗
PubMed2001

Mutation analysis of 4 candidate genes for hereditary neuralgic amyotrophy (HNA).

Hereditary neuralgic amyotrophy (HNA) is a rare autosomal dominant disorder. It is characterised by recurrent episodes of focal neuropathy involving the brachial plexus. Genetic linkage analysis has mapped HNA to chromosome 17q25 within a 3.5-cM interval flanked by the short tandem repeat markers D17S785 and D17S802. Here, we report the mutation analysis of four candidate genes. Mutation analysis was performed on the complete coding regions of these genes. Several exonic and intronic single nucleotide polymorphisms were detected. However, no disease-causing mutations were found, indicating that these genes are most probably not involved in the pathogenesis of HNA. In addition, we have characterised and localised a putative pseudogene of the SEC14-like 1 gene.

Brachial Plexus Neuritis↗
PubMed2001

Kinetic parameters of 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) transport in human GOS3 glioma cells.

The radiolabelled amino acid 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) is a promising tool for the diagnosis and monitoring of brain tumors using single-photon emission tomography (SPECT). However, little is known about the precise kinetics of [(123)I]IMT uptake in human glioma cells. The kinetic analysis of [(123)I]IMT transport in human GOS3 glioma cells yielded a high-affinity apparent Michaelis constant (K(m) = 20.1 +/- 1.5 microM). The maximum transport velocity (V(max)) amounted to 34.8 +/- 1.9 nmol/mg protein/10 min. Competitive inhibition experiments revealed that [(123)I]IMT transport is mediated principally by the sodium-independent system L.

Biological Transport↗
PubMed2001

Characterization of 3-[(123)I]iodo-L-alpha-methyl tyrosine transport in astrocytes of neonatal rats.

3-[(123)I]Iodo-L-alpha-methyl tyrosine ((123)I-IMT) is used for diagnosis and monitoring of brain tumours by means of single-photon emission tomography. As recently shown, (123)I-IMT is predominantly mediated into rat C6 glioma cells by sodium-independent system L for large neutral amino acids. Until now, (123)I-IMT transport in non-neoplastic glial cells has not been examined. Therefore, the aim of this study was to examine the cellular pathways and precise transport kinetics of (123)I-IMT uptake into astrocytes of neonatal rats. In particular sodium-independent (123)I-IMT transport into neonatal astrocytes was compared with sodium-independent (123)I-IMT uptake into neoplastic rat C6 glioma cells. Competitive inhibition experiments showed that (123)I-IMT is exclusively transported via sodium-independent system L into the neonatal astrocytes (92%). Kinetic analysis of sodium-independent (123)I-IMT uptake into neonatal astrocytes and into C6 glioma cells revealed apparent Michaelis constants K(M) = 13.9 +/- 0.5 microM and K(M) = 33.9 +/- 4.1 microM, respectively, which are in the same range of K(M) values as those recently determined for amino acid transport into neoplastic and non-neoplastic glial cells. Indeed, the K(M) values in the micromolar range correspond to the expression of the LAT-1 subunit of system L both in the neonatal astrocytes and in C6 glioma cells. However, sodium-independent maximum transport velocities (V(max)) differed significantly between neonatal astrocytes and C6 glioma cells (11.1 +/- 0.3 and 39.9 +/- 3.3 nmol/mg protein/10 min, respectively).

Amino Acid Transport Systems↗
PubMed2001

Complete inhibition of in vivo glioma growth by oncostatin M.

We describe here the oncostatin M (OSM)-dependent inhibition of in vivo tumour formation after intracerebral inoculation of glioblastoma cells in mice. We generated human glioblastoma cells transfected with the OSM gene under the control of a tetracycline-response promoter. Upon removal of tetracycline from the medium, cells exhibited a differentiated cell morphology, while proliferation was significantly inhibited. After implantation of these cells into nude mice brains, large tumours developed in animals lacking OSM expression, whereas no tumour formation was observed in mice with induced OSM expression. Our results suggest that OSM exerts pronounced antitumorigenic effects on glioblastoma cells in vivo and provide arguments for a therapeutic application of OSM in humans.

Animals↗
PubMed2001

Clinically silent circulating microemboli in 20 patients with carotid or vertebral artery dissection.

BACKGROUND AND PURPOSE: Carotid and vertebral artery dissections are frequently complicated by cerebral embolism. Detection of clinically silent circulating microemboli by transcranial Doppler sonography (TCD) is now widely investigated in patients with carotid artery disease in the hope to identify patients at increased risk for stroke. METHODS: In 20 patients with carotid (n = 17) or vertebral (n = 2) artery dissection, or both (n = 1), we performed a 1-hour microembolus detection downstream to the dissection in the middle or in the posterior cerebral artery, respectively. RESULTS: Five patients with a carotid artery stenosis of > or = 90% or with carotid artery occlusion showed microembolic signals at a rate of up to 15 events/h. In all these patients, the onset of the dissection was within the last 58 days. Patients with lower degrees of stenosis or onset of symptoms beyond 58 days did not show microembolic signals at all. Three patients who had presented with recurrent ischaemic events prior to TCD monitoring unexceptionally had microembolic signals. CONCLUSION: Microembolic signals occur in patients with high-grade stenosis or occlusion due to acute cervical artery dissection. Patients with microemboli seem to be at increased macroembolic risk, i.e. stroke recurrence, and may require close-meshed clinical follow-up and possibly stronger antithrombotic treatment.

Adult↗
PubMed2000

Activation of the Jak-Stat- and MAPK-pathways by oncostatin M is not sufficient to cause growth inhibition of human glioma cells.

We have recently described that oncostatin M (OSM), a member of the IL-6 family of cytokines, induces the differentiation of human glioma cells in culture. In order to extend this studies, we analyzed the effect of OSM on other human glioma cell lines including A172, U343-MG and T98G. All of these cell lines express the receptor components of OSM and leukemia inhibitory factor (LIF) gp130, LIFR and the OSM specific OSMRbeta. Therefore, we expected these cell lines to respond to OSM and LIF. Using specific antibodies recognizing proteins of the janus kinase (Jak-)/signal transducers and activator of transcription (Stat-) signaling cascade that has been shown to transduce the signals of the IL-6 cytokines to the nucleus, we could show that Jak1, Jak2 and Tyk2, as well as the Stat proteins Stat1, Stat3 and Stat5b were phosphorylated in all three cell lines by OSM and, at least in part, by LIF. Activation of the Stat proteins was also detected by EMSA which revealed complex formation on the Stat3 DNA-binding element and on a Stat5 binding site. Consistent with our recent findings, OSM treatment also induced the activation of the MAPK erk2 and the tyrosine phosphatase SHP-2 in cells of the A172, T98G and U343-MG cell lines. Although this activation pattern was very close to what we had observed in the GOS3 glioma cells, only T98G showed a growth inhibition in response to OSM while the A172 and the U343-MG cell lines did not respond to OSM treatment in terms of growth inhibition.

Antigens, CD↗
PubMed2000

Hereditary recurrent focal neuropathies: clinical and molecular features.

The authors review the molecular genetics and pathophysiology of hereditary recurrent focal neuropathies: hereditary neuropathy with liability to pressure palsies (HNPP) and hereditary neuralgic amyotrophy (HNA). Significant progress in the understanding of HNPP and HNA has been achieved. HNPP and HNA are distinct clinical and pathologic disease entities with autosomal dominant inheritance. Molecular genetic studies have shown that HNPP and HNA are located on chromosome 17 but at distinct genetic loci (17p11.2 for HNPP, 17q25 for HNA). The 1.5 megabase deletion in 17p11.2 is the major cause of HNPP. This interstitial deletion causes the complete loss of one allele of the peripheral myelin protein 22 (PMP22) gene. Interestingly, rare HNPP patients are found without the 1.5 megabase deletion. However, these patients have distinct mutations in the PMP22 gene resulting in altered expression of the PMP22 protein. Current molecular genetic tests and clinical guidelines allow improved diagnosis, prognosis, and genetic counseling for patients with HNPP. Such tests are not available for HNA, because the disease-causing gene remains unknown. Molecular genetic advances in HNPP and HNA, as well as the study of transgenic animal and cellular models, will provide a more precise understanding of the disease mechanisms and will lead to the development of effective therapeutic tools for patients with inherited and sporadic recurrent peripheral neuropathies.

Charcot-Marie-Tooth Disease↗
PubMed2000

PMP22 Thr118Met is not a clinically relevant CMT1 marker.

It is controversial if peripheral myelin protein 22 gene (PMP22) Thr118Met represents a functionally irrelevant polymorphism or, since hemizygosity for this variant has been found in two patients with Charcot-Marie-Tooth disease type 1 (CMT1 patients), it can act as a recessive CMT1 mutation. To shed further light on this variant and its diagnostic value we searched for carriers in 1018 individuals from the German general population, in 104 probands with hereditary neuropathy with liability to pressure palsies (HNPP) who were carriers of the 1.5-Mb deletion frequently associated with this disorder, in 187 patients with the 1.5-Mb duplication, and in 22 patients with a CMT1 phenotype who did not have any detectable anomaly in the PMP22 gene. Using allele-specific PCR we identified 14 [allele frequency (AF)=0.007] in the German general population, one (AF=0.01) in the HNPP group and six (AF=0.016) and two (AF=0.05) carriers of the PMP22 Thr118Met mutation in the CMT1 groups with and without gene defect. Carriers from all groups showed nerve conduction velocities which did not differ from typical values for these groups. We conclude that the hemizygous occurrence of the 118Met allele does not usually cause CMT1. Because of previous reports on its association with disease, and because its allele product shows abnormalities in in vitro expression systems, it seems possible that this mutation, together with yet unidentified factors, predisposes to CMT1. Alternatively, previously reported disease associations occurred by chance, and the 118Met allele causes biochemical abnormalities irrelevant for CMT1 formation. In either case this mutation is not a clinically relevant disease marker.

Biomarkers↗
PubMed2000

Oncostatin M-mediated growth inhibition of human glioblastoma cells does not depend on stat3 or on mitogen-activated protein kinase activation.

Oncostatin M (OSM) and other members of the interleukin-6 cytokines, like ciliary neurotrophic factor and leukemia inhibitory factor, can induce differentiation of glial cells. We have recently described that OSM inhibited the growth of human glioma cells in vitro and induced a cell morphology resembling that of mature astrocytes. Using the glioblastoma cell line 86HG39, we demonstrated that treatment of the glioma cells with OSM also leads to a differentiation of the malignant glioma cells as judged by a strong increase in glial fibrillary acidic protein expression. The differentiation and the growth inhibition were not significantly blocked by expression of a dominant-negative (dn) signal transducer and activator of transcription (Stat) 3 protein. OSM exerted a reduction in DNA synthesis even in the presence of a high expression level of dnStat3. Moreover, inhibition of the ras-raf-mitogen-activated protein kinase (MAPK) pathway by the MAPK kinase 1 inhibitor PD98059 resulted in a synergistic enhancement of the OSM effect, indicating that the activation of this pathway counteracts the activity of the cytokine.

Antineoplastic Agents↗
PubMed2000

Electromagnetic fields (1.8 GHz) increase the permeability to sucrose of the blood-brain barrier in vitro.

We report an investigation on the influence of high frequency electromagnetic fields (EMF) on the permeability of an in vitro model of the blood-brain barrier (BBB). Our model was a co-culture consisting of rat astrocytes and porcine brain capillary endothelial cells (BCEC). Samples were characterized morphologically by scanning electron microscopy and immunocytochemistry. The BBB phenotype of the BCEC was shown by the presence of zona occludens protein (ZO-1) as a marker for tight junctions and the close contact of the cells together with the absence of intercellular clefts. Permeability measurements using (14)C-sucrose indicated a physiological tightness which correlated with the morphological findings and verified the usefulness of our in vitro model. Samples were exposed to EMF conforming to the GSM1800-standard used in mobile telephones (1.8 GHz). The permeability of the samples was monitored over four days and compared with results of samples that were cultured identically but not exposed to EMF. Exposure to EMF increased permeability for (14)C-sucrose significantly compared to unexposed samples. The underlying pathophysiological mechanism remains to be investigated.

Animals↗
PubMed1999

A sequence-ready BAC/PAC contig and partial transcript map of approximately 1.5 Mb in human chromosome 17q25 comprising multiple disease genes.

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy mapped to a 4-cM interval on chromosome 17q25 between the short tandem repeat (STR) markers D17S1603 and D17S802. Chromosome 17q25 in general and the 4-cM HNA region in particular are also implicated in the pathogenesis of a number of tumors (tylosis with esophageal cancer, sporadic breast and ovarian tumors) and harbor a psoriasis susceptibility locus. Initial attempts to construct a yeast artificial chromosome contig failed. Therefore, we have now constructed a complete P1 artificial chromosome (PAC) and bacterial artificial chromosome (BAC) contig of the region flanked by the STR markers D17S1603 and D17S802. The contig contains 22 PAC and 64 BAC clones and covers a physical distance of approximately 1. 5 Mb. A total of 83 sequence-tagged site (STS) markers (10 known STSs and STRs, 56 STSs generated from clone end-fragments, 12 expressed sequence tags, and 5 known genes) were mapped on the contig, resulting in an extremely dense physical map with approximately 1 STS per 20 kb. This sequence-ready PAC and BAC contig will be pivotal for the positional cloning of the HNA gene as well as other disease genes mapping to this region.

Bacteriophage P1↗