Enhanced spasticity in primary progressive MS patients treated with interferon beta-1b.
Explore the source record for details and available documents.
Adjuvants, Immunologic↗
Biomedical subjects
F Stögbauer
Publications and source records attributed to F Stögbauer.
Hereditary neuralgic amyotrophy: mutation analysis of candidate genes.
Explore the source record for details and available documents.
Antigens, CD7↗
Activation of Jak-Stat and MAPK2 pathways by oncostatin M leads to growth inhibition of human glioma cells.
Oncostatin M (OSM) is a cytokine of the IL-6 family that modulates the growth of various cell types, at least in vitro. We have recently described that OSM inhibits growth and changes cell morphology of human glioma cell lines. Although leukemia inhibitory factor (LIF) receptor components are also expressed by these cells, the response to LIF was significantly weaker compared to OSM. We have therefore analyzed the signal transduction pathways induced by these cytokines. While OSM induces a number of strong tyrosine phosphorylations, including Janus tyrosine kinases (Jak) and the signal transducer and activator of transcription (Stat) proteins, LIF induces only minor tyrosine phosphorylation of Tyk2 and Stat3. Specific activation of the tyrosine phosphatase SHP-2 as well as the mitogen-activated kinase 2 (MAPK2) was found in glioma cells upon OSM treatment. MAPK2 turns out to be a crucial mediator of the OSM effect in glioma cells since inhibition of MAPK activity by the Mek1 inhibitor PD98059 blocks the OSM-induced inhibition of DNA synthesis by about 70%.
Blotting, Western↗
Kinetics of 3-[(123)I]iodo-l-alpha-methyltyrosine transport in rat C6 glioma cells.
3-[(123)I]Iodo-l-alpha-methyltyrosine ((123)I-IMT) is used for the diagnosis and monitoring of brain tumours by means of single-photon emission tomography (SPET). To date, little has been known about the system for the transport of (123)I-IMT into brain tumour cells. It is assumed that (123)I-IMT is transported by a specific carrier for large, neutral amino acids (L-system). In this study, rat C6 glioma cells were used to characterize the uptake system of (123)I-IMT and to investigate its precise kinetics. The time course of (123)I-IMT uptake into the cells was examined for a range of 1-60 min. (123)I-IMT uptake rates with varying concentrations of (123)I-IMT (2. 5-50 microM) in the medium were quantified to assess the kinetic parameters of (123)I-IMT transport. Furthermore, competition of (123)I-IMT with other amino acids was investigated to identify the distinct transport systems involved in (123)I-IMT uptake. (123)I-IMT uptake into C6 glioma cells was linear for approximately 10 min and reached a steady-state level within 30 min. The analysis of the rate of uptake of (123)I-IMT at different concentrations was concordant with the predominance of a single uptake system. The apparent Michaelis constant (K(m)) of (123)I-IMT was 26.2+/-1.9 microM, and the maximum transport velocity (V(max)) was 35.4+/-1.7 nmol/mg protein per 10 min. 77%+/-10% of (123)I-IMT transport was sodium independent and 23%+/-3% was sodium dependent. Competitive inhibition of (123)I-IMT uptake by 2-aminobicyclo[2.2. 1]heptane-2-carboxylic acid, alpha-(methylamino)isobutyric acid and naturally occurring amino acids revealed a major (123)I-IMT transport via the sodium-independent system L (72%) and a minor uptake via the sodium-dependent system B(0,+) (17%). Our results show that (123)I-IMT transport into C6 glioma cells is principally mediated by the L-system and to a minor extent by the B(0,+)-system. The kinetic parameters of (123)I-IMT uptake are in the range of those of naturally occurring amino acids.
Animals↗
Craniocervical artery dissection: MR imaging and MR angiographic findings.
Dissection of the carotid and vertebral arteries is a not so uncommon cause of stroke and has to be considered as a differential diagnosis especially in younger patients. Therapeutic and prognostic implications are different from those in extracranial atherosclerotic disease. Dissection results from hemorrhage into the vessel wall usually between the layers of the media. Digital subtraction angiography (DSA) depicts the resulting luminal compromise that may reveal some typical, but not specific, findings. The same is true for non-invasive angiographic techniques such as time-of-flight magnetic resonance angiography (MRA) and computed tomography angiography (CTA), which have shown accurate results compared with DSA. The main advantage of these techniques is the direct visualization of the vessel wall confirming the intramural hematoma. This is achieved best with MR imaging due to the high signal of blood degradation products on T1- and T2-weighted images. Therefore, MRI in combination with MRA is presently the method of choice for initial diagnosis and follow-up of craniocervical artery dissection (CCAD). In some questionable cases, CTA is a non-invasive alternative that is independent of flow phenomena.
Adolescent↗
CNTF and its receptor subunits in human gliomas.
Ciliary neurotrophic factor (CNTF) promotes the survival of various neuronal cell populations. It is produced by astrocytes and influences the development and differentiation of glial cells. CNTF and related neuropoietic cytokines affect growth and differentiation of various neoplasms. Moreover, they induce the reactive transformation of astrocytes (gliosis) and influence growth and differentiation of neuroectodermal tumor cell lines in vitro. However, their role in gliomas is largely unknown. We studied the expression of CNTF and its receptor subunits in human astrocytomas and glioblastomas. In more than 95% of the tumors, CNTF transcripts were found by RNAase protection assay; in more than 80% of the cases, tumor cells were CNTF immunoreactive. CNTF receptor alpha (CNTFR alpha), the specific component of the tripartite CNTF receptor system, was detectable by Northern blot analysis in 80% of the cases. In situ hybridization revealed CNTFR alpha mRNA in the cytoplasm of neoplastic cells. Transcripts of the remaining two components of the CNTF receptor system, gp130 and LIFR beta, were found by Northern blotting in 83% and 70% of the tumors, respectively. Simultaneous expression of CNTF and all its receptor components was detected in approximately half of the tumors. These results indicate that CNTF and its receptor components are expressed by human glioma cells. The simultaneous expression of ligands and receptor subunits suggests that CNTF might act on human glioma cells via an auto- or paracrine mechanism.
Adolescent↗
Genetic refinement of the hereditary neuralgic amyotrophy (HNA) locus at chromosome 17q25.
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant, recurrent focal neuropathy. HNA is characterised by episodes of painful brachial plexus neuropathy with muscle weakness and atrophy, as well as sensory disturbances. Single episodes are commonly preceded by non-specific infections, immunisations or parturition. Mild dysmorphic features and short stature are present in some HNA families, but absolute co-segregation with HNA has not been described. To refine the previously described HNA locus on chromosome 17q25, we performed a genetic linkage study in five HNA families with different geographic origins. Significant linkage was obtained with chromosome 17q24-q25 short tandem repeat (STR) markers in three HNA families and suggestive linkage was found in the other two HNA families. Analysis of the informative recombinations in affected individuals allowed us to reduce the HNA linkage interval to a candidate region of 3.5 cM.
Brachial Plexus Neuritis↗
Autosomal dominant burning feet syndrome.
Familial burning feet syndrome inherited as an autosomal dominant trait has been described in only one family. Due to an associated sensory neuropathy the autosomal dominant burning feet syndrome was suggested to represent a variant form of hereditary sensory and autonomic neuropathy type I (HSAN I). Clinical, histopathological, and molecular genetic studies were performed in a large German kindred with autosomal dominant burning feet syndrome. The autosomal dominant burning feet syndrome was associated with a neuropathy predominantly affecting small unmyelinated nerve fibres. Linkage to the HSAN I locus on chromosome 9q22 and to the Charcot-Marie-Tooth disease type 2B (CMT 2B) locus on chromosome 3q13-q22 was excluded. The autosomal dominant burning feet syndrome is neither allelic to HSAN I nor to CMT 2B and thus represents a distinct genetic entity.
Female↗
Absence of mutations in peripheral myelin protein-22, myelin protein zero, and connexin 32 in autosomal recessive Dejerine-Sottas syndrome.
Motor and sensory neuropathies with the clinical features of HMSN III (Dejerine-Sottas syndrome, DSS) are etiologically related to heterozygous mutations in either peripheral myelin protein-22 (PMP22) or myelin protein zero (MPZ). Heterozygous mutations in either of these two genes are also responsible for other hereditary peripheral neuropathies (HNPP, CMT1A, CMT1B or CH). In two families DSS was related to the homozygous presence of a MPZ mutation while heterozygosity showed a much milder phenotype. It has therefore been suggested that the clinical phenotype in peripheral neuropathies is related to the mutated gene, the type of mutation and confounding effects from other sources. In this study we describe a family with recessive DSS in which mutations were absent from the PMP22, MPZ, and connexin 32 (Cx32) genes. We conclude that DSS also exists as a distinct genetic entity with autosomal recessive inheritance as originally defined by Dejerine and Sottas in 1893.
Child, Preschool↗
Familial autosomal-dominant carpal tunnel syndrome presenting in a 5-year-old case.
Explore the source record for details and available documents.
Carpal Tunnel Syndrome↗
Recurrent brachial plexus palsies as the only clinical expression of hereditary neuropathy with liability to pressure palsies associated with a de novo deletion of the peripheral myelin protein-22 gene.
There is phenotypic heterogeneity in patients with hereditary neuropathy with liability to pressure palsies. In rare cases, recurrent brachial plexopathy is the only expression of the disease. We describe a patient with three episodes of plexus brachialis palsy and a de novo deletion of the peripheral myelin protein-22 gene. We conclude that DNA analysis is a key issue not only for the differentiation of peripheral neuropathies but also in the diagnosis of recurrent plexopathies.
Adult↗
[X-chromosomal recessive spinobulbar muscular atrophy (Kennedy type). Description of a family, clinical aspects, molecular genetics, differential diagnosis and therapy].
The Kennedy-Syndrome is a X-linked recessive bulbospinal muscular atrophy, in some cases associated with endocrinological disturbances such as androgen resistance and diabetes mellitus. The age of onset is usually between 20 and 40. Presenting symptoms are proximal flaccid weakness, fasciculations, cramps or tremor. Disease progression is usually slow and live expectancy is normal. It is important to distinguish the Kennedy-Syndrome from amyotrophic lateral sclerosis, spinal muscular atrophy, muscular dystrophies and other types of motor neuron disease. Kennedy disease is caused by an expanded trinucleotide repeat in the androgen receptor gene. Genetic analysis allows a precise-diagnosis on an individual basis and reliable genetic counselling. An effective medical treatment does not yet exist.
Diagnosis, Differential↗
Growth inhibition of newly established human glioma cell lines by leukemia inhibitory factor.
We have established three new cell lines deriving from malignant human gliomas. The cell lines were described in terms of both morphology and growth characteristics. Most cells in all three cell lines expressed the neuroepithelial marker protein GFAP. In terms of growth characteristics, the cells showed only slight differences. The cell lines showed no expression of the neural form of the c-src gene, pp60c-srcN, but did express the ubiquitous form, pp60c-src. The established glioma cell lines were also examined for expression of members of the neuropoietic cytokine family, CNTF and LIF, and their respective receptor components CNTFRalpha, LIFRbeta and gp130. With the exception of CNTFRalpha both the ligands and their receptor components were expressed in similar amounts in all three cell lines. The presence of ligand and receptor prompted us to study the effects of exogenously supplied factors on the growth of the glioma cell lines. Whereas LIF induced a high c-fos expression, only low c-fos induction was observed upon CNTF treatment. Accordingly, CNTF did not have any noticeable effects on glioma cell growth in culture, while LIF mediated an inhibiting effect on the growth of the three glioma cell lines in culture.
Aneuploidy↗
[Hereditary neural amyotrophy (HNA): clinical and molecular genetic basis].
Hereditary neuralgic amyotrophy (HNA) and hereditary neuropathy with liability to pressure palsies (HNPP) are hereditary focal neuropathies. In this study we describe three families suffering from HNA. These families were examined clinically and electrophysiologically. Linkage analysis with markers from distal chromosome 17 was performed in a three-generation family. HNA could be separated from HNPP in all three families based on clinical and electrophysiological findings. HNA was characterised by recurrent episodes of painful brachial plexus lesions. In contrast to HNPP, no evidence for generalised neuropathy was found in the HNA families. Linkage analysis confirmed the HNA locus on distal chromosome 17. Additionally, we were able to refine the HNA locus to a 16 cM region on chromosome 17q24-q25.
Amyloid Neuropathies↗
Incidence and risk factors for stroke in an occupational cohort: the PROCAM Study. Prospective Cardiovascular Muenster Study.
BACKGROUND AND PURPOSE: The purpose of this study was to assess the incidence of stroke and the magnitude of classic stroke risk factors in an occupational cohort of white-collar and blue-collar workers. METHODS: We studied a prospective cohort of 12 866 male employees, aged 30 to 65 years, in 52 companies in northwestern Germany, with an average follow-up of 7.2 years. Participants were free of self-reported stroke, transient ischemic attack, and myocardial infarction at baseline. Physical examination, blood tests, and a face-to-face interview to assess presence of various risk factors were performed at the workplace. Follow-up was done by standardized mailed questionnaire. Main outcome measure was first stroke occurrence. RESULTS: Overall stroke incidence was 42.4 per 100000 person-years, increasing from 10.1 per 100000 person-years in the age category 30 to 39 years to 33.6, 80.6, and 159.2 per 100000 person-years in the age categories 40 to 49, 50 to 59, and 60 years and older, respectively. After adjustment for potential confounders, the relative risks of total stroke associated with systolic blood pressure < or = 120, 121 to 140, and > or = 141 mm Hg were 1.00 (reference), 2.99 (95% confidence interval, 0.85 to 10.49), and 5.56 (1.56 to 19.88). The risks associated with smoking status of never/past, < or = 20 cigarettes per day, and >20 cigarettes per day) were 1.00 (reference), 1.65 (0.62 to 4.42), and 3.56 (1.78 to 7.15), respectively. A history of hypertension at baseline (yes versus no) was independently associated with a relative risk of 2.37 (1.20 to 4.71) for total stroke and a history of diabetes mellitus (yes versus no) with a risk of 2.21 (1.00 to 4.87). A comparison of risk factor levels with a general population study revealed only small differences. CONCLUSIONS: This occupational cohort had a 2-fold lower stroke incidence than that observed in cohorts of the general population. In the absence of a strong healthy-worker effect, moderate differences in behavioral risk factors and a higher treatment rate for hypertension contribute to the explanation of this favorable stroke incidence.
Adolescent↗
PCR-based strategy for the diagnosis of hereditary neuropathy with liability to pressure palsies and Charcot-Marie-Tooth disease type 1A.
Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are inherited peripheral neuropathies. In most cases these disorders are caused by either the duplication (in CMT1A) or the deletion (in HNPP) of a 1.5-megabase DNA fragment on chromosome 17p11.2, which contains the peripheral myelin protein 22 gene (PMP22). We developed a rapid and simple quantitative PCR assay for the detection of the CMT1A duplication or the HNPP deletion. The assay is based on the quantitative determination of the copy number of a 240-base pair DNA fragment from exon 4 of the PMP22 gene. Quantification was done on an automated fluorescence sequencer. Using this method we analyzed four families with the HNPP phenotype. In these families we identified the deletion in all affected individuals. To test the validity of the method, we compared the quantitative PCR results from 50 DNA samples, including 15 samples from individuals with HNPP, 15 samples from CMT1A patients, and 20 from normal controls, with the results obtained by Southern blot analysis. Concordant results were obtained in 49 of the 50 cases.
Blotting, Southern↗
Refinement of the hereditary neuralgic amyotrophy (HNA) locus to chromosome 17q24-q25.
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant, recurrent focal neuropathy characterized by episodes of painful brachial plexus neuropathy with muscle weakness and atrophy, as well as sensory disturbances. Single episodes are commonly preceded by unspecific infections or immunization, or are associated with parturition. Minor facial dysmorphic features are present in some pedigrees but do not clearly segregate with the disease. To confirm the recently described HNA locus on distal chromosome 17q, we performed a genetic linkage study in an extended Turkish pedigree. We were able to refine the HNA locus on chromosome 17q24-q25 in a 16-cM region.
Brachial Plexus Neuritis↗
A novel frameshift mutation in PMP22 accounts for hereditary neuropathy with liability to pressure palsies.
Peripheral myelin protein PMP22 deficiency is associated with hereditary neuropathy with liability to pressure palsies (HNPP). Most HNPP cases are caused by a 1.5-megabase deletion in chromosome 17p11.2-12, a region that contains the PMP22 gene, whereas point mutations leading to HNPP are extremely rare. We have identified a family with clinical and electrophysiologic features of HNPP,in which all affected members are heterozygous carriers of a single base insertion in codon 94. This mutation is predicted to alter the reading frame and to result in a delayed termination signal. We conclude that the functional consequences of the frameshift are equivalent to those of the PMP22 deletion allele.
Adult↗