Biomedical subjects

Wolfgang Roggendorf

Publications and source records attributed to Wolfgang Roggendorf.

9 recordsLinked to original sources

PubMed2006

Glioblastoma multiforme with oligodendroglial component (GBMO): favorable outcome after post-operative radiotherapy and chemotherapy with nimustine (ACNU) and teniposide (VM26).

BACKGROUND: The presence of an oligodendroglial component within a glioblastoma multiforme (GBM) is considered a prognostically favorable factor, but the clinical outcome of patients with glioblastoma multiforme with oligodendroglial component (GBMO) after combined post-operative radiotherapy and chemotherapy has rarely been reported. METHODS: We analyzed overall and progression-free survival in a group of ten consecutive patients initially diagnosed with GBMO between 1996 and 2004 (4.2% of all GBM patients). Median (range) age was 54 (34-73) years, 90% were resected and median radiotherapy dose was 54 (45-60.6) Gy. 80% of patients received post-operative chemotherapy with nimustine (ACNU) and VM26 (teniposide) for a median of 3.5 (1-6) cycles, the remainder were treated with post-operative radiotherapy alone. All specimens were reviewed by an experienced neuropathologist. RESULTS: Neuropathological re-evaluation revealed GBM with an oligodendroglial component of 30% or less in five cases, predominant oligoastrocytic tumors with focal areas of GBM in four patients and WHO grade III oligoastrocytoma with questionable transition to GBM in one patient. Four of ten patients were alive at at 40, 41, 41 and 82 months. The median overall survival (Kaplan-Meier) was 26 months, the 2-year survival rate was 60% (progression-free survival: 9.8 months and 40%, respectively). CONCLUSION: In conclusion, patients with GBMO treated with post-operative radiotherapy and chemotherapy with ACNU/VM26 had a better prognosis than reported for GBM in modern chemoradiation series.

Adult↗

PubMed2006

Biological activity of paediatric cerebral cavernomas: an immunohistochemical study of 28 patients.

OBJECTIVE: According to the hypothesis that paediatric cerebral cavernomas may have different biological activity compared to adult cavernomas, immunohistochemical analysis was used to elucidate the biological nature of paediatric cavernomas. PATIENTS AND METHODS: We examined the histological features and the proliferative and angiogenic capacity of the tissue specimens acquired from 28 paediatric patients. Normal paediatric brain tissues obtained from paediatric autopsy cases were used as a control group. The proliferative activity of the endothelium and the neoangiogenetic capacity were investigated by immunohistochemistry for proliferating cell nuclear antigen (PCNA), Ki-67 epitope (MIB-1), Flk-1 receptor, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1 alpha, and endoglin antibody, respectively. Afterwards, the results of the paediatric lesions were analysed and compared with the correspondent values of previously reported immunohistochemical analysis in adult cavernomas. RESULTS: Positive immunostaining of VEGF was detected significantly less in paediatric cavernomas compared to adult cases (p<0.05). In contrast, endoglin, a protein that is upregulated during an increased vascular shear stress, was expressed more often in paediatric cavernomas (p<0.05). Neither the expression of the PCNA nor the expression of the HIF-1alpha was found significantly different between paediatric and adult cavernomas. However, the positive immunoreaction for MIB-1 occurred more often in the paediatric cases (p<0.05). CONCLUSIONS: The immunohistochemical study indicates that paediatric cavernomas are dynamic lesions. The VEGF/Flk-1 associated neoangiogenesis may play a minor role for the biology of paediatric cavernomas, while endoglin seems to act more prominently than previously thought, particularly for the biology of paediatric cavernomas.

Adolescent↗

PubMed2006

Interlaboratory comparison of assessments of Alzheimer disease-related lesions: a study of the BrainNet Europe Consortium.

This interlaboratory study evaluated the reproducibility of the assessments of neuritic plaques and neurofibrillary tangles (NFTs)--the hallmark lesions of Alzheimer disease--and compared the staining between the BrainNet Europe centers. To reduce the topography-related inconsistencies in assessments, we used a 2-mm tissue microarray (TMA) technique. The TMA block included 42 core samples taken from 21 paraffin blocks. The assessments were done on Bielschowsky and Gallyas silver stains using an immunohistochemical (IHC) method with antibodies directed to beta-amyloid (IHC/Abeta) and hyperphosphorylated tau (IHC/HPtau). The staining quality and the assessments differed between the participants, being most diverse with Bielschowsky (good/acceptable stain in 53% of centers) followed by Gallyas (good/acceptable stain in 57%) and IHC/Abeta (good/acceptable stain in 71%). The most uniform staining quality and assessment was obtained with the IHC/HPtau method (good/acceptable stain in 94% of centers). The neuropathologic diagnostic protocol (Consortium to Establish a Registry for Alzheimer Disease, Braak and Braak, and the National Institute of Aging and Reagan [NIA-Reagan] Institute) that was used significantly influenced the agreement, being highest with NIA-Reagan (54%) recommendations. This agreement was improved by visualization of NFTs using the IHC/HPtau method. Therefore, the IHC/HPtau methodology to visualize NFTs and neuropil threads should be considered as a method of choice in a future diagnostic protocol for Alzheimer disease.

Aged↗

PubMed2003

Human ependymomas reveal frequent deletions on chromosomes 6 and 9.

Ependymomas are glial tumors of the brain and spinal cord. Genetic aberrations associated with the development of these tumors have not been fully identified yet. In previous cytogenetic and comparative genomic hybridization studies, multiple genomic imbalances in ependymomas were found, including partial or whole chromosome losses (1p, 4q, 6q, 9, 10, 11, 13, 16, 17, 19q, 20q and 22q). The aim of this study was to map particularly the commonly affected regions in ependymomas. Thirty-three pairs of matched normal and tumor specimens from ependymoma patients were genotyped using 34 polymorphic microsatellite markers distributed over 15 chromosomes. Loss of heterozygosity (LOH) was found in 26 of 33 tumors (78.8%). The most frequent LOHs were found on the long arms of chromosomes 6 (30.3%) and 9 (27.3%). LOH was also detected on 3p14 (13.3%), 10q23 (10.3%) and 11q (18.2%). Because of the high percentage of LOH on chromosome 6 and 9, we conclude that important tumor suppressor genes are situated on these two chromosomes.

Adult↗

PubMed2003

Metabolic patterns in meningiomas.

The aim of this investigation was to define characteristic properties of cellular energy metabolism in meningiomas in vitro dependent on the histological subtype. We analysed marker enzymes of representative metabolic pathways localized in the mitochondria (respiratory chain, citric acid cycle, beta-oxidation of fatty acids) and in the cytoplasm (glycolysis, pentose phosphate shunt). The activities of the intramitochondrial enzymes were significantly reduced in the meningiomas compared to normal cortex tissue. Glycolytic enzymes were not significantly different, but the marker enzyme of the pentose phosphate shunt was increased by a factor of 3.5-6 in the tumours. Further analysis of the histological subtypes showed that phosphofructokinase and lactate dehydrogenase were significantly increased in the anaplastic meningiomas compared to the benign subtypes.

Biomarkers, Tumor↗

PubMed2003

Primary anaplastic large cell lymphoma of the central nervous system: prognostic effect of ALK-1 expression.

Anaplastic large cell lymphoma (ALCL) rarely occurs in the central nervous system. Although defined by its composition of large, pleomorphic, CD30-positive lymphocytes, ALCL is heterogeneous. Most are T cell but some are null cell. Most but not all have a characteristic 2:5 translocation producing the fusion protein ALK-1, which is reliably detected by immunohistochemistry. In systemic ALCL, ALK-1 expression correlates with young patient age and a favorable prognosis. Herein we report four new cases of primary central nervous system ALCL from the Mayo Clinic and incorporate additional data from five previously published cases. ALK-1 expression was determined in all nine tumors. Patient age was 4-66 years (mean 29 years) with a bimodal distribution: 6 < or = 22 years, 3 > or = 50 years. Six were female. Tumors were mostly supratentorial, five were multifocal, and seven had involvement of dura or leptomeninges. Seven tumors were T cell, two were null cell, and five of nine were ALK-1 immunopositive. Total mortality was six of nine. Three patients, 4-18 years of age (mean 13 years), were alive at 4.8-6.1 years postdiagnosis; these tumors were all ALK positive. Five patients, 13-66 years of age (mean 43 years), died of tumor 4 days to 11 weeks postdiagnosis; four of five of these tumors were ALK negative. One 10-year-old child with an ALK-positive tumor died of sepsis, but in remission. Central nervous system ALCL is aggressive. Our study suggests that a better outcome may be associated with young age and ALK-1 positivity, prognostic parameters similar to systemic ALCL.

Activin Receptors, Type I↗

PubMed2002

Loss of heterozygosity on chromosome 22 in human ependymomas.

Ependymomas are glial tumors of the brain and spinal cord. The most frequent genetic change in sporadic ependymomas is monosomy 22, suggesting the presence of an ependymoma tumor suppressor gene on chromosome 22. Thirty-three pairs of matched normal and tumor specimens from ependymoma patients were genotyped using 12 polymorphic microsatellite markers spanning the long arm of chromosome 22. Allelic deletion was found in 12 of 33 tumors (36.4%). Eight tumors showed partial deletions and 4 tumors exhibited loss of the entire arm of 22q. We identified two common regions of deletion: one at 22q11.21-12.2 flanked by markers D22S420 and D22S300, and a second candidate region at 22q13.1-13.3 between D22S274 and D22S1149. The size of each region was 21.1 and 2.4 cM, respectively. Thus, our results suggest that one or more tumor suppressor genes associated with ependymoma may be present on chromosome 22. Comparison of these results with clinicopathological data indicate that allelic losses on 22q tend to occur more frequently in intracranial anaplastic ependymomas in children and intraspinal ependymomas in adults.

Adult↗

PubMed2002

Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury.

BACKGROUND: Patients with Parkinson disease characteristically exhibit an increased echogenicity of the substantia nigra (SN) on transcranial sonography, a new neuroimaging technique. The same echo feature of the SN can be identified in 9% of healthy adults. OBJECTIVE: To evaluate the relevance of the echogenic SN in healthy adults. DESIGN: In the first part of the study, 10 healthy subjects younger than 40 years with a distinct SN hyperechogenicity underwent extensive neurological, motor, neuropsychological, and fluorine 18-dopa positron emission tomographic ([18F]-dopa PET) examinations. Results were compared with those of 10 subjects with a low echogenic SN. In the second part of the study, the postmortem brains of 20 patients without extrapyramidal disorders during their lifetime were sonographically examined with a particular focus on SN echogenicity. Subsequently, one half of the brain was prepared for heavy metal analysis, the other for a histological examination. RESULTS: Healthy subjects with SN hyperechogenicity exhibited a significant reduction of the [18F]-dopa uptake, especially in the putamen (Wilcoxon matched pair test: left side, P =.006; right side, P =.009), whereas their neuropsychological and motor performance were normal. Postmortem studies showed that the echogenicity of the SN correlated with its iron content. CONCLUSIONS: Increased echogenicity of the SN, characteristically seen in Parkinson disease, is related to a functional impairment of the nigrostriatal system (even in young healthy adults) that can be revealed by [18F]-dopa PET studies. Substantia nigra hyperechogenicity is related to a higher tissue iron level, which is known to enhance the cells' generation of reactive oxygen specimens. Therefore, we hypothesize that transcranial sonography may identify a susceptibility marker for the development of nigral injury that can be detected early in life, prior to the onset of Parkinson disease.

Adolescent↗

PubMed2002

Expression of foetal type acetylcholine receptor is restricted to type 1 muscle fibres in human neuromuscular disorders.

In adult muscle, acetylcholine receptors (AChR) are restricted mainly to the motor endplate where the adult isoform (alphabetadeltaepsilon) is expressed. When skeletal muscle is denervated in animal models, there is atrophy of the muscle and a marked increase in expression of the AChR foetal isoform (alphabetagammadelta) containing a gamma-subunit. Similar changes in AChR expression are thought to occur in human muscle. While the role of denervation in regulating AChR gene expression has been widely studied, it has not been determined whether the transcriptional programmes responsible for defining different fibre types have an impact on the expression of AChR genes. We investigated biopsies from patients with a wide spectrum of neuromuscular diseases for expression of the AChR alpha- and gamma-subunits using RNase protection assays, alpha/gamma-duplex reverse transcriptase polymerase chain reaction, immunohistochemistry for foetal AChR and RNA in situ hybridization. Muscle from all patients with neurogenic disorders and, to a lesser extent, myogenic disorders, exhibited markedly increased transcription of the AChR gamma-subunit but, in contrast to previous animal studies, did not show increased AChR alpha-subunit. Moreover, both immunohistochemistry and RNA in situ hybridization revealed that AChR gamma-subunit hyperexpression occurred exclusively in atrophic type 1 and not in atrophic type 2 muscle fibres, irrespective of the underlying neuromuscular disease. We conclude that up-regulation of the AChR gamma-subunit in human muscle disorders is restricted to type 1 muscle fibres and, therefore, that AChR gamma-subunit expression is controlled by a muscle fibre type-restricted transcriptional programme. The factors influencing expression of this and other functional proteins should be relevant to the understanding and treatment of a range of neuromuscular disorders.

Atrophy↗