Search PubMed⌕ Search

Biomedical subjects

R Meyermann

Publications and source records attributed to R Meyermann.

At least 19 recordsLinked to original sources
PubMed2006

Surviving glioblastoma for more than 5 years: the patient's perspective.

The authors performed a comprehensive analysis of the functional outcome of 10 patients who had survived 5 years from a diagnosis of glioblastoma. Neurologic deficits were mild in most patients, but neuropsychological testing demonstrated cognitive deficits in all patients. Depression and anxiety were common. Although most patients thought that their social functioning and work ability were impaired, little reduction in overall quality of life was perceived.

Activities of Daily Living↗
PubMed2006

Upregulation of frizzled 9 in astrocytomas.

Wnt/frizzled (FZD) cascades play important roles in controlling cell fate, proliferation, migration, tissue architecture and organogenesis during embryonic development and in adult organisms. The potential involvement of this pathway in tumorigenesis has been established in several types of cancers. Frizzled 9 (FZD9) is expressed in brain and its aberrant expression in gastric cancer was observed. However, its association with astrocytomas remains unknown therefore we studied FZD9 expression in astrocytomas of different malignancy. In the present study, FZD9 expression in 25 astrocytomas was investigated using immunohistochemistry with specific antibodies. Further FZD9 expression in native human brain tissue and glioblastoma cell line were analysed using real-time reverse transcription polymerase chain reaction (RT-PCR). In human astrocytomas, FZD9 immunoreactivity (IR) was observed in both microvessels and neoplastic cells. The percentage of FZD9+ microvessels in relation to FZD9+ vessels was significantly higher in malignant astrocytomas than in low-grade astrocytomas and positively correlated with the astrocytoma World Health Organization (WHO) grading (r = 1, P = 0.04). Furthermore, the FZD9 IR scores positively correlated with astrocytoma WHO grading (r = 1, P = 0.04) and proliferating activity (r = 0.77, P < 0.001). Real-time RT-PCR data showed that FZD9 expression in human glioblastoma was significant higher than in normal brain (P < 0.05) but FZD9 expression was only slightly induced in cobalt chloride-treated human glioblastoma T98G cells compared with untreated cells (P > 0.05). FZD9 is upregulated in astrocytomas, suggesting that FZD9 could be important in the tumorigenesis of human astrocytomas.

Adult↗
PubMed2006

Differential microglial regulation in the human spinal cord under normal and pathological conditions.

As the primary intrinsic immune effector cells of the central nervous system, microglia are involved in virtually all pathological processes of the brain and spinal cord including inflammatory, neurodegenerative, traumatic, neoplastic and vascular diseases. Despite this important role, there is a lack of data concerning microglial distribution and protein expression in the human spinal cord. In this study, we immunohistochemically investigated 10 normal human spinal cords to establish reference data and compared these results with 15 pathological human spinal cords deriving from distinct pathologies. Each spinal cord was evaluated at eight different levels for three white and two grey matter areas for both constitutive (MHC-II, CD68, IL-16, AIF-1, LCA, CD4) and reactive (MRP-8, MRP-14) microglial antigens. Whereas previous studies revealed significant regional differences in microglial distribution and protein expression in human brain, normal spinal cord displayed a uniform expression pattern, reaching levels of up to 17% MHC-II positive cells of the total cell population. This datum formed the basis for the further evaluation of microglia expression levels in pathological spinal cords, where levels of up to 45% positive cells were observed. Our results represent important reference values for future neuropathological diagnostic and therapeutical approaches in spinal cord pathologies.

Adult↗
PubMed2006

Atypical teratoid-rhabdoid tumor spreading along the trigeminal nerve.

We here describe the case of a boy with an atypical teratoid-rhabdoid tumor (ATRT) of the 4th ventricle at 1 year of age and a local tumor recurrence at 19 months of age. Due to brainstem infiltration, only incomplete tumor resection was possible each time. High-dose chemotherapy, stem cell transplantation and irradiation resulted in complete tumor remission on a control MRI. At 8 years of age, another tumor appeared extending from the cerebellopontine angle along the right trigeminal nerve through Meckel's cave into the cavernous sinus. The trigeminal tumor was not in continuity with the primary ATRT but was located within the field of prior irradiation, neuroradiologically mimicking a schwannoma or a meningioma. The origin of the trigeminal tumor as a late metastasis of the former ATRT or as a less likely irradiation-induced secondary ATRT and the operative approach are discussed.

Brain Neoplasms↗
PubMed2005

Adult medulloblastoma: prognostic factors and response to therapy at diagnosis and at relapse.

Adult medulloblastoma is a rare tumor with few retrospective studies published so far. The role of adjuvant chemotherapy or chemotherapy at relapse is unclear. This study reports therapy and outcome in all adult (>or=16 years old) medulloblastoma (n=34) and supratentorial primitive neuroectodermal tumor (PNET) patients (n=2) treated in 2 neuro-oncological centers between 1976 and 2002. The median age was 24.5 years (range 16-76). After resection, 16 patients were treated with craniospinal radiotherapy alone, 20 patients also received adjuvant chemotherapy (8 vincristine, CCNU, cisplatin; 7 methotrexate alone or methotrexate/vincristine-based polychemotherapy; 5 other protocols). Median survival in the whole cohort was 126 months (2+ - 200+months). Five-year and 10-year survival rates were 79 % and 56%. Adjuvant chemotherapy was associated with a non-significant trend to prolonged survival (relative risk (RR) 1.89; p=0.068). The median progression-free survival (PFS) after primary therapy was 83 months. At relapse, 10 of 12 evaluable patients achieved a complete response upon second-line therapy. The median survival times from first (n=17) and second relapse (n=9) were 21 months (0-67+ months; 5/17 without second relapse) and 20 months (1-29 months). Cox regression analysis revealed the infiltration of the floor of the 4(th) ventricle at diagnosis as the only therapy-independent prognostic factor (RR 0.48; p=0.03). In conclusion, adjuvant chemotherapy may prolong survival in adult medulloblastoma patients. Moreover, second-line therapy may be beneficial for these patients. As in pediatric medulloblastoma patients, primary infiltration of the floor of the 4(th) ventricle indicates a poor prognosis.

Adolescent↗
PubMed2005

A new family with frontotemporal dementia with intronic 10+3 splice site mutation in the tau gene: neuropathology and molecular effects.

Mutations in the tau gene cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 characterized by filamentous tau protein deposits. Here we describe the clinical and neuropathological features of a case from a newly identified family with an intron 10+3-splice site mutation in the tau gene. The proband presented with severe personality changes and stereotyped speech followed by parkinsonian symptoms. He died at age 56 after a disease duration of approximately 6 years. At autopsy, there was marked frontotemporal degeneration with abundant tau-immunoreactive neuronal and glial inclusions widespread in the cortex and brainstem. RT-PCR analysis revealed a 3.7-fold increase of tau transcripts with exon 10, resulting in an 1.7-fold higher expression level of 4-repeat tau isoforms in soluble tau fractions when compared to control brains and exclusively 4-repeat tau isoforms in the sarcosyl-insoluble tau fractions. In accordance with the hypothesis that the overexpression leads to saturation of microtubule binding sites and an increase of unbound 4-repeat tau isoforms which assemble into filaments, the neuronal and glial inclusions in this case were exclusively composed of 4-repeat tau isoforms. The clinical and neuropathological data of this family are compared with results from the two other published families with the intron 10 + 3 mutation, the MSTD and the SOT 254 family.

Base Sequence↗
PubMed2003

Expression and functional activity of osteoprotegerin in human malignant gliomas.

Apo2L/TRAIL-based therapy is a promising experimental approach to the treatment of human malignant gliomas. Osteoprotegerin (OPG) is a soluble decoy receptor for Apo2L/TRAIL that antagonizes Apo2L/TRAIL-induced apoptosis. High levels of OPG expressed by tumor cells might therefore abrogate the activity of exogenously added or adenovirally expessed Apo2L/TRAIL. Here we assessed the expression of OPG in human gliomas in vivo, in primary glioma cell cultures and in established glioma cell lines. Immunohistochemistry revealed weak OPG immunoreactivity in up to 5% of the tumor cells in 8 of 13 glioblastomas. Strong OPG labeling was detected in single scattered tumor cells in one of these specimens. Five glioblastomas did not express OPG. High OPG expression was found in 1 of 6 primary glioma cell cultures and in 1 of 12 established glioma cell lines, T98G. OPG released by T98G cells was biologically active in that it inhibited Apo2L/TRAIL-induced apoptosis in sensitive glioma cells. Altogether, however, these data suggest that OPG expression may not be a major pathway of glioma cell resistance to future Apo2L/TRAIL-based therapeutic approaches.

Apoptosis↗
PubMed2003

The allograft inflammatory factor-1 in Creutzfeldt-Jakob disease brains.

The allograft inflammatory factor-1 (AIF-1) is a 17-kDa IFN-gamma inducible Ca(2+)-binding EF-hand protein that is encoded within the HLA class III genomic region and is involved in immune dysfunction and smooth muscle cell activation. We used immunohistochemistry double labelling experiments to analyse the spatial distribution and cell-type-specific localization of AIF-1 in the brains of patients who died as a result of sporadic Creutzfeldt-Jakob disease (CJD) and neuropathologically unaltered controls. Significantly more AIF-1 immunoreactive macrophages/microglial cells and, interestingly, neurones were observed in CJD patients compared to controls. Western blotting confirmed more prominent AIF-1 immunoreactive bands of approximately 50 kDa in four CJD patients compared to three controls. Chaotropic SDS-PAGE of the recombinant AIF-1 resulted in almost complete reduction of the 50 kDa band and mass spectrometry revealed only AIF-1-specific tryptic protein fragments suggesting that trimerized AIF-1 is the predominant form in vivo. Finally, we analysed mechanisms of neuronal AIF-1 induction. Following H2O2 challenge, a model of general cell stress, we observed the gradual induction of AIF-1 and, more interestingly, release to the supernatant of SKNSH neurones. Parallel reverse transcriptase polymerase chain reaction and sequencing was used to confirm AIF-1 mRNA expression.

Adult↗
PubMed2002

Cortical neurons of Creutzfeldt-Jakob disease patients express the urokinase-type plasminogen activator receptor.

Plasminogen belongs to the plasminogen activator system of cell signaling proteins and has recently been identified to bind to pathological prion protein PrPSC, but not to its normal conformer, PrPC. Plasminogen binds specifically to the urokinase-type plasminogen activator receptor (uPAR) to promote pericellular proteolysis, regulate integrin function, and mediate cell signaling. By using immunohistochemistry, we observed that significantly more cortical neurons in eight postmortem brains of patients who died with sporadic Creutzfeldt-Jakob disease (CJD) are immunoreactive for uPAR compared with controls. These data provide the pathophysiological basis for detailed analyses of the role of the plasminogen activator system in CJD and related diseases.

Adult↗
PubMed2001

AMP deaminase in rat brain: localization in neurons and ependymal cells.

The purine nucleotide cycle enzyme AMP deaminase (AMPD) catalyzes the irreversible hydrolytic deamination of AMP. The physiological function of the purine nucleotide cycle in the brain is unknown. In situ hybridization and immunocytochemical studies were performed to identify the regional and cellular expression of AMPD in rat brain with the goal of elucidating the neural function of the purine nucleotide cycle. AMPD messenger RNA was detected in ventricular ependymal cells and cells of the choroid plexus and in neurons of distinct brain areas. Although only low antibody titers were obtained by immunization with the purified sheep brain AMPD, immunization of mice with synthetic lipopeptide vaccines containing oligopeptides derived from a known partial complementary DNA sequence of the enzyme yielded an antiserum suitable for immunocytochemistry. Immunostaining of cells in culture showed that neurons but not astroglial cells express appreciable amounts of the enzyme. Results of immunocytochemical staining performed on rat brain slices were in accord with the localization of AMPD messenger RNA, thus confirming the expression of AMPD in neurons of the brain stem, hippocampus, cerebellar nuclei and mesencephalic nuclei, as well as in ventricular ependymal cells and their cilia.

AMP Deaminase↗
PubMed2001

Cerebral localization and regulation of the cell volume-sensitive serum- and glucocorticoid-dependent kinase SGK1.

The serum- and glucocorticoid-dependent kinase SGK1 is regulated by alterations of cell volume, whereby cell shrinkage increases and cell swelling decreases the transcription, expression and activity of SGK1. The kinase is expressed in all human tissues studied including the brain. The present study was performed to localize the sites of SGK1 transcription in the brain, to elucidate the influence of the hydration status on SGK1 transcription and to explore the functional significance of altered SGK1 expression. Northern blot analysis of human brain showed SGK1 to be expressed in all cerebral structures examined: amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra, subthalamic nucleus and thalamus. In situ hybridization and immunohistochemistry in the rat revealed increased expression of SGK1 in neurons of the hippocampal area CA3 after dehydration, compared with similar slices from brains of euvolaemic rats. Additionally, several oligodendrocytes, a few microglial cells, but no astrocytes, were positive for SGK1. The abundance of SGK1 mRNA in the temporal lobe, including hippocampus, was increased by dehydration and SGK1 transcription in neuroblastoma cells was stimulated by an increase of extracellular osmolarity. Co-expression studies in Xenopus laevis oocytes revealed that SGK1 markedly increased the activity of the neuronal K+ channel Kv1.3. As activation of K+ channels modifies excitation of neuronal cells, SGK1 may participate in the regulation of neuronal excitability.

Animals↗
PubMed2001

Human focal cerebral infarctions induce differential lesional interleukin-16 (IL-16) expression confined to infiltrating granulocytes, CD8+ T-lymphocytes and activated microglia/macrophages.

Focal cerebral ischemia elicits a strong inflammatory response which readily participates in lipid oxygenation, edema formation, apoptotic cell death and tissue remodeling. Within these conditions, cytokines are key players of cell activation and are crucial for delayed mechanisms of ischemic damage. Mature IL-16 is an immunomodulatory cytokine, exerting CD4 dependent and independent effects and is characterized by chemotactic activity, induction of early gene phosphorylation, stimulation of pro-inflammatory IL-1beta, IL-6, TNFalpha expression in monocytic cells and also modulates apoptosis. We have now analyzed expression of IL-16 in 20 brains of patients following focal cerebral infarctions (FCI, n=20). Compared to normal control brains (n=3), IL-16 was expressed by infiltrating immune cells such as neutrophils, CD8+ lymphocytes and activated CD68+ microglia/macrophages accumulating in lesion associated reactive zones and in peri-vascular regions. IL-16+ cells accumulated significantly (P<0.0001) in the necrotic lesion and at bordering peri-lesional areas at day 1-2 reaching maximum levels at day 3-4 (P<0.0001). Also, peri-vascular IL-16+ cells reached maximum levels at day 3-4 (P<0.0001) following infarction and decreased after several weeks. During the early microglial activation period, IL-16+ microglia/macrophages coexpress the activation antigen MRP-8. The accumulation of IL-16+ granulocytes, IL-16+, CD8+ lymphocytes and activated IL-16+, CD68+, CD4- microglia/macrophages, early after infarction suggest a CD4 independent, paracrine role of IL-16 in the postinjury inflammatory response, such as recruitment and activation of immune cells leading to microvessel clustering and blood-brain barrier disturbance resulting in secondary damage.

Aged↗
PubMed2001

Localization of endostatin in rat and human gliomas.

BACKGROUND: Endostatin is a potent inhibitor of endothelial cell proliferation, angiogenesis, and tumor growth. Its occurrence and localization has not yet been examined in human brain tumors. The authors report the production of a monoclonal antibody and detection of endostatin in rat and human gliomas by immunohistochemistry. METHODS: The authors analyzed localization and tissue distribution of endostatin in 41 paraffin embedded glioma samples (18 glioblastoma multiforme, 7 WHO Grade III astrocytomas, 13 fibrillary, and 3 protoplasmic WHO Grade II astrocytomas) of human origin and 21 rat C6 gliomas by immunohistochemistry. Double labeling experiments confirmed the origin of endostatin-labeled cells. RESULTS: Endostatin immunoreactivity was detected in tumor cells, endothelial cells, macrophages, and lymphocytes of both rat and human gliomas. The percentage of cells labeled with the endostatin antibody was significantly lower (P = 0.0126) in the tumor parenchyma of human glioblastomas than in WHO Grade II astrocytomas. CONCLUSIONS: Endostatin was present in various cell types in rat and human gliomas in vivo. Lower levels in glioblastomas than in WHO Grade II astrocytomas might have reflected the shift of a probable regulatory balance between promoters and inhibitors of angiogenesis towards facilitation of neovascularization.

Adult↗
PubMed2001

Preirradiation gemcitabine chemotherapy for newly diagnosed glioblastoma. A phase II study.

BACKGROUND: The median survival for patients with glioblastoma is reported to be 12 months. To improve the outcome for glioblastoma patients, the authors evaluated the therapeutic efficacy of preirradiation gemcitabine chemotherapy followed by standard radiotherapy. METHODS: Twenty-one patients with newly diagnosed glioblastoma were enrolled in a prospective unicenter trial of preirradiation gemcitabine chemotherapy. Chemotherapy included up to 4 monthly cycles of intravenous gemcitabine (Day 1, Day 8, and Day 15; 1000 mg/m2). Involved field radiotherapy was given after chemotherapy or earlier in the case of disease progression or gemcitabine intolerance. RESULTS: With gemcitabine chemotherapy alone, there was a median progression free survival of 11 weeks and a progression free survival rate at 4 months of 24%. In 18 of 21 patients who subsequently received a full course of radiotherapy, the median progression free survival from the time of diagnosis was 8 months and the progression free survival rate at 12 months was 17% (3 of 18 patients). The median overall survival was 11 months. There was no specific treatment-related neurotoxicity reported. Neither age nor extent of residual postoperative tumor predicted the duration of progression free survival in patients treated with gemcitabine chemotherapy alone or in those treated with gemcitabine plus radiotherapy. CONCLUSIONS: Gemcitabine followed by radiotherapy is a safe regimen for patients with newly diagnosed glioblastoma but the gemcitabine schedule used in the current study did not appear to confer any survival advantage compared with standard involved field radiotherapy alone.

Adult↗
PubMed2001

Heme oxygenase-1 in lesions of human cerebral malaria.

Human cerebral malaria is a life threatening complication of Plasmodium falciparum infection. The cascades of signaling events resulting in tissue trauma, lesion formation, coma or resolution of lesions are only slowly becoming unraveled. Understanding the generation of local tissue protective cellular reactions might pave the way for generation of novel drugs limiting the formation of cerebral malaria lesions. Heme oxygenase-1 (HO-1) is an inducible enzyme degrading heme into the gaseous mediator carbon monoxide (CO) and biliverdin, a local antioxidant. Expression of HO-1 is considered a protective reaction against inflammatory and other insults to the brain. We have localized HO-1 to Durck's granulomas, typical lesions of advanced cerebral malaria. Here, activated monocytic cells and ramified microglia in direct vicinity to the lesions express HO-1. The striking association of HO-1 expression with areas of bleedings suggests that released hemoglobin and heme-- known inducers of HO-1--are mainly responsible for induction of monocytic HO-1 expression. HO-1 is expressed rather late to play a protective role in lesion formation and appears to have only a major role in Durck's granulomas. Further, generation of the gaseous mediator CO might contribute to the neurological derangements of advanced cerebral malaria.

Antigens, CD↗
PubMed2001

Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude.

Although microglia are considered to be a sensitive sensor for pathological processes in the central nervous system, there are only a few studies about the distribution and density of microglia in the normal human brain. Therefore, a study of local density of microglial cells was conducted by investigating 20 normal human brains with no clinical neurological symptoms or diseases and no neuropathological alterations. Microglial cells were visualized by immunolabeling of proteins which are known to be expressed either constitutively or facultatively, such as CD68, major histocompatibility complex class II (MHC-II), leukocyte common antigen (LCA), leukocyte chemotactic factor (LCF), macrophage inhibitory factor-related protein (MRP) 8, MRP14, CD4 and allograft-inflammatory factor-1 (AIF-1). CD68, MHC-II and AIF-1 showed the highest densities with significant regional differences ranging from 0.5% to 16.6% of all cells in the brain parenchyma with significantly more microglia in white than in gray matter. LCF and LCA showed a similar pattern of distribution as the proteins described above, but with lower percentages of microglial cells. CD4 was not found in the brain parenchyma. We conclude that CD68, MHC-II and AIF-1 define the main microglial cell population, whereas LCF and LCA are expressed by a subpopulation of microglial cells. The brains showed no or a negligible vascular expression of MRP8 and MRP14. Information about the local microglia density in the normal human brain can serve as a reference for the evaluation of pathological microglial responses.

Adult↗
PubMed2001

Differential activation of microglial cells in local and remote areas of IRBP1169-1191-induced rat uveitis.

Using a Lewis rat model of interphotoreceptor retinoid binding protein (IRBP)-induced experimental autoimmune uveitis (EAU) we examined cellular reactions in the optic pathway (retina, choroid, optic nerve, optic tract, colliculus superior, and visual cortex). Two to six animals were studied at days 0, 7, 9, 11, 12, 13, 14, 18 and 22 after immunization by immunohistochemistry with monoclonal antibodies against ED , ED2, OX6, OX22, EMAP II, AIF-1 and W3/13. In the retina, choroid and distal optic nerve increased immunoreactivity to ED1, OX6, OX22, EMAP II, AIF-1 and W3/13 was initially observed at day 9, peaked at days 13-14 and diminished rapidly from day 18 onwards. No changes were seen in the density of ED2-positive resident macrophages. In the optic tract, ED1 and OX6 expression was induced in microglial cells beginning with day 11 and persisted until day 22. AIF-1, EMAP II and ED2 expression was not visibly up-regulated and no lymphocytic infiltrates (OX22-, W3/13-positive cells) were observed. In the central projection fields, no cellular reaction could be found. Thus, cellular response in IRBP-induced rat uveoretinitis is not restricted to the eye. Microglial activation is also seen in the distal optic nerve and optic tract. This remote microglial activation, however, differs in intensity, time course and expression of activation markers, thus indicating different activation cascades. The mild remote microglial activation is probably due to neuronal-microglial interactions resulting from neuronal damage in the retinal ganglion cell layer and nerve fiber layer with consecutive axonal degeneration and not from an inflammatory reaction as seen in the eye.

Animals↗