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Werner Paulus

Publications and source records attributed to Werner Paulus.

At least 19 recordsLinked to original sources
PubMed2006

Time-resolved in situ studies of oxygen intercalation into SrCoO2.5, performed by neutron diffraction and X-ray absorption spectroscopy.

Electrochemical oxidation of the antiferromagnetically ordered SrCoO(2.5), with brownmillerite-type structure, to the cubic ferromagnet SrCoO(3), with perovskite structure, has been investigated in situ by neutron diffraction as well as by X-ray absorption fine structure (XAFS) spectroscopy in specially designed electrochemical cells. The neutron diffraction experiments were performed twice, using two different wavelengths (lambda = 1.2921(2) and 4.74 A) in order to better discriminate structural and magnetic changes as functions of the charge transfer. From the neutron diffraction experiments, two intermediate phases, SrCoO(2.75) and SrCoO(2.82)(+/-)(0.07), were characterized. No superstructure reflections were observed for the corresponding SrCoO(2.75) phase. Instead we observed here, for the first time, 3D oxygen ordering during an oxygen intercalation reaction, as established for SrCoO(2.82)(+/-)(0.07), which can be described as a tetragonal unit cell, related to the perovskite cell by a approximately 2(a radical2) and c approximately 2a. The structure of this intermediate phase confirms the strongly topotactic character of the oxygen intercalation reaction. We were also able to prove, from in situ XAFS spectroscopy at the Co absorption edge, that the evolution of the Co valence state from formally +3 for SrCoO(2.5) to +4 for the final reaction product (SrCoO(3.0)) does not proceed continuously but gives evidence for the formation of O(-) species for stoichiometries corresponding to SrCoO(2.82)(+/-)(0.07). The use of neutrons (vs X-rays) in the diffraction experiments and the choice of the transmission (vs fluorescence) mode in the XAFS experiment guarantee that the obtained data well represent bulk and not just surface properties.

Journal Article↗
PubMed2006

Contributions to the application of the transferability principle and the multipolar modeling of H atoms: electron-density study of L-histidinium dihydrogen orthophosphate orthophosphoric acid. I.

The electron density of L-histidinium dihydrogen orthophosphate orthophosphoric acid has been determined from X-ray and neutron diffraction data at low temperature (120 K). Topological analysis of the electron density has been used to analyse the effect of the multipolar refinement strategy on the electron-density model in the hydrogen-bonding regions. The electron density at low temperature has also been used to acquire high-quality experimental thermal parameters at room temperature using the transferability principle. Molecular vibrations, TLS and normal mode analysis are discussed and studied at both temperatures.

Journal Article↗
PubMed2006

Cellular and reticular variants of hemangioblastoma differ in their cytogenetic profiles.

Capillary hemangioblastomas of the central nervous system are benign tumors and occur either sporadically or as a manifestation of von Hippel-Lindau disease. A rarer cellular and a more common reticular variant can be distinguished on the basis of the abundance of the stromal cell component, with the cellular variant being significantly associated with a greater probability of recurrence. To investigate whether these subtypes differ in their cytogenetic profile, a comparative genomic hybridization analysis of 10 cellular and 10 reticular hemangioblastomas was undertaken. Comparative genomic hybridization revealed DNA copy number changes in 14 of 20 cases (8 of 10 cellular and 6 of 10 reticular hemangioblastomas). The most common changes overall were losses of chromosomes 19 (35%), 6 (30%), and 22q (15%), whereas loss of 3 and gain of 4 were encountered in one case each (5%). The cellular variant showed losses of chromosomes 6 (60%), 22q and 19 (20% each), as well as gain of 4 (10%), whereas the reticular variant presented with losses of chromosomes 19 (50%), 22q and 3 (10% each). Loss of chromosome 6 was significantly associated with the cellular subtype (P < .005), whereas loss of 19/19p was found more frequently in the reticular variant, albeit not significantly (P = .16). In conclusion, our data may point toward different genetic pathways in the pathogenesis of the 2 histologic subtypes of capillary hemangioblastoma.

Adolescent↗
PubMed2006

Nitric oxide synthase is up-regulated in muscle fibers in muscular dystrophy.

Nitric oxide (NO) mediates fundamental physiological actions on skeletal muscle. The neuronal NO synthase isoform (NOS1) was reported to be located exclusively in the sarcolemma. Its loss from the sarcolemma was associated with development of Duchenne muscular dystrophy (DMD). However, new studies evidence that all three NOS isoforms-NOS1, NOS2, and NOS3-are co-expressed in the sarcoplasm both in normal and in DMD skeletal muscles. To address this controversy, we assayed NOS expression in DMD myofibers in situ cytophotometrically and found NOS expression in DMD myofibers up-regulated. These results support the hypothesis that NO deficiency with consequent muscle degeneration in DMD results from NO scavenging by superoxides rather than from reduced NOS expression.

Biopsy↗
PubMed2006

Chromosomal imbalances in clear cell ependymomas.

Clear cell ependymoma is a rare and diagnostically challenging subtype of ependymoma, whose genetic features are essentially unknown. We studied 13 clear cell ependymomas (five cases WHO grade II, eight cases WHO grade III) by comparative genomic hybridization (CGH). Chromosomal imbalances were found in 12/13 cases. The most common aberrations overall were +1q (38%), -9 (77%), -3 (31%), and -22q (23%). Clear cell ependymomas of WHO grade II were characterized by -9 (40%), whereas WHO grade III cases mainly showed +1q (63%), and +13q (25%), as well as -9 (100%), -3 (38%), and -22q (25%). In contrast to other ependymal tumors, clear cell ependymomas of WHO grade II showed fewer imbalances than WHO grade III samples (1.4 vs 3.5 per case). Although some of the implicated chromosomes have previously been shown to be involved in other ependymoma variants, the striking frequency of +1q, -9, and -3 suggests that aberrations differ between clear cell and other types of ependymomas, in particular, for loss of chromosome 9 which can be regarded as the molecular hallmark of clear cell ependymomas.

Adolescent↗
PubMed2006

Astrocytic gene expression profiling upon hypoxia.

Astrocytes play a pivotal role in supporting neuronal survival. In order to better understand the contribution of astrocytes towards adaptive mechanisms, gene expression profiles were analyzed after exposure of primary rat astrocyte cultures to normoxic or hypoxic (<3% O2) conditions using high-density oligonucleotide microarrays and quantitative reverse transcriptase polymerase chain reaction. Twenty-five genes were more than 1.5 fold upregulated, whereas 12 genes were more than 1.5-fold downregulated upon hypoxia (P<0.05). Upregulation of established hypoxia-inducible factor 1 target genes as well as novel transcripts related to energy metabolism, astrocyte survival and differentiation, and lipoprotein binding was confirmed by quantitative reverse transcriptase polymerase chain reaction. Further analysis of these genes might provide a better understanding of astrocyte function upon hypoxic conditions.

Animals↗
PubMed2006

Prognosis and histopathologic features in papillary tumors of the pineal region: a retrospective multicenter study of 31 cases.

Papillary tumor of the pineal region (PTPR) is a recently described tumor entity thought to arise from the specialized ependyma of the subcommissural organ. Whereas histologic features of PTPR are well defined, data on the prognostic value of PTPR remain scarce. We therefore investigated clinicopathologic features, including data on progression-free survival and overall survival, in a retrospective series of 31 PTPR. The age of the 14 males and 17 females ranged from 5 to 66 years (median age, 29 years). Histologically, all tumors were characterized by an epithelial-like growth pattern in which the vessels were covered by layers of columnar or cuboidal tumor cells forming perivascular pseudorosettes. Most of the tumor cells showed strong expression of neuron-specific enolase, cytokeratins (particularly CK18), S-100 protein, and vimentin. Most PTPRs examined also expressed microtubule-associated protein-2. Expression of synaptophysin, epithelial membrane antigen, transthyretin, neural cell adhesion molecule, and nestin was encountered in some tumors. Gross total resection could be achieved in 21 of 31 cases; 15 patients received radiotherapy on resection of the primary tumor. Nevertheless, the majority of patients experienced recurrences; 5-year estimates for overall survival and progression-free survival were 73% and 27%, respectively. To conclude, the clinical course of PTPR is characterized by frequent local recurrence, and the value of radiotherapy on disease progression will need to be investigated in future prospective trials.

Adolescent↗
PubMed2006

Prognostic implications of atypical histologic features in choroid plexus papilloma.

The prognostic significance of atypical histologic features in choroid plexus tumors remains uncertain. Therefore, a series of 164 choroid plexus tumors was evaluated for the presence of atypical histologic features, including mitotic activity, increased cellularity, nuclear pleomorphism, blurring of papillary growth pattern, and necrosis. The impact of histopathologic and clinical features on the probability of recurrence and survival was investigated. Twenty-four tumors displaying frank signs of malignancy were diagnosed as choroid plexus carcinoma according to World Health Organization criteria. Of 124 choroid plexus papillomas that had not received adjuvant treatment, 46 tumors (37%) displayed at least one atypical feature, including increased cellularity (n = 25 [20%]), mitotic activity (> or =2 mitoses per 10 high-power fields; n = 19 [15%]), nuclear pleomorphism (n = 16 [13%]), solid growth (n = 15 [12%]), and necrosis (n = 5 [4%]). Only one tumor-related death, but 10 recurrences, were observed on a mean observation time of 58 months. On univariate analysis, incomplete surgical resection (p = 0.03) and mitotic activity (p < 0.001) were the only clinicopathologic factors associated with recurrence. Using a multivariate model, an independent effect of mitotic activity on the probability of recurrence could be confirmed (p = 0.001). Because mitotic activity is the sole atypical histologic feature independently associated with recurrence, we propose to define atypical choroid plexus papilloma by mitotic activity (> or =2 mitoses per 10 high-power fields) corresponding to World Health Organization grade II, thus adjoining other intermediate tumor entities associated with increased mitotic activity such as atypical meningioma. Close follow up of patients harboring atypical choroid plexus papillomas may be warranted.

Adult↗
PubMed2006

Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach.

To identify specific markers for the diagnosis of choroid plexus tumors, gene expression profiles of choroid plexus epithelial cells (n = 8) and ependymal cells (n = 6) microdissected from human autopsy brains as well as choroid plexus papilloma tissue were investigated using DNA microarrays. Protein expression of genes overexpressed in choroid plexus was evaluated in normal choroid plexus, choroid plexus papilloma, choroid plexus carcinoma, other primary brain tumors, and cerebral metastases. Forty-six genes found to be overexpressed in normal choroid plexus epithelial cells were also present in choroid plexus papilloma. Among those, 11 were further analyzed by immunohistochemistry. Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases. Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases. Transthyretin stained choroid plexus (33 of 35), choroid plexus papilloma (14 of 18), and plexus carcinoma (2 of 5), but its specificity was significantly lower. Antibodies directed against coagulation factor V, glutathione peroxidase 3, pigment epithelium derived factor, serotonin receptor 5-HTR2C, lumican, fibulin-1, plastin-1, and cytokeratin 18 revealed varying degrees of specificity and sensitivity. Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors.

Adult↗
PubMed2006

NF2 mutations in secretory and other rare variants of meningiomas.

The WHO classification defines different histological variants of meningiomas. Mutations of the tumor suppressor gene NF2 on 22q have been described in 30% to 60 % of sporadic meningiomas. However, the vast majority of the meningiomas that have been subject to NF2 analysis belong to the most frequent variants like transitional, fibroblastic and meningothelial meningiomas. Within these subtypes, transitional and fibroblastic meningiomas harbor significantly more NF2 mutations than meningothelial meningiomas, indicating molecular subsets of these tumors. To determine whether rare meningioma variants carry NF2 mutations we analyzed 80 tumors. NF2 mutations were detected in 5 (36%) of 14 psammomatous, 1 (11%) of 9 angiomatous, 2 (22%) of 9 clear cell, 1 (33%) of 3 chordoid and 1 (100%) of 1 papillary meningioma. In the single papillary meningioma, 2 different NF2 mutations were observed. No NF2 mutations were found in 33 secretory, 7 microcystic, 2 lymphoplasmacyte-rich, one rhabdoid and one metaplastic meningioma. In the control group of 25 fibroblastic meningiomas, 11 cases were identified to carry an NF2 mutation. These results support the concept of different molecular subgroups of meningiomas which overlap with histological variants.

Adult↗
PubMed2006

Tissue expression of the nuclear progesterone receptor in male non-human primates and men.

In females, progesterone is associated with reproductive functions. In males, its role and the expression of its genomic receptor are not very well understood. In attempts to achieve a hormonal male contraceptive method, gestagens are used to downregulate gonadotropin and sperm production. It is therefore essential to understand the mechanism of action of progesterone at the molecular level in males, especially in primates. This investigation was undertaken: (a) to determine whether the genomic progesterone receptor is expressed in males; and (b) to locate it in various organs that are potential targets of gestagens. Human tissues were obtained at surgery for benign prostatic hyperplasia or prostate cancer and at autopsy. Non-human primate tissues were obtained at autopsy. This study was performed by analyzing the genomic progesterone receptor by immunohistochemistry, Western blot and RT-PCR. The nuclear progesterone receptor was expressed in pituitary and hypothalamus of both monkeys and men. In the testis progesterone receptor expression was found in a few peritubular and interstitial cells, but not in germ cells. In addition, expression was detected in the epididymis, prostate and male mammary gland. Reverse transcriptase (RT)-PCR experiments indicated that progesterone receptor A and B are expressed in all tissues analyzed. These data exclude direct genomic effects of gestagens at the spermatogenic level but indicate that a male contraceptive based on gestagens might have some effects on other tissues, such as the epididymis, prostate and mammary gland.

Animals↗
PubMed2006

Reduction of amyloid angiopathy and Abeta plaque burden after enriched housing in TgCRND8 mice: involvement of multiple pathways.

Diversity and intensity of intellectual and physical activities seem to have an inverse relationship with the extent of cognitive decline in Alzheimer's disease (AD). To study the interaction between an active lifestyle and AD pathology, female TgCRND8 mice carrying human APPswe+ind were transferred into enriched housing. Four months of continuous and diversified environmental stimulation resulted in a significant reduction of beta-amyloid (Abeta) plaques and in a lower extent of amyloid angiopathy. Neither human amyloid precursor protein (APP) mRNA/protein levels nor the level of carboxy-terminal fragments of APP nor soluble Abeta content differed between both groups, making alterations in APP expression or processing unlikely as a cause of reduced Abeta deposition. Moreover, DNA microarray analysis revealed simultaneous down-regulation of proinflammatory genes as well as up-regulation of molecules involved in anti-inflammatory processes, proteasomal degradation, and cholesterol binding, possibly explaining reduced Abeta burden by lower aggregation and enhanced clearance of Abeta. Additionally, immunoblotting against F4/80 antigen and morphometric analysis of microglia (Mac-3) revealed significantly elevated microgliosis in the enriched brains, which suggests increased amyloid phagocytosis. In summary, this study demonstrates that the environment interacts with AD pathology at dif-ferent levels.

Amyloid beta-Protein Precursor↗
PubMed2006

Frequency of unexpected and important histopathological findings in routine intervertebral disc surgery.

OBJECT: The value of routine histopathological examination of intervertebral disc tissue has been questioned, but sufficient numbers of studies have yet to be conducted to provide a definitive sense of its importance. The aim of this study was to investigate the nature and frequency of unexpected histopathological findings in intervertebral disc surgery. METHODS: The authors conducted a retrospective examination of consecutive surgical specimens obtained in patients with benign indication for discectomy at four neurosurgical centers. Surgical specimens obtained during 2102 operations (2177 intervertebral discs) in 2017 patients were evaluated. In addition to one case of cavernous malformation, two specimens (obtained in 0.1% of patients) revealed unexpected pathological diagnoses of malignancy (metastasized prostate carcinoma and diffuse large B-cell lymphoma). CONCLUSIONS: The results of this retrospective study suggest that routine histopathological examination of specimens obtained during intervertebral disc procedures is both justified and cost effective.

Adult↗
PubMed2005

Epileptiform activity preferentially arises outside tumor invasion zone in glioma xenotransplants.

Seizures occur commonly with brain tumors. The underlying mechanisms are not understood. We analyzed network and cellular excitability changes in tumor-invaded and sham neocortical tissue in vitro using a rat glioblastoma model. Rat C6 glioma cells were transplanted into rat neocortex, yielding diffusely invading gliomas resembling human glioblastomas. We hypothesized that network excitability would increase in regions neighboring the tumor, and that initiation of epileptic discharges might be correlated to a higher density of intrinsically bursting neurones. Voltage-sensitive dye imaging revealed epileptic activity to be initiated in paratumoral zones (1-2 mm from main tumor mass), in contrast to control tissue, where epileptic foci appeared randomly throughout the neocortex. Neuronal firing patterns revealed significantly more intrinsically bursting neurones within these initiation zones than in regions directly adjacent to the tumor or in control tissue. We conclude that gliomas are associated with a higher density of intrinsically bursting neurones, and that these may preferentially initiate epileptiform events.

Action Potentials↗
PubMed2005

Activity changes and marked stereotypic behavior precede Abeta pathology in TgCRND8 Alzheimer mice.

Alzheimer's disease (AD) is not only characterized by cognitive decline and neuropathological changes, but also by non-cognitive behavioral symptoms like restlessness, sleep disturbance, and wandering. These symptoms are categorized in the "Behavioral and Psychological Symptoms of Dementia" (BPSD). We investigated transgenic and wildtype mice of an APP transgenic mouse model of AD (TgCRND8) with respect to 24 h activity and spontaneous home cage behavior at 30, 60, 90 and 120 days of age. At all test days, transgenic and wildtype animals differed significantly with respect to activity patterns. In addition, activity rhythms changed distinctly in transgenic mice with increasing age. Transgenic mice also clearly showed more stereotypic behavior, which correlated significantly at 90 and 120 days of age with elevated corticosterone metabolite concentrations in fecal samples. Activity patterns in TgCRND8 mice resemble altered rhythms of activity in AD patients. Stereotypic behaviors may be caused by the same mechanisms as non-cognitive behavioral symptoms of AD. Thus, it is likely that analogies to BPSD that precede Abeta pathology are found in APP-overexpressing TgCRND8 mice.

Adrenal Medulla↗
PubMed2005

Prognosis-related histomorphological and immunohistochemical markers in central nervous system tumors of childhood and adolescence.

Brain tumors account for approximately 20% of all childhood cancers, and are the leading cause of cancer morbidity and mortality among children. Although numerous demographic, clinical and therapeutic parameters have been identified over the past few years that have significant prognostic bearing for some pediatric brain tumors, predicting the clinical course and outcome among children with central nervous system tumors is still difficult. A survey of publications on prognosis-related histopathological and immunohistochemical features among pediatric brain tumors revealed 172 series, of which 91 presented statistically significant outcome-associated parameters as defined by a P value of less than 0.05. Most investigations revealing significant prognosis-related markers were performed on medulloblastomas (30 publications), ependymomas (25) and astrocytic tumors (18). In total, 16 cohorts consisted of more than 100 cases (5 on ependymomas, 3 each on medulloblastomas and astrocytic tumors). On the other hand, there were also 13 series with fewer than 20 cases (5 on medulloblastomas). Potentially prognostic histopathological markers vary among different entities and consist of assessment of necroses, mitoses, differentiation, vascular proliferation, and growth pattern, whereas immunohistochemical features include proliferation markers (Ki-67, MIB-1), expression of oncogenes/tumor suppressor genes and their proteins (TP53, c-erbB2), growth factor and hormonal receptors (VEGF, EGFR, HER2, HER4, ErbB-2), cell cycle genes (p27, p14ARF) and cell adhesion molecules, as well as factors potentially related to therapeutic resistance (DNA topoisomerase IIalpha, metallothionein, P-glycoprotein, tenascin). This review discusses the prognostic potential of histopathological and immunohistochemical markers that can be investigated by the practicing neuropathologist as part of the routine diagnostic workload, and scrutinizes their benefit for predicting therapy response and patient outcome among children with brain tumors.

Adolescent↗
PubMed2005

Functional measurement of local proteolytic activity in living cells of invasive and non-invasive tumors.

Proteolytic cleavage of extracellular matrix (ECM) and disruption of tissue architecture are fundamental features of tumor cell invasion. The proteolytic activity is focused in close proximity to the tumor cells. Here, we describe the possibility to quantify local proteolytic activity in the microenvironment of larger cell populations by the electrical resistance breakdown assay. The assay utilizes the transepithelial electrical resistance (TEER) of an epithelial monolayer as a sensitive indicator of monolayer integrity and permeability. Local destruction of ECM by single tumor cells was demonstrated by a second assay, based on a fluorescent matrix coating on cover slides. Local digestion of the matrix results in a reduction of fluorescence. Primary cells derived from high and low grade brain tumors as well as established cell lines of malignant gliomas and non-neural tumors of different origin (melanoma, cervical carcinoma, and breast carcinoma) were compared. Differences in proteolytic activity between tumor entities were demonstrated in both assays. Primary cells of high grade gliomas and cell lines showed TEER breakdown and local matrix destruction, while low grade brain tumors lacked matrix disintegration and disruption of cell monolayers. Taken together, both assays are capable of demonstrating local proteolytic activity and thus are versatile tools for distinguishing high and low invasive tumor cells with a potential application as diagnostic and prognostic markers in clinical investigations. The advantage of the matrix digestion assay is the requirement of only very low tumor cell numbers, whereas measurement of TEER enables precise quantification of local proteolytic processes in large and even heterogeneous tumor cultures.

Animals↗