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Biomedical subjects

W Feiden

Publications and source records attributed to W Feiden.

At least 19 recordsLinked to original sources
PubMed2006

How a neuropsychiatric brain bank should be run: a consensus paper of Brainnet Europe II.

The development of new molecular and neurobiological methods, computer-assisted quantification techniques and neurobiological investigation methods which can be applied to the human brain, all have evoked an increased demand for post-mortem tissue in research. Psychiatric disorders are considered to be of neurobiological origin. Thus far, however, the etiology and pathophysiology of schizophrenia, depression and dementias are not well understood at the cellular and molecular level. The following will outline the consensus of the working group for neuropsychiatric brain banking organized in the Brainnet Europe II, on ethical guidelines for brain banking, clinical diagnostic criteria, the minimal clinical data set of retrospectively analyzed cases as well as neuropathological standard investigations to perform stageing for neurodegenerative disorders in brain tissue. We will list regions of interest for assessments in psychiatric disorder, propose a dissection scheme and describe preservation and storage conditions of tissue. These guidelines may be of value for future implementations of additional neuropsychiatric brain banks world-wide.

Brain↗
PubMed2006

[Histopathology of space-occupying lesions of the spine].

The first step in diagnosing spinal lesions is to define the anatomical location, especially via magnetic resonance tomography, which is also helpful for histopathologists. However, definite diagnosis is based on histologic and cytologic examinations especially in the case of fine-needle biopsies. In this short review the principal histopathologic diagnoses of primary and secondary tumors and tumor-like lesions of the spine itself, the epidural space, the spinal meninges and nerve roots, and the spinal cord are addressed. The significance of immunohistochemistry for differential diagnosis or, in cases of spinal metastasis, for determination of the primary is discussed.

Biopsy, Fine-Needle↗
PubMed2005

The value of micro-Doppler in stereotactic brain biopsy.

OBJECTIVE: The aim of this study was to analyse the value of intraoperative micro-Doppler in stereotactic brain biopsy (SBB). So far, only a few studies have reported about the usefulness of micro-Doppler in stereotactic brain biopsy. METHODS: Between 1998 and 2003, 155 SBBs were performed in 153 patients with micro-Doppler (81 males, 72 females, mean age: 59 years). All operations were performed using a ZD-frame and a multiplanar computer tomography-guided trajectory planning system (Leibinger SPP). A 16 MHz micro-Doppler probe (diameter 1 mm, DWL) was used in all cases to explore the area of biopsy before the tissue probes were taken. Serial biopsies (mean, 6 samples) were taken with the Sedan side-cutting cannula (n = 145) or the small forceps (n = 10). We evaluated the number of intraoperative detectable vessel signals by micro-Doppler, intraoperative bleedings as well as bleedings detected by postoperative CT (which was performed in all cases). We compared our results according to bleeding-related complications with the data of stereotactic biopsy series from the recent literature. RESULTS: A conclusive histopathological diagnosis was achieved in 150/153 patients (98 %). A re-biopsy had to be undertaken in 2 cases. In 98 biopsies (63 %), no vessel could be detected with the micro-Doppler. In the remainder, a signal of arterial vessels was detected in 22 (14 %) and a signal of venous vessels in 35 cases (23 %). Detection of a vessel in the micro-Doppler led to a change of the biopsy site in each case within the same trajectory. Biopsy-related bleedings were detected in 4 cases (2.6 %). Among these, the only bleeding which occurred without any signs of vessels in the micro-Doppler happened in a case of a melanoma. The overall biopsy-related permanent morbidity was 0.6 % (n = 1). The biopsy-related mortality was 0. CONCLUSIONS: Despite the overall high security of SBB, the use of intraoperative micro-Doppler may lead to an additional reduction of the risk for a biopsy-related bleeding without enormous expense.

Biopsy↗
PubMed2003

Paragangliomas of the parasellar region.

Parasellar paragangliomas are rare tumors. As far as we know, only ten cases are described in the literature. Their clinical, pathological, and radiological features and possible origin are discussed in this article and a review of the literature is given. Additionally, we report a new case of a 51-year-old woman with paraganglioma growing in the anterior, middle, and posterior cranial fossa with extended destruction of the skull base. The patient had been suffering from long-standing headaches and facial nerve paresis. Preoperatively, this tumor was suspected to be a meningioma.

Female↗
PubMed2003

Monostotic lumbar manifestation of fibrous dysplasia--a rare entity.

Monostotic manifestation of fibrous dysplasia in the spine is exceedingly rare. We report the case of a 30 year-old woman suffering from slowly increasing low back pain. Radiologically a polycyclic, slightly gadolinium-enhancing, solitary lesion within the first lumbar vertebral body was detected. The lesion was removed and stabilized with bone marrow transplant. We describe the radiological and histopathological findings.

Adult↗
PubMed2003

March 2003: a 41 -year-old female with a solitary lesion in the liver.

The March COM. A 41-year-old woman presented in 1997 with diffuse abdominal pain, meteorism and intermittent diarrhea. Imaging studies revealed a focal rounded lesion in the liver. Although there was no history of progesterone or estrogen therapy, the radiographic appearance was considered to be suggestive of adenoma. The lesion was monitored by ultrasound until October 2000 when a resection was performed because of the presumed risk of a malignant transformation. H&E stained sections revealed an ectopic ependymoma that was strongly positive for GFAP. The surrounding hepatic tissue was negative for GFAP. An extensive search for a CNS manifestation or any other extraspinal localization was unrevealing. We believe we have encountered the first case of an ectopic ependymoma presenting as a solitary hepatic lesion in the absence of CNS disease. Ependymomas generally arise in the CNS in relation to the ventricular system. Extraneural metastasis from ependymomas may occasionally occur even years after detection and treatment of the primary lesion and have been the subject of several reports. In contrast, there are only anecdotal reports of primary extraneural "ectopic" ependymomas. So far those rare cases have only been found in close vicinity to the neural axis, eg, in the sacrococcygeal region, the posterior mediastinum or the ovaries and are there thought to originate from embryonic remnant cells around the neural tube. Distant metastases of ependymomas invading or arising within the extraneural lumbosacral soft tissue may occur in this situation. Here, we report what appears to be the first case of a primary ectopic ependymoma originating in the liver, with no signs of CNS or other systemic involvement.

Abdominal Pain↗
PubMed2002

[Human prion diseases].

Prion diseases are rare neurodegenerative transmissible fatal diseases affecting humans and mammals. The causative agent is a novel pathogen termed the prion. Unlike classical infectious agents such as bacteria or viruses, prions lack an independent genome and consist largely of an abnormal form of the host-encoded prion protein. Creutzfeldt-Jakob disease (CJD) is the main representative of human prion diseases that may be sporadic in most cases, hereditary, or acquired. Clinical examination yields only a suspected diagnosis with formal criteria for probable or possible. Definite diagnosis relies on autopsy and neuropathology findings. This is also true for the new variant CJD (vCJD), a previously unknown prion disease of humans that is connected with the same strain of prions as found in bovine spongiform encephalopathy (BSE). The autopsy and handling of laboratory material for histopathological examination requires specific precautionary measures and decontamination. For definite histopathological diagnosis of a human prion disease, immunohistochemical detection of the prion protein deposits is the gold standard. Furthermore, molecular and genetic investigations are necessary for classification because a close correlation could be established between distinct CJD phenotypes, codon 129 genotypes of the prion protein gene, and the prion protein type.

Animals↗
PubMed2002

[Primary CNS lymphomas. Morphology and diagnosis].

Diagnostically primary central nervous system lymphomas (PCNSL) have to be differentiated from glioblastoma and brain metastases. Histologically the overwhelming majority of PCNSL is represented by diffuse large B-cell lymphomas, in this series with a BCL6 expression in 80% of the cases detected by immunohistochemistry. Stereotactic biopsy is the method of choice in establishing the definite diagnosis and intraoperative smear cytology will detect the lymphoid blasts. To confirm the B-cell lineage, immunohistochemistry is needed (CD20, CD79a). Small reactive T-lymphocytes and monohistiocytic cells and activated "microglia" are found within and at the periphery of PCNSL foci. The infiltrated brain tissue shows partially pleomorphic reactive astrocytes that can be confused with neoplastic astrocytes, especially in small specimens. In contrast to high-grade gliomas, however, PCNSLs do not show endothelial proliferations. Subtypes or variants of diffuse large B-cell lymphomas can also be observed in cases of PCNSL: the anaplastic variant with large multinucleated tumour cells resembling Reed-Sternberg cells, T-cell rich B-cell lymphoma and intravascular B-cell lymphoma with primary manifestation within the brain or the spinal cord. HIV/AIDS-associated PCNSLs are characterised by large plasmoblastic or small Burkitt-like cells and tumour necrosis. Primary leptomeningeal large B-cell lymphomas do occur very rarely and are diagnosed by cerebrospinal fluid cytology.

Central Nervous System Neoplasms↗
PubMed2002

[Diagnostic value of the monoclonal antibody to thyroid transcription factor -1(TTF-1) in CNS metastases. An immunohistochemical study of 65 cases].

Thyroid transcription factor-1 (TTF-1) is used as an immunohistochemical marker for the identification of the lungs or thyroid gland as the site of origin in patients with metastatic disease and unknown primary tumor. In this study the reliability of anti-TTF-1 was assessed in 65 metastases of the central nervous system (CNS), among which there were also small stereotactic biopsies (n = 22) and poorly preserved specimens. Eight out of nine CNS metastases of patients with known adenocarcinoma of the lungs, as well as seven adenocarcinoma metastases of patients with radiologically detected or anamnestically presumed pulmonary carcinoma, expressed TTF-1 immunohistochemically. One CNS metastasis from a follicular thyroid carcinoma was positive and one from an anaplastic thyroid carcinoma was negative. All CNS metastases from patients with known primary tumors outside the lungs or thyroid gland were negative. TTF-1 is a sensitive (up to 90%) and specific (100%) immunohistochemical marker for CNS metastases of adenocarcinomas of the lungs and also functions reliably on small or stereotactic biopsies and poorly preserved samples.

Antibodies, Monoclonal↗
PubMed2002

Initial evaluation of the feasibility of single photon emission tomography with p-[123 I]iodo-L-phenylalanine for routine brain tumour imaging.

p-[123I]iodo-L-phenylalanine (IPA) is a recently described radiopharmaceutical which is highly accumulated in gliomas. The present investigation was designed to evaluate the feasibility of single photon emission tomography (SPET) with IPA to image brain tumours under routine clinical conditions. Using a dual- and a triple-headed SPET camera, whole-body kinetic and brain SPET, as well as plasma, urinary and dosimetric analysis were determined in four patients with gliomas after intravenous injection of IPA. Results obtained by IPA SPET were retrospectively compared with histopathology, magnetic resonance imaging and positron emission tomography with [18F]fluorodeoxyglucose. Tumour lesions were clearly demonstrated by IPA SPET at 30 min, 1h and 4.5h post-injection, even in patients with low grade gliomas. In patients with glioblastoma, excellent visualization of the tumour was possible even at 7h p.i., indicative of the high retention of the radiopharmaceutical in cerebral gliomas. Analysis of the radioactivity in plasma and urine attested to the high in vivo stability of IPA. Blood clearance was rapid (> 65% after 10 min) and IPA was excreted predominantly by the kidneys, the urinary radioactivity excretion ranging from 27% at 1h to 54% of injected doses at 5h p.i. The average effective dose for adults was estimated to be 0.0152mSv*MBq(-1), leading to an effective dose of 3.8mSv in a typical brain SPET investigation with 250 MBq IPA. This result strongly suggests that IPA is a potentially valuable brain tumour imaging agent for widespread clinical studies with SPET. Its high specific tumour uptake and retention even in low grade gliomas represent a major advantage compared to presently available SPET radiopharmaceuticals. Moreover, the radiation dose estimates indicate that clinical use of IPA will result in acceptable radiation dose levels in humans.

Adult↗
PubMed2001

Expression, cellular distribution and protein binding of the glioma amplified sequence (GAS41), a highly conserved putative transcription factor.

The glioma amplified sequence 41 (GAS41) was previously isolated by microdissection mediated cDNA capture from the glioblastoma multiforme cell line TX3868 and shown to be frequently amplified in human gliomas. We determined the complete cDNA sequence of the GAS41 gene, demonstrated that the GAS41 protein is evolutionarily conserved, specifically at the N-terminus, and identified the yeast transcription factor tf2f domain within the GAS41 sequence. A human multiple-tissue Northern blot revealed ubiquitous expression of GAS41 with the highest expression in human brain. After generating polyclonal antibodies we found GAS41 protein expression in the nucleus of the TX3868 cell line by Western blot analysis and immunofluorescence microscopy. The nuclear localization was confirmed for several human tumors including gliomas of different grades of malignancy. In neuroblastoma however, GAS41 was found in the nucleoli but not in the nucleoplasm. Yeast two-hybrid screening of the TX3868 cell line identified the nuclear mitotic apparatus protein (NuMA), the KIAA1009 protein, and prefoldin subunit 1 (PFDN1) as potential interacting partners of GAS41. We generated a polyclonal antibody against the KIAA1009 protein and we demonstrated that the KIAA1009 protein is a nuclear protein, which appears to be co-localized with the GAS41 protein and NuMA.

Amino Acid Sequence↗
PubMed2001

PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme.

Glioblastoma multiforme (GBM), a malignant astrocytic tumour, represents the most frequent tumour of the human brain. Nevertheless, its molecular pathology is not well understood. We utilized the immune system, which contributes to cancer protection, to help identify new GBM-related genes. By screening a human GBM cDNA library with autologous patient serum (SEREX-approach), we isolated a gene termed PHF3 (PHD finger protein 3). The gene product of PHF3 is immunogenic in GBM as tested in an allogenic patient serum screening demonstrating antibodies in 24 of 39 (61.53%) sera, whereas none of the 14 healthy persons had antibodies against PHF3. While previous SEREX studies revealed allogenic antibody responses up to 40%, our results for PHF3 represent the highest reported rate for a specific antibody response. We show that GBM patients with an antibody response against PHF3 show significant better survival than patients without PHF3-specific antibodies. Because the amino acid sequence of PHF3 contains a PHD finger (also termed LAP motif), a TFIIS homology, a proline rich region and nuclear localization signals, it supposedly functions as a transcription factor. A polyclonal antibody generated against PHF3 shows nuclear expression in most investigated formalin-fixed, paraffin embedded tissues. In GBM, PHF3 expression is concentrated in cells surrounding necroses.

Adult↗
PubMed2001

KUB3 amplification and overexpression in human gliomas.

Gene amplification is known to occur frequently in human glioma. Recently we reported cloning of a novel gene termed glioma-amplified sequence 16 (GAS16) by microdissection-mediated cDNA capture. In this article, we demonstrate that GAS16 results from an alternative splicing process of the Ku70 binding protein 3 (KUB3) that is essential for DNA double-strand break repair. The alternative splice product was found in glioblastoma and in normal fetal brain. We determined the amplification frequency of KUB3 in glioma with different grading. We analyzed a total of 102 glioma primary tumors and found KUB3 to be amplified in 12/82 (14%) glioblastomas, 4/13 anaplastic astrocytomas (30%), and 2/4 astrocytomas, but in none of three pilocytic astrocytomas. Northern blot analysis of glioblastoma shows a strong correlation between KUB3 amplification and overexpression. Amplification of KUB3 appears to be independent of other genetic changes frequently associated with the development of gliomas, including EGFR amplification, LOH of TP53, and LOH of chromosome 10. The KUB3 amplification and overexpression may interfere with the function of KUB3 in the DNA-PK complex involved in the maintenance of genome stability and reduction of mutation frequency.

Alternative Splicing↗
PubMed2001

Distribution of epidermal growth factor receptor protein correlates with gain in chromosome 7 revealed by comparative genomic hybridization after microdissection in glioblastoma multiforme.

In a recent study, 23 microdissected areas of 10 glioblastoma multiforme (GBM) were investigated for quantitative genomic aberrations using comparative genomic hybridization (CGH). To validate the chromosomal aberrations, as revealed by CGH after microdissection, parallel tissue sections were stained immunohistochemically with an antibody that detects both wild-type epidermal growth factor receptor (EGFR) and the deletion mutant form of the receptor (EGFRvIII). Immunostaining was correlated with CGH data of chromosome 7, because chromosome 7 is the most frequently aberrant chromosome in GBM (here four of 10 tumors), and this aberration often indicates an abnormality of EGFR. Nine of nine areas that showed gain in or amplification (2 areas) of chromosome 7 with CGH contained EGFR-immunoreactive cells. Only three of 14 areas without abnormality of chromosome 7 in CGH contained EGFR-immunoreactive cells; eleven of 14 areas were immunonegative. Our findings demonstrate a strong correlation between immunohistochemistry of EGFR and the copy numbers of chromosome 7, as revealed by CGH after microdissection in glioblastoma multiforme.

Adult↗
PubMed2001

Frequent mitotic errors in tumor cells of genetically micro-heterogeneous glioblastomas.

Glioblastoma multiforme (GBM) is characterized by intratumoral heterogeneity as to both histomorphology and genetic changes, displaying a wide variety of numerical chromosome aberrations the most common of which are monosomy 10 and trisomy 7. Moreover, GBM in vitro are known to have variable karyotypes within a given tumor cell culture leading to rapid karyotype evolution through a high incidence of secondary numerical chromosome aberrations. The aim of our study was to investigate to what extent this mitotic instability of glioblastoma cells is also present in vivo. We assessed the spatial distribution patterns of numerical chromosome aberrations in vivo in a series of 24 GBM using two-color in situ hybridization for chromosomes 7/10, 8/17, and 12/18 on consecutive 6-microm paraffin-embedded tissue slides. The chromosome aberration patterns were compared with the histomorphology of the investigated tumor assessed from a consecutive HE-stained section, and with the in vitro karyotype of cell cultures established from the tumors. All investigated chromosomes showed mitotic instability, i.e., numerical aberrations within significant amounts of tumor cells in a scattered distribution through the tumor tissue. As to chromosomes 10 and 17, only monosomy occurred, as to chromosome 7 only trisomy/polysomy, apparently as a result of selection in favor of the respective aberration. Conversely, chromosomes 8, 12, and 18 displayed scattered patterns of monosomy as well as trisomy within a given tumor reflecting a high mitotic error rate without selective effects. The karyotypes of the tumor cell cultures showed less variability of numerical aberrations apparently due to clonal adaptation to in vitro conditions. We conclude that glioblastoma cells in vivo are characterized by an extensive tendency to mitotic errors. The resulting clonal diversity of chromosomally aberrant cells may be an important biological constituent of the well-known ability of glioblastomas to preserve viable tumor cell clones under adaptive stress in vivo, in clinical terms to rapidly recur after antitumoral therapy including radio- or chemotherapy.

Adult↗