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PubMed2003

Spectral biclustering of microarray data: coclustering genes and conditions.

Global analyses of RNA expression levels are useful for classifying genes and overall phenotypes. Often these classification problems are linked, and one wants to find "marker genes" that are differentially expressed in particular sets of "conditions." We have developed a method that simultaneously clusters genes and conditions, finding distinctive "checkerboard" patterns in matrices of gene expression data, if they exist. In a cancer context, these checkerboards correspond to genes that are markedly up- or downregulated in patients with particular types of tumors. Our method, spectral biclustering, is based on the observation that checkerboard structures in matrices of expression data can be found in eigenvectors corresponding to characteristic expression patterns across genes or conditions. In addition, these eigenvectors can be readily identified by commonly used linear algebra approaches, in particular the singular value decomposition (SVD), coupled with closely integrated normalization steps. We present a number of variants of the approach, depending on whether the normalization over genes and conditions is done independently or in a coupled fashion. We then apply spectral biclustering to a selection of publicly available cancer expression data sets, and examine the degree to which the approach is able to identify checkerboard structures. Furthermore, we compare the performance of our biclustering methods against a number of reasonable benchmarks (e.g., direct application of SVD or normalized cuts to raw data).

Breast Neoplasms↗
PubMedDate not supplied

Rosenthal fibres are based on the ubiquitination of glial filaments.

Immunocytochemical localization of the cell stress-associated protein ubiquitin was performed on human lesions containing Rosenthal fibres. Ubiquitin was localized around the periphery of classical Rosenthal fibres but not in the amorphous central areas; the ubiquitin-positive regions corresponded to the immunocytochemical localization of glial fibrillary acidic protein (GFAP). Compact bundles of GFAP in glial processes without a non-staining core were also associated with ubiquitin, while loosely aggregated cellular GFAP was not. The relationship between compact bundles of GFAP and the amorphous osmiophilic central component of Rosenthal fibres has been uncertain. These data, however, show that the compact bundles of glial filaments are distinct from normal GFAP in being associated with ubiquitin. A role for ubiquitin in Rosenthal fibre formation is suggested. We propose that the term Rosenthal fibre be restricted to mean the hyaline amorphous core of these structures, while realizing that this is based on a wider abnormality of surrounding glial fibrillary acidic protein filaments.

Astrocytes↗
PubMed2006

Risk of cancer in children with the diagnosis immaturity at birth.

Cancer risk in children born before term has been assessed in a large number of case-control studies but very rarely in cohort studies. We carried out a cohort study of 35 178 children with the diagnosis immaturity at birth in the Hospital Discharge Register during 1977-89. The children were followed for cancer in the Danish Cancer Registry until 1994 and comparisons were made with incidence rates for all children in Denmark. The 64 observed cases of childhood cancer in the cohort corresponded closely to the expected number {standardised incidence ratio (SIR) = 1.03; [95% confidence interval (CI) 0.80, 1.32]}. The only cancer site with an observed number that deviated significantly from the expected number was central nervous system (CNS) tumours (26 cases observed; SIR = 1.57; [95% CI 1.02, 2.30]) in particular medulloblastoma (9 cases observed; SIR = 3.1; [95% CI 1.4, 5.9]). In a nested case-control study of the CNS tumours, we found that more cases than controls had been exposed to diagnostic X-rays, but the result was not significant. Surprisingly, for those born before term, the risk of CNS tumours increased with increasing gestational age in the nested case-control data. Our results are in line with previous evidence that children born before term are not at increased risk for childhood cancer in general. An explanation behind the excess of CNS tumours could not be identified, but the effect of diagnostic X-rays in newborns may deserve further attention.

Adolescent↗
PubMed1985

Decreased cerebrospinal fluid glutamine levels in patients with benign brain tumors.

CSF glutamine concentrations were studied in 12 patients with benign brain tumors (meningioma, craniopharyngioma, or osteofibroma), 12 patients with malignant brain tumors (astrocytoma, medulloblastoma, pinealoblastoma, or chondrosarcoma), 9 patients with noncerebral tumors, and a reference group of 24 patients. The mean +/- SD levels in the benign tumor group (424 +/- 124 microM) were significantly lower (p less than 0.0004) than those in the reference group (642 +/- 195 microM). There was no significant difference between the CSF glutamine concentrations in the malignant cerebral tumor group (643 +/- 210 microM) or noncerebral tumor group (599 +/- 127 microM) and those in the reference group. In patients with benign brain tumors there was indication of an inverse linear relationship between the logarithm of CSF glutamine concentration and tumor diameter.

Adolescent↗
PubMed1992

Malignant meningioma metastasizing through the cerebrospinal pathway.

A case of malignant meningioma metastasizing through the cerebrospinal pathway is presented. The primary tumor was a parasagittal malignant meningioma invading into the brain. The tumor seeded to the cerebellopontine angle cistern and thoracic spine after multiple operations. Although this type of tumor borders the CSF, metastasis through the cerebrospinal pathway is rare, and only 18 such cases have been reported (2, 3, 10, 12).

Brain Neoplasms↗
PubMed1956

Medulloblastomas.

Explore the source record for details and available documents.

Brain Neoplasms↗
PubMed2000

Low frequency of SV40, JC and BK polyomavirus sequences in human medulloblastomas, meningiomas and ependymomas.

Several reports have suggested a role for polyomaviruses in the pathogenesis of human brain tumors. This potential involvement is not conclusively resolved. For the present study, a highly sensitive PCR-assay with fluorescence-labelled primers was developed to search for polyomavirus sequences in human brain tumor and control DNA samples. The assay was shown to detect approximately one viral large T-antigen (TAg) gene per 250 cells. We identified simian virus 40 (SV40)-like sequences in 2/116 medulloblastomas, in 1/131 meningiomas, in 1/25 ependymomas and in 1/2 subependymomas. A single case of ependymoma contained SV40 VP-1 late gene sequences. Moreover, one of the meningioma samples showed JC virus sequences. In contrast, 60 hepatoblastoma samples and 31 brain samples from schizophrenic patients were consistently negative. BK virus sequences were not detectable in any of our samples. Immunohistochemical analysis of two SV40 positive tumor biopsies failed to detect large TAg in the tumor cells. In the JC positive meningioma, immunoreactivity for the viral late gene product (VP-1) was not observed. Our data do not entirely rule out SV40 and JC virus as an initiative agent with a hit-and-run mechanism. However the low frequency of virus sequences and the absence of TAg protein expression argue against a major role of these viruses in the pathogenesis of human medulloblastomas, meningiomas and ependymomas.

BK Virus↗
PubMed2003

Cerebrospinal fluid from a dog with neurologic collapse.

A 3-year-old Staffordshire Terrier was presented to the Texas Veterinary Medical Center with a short progressive history of anorexia, weight loss, and weakness that had progressed to ataxia and collapse with empirical treatment. The dog was tetraparetic and obtunded. Results of a complete neurologic evaluation were consistent with severe, multifocal to diffuse disease involving the forebrain, spinal cord, and brainstem. Cerebrospinal fluid, obtained via cerebellomedullary cisternal puncture, was highly cellular and contained large atypical round cells with small numbers of nondegenerate neutrophils and large mononuclear cells. Rare eosinophils and small lymphocytes were noted. The atypical round cells were approximately 15-25 micro m in diameter with a single nucleus set in a small amount of cytoplasm. The nuclei were typically round to slightly ovoid; however, occasional notched, lobulated, and reniform nuclei were observed. These cells were interpreted as malignant lymphocytes. Owing to a grave prognosis, the animal was euthanized and a necropsy was performed. No gross lesions were found in the central nervous system. Multiple sections of cerebellum, medulla, and spinal cord contained a diffuse neoplastic infiltrate that was predominantly meningeal with rare superficial neuropil invasion. The neoplastic cells were arranged in sheets, cords, and rosettes. Immunohistochemical staining for vimentin, pancytokeratin, CD3, CD79a, synaptophysin, S-100, and neuron-specific enolase was negative; glial fibrillary acidic protein (GFAP) staining was equivocal. Based on histologic findings, a diagnosis of medulloblastoma was made. This case documents the rare occurrence of a canine medulloblastoma and illustrates the difficulty in distinguishing between some embryonal brain tumors and lymphoma.

Animals↗
PubMed1981

Psychological sequelae of brain tumours in childhood: a retrospective study.

Forty-seven patients who had been treated for brain tumours during childhood were assessed on standardized measures of intellectual ability. Five patients could not be satisfactorily assessed. For the remaining 42, the mean IQ was lower than expected (09.0), with 20 patients having scores in the 'below average' categories. There were no apparent effects in IQ between patients treated for different tumours, but patients treated before five years of age had significantly lower scores (mean equal 76.54) than patients treated from 6-10 years (mean 91.86) and 10-16 years (99-93). There was wide variability in educational achievement and type of employment among the group.

Achievement↗
PubMedDate not supplied

Solution to treatment planning problems using coordinate transformations.

The majority of radiation treatment planning problems are relatively straightforward, involving only specified gantry angles in a treatment plane which is perpendicular to the patient longitudinal axis. In addition, there are a number of more complex three-dimensional problems which require combined rotation of the gantry, collimator, and turntable for their solutions. These include, for example, the use of non-coplanar fields and oblique treatment planes, the matching of field edges in three dimensions, the treatment of the breast with opposing tangential fields, and the treatment of inclined elongated lesions. Unfortunately, there is no general systematic approach to the solution of these more complex problems. One may attempt an analytic solution, but this approach is often too cumbersome and tedious. On the other hand, one may resort to a "trial and error" session with the simulator. This paper, therefore, presents a mathematical method which is easily applied and applicable to a wide variety of complex three-dimensional treatment planning problems. The method considers the gantry, collimator, and turntable as coordinate systems. These coordinate systems are derivable from each other by specified coordinate transformations, which contain the rotation angles of the gantry, collimator, and turntable. Within this mathematical framework, the treatment planning problems are found to reduce to two general types, of which various clinical examples are then given.

Breast Neoplasms↗
PubMed1964

TUMOURS OF THE CENTRAL NERVOUS SYSTEM IN CHILDREN.

One hundred and fifty-five tumours of the central nervous system which occurred in children in the north west of England during a period of nine years are analysed from a pathological point of view. It is probable that these represent over 90% of all such tumours occurring in the region at that time and that the relative incidence of various tumour types is, therefore, a true one: just over a fifth (35) were medulloblastomas; just under a fifth (29) were juvenile astrocytomas; a similar group (33) were of the adult astrocytic type; there were 24 ependymomas and 34 in miscellaneous minor groups.

Adolescent↗
PubMed2000

Gene amplification in PNETs/medulloblastomas: mapping of a novel amplified gene within the MYCN amplicon.

OBJECTIVES: The pathological entity of primitive neuroectodermal tumour/medulloblastoma (PNET/MB) comprises a very heterogeneous group of neoplasms on a clinical as well as on a molecular level. We evaluated the importance of DNA amplification in medulloblastomas and other primitive neuroectodermal tumours (PNETs) of the CNS. METHOD: Restriction landmark genomic scanning (RLGS), a method that allows the detection of low level amplification, was used. RLGS provides direct access to DNA sequences circumventing positional cloning efforts. Furthermore, we analysed several samples by CGH. DESIGN: Twenty primary medulloblastomas, five supratentorial PNETs, and five medulloblastoma cell lines were studied. RESULTS: Although our analysis confirms that gene amplification is generally a rare event in childhood PNET/MB, we found a total of 17 DNA fragments that were amplified in seven different tumours. Cloning and sequencing of several of these fragments confirmed the previous finding of MYC amplification in the cell line D341 Med and identified novel DNA sequences amplified in PNET/MB. We describe for the first time amplification of the novel gene, NAG, in a subset of PNET/MB. Despite genomic amplification, NAG was not overexpressed in the tumours studied. We have determined that NAG maps less than 50 kb 5' of DDX1 and approximately 400 kb telomeric of MYCN on chromosome 2p24. CONCLUSION: We found a similar but slightly higher frequency of amplification than previously reported. We present several DNA fragments that may belong to the CpG islands of novel genes amplified in a small subset of PNET/MB. As an example we describe for the first time the amplification of NAG in the MYCN amplicon in PNET/MB.

Blotting, Northern↗